Preface

Pulmonary medicine obviously continues to be a discipline that is attracting bright, dedicated, and sincerely adventurous individuals, a discipline that is rapidly evolving and changing. Though asthma and chronic obstructive pulmonary disease still claim the role of "kings" in respiratory medicine, huge progress is being made also in other areas.

Today, we live in an era of transition for pulmonologists, prompting John Hansen-Flaschen, Professor of Medicine at the University of Pennsylvania, to call them "spironauts": scientists with a wider role both in critical care and sleep medicine.

Within this frame, this book, published by IntechOpen, focuses on interesting aspects of pulmonary medicine. The first section of the book is dedicated to interventional pulmonology, and includes updates on bronchial thermoplasty, virtual bronchoscopy, and endobronchial ultrasound. The second section highlights special aspects of pulmonary circulation and pulmonary hypertension. Throughout the book, the authors offer us not only a "vigorous" review of the current literature but also a research path to further advancement.

> **Dr. Theodoros Aslanidis** Intensive Care Unit, St. Paul General Hospital, Thessaloniki, Greece

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

Introductory Chapter: Whole

Since its first description in 1958 by Samuel H. Rosen et al., understanding pulmonary alveolar proteinosis (PAP) (or pulmonary alveolar lipoproteinosis or pulmonary alveolar phospholipidosis) has made a tremendous advance [1].

Today, PAP remains a rare lung disease. Prevalence ranges from 3.7 to 40 cases per million, depending on the country, and the incidence has been estimated to be 0.2 cases per million. The main pathological mechanism behind the disease is the accumulation of lipoproteinaceous material in the alveoli due to dysfunctional clearance by alveolar macrophages or type II epithelial cells. There are three clinically distinct forms: (1) congenital, caused by mutations in the CSF2RA gene on chromosome Xp22.33 or impaired CSF2RB expression. The result is a dysfunctional α or β granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor subunit. (2) Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages (hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections). (3) Finally, autoimmune PAP is initiated by immunoglobulin (Ig)-G anti-granulocyte-macrophage colonystimulating factor (anti-GM-CSF) antibodies, which decrease functional alveolar

Clinical presentation of PAP varies: dyspnea, cough, hemoptysis, fever, and chest pain appear in a different range, while signs of chronic respiratory failure (cyanosis, clubbing, inspiratory crackles) can be found in clinical examination. Diagnosis demands appropriate serological, radiological, and bronchoscopic

Unfortunately, apart from the conditions in which etiological therapy is available,

therapeutic options remain limited. Supplementation of exogenous granulocytemacrophage colony-stimulating factor (GM-CSF) or strategies aimed at reducing the levels of the autoantibodies, like plasmapheresis or rituximab—a monoclonal antibody directed against the CD20 antigen of B-lymphocytes and ameliorates PAP by decreasing anti-GM-CSF antibody concentration—are promising approaches. Other options like stem cell or lung transplantation have more limited use.

evaluation and opting out other interstitial lung diseases [3].

Lung Lavage for Pulmonary

Alveolar Proteinosis—The

Challenges Remain

**1. Pulmonary alveolar proteinosis**

*Theodoros Aslanidis*

macrophages [2].

**2. Therapeutic options**

#### **Chapter 1**

## Introductory Chapter: Whole Lung Lavage for Pulmonary Alveolar Proteinosis—The Challenges Remain

*Theodoros Aslanidis*

#### **1. Pulmonary alveolar proteinosis**

Since its first description in 1958 by Samuel H. Rosen et al., understanding pulmonary alveolar proteinosis (PAP) (or pulmonary alveolar lipoproteinosis or pulmonary alveolar phospholipidosis) has made a tremendous advance [1].

Today, PAP remains a rare lung disease. Prevalence ranges from 3.7 to 40 cases per million, depending on the country, and the incidence has been estimated to be 0.2 cases per million. The main pathological mechanism behind the disease is the accumulation of lipoproteinaceous material in the alveoli due to dysfunctional clearance by alveolar macrophages or type II epithelial cells. There are three clinically distinct forms: (1) congenital, caused by mutations in the CSF2RA gene on chromosome Xp22.33 or impaired CSF2RB expression. The result is a dysfunctional α or β granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor subunit. (2) Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages (hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections). (3) Finally, autoimmune PAP is initiated by immunoglobulin (Ig)-G anti-granulocyte-macrophage colonystimulating factor (anti-GM-CSF) antibodies, which decrease functional alveolar macrophages [2].

Clinical presentation of PAP varies: dyspnea, cough, hemoptysis, fever, and chest pain appear in a different range, while signs of chronic respiratory failure (cyanosis, clubbing, inspiratory crackles) can be found in clinical examination.

Diagnosis demands appropriate serological, radiological, and bronchoscopic evaluation and opting out other interstitial lung diseases [3].

#### **2. Therapeutic options**

Unfortunately, apart from the conditions in which etiological therapy is available, therapeutic options remain limited. Supplementation of exogenous granulocytemacrophage colony-stimulating factor (GM-CSF) or strategies aimed at reducing the levels of the autoantibodies, like plasmapheresis or rituximab—a monoclonal antibody directed against the CD20 antigen of B-lymphocytes and ameliorates PAP by decreasing anti-GM-CSF antibody concentration—are promising approaches. Other options like stem cell or lung transplantation have more limited use.

On the other hand, whole lung lavage (WLL) is the standard first-line therapy [4]. Theoretic concept behind WLL is simple. Clinical and physiological improvement is caused by the removal of lipoproteinaceous material and anti-GM-CSF antibodies from the alveolar space. Additional immunological effects on the effector cells (e.g., alveolar macrophages or type II epithelial cells) may also be included.

#### **3. Whole lung lavage: the challenges**

Due to the rarity of the disease, there are no guidelines regarding technical details about WLL. Usually, a dedicated team, which includes experienced anesthesia and respiratory nurses, anesthesiologist, respiratory physiotherapist, and a pulmonologist experienced in interventional pulmonology, is needed to perform the procedure [5].

Indications for WLL also vary. In general, dyspnea-induced limitation of daily activities is the rule, although decline in SpO2 (>70% in room air), radiographic worsening, decline in DLCO or FVC, and other symptoms have also been used [6].

Thus, timing between diagnosis of PAP and WLL varies from 2 months to 17 years, although most of the patients need WLL within a year from diagnosis [5]. Time of repeating WLL depends on patient's condition [2]. Available literature reports an interval between 15 months and 3 years [7, 8]. Three (3) weeks interval between right and left lung WLL is considered safe and long enough for clinical improvement to arise [6]. However, bilateral WLL has also been performed without any problems [9].

Usually, the procedure is performed first in the most severely affected lung. Imaging techniques such as perfusion/ventilation scan can help in the final selection. Patient is positioned usually supine, although multiple positions, like lateral decubitus, Trendelenburg, and prone, have also been reported [10].

The procedure is carried out under general anesthesia. The preferred technique is total intravenous anesthesia, while volatile anesthetics has been used in cases of bronchospasm. After preoxygenation, a left double-lumen endotracheal tube (DLT) with minimum size 26 Fr is used for intubation and lung isolation. Right DLT is avoided due to risk of right upper lobe orifice block [6]. Recently, there also reports—still rare—of noninvasive ventilation (NIV) as alternative to intubation with DLT [11]. The same is valid also for anesthesia, as reports are published for WLL during local anesthesia and the use of fiber-optic bronchoscope [12].

Hypoxemia is common during WLL. Several strategies are suggested in order to cope with the problem: positive end-expiratory pressure (PEEP) application, manual ventilation of partially fluid-filled lung, intermittent double-lung ventilation, concomitant use of inhaled nitric oxide, ipsilateral occlusion of pulmonary artery of the non-ventilated lung via pulmonary artery catheter, hyperbaric oxygen therapy, and parallel use of veno-venous extracorporeal membrane oxygenation (ECMO) [6, 10, 13–16]. No guideline or data exist for the use of one method over the others.

In most of the literature warmed (to 37°C) NaCl 0.9% is reported as lung fluid. The total volume needed ranges from 30 to 50 liters [6]. The fluid can flow by gravitational force in 500–1000 ml or FRC equivalent volume aliquots for 10–30 cycles. The maximum pressure allowed should be below the sealing pressure of the ventilated lung (between 30 and 50 cm). In case of fiber-optic bronchoscopic lavage under local anesthesia, 50 ml aliquots are used [12].

The mechanism of protein transfer from the surfactant and blood into the lavage fluid during WLL has not been sufficiently studied. A recent report suggests a mathematical model—expressed with several differential equations—based on

**5**

provided the original work is properly cited.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Intensive Care Unit, St. Paul General Hospital, Thessaloniki, Greece

\*Address all correspondence to: thaslan@hotmail.com

*Introductory Chapter: Whole Lung Lavage for Pulmonary Alveolar Proteinosis—The Challenges…*

diffusion for the transfer of most of the substances. However, there are still components of the alveolar proteinaceous material—mainly with low molecular weight—

Chest percussion with a wraparound vest or manual percussion by a physiotherapist is applied for 3–5 minutes, in order to increase clearance of proteinaceous material. This can be performed throughout the procedure (from installation to removal of the fluid). Till now, there is no comparative study for the method of percussion; still, some authors claim that mechanical percussion with vest is best

Intraoperative monitoring varies, yet it generally includes invasive arterial blood pressure for serial arterial blood gases examination. Recently, lung ultrasound has been also suggested as a promising method of monitoring the amount of saline used

In the immediate post-procedure phase, diuretics can help clearing fluid from the lung [8], while follow-up is usually performed via chest X-ray or computer

Complication rate ranges from 0.8% for pneumothorax to 18% for transient fever; other complications are hypoxemia, pleural effusion, pneumonia, wheezing, etc. [6]. Long-term efficiency of the procedure is generally good, though available

Almost 70 years after its first application and despite the lack of an alternative option, WLL performance and efficiency continues to rely mostly on local expertise and experience. Yet, as the available database knowledge is increasing (especially after 1990) and the indication for WLL include more and more conditions (i.e., pneumoconiosis, silicosis, lipoid pneumonia), it may be the time for a guideline or for a minimum consensus upon to improve future procedure's safety and efficiency

*DOI: http://dx.doi.org/10.5772/intechopen.86073*

tolerated [10].

tomography imaging [6].

**4. Conclusion: time for a consensus?**

and facilitate everyday clinical decision-making.

The author has no conflict of interest.

literature is limited.

**Conflict of interests**

**Author details**

Theodoros Aslanidis

which do not follow the suggested model [17].

for lavage and pick-up complications like pleural effusion [18].

*Introductory Chapter: Whole Lung Lavage for Pulmonary Alveolar Proteinosis—The Challenges… DOI: http://dx.doi.org/10.5772/intechopen.86073*

diffusion for the transfer of most of the substances. However, there are still components of the alveolar proteinaceous material—mainly with low molecular weight which do not follow the suggested model [17].

Chest percussion with a wraparound vest or manual percussion by a physiotherapist is applied for 3–5 minutes, in order to increase clearance of proteinaceous material. This can be performed throughout the procedure (from installation to removal of the fluid). Till now, there is no comparative study for the method of percussion; still, some authors claim that mechanical percussion with vest is best tolerated [10].

Intraoperative monitoring varies, yet it generally includes invasive arterial blood pressure for serial arterial blood gases examination. Recently, lung ultrasound has been also suggested as a promising method of monitoring the amount of saline used for lavage and pick-up complications like pleural effusion [18].

In the immediate post-procedure phase, diuretics can help clearing fluid from the lung [8], while follow-up is usually performed via chest X-ray or computer tomography imaging [6].

Complication rate ranges from 0.8% for pneumothorax to 18% for transient fever; other complications are hypoxemia, pleural effusion, pneumonia, wheezing, etc. [6].

Long-term efficiency of the procedure is generally good, though available literature is limited.

#### **4. Conclusion: time for a consensus?**

Almost 70 years after its first application and despite the lack of an alternative option, WLL performance and efficiency continues to rely mostly on local expertise and experience. Yet, as the available database knowledge is increasing (especially after 1990) and the indication for WLL include more and more conditions (i.e., pneumoconiosis, silicosis, lipoid pneumonia), it may be the time for a guideline or for a minimum consensus upon to improve future procedure's safety and efficiency and facilitate everyday clinical decision-making.

#### **Conflict of interests**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

**3. Whole lung lavage: the challenges**

the procedure [5].

any problems [9].

On the other hand, whole lung lavage (WLL) is the standard first-line therapy [4]. Theoretic concept behind WLL is simple. Clinical and physiological improvement is caused by the removal of lipoproteinaceous material and anti-GM-CSF antibodies from the alveolar space. Additional immunological effects on the effector cells (e.g., alveolar macrophages or type II epithelial cells) may also be included.

Due to the rarity of the disease, there are no guidelines regarding technical details about WLL. Usually, a dedicated team, which includes experienced anesthesia and respiratory nurses, anesthesiologist, respiratory physiotherapist, and a pulmonologist experienced in interventional pulmonology, is needed to perform

Indications for WLL also vary. In general, dyspnea-induced limitation of daily activities is the rule, although decline in SpO2 (>70% in room air), radiographic worsening, decline in DLCO or FVC, and other symptoms have also been used [6]. Thus, timing between diagnosis of PAP and WLL varies from 2 months to 17 years, although most of the patients need WLL within a year from diagnosis [5]. Time of repeating WLL depends on patient's condition [2]. Available literature reports an interval between 15 months and 3 years [7, 8]. Three (3) weeks interval between right and left lung WLL is considered safe and long enough for clinical improvement to arise [6]. However, bilateral WLL has also been performed without

Usually, the procedure is performed first in the most severely affected lung. Imaging techniques such as perfusion/ventilation scan can help in the final selection. Patient is positioned usually supine, although multiple positions, like lateral

The procedure is carried out under general anesthesia. The preferred technique is total intravenous anesthesia, while volatile anesthetics has been used in cases of bronchospasm. After preoxygenation, a left double-lumen endotracheal tube (DLT) with minimum size 26 Fr is used for intubation and lung isolation. Right DLT is avoided due to risk of right upper lobe orifice block [6]. Recently, there also reports—still rare—of noninvasive ventilation (NIV) as alternative to intubation with DLT [11]. The same is valid also for anesthesia, as reports are published for WLL during local anesthesia and the use of fiber-optic bronchoscope [12].

Hypoxemia is common during WLL. Several strategies are suggested in order to cope with the problem: positive end-expiratory pressure (PEEP) application, manual ventilation of partially fluid-filled lung, intermittent double-lung ventilation, concomitant use of inhaled nitric oxide, ipsilateral occlusion of pulmonary artery of the non-ventilated lung via pulmonary artery catheter, hyperbaric oxygen therapy, and parallel use of veno-venous extracorporeal membrane oxygenation (ECMO) [6, 10, 13–16]. No guideline or data exist for the use of one method over

In most of the literature warmed (to 37°C) NaCl 0.9% is reported as lung fluid. The total volume needed ranges from 30 to 50 liters [6]. The fluid can flow by gravitational force in 500–1000 ml or FRC equivalent volume aliquots for 10–30 cycles. The maximum pressure allowed should be below the sealing pressure of the ventilated lung (between 30 and 50 cm). In case of fiber-optic bronchoscopic lavage

The mechanism of protein transfer from the surfactant and blood into the lavage fluid during WLL has not been sufficiently studied. A recent report suggests a mathematical model—expressed with several differential equations—based on

under local anesthesia, 50 ml aliquots are used [12].

decubitus, Trendelenburg, and prone, have also been reported [10].

**4**

the others.

The author has no conflict of interest.

#### **Author details**

Theodoros Aslanidis Intensive Care Unit, St. Paul General Hospital, Thessaloniki, Greece

\*Address all correspondence to: thaslan@hotmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. The New England Journal of Medicine. 1958;**258**(23):1123-1142

[2] Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, et al. Pulmonary alveolar proteinosis. European Respiratory Review. 2011;**20**(120):98-107

[3] Campo I, Mariani F, Rodi G, Paracchini E, Tsana E, Piloni D, et al. Assessment and management of pulmonary alveolar proteinosis in a reference center. Orphanet Journal of Rare Diseases. 2013;**8**:40

[4] Suzuki T, Trapnell BC. Pulmonary alveolar proteinosis syndrome. Clinics in Chest Medicine. 2016;**37**(3):431-440

[5] Gay P, Wallaert B, Nowak S, Yserbyt J, Anevlavis S, Hermant C, et al. Efficacy of whole-lung lavage in pulmonary alveolar proteinosis: A multicenter international study of GELF. Respiration. 2017;**93**:198-120

[6] Campo I, Luisetti M, Griese M, et al. Whole lung lavage therapy for pulmonary alveolar proteinosis: A global survey of current practices and procedures. Orphanet Journal of Rare Diseases. 2016;**11**:115

[7] Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: Progress in the first 44 years. American Journal of Respiratory and Critical Care Medicine. 2002;**166**:215-235

[8] Beccaria M, Luisetti M, Rodi G, et al. Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. The European Respiratory Journal. 2004;**23**:526-531

[9] Silva A, Moreto A, Pinho C, et al. Bilateral whole lung lavage in pulmonary alveolar proteinosis—A retrospective study. Revista Portuguesa de Pneumologia. 2014;**20**:254-259

[10] Awab A, Khan MS, Youness HA. Whole lung lavage-technical details, challenges and management of complications. Journal of Thoracic Disease. 2017;**9**(6):1697-1706

[11] Skoczynski S, Wyskida K, Rzepka-Wrona P, et al. Novel method of noninvasive ventilation supported therapeutic lavage in pulmonary alveolar proteinosis proves to relieve dyspnea, normalize pulmonary function test results and recover exercise capacity: A short communication. Journal of Thoracic Disease. 2018;**10**(4):2467-2473

[12] Cheng S, Chang HI, Lau HP, Lee LN, Yang PC. Treatment by bronchofiberscopic lobar lavage: Pulmonary alveolar proteinosis. Chest. 2002;**122**:1480-1485

[13] Rebelo H, Guedes L, Veiga D, Fiuza A, Abelha F. Anaesthetic, procedure and complication management serial lung lavagein an obese patient with alveolar proteinosis: A case report. Revista Brasileira de Anestesiologia. 2012;**62**(6):869-877

[14] Ahmed R, Iqbal M, Kashef SH, Almomatten MI. Whole lung lavage with intermittent double lung ventilation. A modified technique for managing pulmonary alveolar proteinosis. Saudi Medical Journal. 2005;**26**(1):139141

[15] Moutafis M, Dalibon N, Colchen A, Fischler M. Improving oxygenation during bronchopulmonary lavage using nitric oxide inhalation and almitrine infusion. Anesthesia and Analgesia. 1999;**89**(2):302

[16] Nadeau MJ, Côté D, Bussières JS. The combination of inhaled nitric oxide

**7**

*Introductory Chapter: Whole Lung Lavage for Pulmonary Alveolar Proteinosis—The Challenges…*

*DOI: http://dx.doi.org/10.5772/intechopen.86073*

and pulmonary artery balloon inflation improves oxygenation during wholelung lavage. Anesthesia and Analgesia.

[17] Akasaka K, Tanaka T, Maruyama T, Kitamura N, Hashimoto A, Ito Y, et al. A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2015;**308**:L105-L117. (First published November 14, 2014. DOI: 10.1152/

[18] Ramachandran P, Chaudhury A, Devaraj U, Maheshwari KU, D'Souza G. Monitoring whole-lung lavage using lung ultrasound: The changing phases of the lung. Lung India. 2018;**35**:350-353

2004;**99**(3):676-679

ajplung.00239.2014

*Introductory Chapter: Whole Lung Lavage for Pulmonary Alveolar Proteinosis—The Challenges… DOI: http://dx.doi.org/10.5772/intechopen.86073*

and pulmonary artery balloon inflation improves oxygenation during wholelung lavage. Anesthesia and Analgesia. 2004;**99**(3):676-679

[17] Akasaka K, Tanaka T, Maruyama T, Kitamura N, Hashimoto A, Ito Y, et al. A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2015;**308**:L105-L117. (First published November 14, 2014. DOI: 10.1152/ ajplung.00239.2014

[18] Ramachandran P, Chaudhury A, Devaraj U, Maheshwari KU, D'Souza G. Monitoring whole-lung lavage using lung ultrasound: The changing phases of the lung. Lung India. 2018;**35**:350-353

**6**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

retrospective study. Revista Portuguesa de Pneumologia. 2014;**20**:254-259

[11] Skoczynski S, Wyskida K, Rzepka-Wrona P, et al. Novel method of noninvasive ventilation supported therapeutic lavage in pulmonary alveolar proteinosis proves to relieve dyspnea, normalize pulmonary function

[10] Awab A, Khan MS, Youness HA. Whole lung lavage-technical details, challenges and management of complications. Journal of Thoracic

Disease. 2017;**9**(6):1697-1706

test results and recover exercise capacity: A short communication. Journal of Thoracic Disease. 2018;**10**(4):2467-2473

[12] Cheng S, Chang HI, Lau HP, Lee LN, Yang PC. Treatment by bronchofiberscopic lobar lavage: Pulmonary alveolar proteinosis. Chest.

[13] Rebelo H, Guedes L, Veiga D, Fiuza A, Abelha F. Anaesthetic, procedure and complication management serial lung lavagein an obese patient with alveolar proteinosis: A case report. Revista Brasileira de Anestesiologia.

2002;**122**:1480-1485

2012;**62**(6):869-877

2005;**26**(1):139141

1999;**89**(2):302

[14] Ahmed R, Iqbal M, Kashef SH, Almomatten MI. Whole lung lavage with intermittent double lung ventilation. A modified technique for managing pulmonary alveolar proteinosis. Saudi Medical Journal.

[15] Moutafis M, Dalibon N, Colchen A, Fischler M. Improving oxygenation during bronchopulmonary lavage using nitric oxide inhalation and almitrine infusion. Anesthesia and Analgesia.

[16] Nadeau MJ, Côté D, Bussières JS. The combination of inhaled nitric oxide

[1] Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. The New England Journal of Medicine.

[2] Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, et al. Pulmonary alveolar proteinosis. European Respiratory Review.

[3] Campo I, Mariani F, Rodi G, Paracchini E, Tsana E, Piloni D, et al. Assessment and management of pulmonary alveolar proteinosis in a reference center. Orphanet Journal of

[4] Suzuki T, Trapnell BC. Pulmonary alveolar proteinosis syndrome. Clinics in Chest Medicine. 2016;**37**(3):431-440

[5] Gay P, Wallaert B, Nowak S, Yserbyt J, Anevlavis S, Hermant C, et al. Efficacy of whole-lung lavage in pulmonary alveolar proteinosis: A multicenter international study of GELF. Respiration. 2017;**93**:198-120

[6] Campo I, Luisetti M, Griese M, et al. Whole lung lavage therapy for pulmonary alveolar proteinosis: A global survey of current practices and procedures. Orphanet Journal of Rare

[7] Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: Progress in the first 44 years. American Journal of Respiratory and Critical Care Medicine.

[8] Beccaria M, Luisetti M, Rodi G, et al. Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. The European Respiratory

Diseases. 2016;**11**:115

2002;**166**:215-235

Journal. 2004;**23**:526-531

[9] Silva A, Moreto A, Pinho C, et al. Bilateral whole lung lavage in pulmonary alveolar proteinosis—A

1958;**258**(23):1123-1142

**References**

2011;**20**(120):98-107

Rare Diseases. 2013;**8**:40

**9**

Section 2

Interventional

Pulmonology

Section 2

Interventional Pulmonology

**11**

**Chapter 2**

**Abstract**

**1. Introduction**

**2. Technical aspects**

**2.1 EBUS bronchoscope**

EUS-B for the Interventional

Scope in the Esophagus

*Yousef R. Shweihat and Shantanu Singh*

related complications and contraindications are also described.

Pulmonologist Using the EBUS

This chapter aims at introducing the interested Pulmonologist/Interventional Pulmonologist to the esophageal ultrasound. In this chapter, we give short descriptions of some technical aspects of the endobronchial ultrasound (EBUS) scope and explain in detail why we believe the EBUS scope is well suited to be an esophageal scope in the hands of the trained pulmonologist. The chapter then explains indications and benefits of this procedure that we consider central to the practice of chest physicians. We also describe in steps how to reach each lymph node station using the EBUS scope as a EUS scope (EUS-B) from our own experience. Procedure-

**Keywords:** esophageal ultrasound, endobronchial ultrasound, lymph node stations

Interventional pulmonary has witnessed substantial growth in the past few years. A major factor in the growth has been the advent of endobronchial ultrasound (EBUS) as a staging modality for lung cancer and as a diagnostic tool for diseases with mediastinal involvement. The development of EBUS was preceded by esophageal ultrasound (EUS), and the literatures on both techniques have grown in parallel. More recently, the efficacy and utility of an esophageal approach using the EBUS scope (EUS-B) has been described to access nodes and masses accessible during a single sedation to more accurately diagnose and stage disease either via tracheal or esophageal route. Here, we describe relevant anatomy, procedural

techniques, indications, contraindications, and complications for EUS-B.

EBUS can refer to two distinct types of probes/scopes. Radial probe EBUS is the first type, and was commercially available in 1992. It increased the yield of transbronchial needle aspiration of mediastinal lymph nodes and is currently used mainly to biopsy peripheral nodules or examines the different central airways diseases. The second type is the convex/curvilinear probe EBUS bronchoscope. It was introduced in 2002 and commercialized around 2004. In this chapter, our

#### **Chapter 2**

## EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus

*Yousef R. Shweihat and Shantanu Singh*

#### **Abstract**

This chapter aims at introducing the interested Pulmonologist/Interventional Pulmonologist to the esophageal ultrasound. In this chapter, we give short descriptions of some technical aspects of the endobronchial ultrasound (EBUS) scope and explain in detail why we believe the EBUS scope is well suited to be an esophageal scope in the hands of the trained pulmonologist. The chapter then explains indications and benefits of this procedure that we consider central to the practice of chest physicians. We also describe in steps how to reach each lymph node station using the EBUS scope as a EUS scope (EUS-B) from our own experience. Procedurerelated complications and contraindications are also described.

**Keywords:** esophageal ultrasound, endobronchial ultrasound, lymph node stations

#### **1. Introduction**

Interventional pulmonary has witnessed substantial growth in the past few years. A major factor in the growth has been the advent of endobronchial ultrasound (EBUS) as a staging modality for lung cancer and as a diagnostic tool for diseases with mediastinal involvement. The development of EBUS was preceded by esophageal ultrasound (EUS), and the literatures on both techniques have grown in parallel. More recently, the efficacy and utility of an esophageal approach using the EBUS scope (EUS-B) has been described to access nodes and masses accessible during a single sedation to more accurately diagnose and stage disease either via tracheal or esophageal route. Here, we describe relevant anatomy, procedural techniques, indications, contraindications, and complications for EUS-B.

#### **2. Technical aspects**

#### **2.1 EBUS bronchoscope**

EBUS can refer to two distinct types of probes/scopes. Radial probe EBUS is the first type, and was commercially available in 1992. It increased the yield of transbronchial needle aspiration of mediastinal lymph nodes and is currently used mainly to biopsy peripheral nodules or examines the different central airways diseases. The second type is the convex/curvilinear probe EBUS bronchoscope. It was introduced in 2002 and commercialized around 2004. In this chapter, our

discussion is limited to the most widely available curvilinear scope manufactured by multiple companies (Olympus, Fuji, and Pentax) with minimal differences in characteristics. The differences between scopes are beyond the scope of this text. The reader is encouraged to be familiar with the specifications of the scopes and their relative US processors available at his/her institution. Some features are worth mentioning though which are big difference between the EBUS and conventional EUS scopes. The working tube of about 60 cm is much shorter than the EUS. The largest intubating diameter at the tip of the EBUS scopes ranges from 6.7 to 7.4 mm. The remainder of the insertion tubes has a diameter of 6.3–6.4 mm. The working channel diameter is from 2.0 to 2.2 mm. The ultrasonic transducer is situated at the tip of the bronchoscope just distal to the video camera, light source, and the working channel aperture. It emits ultrasonic waves that range from 5 to 12 MHz, and this depends on the ultrasound processor used and settings selected. The ultrasonic scanning range obtained via these scopes is triangular in shape and yields a 60–75° view parallel to the insertion tube. The tissue depth of ultrasonic views and focusing capabilities can be altered and varies according to the ultrasound processor used. Multiple manufacturers offer single-use aspiration needles available in 19G, 21G, and 22G with excellent puncture capability under ultrasonic view. The design improves visibility on ultrasound images to enable a precise puncture. After loading and securing the needle in the working channel, the needle extends out of the channel and intersects with the ultrasonic view enabling the endoscopist to control the depth and location of needle insertion into the lymph node in a real time fashion.

#### **2.2 Why the EBUS scope, not the EUS scope?**

The EBUS scope is different in many ways from its counterpart used in the GI tract. **First**, the diameter is almost half of any available ultrasound endoscope. In our opinion, this makes the bronchoscope more comfortable for the patient, and reduces sedation requirement. **Second**, the control part of the bronchoscope has fewer controllers making it easier for the pulmonologist to handle. It is a design that they are used to and comfortable using with no need for extra training to be able to handle it. This in our opinion shortens the learning curve. **Third**, it enables the thoracic physician to completely evaluate the mediastinum in one session using one piece of equipment. This minimizes the costs of additional equipment and need for additional procedure without compromising on patient management. **Fourth**, the EBUS scope is shorter than the EUS scope, thus enhancing maneuverability. This shorter length is well suited for sampling thoracic and mediastinal structures. Sampling of the pancreas or abdominal lymph nodes is out of the scope and expertise of most thoracic physicians. Added length of the EUS scope does not offer additional advantage to a practicing pulmonologist.

#### **3. Indications**

One of the major advances in the treatment of lung cancer is the advent of non-surgical pathologic staging using EBUS. The combination of EBUS and EUS for sampling of mediastinal nodes allows near complete staging of the mediastinum [1–3], which is equivalent, if not superior to mediastinoscopy in experienced hands [4, 5]. Multiple studies showed the EBUS scope efficacious in serving the EUS scope role (EUS-B) [6, 7]. The added benefit of the esophageal access in staging lung cancer comes from its ability to reach and locate lymph nodal stations that are impossible to reach via the airways such as stations 3p, and paraesophageal lymph nodal

**13**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

**Lymph node station EBUS EUS-B** 1 + − 2R + + 2L + + 3a − − 3p − + 4R + − 4L + + 5 − + 6 − \* 7 + + 8 R,L − + 9 R,L − + 10–12 R,L + −

stations 8 and 9 (see **Table 1** for lymph node stations accessible by EBUS and EUS). Given the literature on combined EBUS and EUS, it can be argued that EBUS and EUS-B should be performed at the same time for all patients with suspected lung cancer at institutions where rapid on-site cytologic evaluation is not available. This approach is recommended by the European Society of Gastrointestinal Endoscopy (ESGE) and European Respiratory Society (ERS) guidelines [8]. The utility of EBUS and EUS-B is not limited to staging or diagnosis of lung cancer. The EBUS has well documented advantages in diagnosing mediastinal lymphoma [9–11], sarcoidosis [12–14], tuberculosis [15, 16], pulmonary parenchymal masses [17, 18], and metastatic disease to the mediastinum [19], among others including infections [9, 20]. EUS-B has the same ability to investigate the mediastinum when such conditions are suspected, since the utility of EUS is well documented in such disease states [21, 22]. In addition, instances where a mediastinal mass or lymphadenopathy is paraesophageal and paratracheal, the esophageal approach might be preferred, especially when there is difficulty to access the airway due to patient intolerance or if accessing the airway predisposes increase risk to hypoxemic, intubated, and critically ill patients [23]. The indications for EUS-B are summarized in **Table 2**.

Mediastinal masses that can be approached through airway and esophagus, esophagus is preferred for patient

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

**\****reported using EUS but not EUS-B.*

**Indications for EUS-B**

*Lymph nodes accessible by EBUS vs. EUS-B.*

Lung cancer staging, stations 3p, 8, 9, 5, and 4L and 7 Paraesophageal abnormalities not accessible via the airways

Sampling mediastinal lymphadenopathy of any etiology Mediastinal pathology in critically ill or intubated patients

Sampling and drainage of mediastinal cysts

Bleeding diathesis (see text)

**Table 1.**

comfort

**Table 2.**

*Indications for EUS-B.*

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*


#### **Table 1.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

discussion is limited to the most widely available curvilinear scope manufactured by multiple companies (Olympus, Fuji, and Pentax) with minimal differences in characteristics. The differences between scopes are beyond the scope of this text. The reader is encouraged to be familiar with the specifications of the scopes and their relative US processors available at his/her institution. Some features are worth mentioning though which are big difference between the EBUS and conventional EUS scopes. The working tube of about 60 cm is much shorter than the EUS. The largest intubating diameter at the tip of the EBUS scopes ranges from 6.7 to 7.4 mm. The remainder of the insertion tubes has a diameter of 6.3–6.4 mm. The working channel diameter is from 2.0 to 2.2 mm. The ultrasonic transducer is situated at the tip of the bronchoscope just distal to the video camera, light source, and the working channel aperture. It emits ultrasonic waves that range from 5 to 12 MHz, and this depends on the ultrasound processor used and settings selected. The ultrasonic scanning range obtained via these scopes is triangular in shape and yields a 60–75° view parallel to the insertion tube. The tissue depth of ultrasonic views and focusing capabilities can be altered and varies according to the ultrasound processor used. Multiple manufacturers offer single-use aspiration needles available in 19G, 21G, and 22G with excellent puncture capability under ultrasonic view. The design improves visibility on ultrasound images to enable a precise puncture. After loading and securing the needle in the working channel, the needle extends out of the channel and intersects with the ultrasonic view enabling the endoscopist to control the depth and location of needle insertion into the lymph

The EBUS scope is different in many ways from its counterpart used in the GI tract. **First**, the diameter is almost half of any available ultrasound endoscope. In our opinion, this makes the bronchoscope more comfortable for the patient, and reduces sedation requirement. **Second**, the control part of the bronchoscope has fewer controllers making it easier for the pulmonologist to handle. It is a design that they are used to and comfortable using with no need for extra training to be able to handle it. This in our opinion shortens the learning curve. **Third**, it enables the thoracic physician to completely evaluate the mediastinum in one session using one piece of equipment. This minimizes the costs of additional equipment and need for additional procedure without compromising on patient management. **Fourth**, the EBUS scope is shorter than the EUS scope, thus enhancing maneuverability. This shorter length is well suited for sampling thoracic and mediastinal structures. Sampling of the pancreas or abdominal lymph nodes is out of the scope and expertise of most thoracic physicians. Added length of the EUS scope does not offer

One of the major advances in the treatment of lung cancer is the advent of non-surgical pathologic staging using EBUS. The combination of EBUS and EUS for sampling of mediastinal nodes allows near complete staging of the mediastinum [1–3], which is equivalent, if not superior to mediastinoscopy in experienced hands [4, 5]. Multiple studies showed the EBUS scope efficacious in serving the EUS scope role (EUS-B) [6, 7]. The added benefit of the esophageal access in staging lung cancer comes from its ability to reach and locate lymph nodal stations that are impossible to reach via the airways such as stations 3p, and paraesophageal lymph nodal

**12**

**3. Indications**

node in a real time fashion.

**2.2 Why the EBUS scope, not the EUS scope?**

additional advantage to a practicing pulmonologist.

*Lymph nodes accessible by EBUS vs. EUS-B.*


#### **Table 2.**

*Indications for EUS-B.*

stations 8 and 9 (see **Table 1** for lymph node stations accessible by EBUS and EUS). Given the literature on combined EBUS and EUS, it can be argued that EBUS and EUS-B should be performed at the same time for all patients with suspected lung cancer at institutions where rapid on-site cytologic evaluation is not available. This approach is recommended by the European Society of Gastrointestinal Endoscopy (ESGE) and European Respiratory Society (ERS) guidelines [8]. The utility of EBUS and EUS-B is not limited to staging or diagnosis of lung cancer. The EBUS has well documented advantages in diagnosing mediastinal lymphoma [9–11], sarcoidosis [12–14], tuberculosis [15, 16], pulmonary parenchymal masses [17, 18], and metastatic disease to the mediastinum [19], among others including infections [9, 20]. EUS-B has the same ability to investigate the mediastinum when such conditions are suspected, since the utility of EUS is well documented in such disease states [21, 22]. In addition, instances where a mediastinal mass or lymphadenopathy is paraesophageal and paratracheal, the esophageal approach might be preferred, especially when there is difficulty to access the airway due to patient intolerance or if accessing the airway predisposes increase risk to hypoxemic, intubated, and critically ill patients [23]. The indications for EUS-B are summarized in **Table 2**.

### **4. Anesthesia**

EBUS bronchoscopy is carried out under either conscious sedation or general anesthesia with laryngeal mask airway (LMA) or intubation. EUS/B can be performed in the same setting under general anesthesia or conscious sedation. Patient tolerance seems to be adequate when conscious sedation is used [24]. Multiple drug regimens are available for conscious sedation. We do not recommend one regimen over the other. Local expertise, hospital policies, availability of an anesthesia team, and costs govern the types of sedatives and techniques used. Institutional protocols should be developed and followed to ensure safety of procedures. Even when LMA is used, EUS-B can still be performed in the same setting as described below. This is one benefit of EUS-B over conventional EUS. It is important to mention in this setting that endotracheal intubation is not prohibitive of performing EUS-B and is actually an indication as mentioned earlier. In the intubated and/or the critically ill patient, EUS-B allows us the easiest and sometimes the only access to mediastinal pathology. It is our experience that this approach does not require more sedation than required for mechanical ventilation.

#### **5. Insertion techniques for EUS-B**

It is necessary to intubate the oral cavity (as opposed to the nares) when using the EBUS scope. A "bite block" (in cases of intubation, in ICU and conscious sedation) should be used to protect the scope from potential damage from a bite if LMA is not used. An added oropharyngeal airway, such as the Williams airway, can facilitate passage of the scope into the supraglottic/posterior pharyngeal space and offer further protection to scope under conscious sedation.

When conscious sedation or endotracheal (ET) tube is used and once in the posterior pharyngeal space, the scope can be advanced into the esophagus using two basic techniques. The first "blind" technique involves holding the scope with the ultrasound transducer facing the posterior pharynx. Patient is instructed to swallow after instillation of topical lidocaine or saline. Once the patient starts swallowing, the

#### **Figure 1.**

*After bypassing the epiglottis, to enter the esophagus, the scope needs to be placed behind the left arytenoid. Vision will cease after that point and US vision should be used to assist locating the probe position in the esophagus. Note: gentle pressure with some corkscrew or alternating mild upward and downward movements on the scope lever will assist in entering the esophagus.*

**15**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

gentle corkscrew maneuver with gentle advancement is all that is required.

The use of the LMA is prohibitive of using the conventional EUS scope but not the EUS-B. The LMA inherently obstructs the esophageal opening. Once the EBUS scope is at the level of the larynx, the tip is pointed and scope placed behind the left arytenoid. An assistant is asked to perform a jaw thrust maneuver that will elevate the laryngeal structures and give enough space for the small EBUS scope to be gently passed into the esophagus. Once in the esophagus, the jaw thrust can be stopped and procedure is continued. In our experience, with over 500 EUS-B procedures, we have not experienced failure or a complication passing the scope into the esophagus

In contrast to EBUS in the airways, EUS-B relies entirely upon ultrasonic images

The mediastinal structures that can be normally seen and examined on EUS-B are:

During the initial training for EUS, it is important to define a point of reference that the endoscopist can refer to during the procedure. In our practice, we first identify the left atrium as a point of reference. The scope is advanced into

1.Cardiac structures: left atrium, left ventricle, aortic valve, mitral valve,

3.Pulmonary vessels: left pulmonary artery, right pulmonary artery

5.Mediastinal pleura and pleural effusion if large enough

for localization; the esophagus has no internal landmarks for nodal mapping. Because of this, lymph node stations are identified and numbered based upon their relationships with other structures "seen" ultrasonographically through esophageal wall. In addition, interpersonal variability exists between patients, and large mediastinal tumors or abnormalities can alter the normal anatomy and displace or compress the esophagus or other structures, thus altering the ultrasonic views and anatomic relations. A computerized tomographic scan is almost invariably available. It is advised that the endoscopist carefully review patient anatomy prior to and

scope can be advanced with gentle pressure, allowing the peristaltic wave to carry it. Rapid minor alternating flexion and release of the scope using the control lever can aid passage of the scope into the esophagus. If the blind technique fails, the scope can be passed under direct visualization. The scope can be inserted with the transducer (and visual field) facing anteriorly. Once in the posterior pharynx, the tip can be retroflexed and the larynx visualized. The tip of the scope can then be passed posterior to the arytenoids and to left with gentle pressure, see **Figure 1**. If resistance is faced, the scope can be withdrawn and another attempt on the right side or midline can be tried. It is important not to use excessive pressure if the scope does not pass easily. A

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

using any of these techniques.

pericardium

4.Vertebral bodies

7.Liver

6.Mediastinal lymph nodes

**6. Anatomic landmarks and organs studied**

during the procedure to avoid sampling normal structures.

2.Thoracic aorta: descending, arch, root

#### *EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

scope can be advanced with gentle pressure, allowing the peristaltic wave to carry it. Rapid minor alternating flexion and release of the scope using the control lever can aid passage of the scope into the esophagus. If the blind technique fails, the scope can be passed under direct visualization. The scope can be inserted with the transducer (and visual field) facing anteriorly. Once in the posterior pharynx, the tip can be retroflexed and the larynx visualized. The tip of the scope can then be passed posterior to the arytenoids and to left with gentle pressure, see **Figure 1**. If resistance is faced, the scope can be withdrawn and another attempt on the right side or midline can be tried. It is important not to use excessive pressure if the scope does not pass easily. A gentle corkscrew maneuver with gentle advancement is all that is required.

The use of the LMA is prohibitive of using the conventional EUS scope but not the EUS-B. The LMA inherently obstructs the esophageal opening. Once the EBUS scope is at the level of the larynx, the tip is pointed and scope placed behind the left arytenoid. An assistant is asked to perform a jaw thrust maneuver that will elevate the laryngeal structures and give enough space for the small EBUS scope to be gently passed into the esophagus. Once in the esophagus, the jaw thrust can be stopped and procedure is continued. In our experience, with over 500 EUS-B procedures, we have not experienced failure or a complication passing the scope into the esophagus using any of these techniques.

#### **6. Anatomic landmarks and organs studied**

In contrast to EBUS in the airways, EUS-B relies entirely upon ultrasonic images for localization; the esophagus has no internal landmarks for nodal mapping. Because of this, lymph node stations are identified and numbered based upon their relationships with other structures "seen" ultrasonographically through esophageal wall. In addition, interpersonal variability exists between patients, and large mediastinal tumors or abnormalities can alter the normal anatomy and displace or compress the esophagus or other structures, thus altering the ultrasonic views and anatomic relations. A computerized tomographic scan is almost invariably available. It is advised that the endoscopist carefully review patient anatomy prior to and during the procedure to avoid sampling normal structures.

The mediastinal structures that can be normally seen and examined on EUS-B are:


During the initial training for EUS, it is important to define a point of reference that the endoscopist can refer to during the procedure. In our practice, we first identify the left atrium as a point of reference. The scope is advanced into

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

EBUS bronchoscopy is carried out under either conscious sedation or general anesthesia with laryngeal mask airway (LMA) or intubation. EUS/B can be performed in the same setting under general anesthesia or conscious sedation. Patient tolerance seems to be adequate when conscious sedation is used [24]. Multiple drug regimens are available for conscious sedation. We do not recommend one regimen over the other. Local expertise, hospital policies, availability of an anesthesia team, and costs govern the types of sedatives and techniques used. Institutional protocols should be developed and followed to ensure safety of procedures. Even when LMA is used, EUS-B can still be performed in the same setting as described below. This is one benefit of EUS-B over conventional EUS. It is important to mention in this setting that endotracheal intubation is not prohibitive of performing EUS-B and is actually an indication as mentioned earlier. In the intubated and/or the critically ill patient, EUS-B allows us the easiest and sometimes the only access to mediastinal pathology. It is our experience that this approach does not require more sedation

It is necessary to intubate the oral cavity (as opposed to the nares) when using

When conscious sedation or endotracheal (ET) tube is used and once in the posterior pharyngeal space, the scope can be advanced into the esophagus using two basic techniques. The first "blind" technique involves holding the scope with the ultrasound transducer facing the posterior pharynx. Patient is instructed to swallow after instillation of topical lidocaine or saline. Once the patient starts swallowing, the

the EBUS scope. A "bite block" (in cases of intubation, in ICU and conscious sedation) should be used to protect the scope from potential damage from a bite if LMA is not used. An added oropharyngeal airway, such as the Williams airway, can facilitate passage of the scope into the supraglottic/posterior pharyngeal space and

offer further protection to scope under conscious sedation.

**4. Anesthesia**

*After bypassing the epiglottis, to enter the esophagus, the scope needs to be placed behind the left arytenoid. Vision will cease after that point and US vision should be used to assist locating the probe position in the esophagus. Note: gentle pressure with some corkscrew or alternating mild upward and downward movements* 

**14**

**Figure 1.**

*on the scope lever will assist in entering the esophagus.*

than required for mechanical ventilation.

**5. Insertion techniques for EUS-B**

#### **Figure 2.**

*At 3–4 cm depth (dashed green), the left atrium (green arrow) can be seen looking anteriorly. Increasing the depth to 5–7 cm and slight rotation can identify the aortic valve (red arrow), root (orange star), and outflow tract from left ventricle (blue x).*

#### **Figure 3.**

*Moving distally with slight rotation to left and increased depth can show the mitral valve (blue arrow) under the LA (white circle).*

the esophagus with the ultrasound transducer facing anteriorly until the atrium can be identified. The atrium is easily identified due to its shape, its pulsating nature, and great variability in size (compared to the great vessels) with contractions (**Figure 2**, also see Video at https://mts.intechopen.com/download/index/ process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621). A thin paper-like echogenic structure can usually be observed moving inside of this anechoic sac (of blood), this is the mitral valve (**Figure 3**, also see Video at https://mts. intechopen.com/download/index/process/324/authkey/bb9c02ba5640a4d-21d4511e0a79f3621). If the patient is in atrial fibrillation, this pulsating characteristic is lost, but the mitral valve movement can still be identified that helps localizing the atrium. In most instances, a slight rotation to the left is necessary to identify the atrium and mitral valve. The depth of field of the ultrasonic view can be altered. We usually leave it at 4 cm, but if in doubt, the depth of the ultrasonic view can be increased to 7.5 cm, and this will allow viewing the left

**17**

the right.

**Figure 4.**

**6.1 Lymph node stations**

*6.1.1 Station seven lymph nodes*

**Anatomic definition**:

**Conventional name**: Subcarinal lymph nodes.

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

ventricle and mitral valve and atrium easily. When using the increased depth on the ultrasonic view, the root of the aorta and the aortic valve are also easily identifiable (**Figure 2**, also see Video at https://mts.intechopen.com/download/ index/process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621). It is necessary to mention here that slight variability exists between patients and moving the scope inferiorly and superiorly or small rotations are necessary to identify all of these structures. The pericardium is an echoic membrane that is almost always separated from the left atrium by a rim of physiologic effusion in this view (a dependent area just posterior to the left atrium in the supine position). When this effusion is big, it can create some confusion to the endoscopist. It is always important to identify the pericardium to avoid puncturing it. Rarely, a mediastinal cyst can occur in this position, which can make the views confusing. Again, increasing the depth on the US screen will help to identify cardiac versus noncardiac structures. In addition, the use of real time color Doppler will help to separate a cystic structure from a vascular structure, see **Figure 2**. The liver can also be noted and inferior vena cava can be examined too at the distal esophagus just before entering the stomach (**Figure 4**, Video at https://mts.intechopen.com/ download/index/process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621).

*and liver (red X); the liver also can be seen anteriorly after the scope is passed distally.*

*At the lower end of the esophagus, looking to the right and anteriorly, one can identify the IVC (Yellow star)* 

In this section, we describe the anatomic definitions according to the eight edition of "Lung Cancer Staging Manual" [25]. We describe "how to reach" the lymph nodal stations, according to our practice. The EUS-B maneuver starts from our point of reference, i.e., the left atrium, in each of the descriptions stated below.

Mediastinal node limited by the carina superiorly and upper border of lower

lobe bronchus on the left and lower border of the bronchus intermedius on

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

#### **Figure 4.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

the esophagus with the ultrasound transducer facing anteriorly until the atrium can be identified. The atrium is easily identified due to its shape, its pulsating nature, and great variability in size (compared to the great vessels) with contractions (**Figure 2**, also see Video at https://mts.intechopen.com/download/index/ process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621). A thin paper-like echogenic structure can usually be observed moving inside of this anechoic sac (of blood), this is the mitral valve (**Figure 3**, also see Video at https://mts. intechopen.com/download/index/process/324/authkey/bb9c02ba5640a4d-21d4511e0a79f3621). If the patient is in atrial fibrillation, this pulsating characteristic is lost, but the mitral valve movement can still be identified that helps localizing the atrium. In most instances, a slight rotation to the left is necessary to identify the atrium and mitral valve. The depth of field of the ultrasonic view can be altered. We usually leave it at 4 cm, but if in doubt, the depth of the ultrasonic view can be increased to 7.5 cm, and this will allow viewing the left

*Moving distally with slight rotation to left and increased depth can show the mitral valve (blue arrow) under* 

*At 3–4 cm depth (dashed green), the left atrium (green arrow) can be seen looking anteriorly. Increasing the depth to 5–7 cm and slight rotation can identify the aortic valve (red arrow), root (orange star), and outflow* 

**16**

**Figure 3.**

**Figure 2.**

*tract from left ventricle (blue x).*

*the LA (white circle).*

*At the lower end of the esophagus, looking to the right and anteriorly, one can identify the IVC (Yellow star) and liver (red X); the liver also can be seen anteriorly after the scope is passed distally.*

ventricle and mitral valve and atrium easily. When using the increased depth on the ultrasonic view, the root of the aorta and the aortic valve are also easily identifiable (**Figure 2**, also see Video at https://mts.intechopen.com/download/ index/process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621). It is necessary to mention here that slight variability exists between patients and moving the scope inferiorly and superiorly or small rotations are necessary to identify all of these structures. The pericardium is an echoic membrane that is almost always separated from the left atrium by a rim of physiologic effusion in this view (a dependent area just posterior to the left atrium in the supine position). When this effusion is big, it can create some confusion to the endoscopist. It is always important to identify the pericardium to avoid puncturing it. Rarely, a mediastinal cyst can occur in this position, which can make the views confusing. Again, increasing the depth on the US screen will help to identify cardiac versus noncardiac structures. In addition, the use of real time color Doppler will help to separate a cystic structure from a vascular structure, see **Figure 2**. The liver can also be noted and inferior vena cava can be examined too at the distal esophagus just before entering the stomach (**Figure 4**, Video at https://mts.intechopen.com/ download/index/process/324/authkey/bb9c02ba5640a4d21d4511e0a79f3621).

#### **6.1 Lymph node stations**

In this section, we describe the anatomic definitions according to the eight edition of "Lung Cancer Staging Manual" [25]. We describe "how to reach" the lymph nodal stations, according to our practice. The EUS-B maneuver starts from our point of reference, i.e., the left atrium, in each of the descriptions stated below.

#### *6.1.1 Station seven lymph nodes*

#### **Anatomic definition**:

Mediastinal node limited by the carina superiorly and upper border of lower lobe bronchus on the left and lower border of the bronchus intermedius on the right.

#### **Conventional name**:

Subcarinal lymph nodes.

#### **Figure 5.**

*Rostrally from Figure 2. White arrow shows the pericardial recess, and the diamond is the right pulmonary artery crossing the mediastinum. Note: a slight rotation right will show part of station 7 LN (green arrow).*

#### **EUS location:**

This station can be located by slightly pulling the scope rostral above the level of atrium. A slight right or left rotation of the scope is necessary to choose the optimal view of the lymph node and avoid puncturing the great vessels. At the level of station seven, the right pulmonary artery can be identified crossing to the other side of the mediastinum (just deeper to the lymph node on the ultrasound screen, see **Figure 5**).

#### *6.1.2 Stations 8 and 9*

#### **Anatomic definition:**

Station 8: superiorly limited by the upper border of lower lobe bronchus on the left and lower border of the bronchus intermedius on the right and extends down to the diaphragm.

Station 9: superiorly limited by the inferior pulmonary vein and extends down to the diaphragm. These lymph nodes are located within the pulmonary ligament.

#### **Conventional name:**

8: Paraesophageal lymph nodes.

9: Pulmonary ligament lymph nodes.

#### **EUS location:**

They are identified by rotating the scope right or left with gently moving it caudally. Station 9 is identified as any node that associated (in close proximity to) the inferior pulmonary vein and are within the pulmonary ligaments. Station 9 lymph nodes can extend in the pulmonary ligament to the diaphragm, but the only "visible" part of the station is at the junction of the inferior pulmonary vein with the left atrium.

Station 8 lymph nodes are paraesophageal lymph nodes. The upper border is difficult to localize precisely by EUS but in general are the nodes that are on either side of the esophagus below the superior border of the left atrium and extend down to the level of the diaphragm. Of note, both superior pulmonary veins and inferior pulmonary vein on the right are not always identifiable, the left inferior pulmonary vein is almost always identifiable on EUS-B and serves as a landmark for both sides of the mediastinum; it identifies the pulmonary ligament. It is hard to differentiate between level 9 and level 8 near the level of the inferior pulmonary vein. The clinical significance of this differentiation is almost nil, since the presence of metastasis to these lymph nodes from a primary lung cancer indicates N2 if on same side or N3 if the primary cancer is on the other side.

**19**

**Figure 6.**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

identify the station 4 lymph nodes and left pulmonary artery, see **Figure 6**.

ligamentum arteriosum, while station 4L is medial to that ligament.

Subaortic (aorto-pulmonary window) lymph nodes.

Superiorly limited by the lower border of the aortic arch and inferiorly by the upper rim of the left main pulmonary artery. Note that this station is lateral to

This lymph node station can be identified using the same technique for the station 4L. The only difference is that the station 5 lymph nodes are those that are deeper to the ligamentum arteriosum and below the lower rim of the aortic arch. The ligamentum arteriosum, when visible, is identified as an elongated hyperechoic

*Red star is the aorta, blue arrow (mass/ LN at station 5), orange cross is station 4L, green is the ligamentum arteriosum separating 4L from station 5. Note: on US view that the ligamentum arteriosum can be seen as* 

*dense, hyper-echoic structure connecting the inferior border of aorta to the pulmonary artery.*

Extends to the upper limits of the aortic arch and down to upper rim of the left

This can be reached with either of two techniques. **First**, from the reference point, the scope can be rotated to the left lateral position then slowly withdrawn until the left pulmonary artery is visualized, if the scope is withdrawn more, the arch of aorta can be visualized. Station 4L is any node that is below the upper border of the arch of aorta in that view and above the upper rim of the main pulmonary artery. The **second** approach involves rotating the scope posteriorly from our reference point anticlockwise; the descending aorta can be seen as a hypoechoic elongated structure. The descending aorta can be followed upward until it starts to disappear. This is the level of the arch, which can be followed through its course at that point by rotating anteriorly (clockwise). Once the arch is identified, advancing the scope caudally will

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

Left lower paratracheal lymph nodes.

*6.1.3 Station 4L*

**Anatomic definition:**

main pulmonary artery. **Conventional name:**

**EUS location:**

*6.1.4 Station 5*

**Anatomic definition:**

**Conventional name:**

**EUS location:**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

#### *6.1.3 Station 4L*

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

This station can be located by slightly pulling the scope rostral above the level of atrium. A slight right or left rotation of the scope is necessary to choose the optimal view of the lymph node and avoid puncturing the great vessels. At the level of station seven, the right pulmonary artery can be identified crossing to the other side of the mediastinum (just deeper to the lymph node on the ultrasound screen, see **Figure 5**).

*Rostrally from Figure 2. White arrow shows the pericardial recess, and the diamond is the right pulmonary artery crossing the mediastinum. Note: a slight rotation right will show part of station 7 LN (green arrow).*

Station 8: superiorly limited by the upper border of lower lobe bronchus on the left and lower border of the bronchus intermedius on the right and extends down to

Station 9: superiorly limited by the inferior pulmonary vein and extends down to

They are identified by rotating the scope right or left with gently moving it caudally. Station 9 is identified as any node that associated (in close proximity to) the inferior pulmonary vein and are within the pulmonary ligaments. Station 9 lymph nodes can extend in the pulmonary ligament to the diaphragm, but the only "visible" part of the station is at the junction of the inferior pulmonary vein with the left atrium. Station 8 lymph nodes are paraesophageal lymph nodes. The upper border is difficult to localize precisely by EUS but in general are the nodes that are on either side of the esophagus below the superior border of the left atrium and extend down to the level of the diaphragm. Of note, both superior pulmonary veins and inferior pulmonary vein on the right are not always identifiable, the left inferior pulmonary vein is almost always identifiable on EUS-B and serves as a landmark for both sides of the mediastinum; it identifies the pulmonary ligament. It is hard to differentiate between level 9 and level 8 near the level of the inferior pulmonary vein. The clinical significance of this differentiation is almost nil, since the presence of metastasis to these lymph nodes from a primary lung cancer indicates N2 if on same side or N3

the diaphragm. These lymph nodes are located within the pulmonary ligament.

**18**

**EUS location:**

**Figure 5.**

*6.1.2 Stations 8 and 9*

the diaphragm.

**Anatomic definition:**

**Conventional name:**

**EUS location:**

8: Paraesophageal lymph nodes. 9: Pulmonary ligament lymph nodes.

if the primary cancer is on the other side.

#### **Anatomic definition:**

Extends to the upper limits of the aortic arch and down to upper rim of the left main pulmonary artery.

**Conventional name:**

Left lower paratracheal lymph nodes.

#### **EUS location:**

This can be reached with either of two techniques. **First**, from the reference point, the scope can be rotated to the left lateral position then slowly withdrawn until the left pulmonary artery is visualized, if the scope is withdrawn more, the arch of aorta can be visualized. Station 4L is any node that is below the upper border of the arch of aorta in that view and above the upper rim of the main pulmonary artery. The **second** approach involves rotating the scope posteriorly from our reference point anticlockwise; the descending aorta can be seen as a hypoechoic elongated structure. The descending aorta can be followed upward until it starts to disappear. This is the level of the arch, which can be followed through its course at that point by rotating anteriorly (clockwise). Once the arch is identified, advancing the scope caudally will identify the station 4 lymph nodes and left pulmonary artery, see **Figure 6**.

#### *6.1.4 Station 5*

#### **Anatomic definition:**

Superiorly limited by the lower border of the aortic arch and inferiorly by the upper rim of the left main pulmonary artery. Note that this station is lateral to ligamentum arteriosum, while station 4L is medial to that ligament.

#### **Conventional name:**

Subaortic (aorto-pulmonary window) lymph nodes.

#### **EUS location:**

This lymph node station can be identified using the same technique for the station 4L. The only difference is that the station 5 lymph nodes are those that are deeper to the ligamentum arteriosum and below the lower rim of the aortic arch. The ligamentum arteriosum, when visible, is identified as an elongated hyperechoic

#### **Figure 6.**

*Red star is the aorta, blue arrow (mass/ LN at station 5), orange cross is station 4L, green is the ligamentum arteriosum separating 4L from station 5. Note: on US view that the ligamentum arteriosum can be seen as dense, hyper-echoic structure connecting the inferior border of aorta to the pulmonary artery.*

structure connecting the left pulmonary artery to the aortic arch (**Figure 6**). It is important to mention here that sometimes, one is faced with large lymph nodes or conglomerate of nodes in this position; the differentiation between 5 and 4L can be difficult. In our opinion, both stations carry the same staging implication if positive for lung cancer (both are N2 or N3 disease, never N1) and the clinical benefit of separating the two stations becomes minimal (this issue remains controversial), see **Figure 6**.

**Note:** Video (https://mts.intechopen.com/download/index/process/324/ authkey/bb9c02ba5640a4d21d4511e0a79f3621) shows EUS-B scope looking posteriorly from the reference point identifying the descending aorta; the scope is withdrawn rostral while following the descending aorta. Once it starts to disappear, the arch is reached. At that point, rotation clockwise to follow the arch is performed. Positioned approximately in the middle of the arch, the scope is pushed slightly caudally until the left pulmonary artery is identified. Station 4L and station 5 are between the arch and the pulmonary artery. The former is closer to the probe and the latter is beyond the echogenic ligamentum arteriosum.

#### *6.1.5 Station 2*

#### **Anatomic definition:**

Superiorly, it is limited by apex of lungs and pleural cavity and upper border of the manubrium on both sides. Station 2R is limited inferiorly by Intersection of caudal margin of the innominate vein and trachea, while on the left (2L) is inferiorly limited by the upper border of the aorta.

#### **Conventional name:**

Upper paratracheal.

#### **EUS location:**

The 2L station are identified by same maneuvers as station 4L, once the aortic arch is identified, withdrawing the scope to above the aortic arch identifies station 2L location, this station extends all the way up to the level of the manubrium anteriorly and the apex of the lung, both are hard to identify ultrasonographically. Station 2R is slightly different. Station 2R is the lymph node station that is above the level of the brachiocephalic vein and trachea intersection. Once the aortic arch is identified, close attention needs to be paid to the vessels sprouting from it, the most anterior one is the right brachiocephalic artery, this can be followed anteriorly and once sight is lost, it is crossing the trachea. At that point, rotation to the right can be done; station 2R lymph nodes are above that point. It should be noted that this is not an accurate localization (since we cannot identify the BC vein), but it is the best approximation that we could attain.

#### *6.1.6 Station 3p*

#### **Anatomic definition:**

Limited superiorly by the apex of the lungs and extends inferiorly to the level of the carina.

**Conventional name:**

#### Retrotracheal.

### **EUS location:**

From the reference point, one can withdraw the scope until right above the level of station 7. The scope is then turned posteriorly. All posterior lymph nodes (mostly with a slight rotation to the right) are considered 3p up to the upper esophagus.

**21**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

The adrenal glands represent the fourth most common site of metastasis for lung cancer. Identifying left adrenal gland is easier than the right. The right adrenal gland cannot be reached by EUS-B. The left adrenal gland is the more common site of adrenal metastasis and easily accessible from the stomach. The endoscopist can identify his presence in the stomach from identification of the stomach folds under US guidance and by visualization of the walls. Several reports of successful biopsy

Most of the data available here comes from the literature studying regular endoscopic devices. Endoscopy has proven to be a safe procedure. The rates of complications are probably comparable to that of bronchoscopy. These complications can be

Oxygen desaturation (defined as 4% decrease in hemoglobin saturation below the baseline) can occur in up to 70% of cases without oxygen supplementation [28]. Desaturations occur in both sedated and non-sedated patients. Sedation significantly increases the risk of hypoxia [29]. Supplementary oxygen via nasal cannula reduces the risk [29, 30]. Difficult intubation, therapeutic procedures, increasing age of the patient, and concurrent pulmonary diseases all increase the risk of these events [31, 32]. It is not known if mild desaturations (a drop of 4% on the pulse oximeter) are clinically significant or not. Severe desaturations (pulse oximetry <90%) are less common and can be abolished by the use of supplemental oxygen [28, 32, 33]. The ASGE recommends the use of continuous monitoring devices (pulse oximetry) to monitor for desaturations and correction of hypoxia.

of the left adrenal gland have been described [26, 27], **Figure 7**.

*Once in the stomach, looking posteriorly, one can identify the left adrenal gland (arrow).*

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

**6.2 Adrenal glands**

**Figure 7.**

**7. Complications**

classified into two main categories.

**7.1 Conscious sedation/anesthesia related**

**Anatomic definition:**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

#### **Figure 7.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

structure connecting the left pulmonary artery to the aortic arch (**Figure 6**). It is important to mention here that sometimes, one is faced with large lymph nodes or conglomerate of nodes in this position; the differentiation between 5 and 4L can be difficult. In our opinion, both stations carry the same staging implication if positive for lung cancer (both are N2 or N3 disease, never N1) and the clinical benefit of separating the two stations becomes minimal (this issue remains controversial), see

**Note:** Video (https://mts.intechopen.com/download/index/process/324/ authkey/bb9c02ba5640a4d21d4511e0a79f3621) shows EUS-B scope looking posteriorly from the reference point identifying the descending aorta; the scope is withdrawn rostral while following the descending aorta. Once it starts to disappear, the arch is reached. At that point, rotation clockwise to follow the arch is performed. Positioned approximately in the middle of the arch, the scope is pushed slightly caudally until the left pulmonary artery is identified. Station 4L and station 5 are between the arch and the pulmonary artery. The former is closer to the probe and the latter is beyond the echogenic ligamentum

Superiorly, it is limited by apex of lungs and pleural cavity and upper border of the manubrium on both sides. Station 2R is limited inferiorly by Intersection of caudal margin of the innominate vein and trachea, while on the left (2L) is inferi-

The 2L station are identified by same maneuvers as station 4L, once the aortic arch is identified, withdrawing the scope to above the aortic arch identifies station 2L location, this station extends all the way up to the level of the manubrium anteriorly and the apex of the lung, both are hard to identify ultrasonographically. Station 2R is slightly different. Station 2R is the lymph node station that is above the level of the brachiocephalic vein and trachea intersection. Once the aortic arch is identified, close attention needs to be paid to the vessels sprouting from it, the most anterior one is the right brachiocephalic artery, this can be followed anteriorly and once sight is lost, it is crossing the trachea. At that point, rotation to the right can be done; station 2R lymph nodes are above that point. It should be noted that this is not an accurate localization (since we cannot identify the BC vein), but it is the best

Limited superiorly by the apex of the lungs and extends inferiorly to the level of

From the reference point, one can withdraw the scope until right above the level of station 7. The scope is then turned posteriorly. All posterior lymph nodes (mostly with a slight rotation to the right) are considered 3p up to the upper

**20**

**Figure 6**.

arteriosum.

*6.1.5 Station 2*

**Anatomic definition:**

**Conventional name:** Upper paratracheal. **EUS location:**

approximation that we could attain.

**Anatomic definition:**

**Conventional name:** Retrotracheal. **EUS location:**

*6.1.6 Station 3p*

the carina.

esophagus.

orly limited by the upper border of the aorta.

*Once in the stomach, looking posteriorly, one can identify the left adrenal gland (arrow).*

#### **6.2 Adrenal glands**

#### **Anatomic definition:**

The adrenal glands represent the fourth most common site of metastasis for lung cancer. Identifying left adrenal gland is easier than the right. The right adrenal gland cannot be reached by EUS-B. The left adrenal gland is the more common site of adrenal metastasis and easily accessible from the stomach. The endoscopist can identify his presence in the stomach from identification of the stomach folds under US guidance and by visualization of the walls. Several reports of successful biopsy of the left adrenal gland have been described [26, 27], **Figure 7**.

#### **7. Complications**

Most of the data available here comes from the literature studying regular endoscopic devices. Endoscopy has proven to be a safe procedure. The rates of complications are probably comparable to that of bronchoscopy. These complications can be classified into two main categories.

#### **7.1 Conscious sedation/anesthesia related**

Oxygen desaturation (defined as 4% decrease in hemoglobin saturation below the baseline) can occur in up to 70% of cases without oxygen supplementation [28]. Desaturations occur in both sedated and non-sedated patients. Sedation significantly increases the risk of hypoxia [29]. Supplementary oxygen via nasal cannula reduces the risk [29, 30]. Difficult intubation, therapeutic procedures, increasing age of the patient, and concurrent pulmonary diseases all increase the risk of these events [31, 32]. It is not known if mild desaturations (a drop of 4% on the pulse oximeter) are clinically significant or not. Severe desaturations (pulse oximetry <90%) are less common and can be abolished by the use of supplemental oxygen [28, 32, 33]. The ASGE recommends the use of continuous monitoring devices (pulse oximetry) to monitor for desaturations and correction of hypoxia.

Cardiac complications during endoscopy are also commonly seen and range from mild arrhythmias to severe hypotension and cardiac arrest. Tachycardia is probably the most common arrhythmia seen [28]. A vasovagal response or discomfort from insertion of the scope can be the cause of such a response. Hypotension related to the sedation can also be seen. This can also result from the vasovagal response due to gas insufflation (which is not used during EUS-B).

#### **7.2 Procedure related**

Procedure-related complications of esophagoscopy are rare. The major complications of diagnostic esophagoscopy include bleeding, perforation, and infection [28]. Rarely, it would cause strictures or ulcerations. Most of the available literature for EUS-B is from studies evaluating EUS and EUS-FNA of the upper GI tract. Very few studies using EUS-FNA for purpose of lung cancer staging are available. These generally do not comment on rate or types of complications.

Infections can be related to inadequate equipment disinfection, which can be avoided by following the manufacturer guidelines. Another form of infection is the introduction of bacteria to the blood stream or a sterile space (the mediastinum in case of EUS/B-FNA). Episodes of transient bacteremia are a well-known occurrence after upper GI endoscopy (up to 8% of patients) [34]. This is similar for EUS and EUS-FNA according to few reports [35]. Most of these episodes of bacteremia are transient and asymptomatic. Infectious endocarditis is extremely rare (1–5 × 10<sup>−</sup><sup>6</sup> ). Prophylactic antibiotics are not necessary for EUS-FNA, unless a cystic mediastinal structure is being sampled [34]. Febrile episodes after endoscopy are also common (about 1%) and are usually transient. Retropharyngeal abscesses have been reported after conventional endoscopy. Isolated reports of benign mediastinal cyst infection have been reported to follow EUS-FNA of these structures [36–38]. The risk for these infections seems to be very small, but one should be aware of the possibility [34]. The ASGE recommends prophylactic antibiotics at time of aspiration and for 3 days.

Perforation of the esophagus with EUS is a known but rare complication (0.03%). Most of the reported data is on radial ultrasonic probes, and limited data exist on the curvilinear probes. It seems that esophageal cancer, stricture, increased age of patient, and an operator with <1 year experience are independent risk factors for perforation [34].

Bleeding occurring can be intra-luminal or extra-luminal. While mild intraluminal bleeds after EUS-FNA is a relatively common and expected occurrence (up to 4% in one report); extra-luminal bleeding is relatively rare or under-reported due to difficulty in diagnosis [34, 39]. The only reported cases of mediastinal bleeding for sampling of lymph nodes for cancer staging was after a transaortic approach to periaortic lymph nodes (station 6) [40].

#### **8. Contraindications**

As for any other technology or procedure, common sense should prevail. If the benefits of the procedure outweigh the risk, then the procedure is probably indicated. We feel that, when present, certain diseases should be avoided and probably considered as contraindications. Esophageal stricture greatly increases the risk of perforation especially that the EUS-B is inserted and maneuvered blindly inside the esophagus. A recent report suggests that the use of EUS-B in the presence of esophageal stricture might be safe. The smaller diameter of the scope enabled the operators to bypass the stricture and attain diagnostic materials in the cases

**23**

provided the original work is properly cited.

Yousef R. Shweihat\* and Shantanu Singh

\*Address all correspondence to: shweihat@marshall.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Section of Pulmonary and Sleep and Critical Care Medicine, Department of Medicine, Marshall University, Huntington, WV, United States of America

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus*

The authors do not have any conflict of interest to disclose.

examined [41]. Esophageal varices and portal hypertension should also be considered a contraindication due to the increased risk of bleeding from trauma to the varices. Coagulopathy needs to be corrected and active GI bleeding is a contraindication to this procedure. We believe this procedure should only be performed where back up GI or general surgery expertise is available, in case a complication arises.

In this review, we have tried to lay out an overview of EUS-B. EUS-B is a natural sequel to EBUS for the interventional pulmonologist diagnosing thoracic disease. EUS/B offers access to some nodes not accessible to EBUS, and to paraesophageal masses, which are not also paratracheal. The esophagus is not housed in cartilaginous rings and structures, a factor, which may make some high thoracic lesions accessible to EUS-B alone. As with EBUS, FNA via the esophagus has an extremely low rate of complications. EUS-B does not directly impair respiration. In some cases, EBUS and EUS-B are appropriately performed concurrently, affecting an economy of time, expense, and sedation risks. In short, EUS-B is complementary to EBUS and should be integrated into the diagnostic armamentarium of interven-

*DOI: http://dx.doi.org/10.5772/intechopen.84280*

**9. Summary**

tional pulmonology.

**Conflict of interest**

**Author details**

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

examined [41]. Esophageal varices and portal hypertension should also be considered a contraindication due to the increased risk of bleeding from trauma to the varices. Coagulopathy needs to be corrected and active GI bleeding is a contraindication to this procedure. We believe this procedure should only be performed where back up GI or general surgery expertise is available, in case a complication arises.

#### **9. Summary**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

to gas insufflation (which is not used during EUS-B).

generally do not comment on rate or types of complications.

**7.2 Procedure related**

Cardiac complications during endoscopy are also commonly seen and range from mild arrhythmias to severe hypotension and cardiac arrest. Tachycardia is probably the most common arrhythmia seen [28]. A vasovagal response or discomfort from insertion of the scope can be the cause of such a response. Hypotension related to the sedation can also be seen. This can also result from the vasovagal response due

Procedure-related complications of esophagoscopy are rare. The major complications of diagnostic esophagoscopy include bleeding, perforation, and infection [28]. Rarely, it would cause strictures or ulcerations. Most of the available literature for EUS-B is from studies evaluating EUS and EUS-FNA of the upper GI tract. Very few studies using EUS-FNA for purpose of lung cancer staging are available. These

Infections can be related to inadequate equipment disinfection, which can be avoided by following the manufacturer guidelines. Another form of infection is the introduction of bacteria to the blood stream or a sterile space (the mediastinum in case of EUS/B-FNA). Episodes of transient bacteremia are a well-known occurrence after upper GI endoscopy (up to 8% of patients) [34]. This is similar for EUS and EUS-FNA according to few reports [35]. Most of these episodes of bacteremia are transient and asymptomatic. Infectious endocarditis is extremely rare (1–5 × 10<sup>−</sup><sup>6</sup>

Prophylactic antibiotics are not necessary for EUS-FNA, unless a cystic mediastinal structure is being sampled [34]. Febrile episodes after endoscopy are also common (about 1%) and are usually transient. Retropharyngeal abscesses have been reported after conventional endoscopy. Isolated reports of benign mediastinal cyst infection have been reported to follow EUS-FNA of these structures [36–38]. The risk for these infections seems to be very small, but one should be aware of the possibility [34]. The ASGE recommends prophylactic antibiotics at time of aspiration and for

Perforation of the esophagus with EUS is a known but rare complication (0.03%). Most of the reported data is on radial ultrasonic probes, and limited data exist on the curvilinear probes. It seems that esophageal cancer, stricture, increased age of patient, and an operator with <1 year experience are independent risk factors

Bleeding occurring can be intra-luminal or extra-luminal. While mild intraluminal bleeds after EUS-FNA is a relatively common and expected occurrence (up to 4% in one report); extra-luminal bleeding is relatively rare or under-reported due to difficulty in diagnosis [34, 39]. The only reported cases of mediastinal bleeding for sampling of lymph nodes for cancer staging was after a transaortic approach

As for any other technology or procedure, common sense should prevail. If the benefits of the procedure outweigh the risk, then the procedure is probably indicated. We feel that, when present, certain diseases should be avoided and probably considered as contraindications. Esophageal stricture greatly increases the risk of perforation especially that the EUS-B is inserted and maneuvered blindly inside the esophagus. A recent report suggests that the use of EUS-B in the presence of esophageal stricture might be safe. The smaller diameter of the scope enabled the operators to bypass the stricture and attain diagnostic materials in the cases

).

**22**

3 days.

for perforation [34].

**8. Contraindications**

to periaortic lymph nodes (station 6) [40].

In this review, we have tried to lay out an overview of EUS-B. EUS-B is a natural sequel to EBUS for the interventional pulmonologist diagnosing thoracic disease. EUS/B offers access to some nodes not accessible to EBUS, and to paraesophageal masses, which are not also paratracheal. The esophagus is not housed in cartilaginous rings and structures, a factor, which may make some high thoracic lesions accessible to EUS-B alone. As with EBUS, FNA via the esophagus has an extremely low rate of complications. EUS-B does not directly impair respiration. In some cases, EBUS and EUS-B are appropriately performed concurrently, affecting an economy of time, expense, and sedation risks. In short, EUS-B is complementary to EBUS and should be integrated into the diagnostic armamentarium of interventional pulmonology.

#### **Conflict of interest**

The authors do not have any conflict of interest to disclose.

#### **Author details**

Yousef R. Shweihat\* and Shantanu Singh Section of Pulmonary and Sleep and Critical Care Medicine, Department of Medicine, Marshall University, Huntington, WV, United States of America

\*Address all correspondence to: shweihat@marshall.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[19] Navani N, Nankivell M, Woolhouse I, Harrison RN, Munavvar M, Oltmanns U, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of intrathoracic lymphadenopathy in patients

*EUS-B for the Interventional Pulmonologist Using the EBUS Scope in the Esophagus DOI: http://dx.doi.org/10.5772/intechopen.84280*

diagnosis of sarcoidosis by EBUS when conventional diagnostics fail. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases. 2010;**27**(1):43-48

[14] Navani N, Booth HL, Kocjan G, Falzon M, Capitanio A, Brown JM, et al. Combination of endobronchial ultrasound-guided transbronchial needle aspiration with standard bronchoscopic techniques for the diagnosis of stage I and stage II pulmonary sarcoidosis. Respirology. 2011;**16**(3):467-472

[15] Hassan T, McLaughlin AM, O'Connell F, Gibbons N, Nicholson S, Keane J. EBUS-TBNA performs well in the diagnosis of isolated thoracic tuberculous lymphadenopathy. American Journal of Respiratory and Critical Care Medicine. 2011;**183**(1):136-137

[16] Lin SM, Ni YL, Kuo CH, Lin TY, Wang TY, Chung FT, et al. Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis. The Journal of Thoracic and Cardiovascular Surgery. 2010;**139**(6):1554-1560

[17] Steinfort DP, Farmer MW, Irving LB, Jennings BR. Pulmonologist-performed per-esophageal needle aspiration of parenchymal lung lesions using an EBUS bronchoscope: Diagnostic utility and safety. Journal of Bronchology and Interventional Pulmonology. 2017;**24**(2):117-124

[18] Tashi E, Kapisyzi P, Xhemalaj D, Andoni A, Peposhi I. Pancoast tumor approach through oesophagus. Respiratory Medicine Case Reports. 2017;**22**:218-219

[19] Navani N, Nankivell M, Woolhouse I, Harrison RN, Munavvar M, Oltmanns U, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of intrathoracic lymphadenopathy in patients

with extrathoracic malignancy: A multicenter study. Journal of Thoracic Oncology;**6**(9):1505-1509

[20] Al Zoby M, Munn N, Shweihat YR. Esophageal diagnosis of a malignant aspergilloma. Endoscopic Ultrasound. 2017;**6**(3):210-211

[21] Annema JT, Veselic M, Rabe KF. Endoscopic ultrasound-guided fineneedle aspiration for the diagnosis of sarcoidosis. The European Respiratory Journal. 2005;**25**(3):405-409

[22] Puri R, Vilmann P, Sud R, Kumar M, Taneja S, Verma K, et al. Endoscopic ultrasound-guided fine-needle aspiration cytology in the evaluation of suspected tuberculosis in patients with isolated mediastinal lymphadenopathy. Endoscopy. 2010;**42**(6):462-467

[23] Bhaskar N, Shweihat YR, Bartter T. The intubated patient with mediastinal disease—A role for esophageal access using the endobronchial ultrasound bronchoscope. Journal of Intensive Care Medicine. 2014;**29**(1):43-46

[24] Steinfort DP, Irving LB. Patient satisfaction during endobronchial ultrasound-guided transbronchial needle aspiration performed under conscious sedation. Respiratory Care. 2010;**55**(6):702-706

[25] Lababede O, Meziane M, Rice T. Seventh edition of the cancer staging manual and stage grouping of lung cancer: Quick reference chart and diagrams. Chest. 2011;**139**(1):183-189

[26] Meena N, Hulett C, Jeffus S, Bartter T. Left adrenal biopsy using the convex curvilinear ultrasound scope. Respiration. 2015;**89**(1):57-61

[27] Meena N, Hulett C, Patolia S, Bartter T. Exploration under the dome: Esophageal ultrasound with the ultrasound bronchoscope is indispensible. Endoscopic Ultrasound. 2016;**5**(4):254-257

**24**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

ultrasound bronchoscope in mediastinal staging of potentially operable lung cancer. Chest. 2010;**138**(4):795-802

[8] Vilmann P, Clementsen PF, Colella S, Siemsen M, De Leyn P, Dumonceau JM, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Endoscopy. 2015;**47**(6):545-559

[9] Ko HM, da Cunha Santos G, Darling G, Pierre A, Yasufuku K, Boerner SL, et al. Diagnosis and subclassification of lymphomas and non-neoplastic lesions involving mediastinal lymph nodes using endobronchial ultrasound-guided transbronchial needle aspiration. Diagnostic Cytopathology. Dec 2013;**41**(12):1023-1030. DOI: 10.1002/

dc.21741. Epub 2011 May 31

Journal of Thoracic Oncology.

Mhatre AD, Lei X, Giles FJ, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma. Thorax.

2010;**5**(6):804-809

2008;**63**(4):360-365

2009;**103**(12):1796-1800

Licht RB. Minimally invasive

[10] Steinfort DP, Conron M, Tsui A, Pasricha SR, Renwick WE, Antippa P, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the evaluation of suspected lymphoma.

[11] Kennedy MP, Jimenez CA, Bruzzi JF,

[12] Nakajima T, Yasufuku K, Kurosu K, Takiguchi Y, Fujiwara T, Chiyo M, et al. The role of EBUS-TBNA for the diagnosis of sarcoidosis—Comparisons with other bronchoscopic diagnostic modalities. Respiratory Medicine.

[13] Eckardt J, Olsen KE, Jorgensen OD,

[1] Vilmann P, Krasnik M, Larsen SS,

Transesophageal endoscopic ultrasoundguided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy: A combined approach in the evaluation of mediastinal lesions.

[2] Wallace MB, Pascual JM, Raimondo M, Woodward TA, McComb BL, Crook JE, et al. Minimally invasive endoscopic staging of suspected lung cancer. Journal of the American Medical Association. 2008;**299**(5):540-546

Jacobsen GK, Clementsen P.

**References**

Endoscopy. 2005;**37**(9):833-839

[3] Rintoul RC, Skwarski KM, Murchison JT, Wallace WA, Walker WS, Penman ID. Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration for mediastinal staging. The European Respiratory Journal. 2005;**25**(3):416-421

[4] Block MI. Transition from

[5] Annema JT, van Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: A randomized trial. Journal of the American Medical Association. 2010;**304**(20):2245-2252

[6] Herth FJ, Krasnik M, Kahn N, Eberhardt R, Ernst A. Combined endoscopic-endobronchial ultrasoundguided fine-needle aspiration of mediastinal lymph nodes through a single bronchoscope in 150 patients with suspected lung cancer. Chest.

[7] Hwangbo B, Lee GK, Lee HS, Lim KY, Lee SH, Kim HY, et al. Transbronchial and transesophageal fine-needle aspiration using an

2010;**138**(4):790-794

mediastinoscopy to endoscopic ultrasound for lung cancer staging. The Annals of Thoracic Surgery. 2010;**89**(3):885-890

[28] Eisen GM, Baron TH, Dominitz JA, Faigel DO, Goldstein JL, Johanson JF, et al. Complications of upper GI endoscopy. Gastrointestinal Endoscopy. 2002;**55**(7):784-793

[29] Wang CY, Ling LC, Cardosa MS, Wong AK, Wong NW. Hypoxia during upper gastrointestinal endoscopy with and without sedation and the effect of pre-oxygenation on oxygen saturation. Anaesthesia. 2000;**55**(7):654-658

[30] Rozario L, Sloper D, Sheridan MJ. Supplemental oxygen during moderate sedation and the occurrence of clinically significant desaturation during endoscopic procedures. Gastroenterology Nursing. 2008;**31**(4):281-285

[31] Alcain G, Guillen P, Escolar A, Moreno M, Martin L. Predictive factors of oxygen desaturation during upper gastrointestinal endoscopy in nonsedated patients. Gastrointestinal Endoscopy. 1998;**48**(2):143-147

[32] Sarwar S, Alam A, Khan AA. Pulse oximetry during gastrointestinal endoscopic procedures. Journal of the College of Physicians and Surgeons– Pakistan. 2006;**16**(2):97-100

[33] Osinaike BB, Akere A, Olajumoke TO, Oyebamiji EO. Cardiorespiratory changes during upper gastrointestinal endoscopy. African Health Sciences. 2007;**7**(2):115-119

[34] Adler DG, Jacobson BC, Davila RE, Hirota WK, Leighton JA, Qureshi WA, et al. ASGE guideline: Complications of EUS. Gastrointestinal Endoscopy. 2005;**61**(1):8-12

[35] Janssen J, Konig K, Knop-Hammad V, Johanns W, Greiner L. Frequency of bacteremia after linear EUS of the upper GI tract with and without FNA. Gastrointestinal Endoscopy. 2004;**59**(3):339-344

[36] Ryan AG, Zamvar V, Roberts SA. Iatrogenic candidal infection of a mediastinal foregut cyst following endoscopic ultrasound-guided fine-needle aspiration. Endoscopy. 2002;**34**(10):838-839

Chapter 3

Kumar Sachin

Abstract

Bronchial Thermoplasty: A New

Bronchial thermoplasty (BT) is a new endoscopic treatment approved by the US Food and Drug Administration (FDA) in the management of severe refractory asthma involving the delivery of controlled, therapeutic radiofrequency (RF) energy to the airway wall. It is based on the premise of controlling bronchospasm through a reduction of airway smooth muscle (ASM). Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. However, several questions remain regarding the use of BT, mechanism of action, selection of appropriate patients, and long-term effects. Further studies are expected to elucidate the underlying mechanisms that result in these improvements. This chapter discusses key aspects of BT with a focus on the potential clinical effects of this promising procedure. It also offers insight into the barriers to implementing a successful BT

Asthma is a common condition affecting more than 235 million people worldwide [1]. Asthma is a chronic inflammatory disease characterized by variable airflow obstruction and bronchial hyperreactivity associated with airway remodeling. Clinically, this manifests as recurrent episodes of wheezing, cough, dyspnea, and chest tightness. Asthma treatment as of current standard is based on reducing inflammation with inhaled corticosteroids (ICS) and relaxing airway smooth muscle (ASM) with inhaled bronchodilators along with minimizing exposure to allergic triggers [2]. While most patients achieve symptom control with these strategies, there remains a significant cohort with severe asthma estimated at 5–10% who are more difficult to treat. This group of severe asthmatics, however, is responsible for a disproportionate share of the morbidity associated with the disease. The severe asthma group is responsible for most of the asthma-related healthcare burden, represented by the costs of hospitalizations, ER visits, physician office visits, and use of medications [3–5]. This increased burden of severe asthma reflects the inability of the existing treatment options to adequately control asthma in patients

Therapeutic Option in Severe

Uncontrolled Asthma

program and strategies for overcoming them.

airway smooth muscle

1. Introduction

with severe disease.

27

Keywords: severe asthma, bronchial thermoplasty, bronchoscopy,

[37] Wildi SM, Hoda RS, Fickling W, Schmulewitz N, Varadarajulu S, Roberts SS, et al. Diagnosis of benign cysts of the mediastinum: The role and risks of EUS and FNA. Gastrointestinal Endoscopy. 2003;**58**(3):362-368

[38] Diehl DL, Cheruvattath R, Facktor MA, Go BD. Infection after endoscopic ultrasound-guided aspiration of mediastinal cysts. Interactive Cardiovascular and Thoracic Surgery. 2009;**10**(2):338-340

[39] Affi A, Vazquez-Sequeiros E, Norton ID, Clain JE, Wiersema MJ. Acute extraluminal hemorrhage associated with EUS-guided fine needle aspiration: Frequency and clinical significance. Gastrointestinal Endoscopy. 2001;**53**(2):221-225

[40] von Bartheld MB, Rabe KF, Annema JT. Transaortic EUS-guided FNA in the diagnosis of lung tumors and lymph nodes. Gastrointestinal Endoscopy. 2009;**69**(2):345-349

[41] Buxbaum JL, Eloubeidi MA. Transgastric endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) in patients with esophageal narrowing using the ultrasonic bronchovideoscope. Diseases of the Esophagus. Sep 2011;**24**(7):458-461. DOI: 10.1111/j.1442-2050.2011.01179.x. Epub 2011 Mar 8

#### Chapter 3

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

[36] Ryan AG, Zamvar V, Roberts SA. Iatrogenic candidal infection of a mediastinal foregut cyst following endoscopic ultrasound-guided fine-needle aspiration. Endoscopy.

[37] Wildi SM, Hoda RS, Fickling W, Schmulewitz N, Varadarajulu S, Roberts SS, et al. Diagnosis of benign cysts of the mediastinum: The role and risks of EUS and FNA. Gastrointestinal

Endoscopy. 2003;**58**(3):362-368

[38] Diehl DL, Cheruvattath R, Facktor MA, Go BD. Infection after endoscopic ultrasound-guided aspiration of mediastinal cysts.

Surgery. 2009;**10**(2):338-340

[39] Affi A, Vazquez-Sequeiros E, Norton ID, Clain JE, Wiersema MJ. Acute extraluminal hemorrhage associated with EUS-guided fine needle aspiration: Frequency and clinical significance. Gastrointestinal Endoscopy. 2001;**53**(2):221-225

[40] von Bartheld MB, Rabe KF, Annema JT. Transaortic EUS-guided FNA in the diagnosis of lung tumors and lymph nodes. Gastrointestinal Endoscopy. 2009;**69**(2):345-349

[41] Buxbaum JL, Eloubeidi MA. Transgastric endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) in patients with esophageal narrowing using the ultrasonic bronchovideoscope. Diseases of the Esophagus. Sep 2011;**24**(7):458-461. DOI: 10.1111/j.1442-2050.2011.01179.x.

Epub 2011 Mar 8

Interactive Cardiovascular and Thoracic

2002;**34**(10):838-839

[28] Eisen GM, Baron TH, Dominitz JA, Faigel DO, Goldstein JL, Johanson JF, et al. Complications of upper GI

endoscopy. Gastrointestinal Endoscopy.

[29] Wang CY, Ling LC, Cardosa MS, Wong AK, Wong NW. Hypoxia during upper gastrointestinal endoscopy with and without sedation and the effect of pre-oxygenation on oxygen saturation. Anaesthesia. 2000;**55**(7):654-658

[30] Rozario L, Sloper D, Sheridan MJ. Supplemental oxygen during moderate

sedation and the occurrence of clinically significant desaturation during endoscopic procedures. Gastroenterology Nursing.

[31] Alcain G, Guillen P, Escolar A, Moreno M, Martin L. Predictive factors of oxygen desaturation during upper gastrointestinal endoscopy in nonsedated patients. Gastrointestinal Endoscopy. 1998;**48**(2):143-147

[32] Sarwar S, Alam A, Khan AA. Pulse oximetry during gastrointestinal endoscopic procedures. Journal of the College of Physicians and Surgeons–

[33] Osinaike BB, Akere A, Olajumoke TO, Oyebamiji EO. Cardiorespiratory changes during upper gastrointestinal endoscopy. African Health Sciences.

[34] Adler DG, Jacobson BC, Davila RE, Hirota WK, Leighton JA, Qureshi WA, et al. ASGE guideline: Complications of EUS. Gastrointestinal Endoscopy.

[35] Janssen J, Konig K, Knop-Hammad V, Johanns W, Greiner L. Frequency of bacteremia after linear EUS of the upper GI tract with and without FNA. Gastrointestinal Endoscopy.

Pakistan. 2006;**16**(2):97-100

2007;**7**(2):115-119

2005;**61**(1):8-12

2004;**59**(3):339-344

2008;**31**(4):281-285

2002;**55**(7):784-793

**26**

## Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma

Kumar Sachin

#### Abstract

Bronchial thermoplasty (BT) is a new endoscopic treatment approved by the US Food and Drug Administration (FDA) in the management of severe refractory asthma involving the delivery of controlled, therapeutic radiofrequency (RF) energy to the airway wall. It is based on the premise of controlling bronchospasm through a reduction of airway smooth muscle (ASM). Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. However, several questions remain regarding the use of BT, mechanism of action, selection of appropriate patients, and long-term effects. Further studies are expected to elucidate the underlying mechanisms that result in these improvements. This chapter discusses key aspects of BT with a focus on the potential clinical effects of this promising procedure. It also offers insight into the barriers to implementing a successful BT program and strategies for overcoming them.

Keywords: severe asthma, bronchial thermoplasty, bronchoscopy, airway smooth muscle

#### 1. Introduction

Asthma is a common condition affecting more than 235 million people worldwide [1]. Asthma is a chronic inflammatory disease characterized by variable airflow obstruction and bronchial hyperreactivity associated with airway remodeling. Clinically, this manifests as recurrent episodes of wheezing, cough, dyspnea, and chest tightness. Asthma treatment as of current standard is based on reducing inflammation with inhaled corticosteroids (ICS) and relaxing airway smooth muscle (ASM) with inhaled bronchodilators along with minimizing exposure to allergic triggers [2]. While most patients achieve symptom control with these strategies, there remains a significant cohort with severe asthma estimated at 5–10% who are more difficult to treat. This group of severe asthmatics, however, is responsible for a disproportionate share of the morbidity associated with the disease. The severe asthma group is responsible for most of the asthma-related healthcare burden, represented by the costs of hospitalizations, ER visits, physician office visits, and use of medications [3–5]. This increased burden of severe asthma reflects the inability of the existing treatment options to adequately control asthma in patients with severe disease.

Severe Asthma is defined by the American Thoracic Society and European Respiratory Society as asthma requiring treatment with high-dose ICS and a second controller medication (and/or systemic corticosteroids) to maintain asthma control [6]. Unfortunately, therapeutic options for patients with severe asthma are limited. Biologic therapy targeting IgE, IL-4 and IL-5 have been of particular interest recently. In the past decade, new therapeutic approaches for asthma have included the use of biological agents, such as omalizumab, a recombinant DNAderived humanized monoclonal antibody to IgE. However, in patients with severe asthma with no indication for or those lacking a response to omalizumab, the new targeted anti-IL-5 monoclonal antibodies including mepolizumab and reslizumab, have been recently approved [7, 8]. However, they only appear effective in certain subgroups of patients with asthma. Hence, new treatment strategies and approaches are urgently needed for these patients. BT is a novel nonpharmacological therapy which targets ASM in an effort to improve asthma control.

Several clinical trials have demonstrated the long-term safety and effectiveness of BT in terms of reducing exacerbations of asthma and improving patient quality

This chapter will summarize the information on mechanism of action, procedure, efficacy, safety and patient selection, to better understand the path

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma

4. Efficacy data in the short and long term: BT trials to real life

reveal any bronchiectasis or parenchymal lung disease [17].

morning PEF, in patients treated with BT [18].

despite the reduction of OCSs and bronchodilators.

5. AIR-2 trial

29

The first randomized clinical trial (RCT) evaluating the efficacy of BT was conducted in 2006 by Cox et al. on 16 patients with stable mild-to-moderate asthma [17]. In general, BT was well tolerated, with most of the procedure-related adverse events occurring in the week following the procedure. Most of the events were mild and transient and resolved spontaneously or required minor changes in medications. There was a significant reduction in airway hyperresponsiveness as reflected by increased PC20 (provocative concentration causing a 20% decline in FEV1). In addition, there was a significant improvement in symptom-free days (47 vs. 73%, P = 0.015) and peak expiratory flow rates measured at 12 weeks following BT. Interestingly, there was no change in FEV1 during the 2 years of follow-up. Chest CT was performed at 1 year and 2 years following BT did not

Asthma Intervention Research (AIR) trial was the next major RCT in 2007. AIR included 112 patients with moderate-to-severe asthma (FEV1 between 60 and 85%

(40.6 39.7% vs. 17.0 37.9%, P = 0.005), scores of the asthma control questionnaire (ACQ) (reduction, 1.2 1.0 vs. 0.5 1.0, P = 0.001) and asthma quality of life questionnaire (AQLQ) (1.3 1.0 vs. 0.6 1.1, P = 0.003). Moreover, there was a significant reduction in mild exacerbations of asthma and an increase in the

In 2007, the Research in Severe Asthma (RISA) designed to evaluate the safety and efficacy of BT in patients with severe, symptomatic asthma was published [19].

of predicted) treated with BT [18]. Although, there were no differences in prebronchodilator FEV1 percentage of predicted (72–74.3% vs. 75.8–75.7%, P = 0.28) between patients who underwent BT and the control group when compared to their pre-randomization baseline. There was, however, a significant improvement in asthma symptoms as reflected by symptom-free days

This smaller trial included 32 patients (15 randomized to BT) with severe persistent asthma as defined by uncontrolled symptoms despite high-dose ICS and LABA use. Patients in BT arm showed a significant improvement in

unblinded [19]. The AIR-2 trial was designed to answer these questions.

pre-bronchodilator FEV1. The improvements in ACQ and AQLQ score persisted

These results were promising, however questions remained over the true efficacy of BT versus potential placebo effect as the RISA and the AIR trials were

The largest RCT, AIR2, was a double-blinded, randomized, sham-controlled study included patients who had uncontrolled asthma despite high-dose ICS and a LABA [20]. A total of 190 patients were treated with BT and 98 control patients received sham thermoplasty. The procedure was performed by an unblinded bronchoscopy team and all the assessments and follow-up visits were conducted by

of life [16].

forward for this promising technique.

DOI: http://dx.doi.org/10.5772/intechopen.84466

#### 2. Airway smooth muscle in asthma

The airway smooth muscle (ASM) plays significant role in multiple normal processes in the healthy airway, including control of bronchomotor tone, immunomodulation, and extracellular matrix deposition. ASM cells in asthma patients proliferate more rapidly than in non-asthmatic patients, resulting in an increase in smooth muscle mass, with airway narrowing and loss of respiratory function [9]. As a result, the proliferation and differentiation of mesenchymal cells to myofibroblasts increases the deposition of extracellular matrix (ECM) and smooth muscle cells [10]. All of the above modifications, in particular, ASM and ECM deposition, increase the airway wall thickness, which correlates with severity and duration of clinical episodes of asthma [11]. Bronchial remodeling, an increase in ASM, has been shown to be related to clinical and functional severity of asthma [9]. It has been shown that those with fatal asthma have an increased volume of smooth muscle compared with nonfatal asthma [12].

These published findings led to the conclusion that smooth muscle cell alteration is the fundamental structural change that distinguishes severe from moderate asthma, and that phenotypic changes in ASM could contribute to reducing control in subjects with severe asthma [13]. As a result, ASM has become a therapeutic target.

#### 3. Bronchial thermoplasty

BT is a nonpharmacological, novel endoscopic therapy that delivers controlled RF thermal energy to the airway wall as part of a series of three bronchoscopic procedures. It was approved by the US Food and Drug Administration for the treatment of severe persistent asthma in patients aged over 18 years in 2010.It involves application of RF thermal energy to the airways in asthma patients with the goal of ablating the ASM. The first study of BT in human airways involved subjects undergoing lobectomy for known or suspected lung cancer [14].

The current understanding is that BT can denature and destroy ASM and allows the reduction of bronchospasm which in turn results in improved control of the symptoms of severe asthma. Previous canine animal models have demonstrated that BT causes almost complete destruction of ASM with moderate connective tissue deposition when lung tissue has been examined histologically [15].

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma DOI: http://dx.doi.org/10.5772/intechopen.84466

Several clinical trials have demonstrated the long-term safety and effectiveness of BT in terms of reducing exacerbations of asthma and improving patient quality of life [16].

This chapter will summarize the information on mechanism of action, procedure, efficacy, safety and patient selection, to better understand the path forward for this promising technique.

#### 4. Efficacy data in the short and long term: BT trials to real life

The first randomized clinical trial (RCT) evaluating the efficacy of BT was conducted in 2006 by Cox et al. on 16 patients with stable mild-to-moderate asthma [17]. In general, BT was well tolerated, with most of the procedure-related adverse events occurring in the week following the procedure. Most of the events were mild and transient and resolved spontaneously or required minor changes in medications. There was a significant reduction in airway hyperresponsiveness as reflected by increased PC20 (provocative concentration causing a 20% decline in FEV1). In addition, there was a significant improvement in symptom-free days (47 vs. 73%, P = 0.015) and peak expiratory flow rates measured at 12 weeks following BT. Interestingly, there was no change in FEV1 during the 2 years of follow-up. Chest CT was performed at 1 year and 2 years following BT did not reveal any bronchiectasis or parenchymal lung disease [17].

Asthma Intervention Research (AIR) trial was the next major RCT in 2007. AIR included 112 patients with moderate-to-severe asthma (FEV1 between 60 and 85% of predicted) treated with BT [18]. Although, there were no differences in prebronchodilator FEV1 percentage of predicted (72–74.3% vs. 75.8–75.7%, P = 0.28) between patients who underwent BT and the control group when compared to their pre-randomization baseline. There was, however, a significant improvement in asthma symptoms as reflected by symptom-free days (40.6 39.7% vs. 17.0 37.9%, P = 0.005), scores of the asthma control questionnaire (ACQ) (reduction, 1.2 1.0 vs. 0.5 1.0, P = 0.001) and asthma quality of life questionnaire (AQLQ) (1.3 1.0 vs. 0.6 1.1, P = 0.003). Moreover, there was a significant reduction in mild exacerbations of asthma and an increase in the morning PEF, in patients treated with BT [18].

In 2007, the Research in Severe Asthma (RISA) designed to evaluate the safety and efficacy of BT in patients with severe, symptomatic asthma was published [19]. This smaller trial included 32 patients (15 randomized to BT) with severe persistent asthma as defined by uncontrolled symptoms despite high-dose ICS and LABA use. Patients in BT arm showed a significant improvement in pre-bronchodilator FEV1. The improvements in ACQ and AQLQ score persisted despite the reduction of OCSs and bronchodilators.

These results were promising, however questions remained over the true efficacy of BT versus potential placebo effect as the RISA and the AIR trials were unblinded [19]. The AIR-2 trial was designed to answer these questions.

#### 5. AIR-2 trial

The largest RCT, AIR2, was a double-blinded, randomized, sham-controlled study included patients who had uncontrolled asthma despite high-dose ICS and a LABA [20]. A total of 190 patients were treated with BT and 98 control patients received sham thermoplasty. The procedure was performed by an unblinded bronchoscopy team and all the assessments and follow-up visits were conducted by

Severe Asthma is defined by the American Thoracic Society and European Respiratory Society as asthma requiring treatment with high-dose ICS and a second

The airway smooth muscle (ASM) plays significant role in multiple normal

These published findings led to the conclusion that smooth muscle cell alteration

BT is a nonpharmacological, novel endoscopic therapy that delivers controlled RF thermal energy to the airway wall as part of a series of three bronchoscopic procedures. It was approved by the US Food and Drug Administration for the treatment of severe persistent asthma in patients aged over 18 years in 2010.It involves application of RF thermal energy to the airways in asthma patients with the goal of ablating the ASM. The first study of BT in human airways involved subjects

The current understanding is that BT can denature and destroy ASM and allows the reduction of bronchospasm which in turn results in improved control of the symptoms of severe asthma. Previous canine animal models have demonstrated that BT causes almost complete destruction of ASM with moderate connective tissue

undergoing lobectomy for known or suspected lung cancer [14].

deposition when lung tissue has been examined histologically [15].

is the fundamental structural change that distinguishes severe from moderate asthma, and that phenotypic changes in ASM could contribute to reducing control in subjects with severe asthma [13]. As a result, ASM has become

processes in the healthy airway, including control of bronchomotor tone, immunomodulation, and extracellular matrix deposition. ASM cells in asthma patients proliferate more rapidly than in non-asthmatic patients, resulting in an increase in smooth muscle mass, with airway narrowing and loss of respiratory function [9]. As a result, the proliferation and differentiation of mesenchymal cells to myofibroblasts increases the deposition of extracellular matrix (ECM) and smooth muscle cells [10]. All of the above modifications, in particular, ASM and ECM deposition, increase the airway wall thickness, which correlates with severity and duration of clinical episodes of asthma [11]. Bronchial remodeling, an increase in ASM, has been shown to be related to clinical and functional severity of asthma [9]. It has been shown that those with fatal asthma have an increased volume of

controller medication (and/or systemic corticosteroids) to maintain asthma control [6]. Unfortunately, therapeutic options for patients with severe asthma are limited. Biologic therapy targeting IgE, IL-4 and IL-5 have been of particular interest recently. In the past decade, new therapeutic approaches for asthma have included the use of biological agents, such as omalizumab, a recombinant DNAderived humanized monoclonal antibody to IgE. However, in patients with severe asthma with no indication for or those lacking a response to omalizumab, the new targeted anti-IL-5 monoclonal antibodies including mepolizumab and reslizumab, have been recently approved [7, 8]. However, they only appear effective in certain subgroups of patients with asthma. Hence, new treatment strategies and approaches are urgently needed for these patients. BT is a novel nonpharmacological therapy

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics

which targets ASM in an effort to improve asthma control.

smooth muscle compared with nonfatal asthma [12].

a therapeutic target.

28

3. Bronchial thermoplasty

2. Airway smooth muscle in asthma

(5 years in total) and an additional 2 years (3 years in total) respectively [21]. In comparison to the control subjects, patients who underwent BT had similar rates of adverse respiratory events, oral corticosteroid bursts requirements, hospitalizations, and emergency department visits. Further, patients treated with BT continued to show improvements in airway hyperresponsiveness lasting up to 3 years,

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma

A long-term follow up of the patients with BT included in the RISA study, performed for a total of 5 years, showed a significant decline in emergency visits and hospitalizations for an exacerbation of asthma, and no further deterioration of

4 years to evaluate the long-term effects of BT [23]. Patients treated with BT showed a definite decrease in severe exacerbations of asthma and emergency hospital visits [23]. Interestingly, a recent large retrospective study of patients with persistent asthma suggests constant exacerbation frequency despite continued highintensity therapy with high doses of ICS and LABAs [24]. Therefore, long-term comparative head to head safety studies for the use of BT in the treatment of asthma

Currently, BT is approved for patients with uncontrolled severe persistent asthma despite the use of an inhaled corticosteroid and LABA. As per the recent Global Initiative for Asthma (GINA) guidelines, it has been suggested that "for

recommended therapeutic regimens and referral to an asthma specialty center, BT is a potential treatment option" (Grade B evidence) [25]. In general, BT remains contraindicated in patients with a pacemaker, internal defibrillator, or any

Prior to consideration of BT, patients should undergo a focused evaluation to ensure that the diagnosis of severe asthma is correct, treatment is optimized, and comorbid conditions are treated. A thorough history and detailed physical examination constitute the next step. In addition, workup as necessary to exclude an alternative diagnosis, such as sarcoidosis, cystic fibrosis (CF), other non-CF bronchiectatic lung disease, alpha-1 antitrypsin deficiency, and chronic obstructive pulmonary disease (COPD) should also be carried out [26]. In general, full pulmonary function testing as well as a high-resolution CT scan of the lungs is also desirable. Before labeling it as severe asthma, the inhaler technique and adherence are also evaluated rigorously, as corrective interventions have shown to improve

BT is based on the principle of endobronchial controlled delivery of RF thermal energy to modify the structure of the airway wall thereby reducing the amount of ASM with a device called the Alair BT System (Boston Scientific, Marlborough, MA, USA). A bronchoscope with a disposable catheter with a diameter of 2.0 mm in the operating channel is used to obtain better visualization and complete treatment of subsegmental bronchi [17]. The distal tip of the catheter has an expandable fourelectrode basket, through which 65°C radio frequencies are delivered in order to visible bronchial areas sequentially [17]. The correct order involves the right lower

highly-selected adult patients with uncontrolled asthma despite use of

Similarly, in the AIR-2 follow up study, patients were also monitored for another

suggesting the long-term efficacy of the procedure [21].

are nevertheless required in future also.

DOI: http://dx.doi.org/10.5772/intechopen.84466

implantable electronic device [25].

asthma control [27].

8. BT procedure

31

7. Patient selection for bronchial thermoplasty

FEV1 [22].


Abbreviations: FEV1, forced expiratory volume in 1 sec; AQLQ, Asthma Quality of Life Questionnaire; ACQ, Asthma Control Questionnaire; AIR, Asthma Intervention Research; RISA, Research in Severe Asthma.

#### Table 1.

Summary of clinical trials and long term follow up with BT in asthma.

a blinded team [20]. The primary outcome measure was to evaluate change from baseline in average group mean Asthma Quality of Life Questionnaire (AQLQ) score. In the BT group, a significantly greater proportion had a significant increase in the AQLQ score compared with those who underwent sham bronchoscopy (79 vs. 64%). There was also a meaningful reduction in the number of exacerbations (32% risk reduction), emergency department visits (84% risk reduction) and days lost from school/work (66% risk reduction) in those in the BT arm [20].

The results of these large RCTs are summarized in Table 1.

#### 6. Long-term follow up and safety of BT

The earlier large clinical trials of BT showed marked improvements in asthmarelated quality of life and a reduction in the number of exacerbations and led to the approval of the use of BT by the FDA in 2010 (Table 1). However, long-term safety of BT was largely unaddressed, especially because of early concerns about thermal tissue damage, possible subsequent risk of bronchial stenosis, and bronchomalacia remained to be investigated. Recently, the results from the long-term follow-up of patients enrolled in the AIR, RISA, and AIR-2 trials have provided some clarity in this regard.

From the original study population of patients in the AIR trial, 45 patients treated with BT and 24 control patients were followed for an additional 4 years Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma DOI: http://dx.doi.org/10.5772/intechopen.84466

(5 years in total) and an additional 2 years (3 years in total) respectively [21]. In comparison to the control subjects, patients who underwent BT had similar rates of adverse respiratory events, oral corticosteroid bursts requirements, hospitalizations, and emergency department visits. Further, patients treated with BT continued to show improvements in airway hyperresponsiveness lasting up to 3 years, suggesting the long-term efficacy of the procedure [21].

A long-term follow up of the patients with BT included in the RISA study, performed for a total of 5 years, showed a significant decline in emergency visits and hospitalizations for an exacerbation of asthma, and no further deterioration of FEV1 [22].

Similarly, in the AIR-2 follow up study, patients were also monitored for another 4 years to evaluate the long-term effects of BT [23]. Patients treated with BT showed a definite decrease in severe exacerbations of asthma and emergency hospital visits [23]. Interestingly, a recent large retrospective study of patients with persistent asthma suggests constant exacerbation frequency despite continued highintensity therapy with high doses of ICS and LABAs [24]. Therefore, long-term comparative head to head safety studies for the use of BT in the treatment of asthma are nevertheless required in future also.

#### 7. Patient selection for bronchial thermoplasty

Currently, BT is approved for patients with uncontrolled severe persistent asthma despite the use of an inhaled corticosteroid and LABA. As per the recent Global Initiative for Asthma (GINA) guidelines, it has been suggested that "for highly-selected adult patients with uncontrolled asthma despite use of recommended therapeutic regimens and referral to an asthma specialty center, BT is a potential treatment option" (Grade B evidence) [25]. In general, BT remains contraindicated in patients with a pacemaker, internal defibrillator, or any implantable electronic device [25].

Prior to consideration of BT, patients should undergo a focused evaluation to ensure that the diagnosis of severe asthma is correct, treatment is optimized, and comorbid conditions are treated. A thorough history and detailed physical examination constitute the next step. In addition, workup as necessary to exclude an alternative diagnosis, such as sarcoidosis, cystic fibrosis (CF), other non-CF bronchiectatic lung disease, alpha-1 antitrypsin deficiency, and chronic obstructive pulmonary disease (COPD) should also be carried out [26]. In general, full pulmonary function testing as well as a high-resolution CT scan of the lungs is also desirable. Before labeling it as severe asthma, the inhaler technique and adherence are also evaluated rigorously, as corrective interventions have shown to improve asthma control [27].

#### 8. BT procedure

BT is based on the principle of endobronchial controlled delivery of RF thermal energy to modify the structure of the airway wall thereby reducing the amount of ASM with a device called the Alair BT System (Boston Scientific, Marlborough, MA, USA). A bronchoscope with a disposable catheter with a diameter of 2.0 mm in the operating channel is used to obtain better visualization and complete treatment of subsegmental bronchi [17]. The distal tip of the catheter has an expandable fourelectrode basket, through which 65°C radio frequencies are delivered in order to visible bronchial areas sequentially [17]. The correct order involves the right lower

a blinded team [20]. The primary outcome measure was to evaluate change from baseline in average group mean Asthma Quality of Life Questionnaire (AQLQ) score. In the BT group, a significantly greater proportion had a significant increase in the AQLQ score compared with those who underwent sham bronchoscopy (79 vs. 64%). There was also a meaningful reduction in the number of exacerbations (32% risk reduction), emergency department visits (84% risk reduction) and days

Abbreviations: FEV1, forced expiratory volume in 1 sec; AQLQ, Asthma Quality of Life Questionnaire; ACQ, Asthma Control Questionnaire; AIR, Asthma Intervention Research; RISA, Research in Severe Asthma.

The earlier large clinical trials of BT showed marked improvements in asthmarelated quality of life and a reduction in the number of exacerbations and led to the approval of the use of BT by the FDA in 2010 (Table 1). However, long-term safety of BT was largely unaddressed, especially because of early concerns about thermal tissue damage, possible subsequent risk of bronchial stenosis, and bronchomalacia remained to be investigated. Recently, the results from the long-term follow-up of patients enrolled in the AIR, RISA, and AIR-2 trials have provided some clarity in

From the original study population of patients in the AIR trial, 45 patients treated with BT and 24 control patients were followed for an additional 4 years

lost from school/work (66% risk reduction) in those in the BT arm [20]. The results of these large RCTs are summarized in Table 1.

6. Long-term follow up and safety of BT

Study Study population Study design Results

trial

trial

study

study

study

Summary of clinical trials and long term follow up with BT in asthma.

Non-randomized, prospective study

Randomized, controlled

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics

Randomized, doubleblind, parallel-group

Randomized, doubleblind, controlled, multicenter-based trial

Long-term follow-up

Long-term follow-up

Long-term follow-up

Significant reduction in airway hyperresponsiveness and increase of symptoms-free days. No changes in FEV1

scores, and reduction in mild exacerbations. No changes in FEV1 and

bronchial hyperreactivity

visits, and lost working days

Significant reduction in airway hyperreactivity and stability of FEV1. No

radiological changes

admissions

Improvements of asthma symptoms, symptom-free days, and AQLQ and ACQ

Significant improvement in FEV1 and ACQ scores. Limitation: effective placebo

Increase of AQLQ score, and reduction of rate of exacerbations, emergency hospital

Significant decrease of emergency hospital admissions. No changes of FEV1 value

Significant decrease of emergency hospital

16 patients with mild-to-moderate stable asthma

112 patients with moderate-tosevere asthma

32 patients with severe uncontrolled asthma

288 patients with severe, uncontrolled asthma

69 patients enrolled in the AIR

14 patients enrolled in RISA

160 patients enrolled in AIR-2

trial

trial

trial

Cox et al. [17]

Cox et al. [18]

Pavord et al. [19]

Castro et al. [20]

Thomson et al. [21]

Pavord et al. [22]

Wechsler et al. [23]

Table 1.

this regard.

30

lobe (first session) then left lower lobe (second session), followed by both upper lobes (third session). The right middle lobe is generally not treated because of the remote possibility of obstruction and right middle lobe syndrome. A typical BT session lasts about 30–45 min.

inflammatory response, BT specifically targets the ASM. Recent clinical trials have established its safety, ability to improve quality of life and reduction in exacerbations in patients with severe asthma. However, the exact mechanisms that underlie these improvements seen with BT remain at best still poorly understood. Future studies on the mechanism of action of BT, including phenotyping of patients and treatment approaches in identifying the patients most likely to respond to this

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma

Pulmonology and Critical Care Medicine, Sakra World Hospital, Bangalore, India

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: sachin.drk@gmail.com

provided the original work is properly cited.

therapy are expected to solve the existing conundrum.

DOI: http://dx.doi.org/10.5772/intechopen.84466

The author does not disclose any conflict of interest.

Conflict of interest

Author details

Kumar Sachin

33

The entire visible length of each bronchus is treated with each pulse targeting a 5 mm section of bronchus between 3 and 10 mm in diameter, starting at the periphery and moving proximally. On an average the full treatment consists of 30–70 activations per lobe, up to 44 for the right lower lobe, 47 for the left lower lobe and 60 for the upper lobes [21]. Successful BT comprises three procedures performed at 20 day intervals [17]. Mild bronchoconstriction, mucous hypersecretion, and minor bleeding related to superficial trauma are the most commonly encountered complications. Patients are given systemic corticosteroids and nebulized. Bronchodilators prior and after the procedure to minimize the complications in the post procedure setting.

BT should be performed by an experienced bronchoscopist in an adequate setting with appropriate clinical monitoring and the facility and expertise to address any potential post-intervention complications. Mayse et al. has described the appropriate assessment and monitoring of the patient before, during and after the procedure [28].

#### 9. What are the current guidelines regarding bronchial thermoplasty?

As per the current European Respiratory Society and American Thoracic Society (ERS/ATS) guidelines BT is recommended in adults with severe refractory asthma, despite optimal therapy, in the context of an institutional review board-approved independent systematic registry, or for use in a clinical study only [29]. A recent Cochrane Database systematic review also has the same recommendation and highlights the need for further studies on BT to determine the mechanisms of action in patients with different phenotypes of asthma [30]. Interestingly the BT Global Registry, a 2 year observational study is expected to provide new and valuable data on BT, is currently recruiting patients [31].

#### 10. Pharmacoeconomics of bronchial thermoplasty

BT is an expensive procedure, but recent studies have shown that the obvious high cost may be at least partially balanced by the reduction in costs due to decrease in acute exacerbations of asthma requiring emergency department visits and the effects of improved quality of life for patients [32]. A subsequent study has confirmed that BT has a 60% chance to be more cost effective as compared with omalizumab and standard therapy on the willingness-to pay of \$100,000/qualityadjusted life year [33]. Zein and colleagues also concluded that BT is a cost effective intervention in patients with asthma at high risk of exacerbations [34]. However, a study carried out in Singapore found that BT is not cost effective compared with optimized asthma therapy unless the cost of the procedure is decreased so as to make it more cost effective [35].

#### 11. Conclusions

BT is the only FDA approved nonpharmacological treatment available for severe asthma patients. In contrast to therapies for asthma targeting the underlying

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma DOI: http://dx.doi.org/10.5772/intechopen.84466

inflammatory response, BT specifically targets the ASM. Recent clinical trials have established its safety, ability to improve quality of life and reduction in exacerbations in patients with severe asthma. However, the exact mechanisms that underlie these improvements seen with BT remain at best still poorly understood. Future studies on the mechanism of action of BT, including phenotyping of patients and treatment approaches in identifying the patients most likely to respond to this therapy are expected to solve the existing conundrum.

### Conflict of interest

lobe (first session) then left lower lobe (second session), followed by both upper lobes (third session). The right middle lobe is generally not treated because of the remote possibility of obstruction and right middle lobe syndrome. A typical BT

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics

The entire visible length of each bronchus is treated with each pulse targeting a 5 mm section of bronchus between 3 and 10 mm in diameter, starting at the periphery and moving proximally. On an average the full treatment consists of 30–70 activations per lobe, up to 44 for the right lower lobe, 47 for the left lower lobe and 60 for the upper lobes [21]. Successful BT comprises three procedures

performed at 20 day intervals [17]. Mild bronchoconstriction, mucous

hypersecretion, and minor bleeding related to superficial trauma are the most commonly encountered complications. Patients are given systemic corticosteroids and nebulized. Bronchodilators prior and after the procedure to minimize the com-

BT should be performed by an experienced bronchoscopist in an adequate setting with appropriate clinical monitoring and the facility and expertise to address any potential post-intervention complications. Mayse et al. has described the appropriate assessment and monitoring of the patient before, during and after the

9. What are the current guidelines regarding bronchial thermoplasty?

As per the current European Respiratory Society and American Thoracic Society (ERS/ATS) guidelines BT is recommended in adults with severe refractory asthma, despite optimal therapy, in the context of an institutional review board-approved independent systematic registry, or for use in a clinical study only [29]. A recent Cochrane Database systematic review also has the same recommendation and highlights the need for further studies on BT to determine the mechanisms of action in patients with different phenotypes of asthma [30]. Interestingly the BT Global Registry, a 2 year observational study is expected to provide new and valuable data

BT is an expensive procedure, but recent studies have shown that the obvious high cost may be at least partially balanced by the reduction in costs due to decrease in acute exacerbations of asthma requiring emergency department visits and the effects of improved quality of life for patients [32]. A subsequent study has confirmed that BT has a 60% chance to be more cost effective as compared with omalizumab and standard therapy on the willingness-to pay of \$100,000/qualityadjusted life year [33]. Zein and colleagues also concluded that BT is a cost effective intervention in patients with asthma at high risk of exacerbations [34]. However, a study carried out in Singapore found that BT is not cost effective compared with optimized asthma therapy unless the cost of the procedure is decreased so as to

BT is the only FDA approved nonpharmacological treatment available for severe

asthma patients. In contrast to therapies for asthma targeting the underlying

session lasts about 30–45 min.

plications in the post procedure setting.

on BT, is currently recruiting patients [31].

make it more cost effective [35].

11. Conclusions

32

10. Pharmacoeconomics of bronchial thermoplasty

procedure [28].

The author does not disclose any conflict of interest.

#### Author details

Kumar Sachin Pulmonology and Critical Care Medicine, Sakra World Hospital, Bangalore, India

\*Address all correspondence to: sachin.drk@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### References

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[2] Mitzner W. Airway smooth muscle: The appendix of the lung. American Journal of Respiratory and Critical Care Medicine. 2004;169:787-790

[3] Godard P, Chanez P, Siraudin L, Nicoloyannis N, Duru G. Costs of asthma are correlated with severity: A 1-yr prospective study. The European Respiratory Journal. 2002; 19(1):61-67

[4] Ivanova JI, Bergman R, Birnbaum HG, Colice GL, Silverman RA, McLaurin K. Effect of asthma exacerbations on health care costs among asthmatic patients with moderate and severe persistent asthma. The Journal of Allergy and Clinical Immunology. 2012;129(5):1229-1235

[5] Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the national heart, lung, and blood institutes severe asthma research program. The Journal of Allergy and Clinical Immunology. 2007;119(2):405-413

[6] Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. The European Respiratory Journal. 2014;43(2):343-373

[7] Menzella F, Lusuardi M, Galeone C, Taddei S, Facciolongo N, Zucchi L. Mepolizumab for severe refractory eosinophilic asthma: Evidence to date and clinical potential. Therapeutic Advances in Chronic Disease. 2016;7(6): 260-277

[8] Máspero J. Reslizumab in the treatment of inadequately controlled asthma in adults and adolescents with elevated blood eosinophils: Clinical trial evidence and future prospects. Therapeutic Advances in Respiratory Disease. 2017;11(8):311-325

energy in dogs. Journal of Applied Physiology (Bethesda, MD: 1985). 2004;

DOI: http://dx.doi.org/10.5772/intechopen.84466

Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma

[23] Wechsler ME, Laviolette M, Rubin AS, et al. Asthma intervention research

[24] Schatz M, Meckley LM, Kim M, Stockwell BT, Castro M. Asthma exacerbation rates in adults are

unchanged over a 5-year period despite high-intensity therapy. The Journal of Allergy and Clinical Immunology. In Practice. 2014;2(5):570-574. e1

[25] Global Initiative for Asthma (GINA) [Internet]. Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/2018-ginareport-global-strategy-for-asthma-ma nagement-and-prevention/ [Accessed

2 trial study group. Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma. The Journal of Allergy and Clinical Immunology. 2013;

132(6):1295-1302

December 25, 2018]

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assessment of difficult-to-treat asthma. The European Respiratory Journal.

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[30] Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database of Systematic Reviews. 2014;3:CD009910

[16] Trivedi A, Pavord ID, Castro M. Bronchial thermoplasty and biological therapy as targeted treatments for severe uncontrolled asthma. The Lancet Respiratory Medicine. 2016;4(7):

[17] Cox G, Miller JD, McWilliams A, Fitzgerald JM, Lam S. Bronchial thermoplasty for asthma. American Journal of Respiratory and Critical Care

[18] Cox G, Thomson NC, Rubin AS, et al. AIR trial study group. Asthma control during the year after bronchial thermoplasty. The New England Journal of Medicine. 2007;356(13):1327-1337

[19] Pavord ID, Cox G, Thomson NC, et al. RISA trial study group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. American Journal of Respiratory and Critical Care Medicine. 2007;176(12):1185-1191

[20] Castro M, Rubin AS, Laviolette M,

Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: A multicenter, randomized, double-blind, sham-controlled clinical trial. American Journal of Respiratory and Critical Care Medicine. 2010;181(2):

[21] Thomson NC, Rubin AS, Niven RM, et al. AIR trial study group. Long-term

thermoplasty: Asthma intervention research (AIR) trial. BMC Pulmonary

[22] Pavord ID, Thomson NC, Niven RM, et al. Research in severe asthma trial study group. Safety of bronchial thermoplasty in patients with severe refractory asthma. Annals of Allergy, Asthma & Immunology. 2013;111(5):

et al. AIR2 trial study group.

(5 year) safety of bronchial

Medicine. 2011;11:8

116-124

402-407

35

Medicine. 2006;173(9):965-969

97(5):1946-1953

585-592

[9] Pascual RM, Peters SP. Airway remodeling contributes to the progressive loss of lung function in asthma: An overview. The Journal of Allergy and Clinical Immunology. 2005; 116:477-486

[10] Noble PB, Pascoe CD, Lan B, et al. Airway smooth muscle in asthma: Linking contraction and mechanotransduction to disease pathogenesis and remodeling. Pulmonary Pharmacology & Therapeutics. 2014;29(2):96-107

[11] Nair P, Martin JG, Cockcroft DC, et al. Airway hyperresponsiveness in asthma: Measurement and clinical relevance. The Journal of Allergy and Clinical Immunology. In Practice. 2017; 5(3):649.e2-659.e2

[12] Carroll N, Elliot J, Morton A, et al. The structure of large and small airways in nonfatal and fatal asthma. The American Review of Respiratory Disease. 1993;147:405-410

[13] Panettieri RA Jr, Kotlikoff MI, Gerthoffer WT, et al. National Heart, Lung, and Blood Institute. Airway smooth muscle in bronchial tone, inflammation, and remodeling: Basic knowledge to clinical relevance. American Journal of Respiratory and Critical Care Medicine. 2008;177(3): 248-252

[14] Miller JD, Cox G, Vincic L, Lombard CM, Loomas BE, Danek CJ. A prospective feasibility study of bronchial thermoplasty in the human airway. Chest. 2005;127(6):1999-2006

[15] Danek CJ, Lombard CM, Dungworth DL, et al. Reduction in airway hyperresponsiveness to methacholine by the application of RF Bronchial Thermoplasty: A New Therapeutic Option in Severe Uncontrolled Asthma DOI: http://dx.doi.org/10.5772/intechopen.84466

energy in dogs. Journal of Applied Physiology (Bethesda, MD: 1985). 2004; 97(5):1946-1953

References

asthma/en/

19(1):61-67

[1] World Health Organization. Chronic Respiratory Disease, Asthma. Available from: www.who.int/respiratory/

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics

evidence and future prospects. Therapeutic Advances in Respiratory

[9] Pascual RM, Peters SP. Airway remodeling contributes to the progressive loss of lung function in asthma: An overview. The Journal of Allergy and Clinical Immunology. 2005;

[10] Noble PB, Pascoe CD, Lan B, et al. Airway smooth muscle in asthma:

[11] Nair P, Martin JG, Cockcroft DC, et al. Airway hyperresponsiveness in asthma: Measurement and clinical relevance. The Journal of Allergy and Clinical Immunology. In Practice. 2017;

[12] Carroll N, Elliot J, Morton A, et al. The structure of large and small airways in nonfatal and fatal asthma. The American Review of Respiratory Disease. 1993;147:405-410

[13] Panettieri RA Jr, Kotlikoff MI, Gerthoffer WT, et al. National Heart, Lung, and Blood Institute. Airway smooth muscle in bronchial tone, inflammation, and remodeling: Basic knowledge to clinical relevance. American Journal of Respiratory and Critical Care Medicine. 2008;177(3):

[14] Miller JD, Cox G, Vincic L, Lombard

methacholine by the application of RF

CM, Loomas BE, Danek CJ. A prospective feasibility study of bronchial thermoplasty in the human airway. Chest. 2005;127(6):1999-2006

[15] Danek CJ, Lombard CM, Dungworth DL, et al. Reduction in airway hyperresponsiveness to

Disease. 2017;11(8):311-325

Linking contraction and

5(3):649.e2-659.e2

248-252

mechanotransduction to disease pathogenesis and remodeling. Pulmonary Pharmacology & Therapeutics. 2014;29(2):96-107

116:477-486

[2] Mitzner W. Airway smooth muscle: The appendix of the lung. American Journal of Respiratory and Critical Care

[3] Godard P, Chanez P, Siraudin L, Nicoloyannis N, Duru G. Costs of asthma are correlated with severity: A 1-yr prospective study. The European Respiratory Journal. 2002;

[4] Ivanova JI, Bergman R, Birnbaum HG, Colice GL, Silverman RA, McLaurin K. Effect of asthma exacerbations on health care costs among asthmatic patients with

moderate and severe persistent asthma. The Journal of Allergy and Clinical Immunology. 2012;129(5):1229-1235

[5] Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the

national heart, lung, and blood institutes severe asthma research program. The Journal of Allergy and Clinical Immunology. 2007;119(2):405-413

[6] Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. The European

Respiratory Journal. 2014;43(2):343-373

[7] Menzella F, Lusuardi M, Galeone C, Taddei S, Facciolongo N, Zucchi L. Mepolizumab for severe refractory eosinophilic asthma: Evidence to date and clinical potential. Therapeutic Advances in Chronic Disease. 2016;7(6):

[8] Máspero J. Reslizumab in the treatment of inadequately controlled asthma in adults and adolescents with elevated blood eosinophils: Clinical trial

260-277

34

Medicine. 2004;169:787-790

[16] Trivedi A, Pavord ID, Castro M. Bronchial thermoplasty and biological therapy as targeted treatments for severe uncontrolled asthma. The Lancet Respiratory Medicine. 2016;4(7): 585-592

[17] Cox G, Miller JD, McWilliams A, Fitzgerald JM, Lam S. Bronchial thermoplasty for asthma. American Journal of Respiratory and Critical Care Medicine. 2006;173(9):965-969

[18] Cox G, Thomson NC, Rubin AS, et al. AIR trial study group. Asthma control during the year after bronchial thermoplasty. The New England Journal of Medicine. 2007;356(13):1327-1337

[19] Pavord ID, Cox G, Thomson NC, et al. RISA trial study group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. American Journal of Respiratory and Critical Care Medicine. 2007;176(12):1185-1191

[20] Castro M, Rubin AS, Laviolette M, et al. AIR2 trial study group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: A multicenter, randomized, double-blind, sham-controlled clinical trial. American Journal of Respiratory and Critical Care Medicine. 2010;181(2): 116-124

[21] Thomson NC, Rubin AS, Niven RM, et al. AIR trial study group. Long-term (5 year) safety of bronchial thermoplasty: Asthma intervention research (AIR) trial. BMC Pulmonary Medicine. 2011;11:8

[22] Pavord ID, Thomson NC, Niven RM, et al. Research in severe asthma trial study group. Safety of bronchial thermoplasty in patients with severe refractory asthma. Annals of Allergy, Asthma & Immunology. 2013;111(5): 402-407

[23] Wechsler ME, Laviolette M, Rubin AS, et al. Asthma intervention research 2 trial study group. Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma. The Journal of Allergy and Clinical Immunology. 2013; 132(6):1295-1302

[24] Schatz M, Meckley LM, Kim M, Stockwell BT, Castro M. Asthma exacerbation rates in adults are unchanged over a 5-year period despite high-intensity therapy. The Journal of Allergy and Clinical Immunology. In Practice. 2014;2(5):570-574. e1

[25] Global Initiative for Asthma (GINA) [Internet]. Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/2018-ginareport-global-strategy-for-asthma-ma nagement-and-prevention/ [Accessed December 25, 2018]

[26] Robinson DS, Campbell DA, Durham SR, et al. Asthma and Allergy Research Group of the National Heart and Lung Institute. Systematic assessment of difficult-to-treat asthma. The European Respiratory Journal. 2003;22(3):478-483

[27] Gamble J, Stevenson M, Heaney LG. A study of a multi-level intervention to improve non-adherence in difficult to control asthma. Respiratory Medicine. 2011;105(9):1308-1315

[28] Mayse ML, Laviolette M, Rubin AS. Clinical pearls for bronchial thermoplasty. Journal of Bronchology. 2007;14:115-123

[29] Wenzel SE. Asthma phenotypes: The evolution from clinical to molecular approaches. Nature Medicine. 2012; 18(5):716-725

[30] Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database of Systematic Reviews. 2014;3:CD009910

[31] Boston Scientific. Bronchial Thermoplasty Global Registry (BT Registry). 2014. Availablefrom: https:// clinicaltrials.gov/ct2/show/ NCT02104856 [Accessed December 25, 2018]. ClinicalTrials.gov identifier: NCT02104856

[32] Menzella F, Zucchi L, Piro R, Galeone C, Castagnetti C, Facciolongo N. A budget impact analysis of bronchial thermoplasty for severe asthma in clinical practice. Advances in Therapy. 2014;31(7):751-761

[33] Zafari Z, Sadatsafavi M, Marra CA, Chen W, FitzGerald JM. Costeffectiveness of bronchial thermoplasty, omalizumab, and standard therapy for moderate-to-severe allergic asthma. PLoS One. 2016;11(1):e0146003

[34] Zein JG, Menegay MC, Singer ME, et al. Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma. The Journal of Asthma. 2016;53:194-200

[35] Nguyen HV, Bose S, Mital S, et al. Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model. Respirology. 2017;22(6): 1102-1109

**37**

**Chapter 4**

**Abstract**

Airways

*Kotlyarov Peter Mikhaylovich*

the success of the reconstructive surgical manual

traumatic bronchus rupture

**1.1 Introduction**

Virtual Bronchoscopy for Tumors

The given MSCT of 26 patients with tumoral damage of a trachea is analyzed. Data of MSCT of 61 patients with tumoral damage of bronchial tubes of primary and secondary genesis and hyperplastic lymph nodes are analyzed. In the analysis, a comprehensive analysis of the native, post-processing data and volumetric reconstructions allows more fully appreciating the nature of the changes, the topography, the extent and prevalence of neoplastic lesions tracheobronchial system. Differential diagnostics of benign and malignant lesions are conducted especially in the stenotic lesions when execution of bronchofibroscopy was impossible. Virtual bronchoscopy (VB) MSCT allowed determining the presence of a complete or partial rupture of the main bronchus, its distance to the bifurcation of the trachea, the state of the collapsed lung, the presence of fluid in the hemithorax, and secondary changes in the bone structures of the chest. The VB played an important role in monitoring the adequacy of reconstructive measures on the damaged bronchus, excluding the occurrence of postoperative stenosis. Virtual bronchoscopy of multispiral computed tomography with the capabilities of multiplanar and volumetric reconstructions and post-processing image processing is an optimal noninvasive method for determining the traumatic lesion of the main bronchi and monitoring

**Keywords:** virtual bronchoscopy, multislice computed tomography, tumor airways,

**1. Virtual bronchoscopy multislice computer tomography in diagnostics** 

The defeat of the tracheobronchial system (TBS) by cancer is 17.8% in men and 3.7% in women [1]. Trachea, in addition to primary tumors, can be affected a second time with cancers of the esophagus, thyroid, and lungs. A number of benign tumors grow inside the lumen of the trachea and bronchi, causing a violation of the lung ventilation. Large bronchi may be secondarily affected in the central and peripheral forms of lung cancer [2–4]. The introduction of clinical practice of multispiral computed tomography (MSCT) clinical practice, new technologies of data collection, and post-processing image processing allowed developing a program of

**of neoplastic lesions of the tracheobronchial systems**

and Traumatic Lesions of the

### **Chapter 4**

[31] Boston Scientific. Bronchial Thermoplasty Global Registry (BT Registry). 2014. Availablefrom: https://

[32] Menzella F, Zucchi L, Piro R, Galeone C, Castagnetti C, Facciolongo N. A budget impact analysis of bronchial thermoplasty for severe asthma in clinical practice. Advances in Therapy.

NCT02104856 [Accessed December 25, 2018]. ClinicalTrials.gov identifier:

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics

[33] Zafari Z, Sadatsafavi M, Marra CA,

effectiveness of bronchial thermoplasty, omalizumab, and standard therapy for moderate-to-severe allergic asthma. PLoS One. 2016;11(1):e0146003

[34] Zein JG, Menegay MC, Singer ME, et al. Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma. The Journal of

[35] Nguyen HV, Bose S, Mital S, et al. Is bronchial thermoplasty cost-effective as treatment for problematic asthma patients? Singapore's perspective on a global model. Respirology. 2017;22(6):

Chen W, FitzGerald JM. Cost-

Asthma. 2016;53:194-200

1102-1109

36

clinicaltrials.gov/ct2/show/

NCT02104856

2014;31(7):751-761

## Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways

*Kotlyarov Peter Mikhaylovich*

### **Abstract**

The given MSCT of 26 patients with tumoral damage of a trachea is analyzed. Data of MSCT of 61 patients with tumoral damage of bronchial tubes of primary and secondary genesis and hyperplastic lymph nodes are analyzed. In the analysis, a comprehensive analysis of the native, post-processing data and volumetric reconstructions allows more fully appreciating the nature of the changes, the topography, the extent and prevalence of neoplastic lesions tracheobronchial system. Differential diagnostics of benign and malignant lesions are conducted especially in the stenotic lesions when execution of bronchofibroscopy was impossible. Virtual bronchoscopy (VB) MSCT allowed determining the presence of a complete or partial rupture of the main bronchus, its distance to the bifurcation of the trachea, the state of the collapsed lung, the presence of fluid in the hemithorax, and secondary changes in the bone structures of the chest. The VB played an important role in monitoring the adequacy of reconstructive measures on the damaged bronchus, excluding the occurrence of postoperative stenosis. Virtual bronchoscopy of multispiral computed tomography with the capabilities of multiplanar and volumetric reconstructions and post-processing image processing is an optimal noninvasive method for determining the traumatic lesion of the main bronchi and monitoring the success of the reconstructive surgical manual

**Keywords:** virtual bronchoscopy, multislice computed tomography, tumor airways, traumatic bronchus rupture

#### **1. Virtual bronchoscopy multislice computer tomography in diagnostics of neoplastic lesions of the tracheobronchial systems**

#### **1.1 Introduction**

The defeat of the tracheobronchial system (TBS) by cancer is 17.8% in men and 3.7% in women [1]. Trachea, in addition to primary tumors, can be affected a second time with cancers of the esophagus, thyroid, and lungs. A number of benign tumors grow inside the lumen of the trachea and bronchi, causing a violation of the lung ventilation. Large bronchi may be secondarily affected in the central and peripheral forms of lung cancer [2–4]. The introduction of clinical practice of multispiral computed tomography (MSCT) clinical practice, new technologies of data collection, and post-processing image processing allowed developing a program of

3D reconstruction of the tracheobronchial system (TBS) with the ability to view its inner surface in real-time virtual bronchoscopy (VB) [2–16]. In addition to VB methods such as minimum and maximum intensity (MinIP, MIP) images, the mode of shaded surfaces—VTR allow to assess the state of the outer wall of the TBS, the relationship with adjacent organs and tissues [4, 5, 8, 16]. Comparison of the data of FBS and VB of the zone of interest showed their coincidence in the evaluation of the macrostructure of the bronchial lumen, the presence of intrabronchial tumor masses, and their type and localization [4, 9, 12]. In addition, the study of the bronchus distal to the stenosis at bronchoscopy is difficult and VB is the only method giving the possibility to evaluate the macrostructure of the bronchus beyond the area of narrowing [2, 5, 16]. The restrained attitude to VB of radiologists of foreign countries at the initial stage of data accumulation was replaced by a wide application of the method in clinical practice, as indicated by a significant increase in publications in recent years [2, 3, 7–13]. The purpose of the study is to clarify the concept of VB techniques and their role in improving the diagnostic information content of CT in the diagnosis and prevalence of neoplastic lesions of TBS.

#### **1.2 Materials and methods of research**

The MSCT data of 26 patients with tracheal tumor lesions were analyzed. Adenoid cystic cancer of the trachea was observed in 10 (32, 25%) patients, squamous cell in 6 (of 19.35%) patients, and neoplastic lesions of the trachea in 5 patients; the process has spread outside the body wall infiltrating the surrounding tissue. Of 10 (32, 25%) patients who had benign tumor, 4 had adenoma of the trachea, 3 had polyp, and 3 had papillomatosis. We analyzed patients' data of 61 MSCT with a neoplastic lesion of the bronchi of primary and secondary origin and hyperplastic lymph nodes. Lung cancer took place in 35 (57.37%) patients, metastatic lung damage and lymph nodes were observed in 5 (8.19%), and postinflammatory hyperplasia of the lymph node adjacent to the bronchus in 4 (6.55%). In 17 (27, 86%) patients, benign bronchial formations of adenoma—8, polyposis—5 and papillomatosis—4 were revealed.

The diagnosis was verified in all patients in the process of material sampling in FBS and morphology according to the results of surgery.

MSCT was performed on 128-slice computed tomography company "GE Healthcare", model "Optima CT 660". Post-processing data processing, obtaining virtual bronchograms, and 3D imaging were performed at the workstation"Optima CT 660". Постпроцессинговая обработка данных, получение виртуальных бронхограмм. 3D изображений проводилась на рабочей станции Advantage Workstation (GE). Toshiba Aquilion 16 (16-slice) and Aquilion ONE (320-slice) according to the previously described method [4–6, 26]. A comparative analysis of the value of different methods of MSCT VB in determining the lesion of TBS showed the need to use them in a complex for the full characteristics of both the intraluminal part of the trachea, сarina, the main bronchi, and the outer wall in the images of the minimum (MinIP) and maximum intensity (MIP). For the reconstruction of 3D data in the images of virtual bronchoscopy, the technique of three-dimensional modeling was used, which produced a three-dimensional array with the display of the inner and the outer surface of the bronchi. Based on these data, a VB examination of the tracheobronchial tree was performed using VB fly-through method and volumetric reconstruction of the lung and its structures. In order to obtain the outer surface of the lung, trachea, or bronchi, the technique of obtaining an image of shaded surfaces and volume conversion was used. The complex analysis necessarily includes the data of native MSCT, the results of which allow avoiding false positive and negative conclusions in the presence of mucus and scar changes in the TBS.

**39**

**Figure 1.**

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

Data of CT VB of 16 patients with cancer of the trachea were analyzed. At VB tumor mass spreading inside the body lumen was multinodular masses presented heterogeneous density and narrowing the lumen of the organ. The tumor was localized on the wall of the trachea with a wide base, spreading along it or circularly. The tracheal rings of the affected area were not visualized. Followed by multiplanar image reconstruction in MinIP mode, shaded surfaces and volume data transformations allowed visualizing the distribution of neoplastic lesions in the wall of the trachea, the length and volume of the lesion, and the degree of overlap of the organ lumen (**Figure 1**). In 11 patients, the tumor was localized within the tissues of the organ, without infiltrating the surrounding tissue, and in 5 patients, the tracheal wall sprouted and spread to the mediastinal tissue and esophagus (1 patient). In 6 out of 11 patients, the outer edge of the wall had a flat surface and the tumor process spread mainly along the inner surface of the organ, without infiltrating the wall. Thickening of the tracheal wall was observed in five patients, indicating its tumor infiltration. The nonorgan part of the tumor was heterogeneous and multi-nodular, without clear contours with the surrounding tissue. Tumors of the trachea chaotically accumulated a contrast material during bolus contrast enhancement. Followed by multiplanar reconstruction in MIP and MinIP modes, an unorganized component of the trachea cancer was clearly identified. Signs of esophageal germination were compression, overlapping of its lumen, and dilation above the site of infiltration (one patient). Increased regional lymph nodes (diameter 13–17 mm) were additionally determined in five patients, indicating a high degree of probability of metastatic lesions. This MSCT VB did not allow determining the morphological variant of malignant lesions

and the state of the tracheal mucosa of the affected area and intact areas.

*AQ-Adenocystic cancer of a trachea – On the right – MSCT – on the right – a sidewall of a trachea is defined the tumor on the wide basis (sagittal section), uneven, hilly contours sprouting the right – a trachea sidewall (an axial cut). At the left below – VB – the hilly tumor on the wide basis stenoses a trachea lumen (carrying* 

*out BFS is impossible); at the left above – VB – distalny tumors a wall of a trachea of an intact.*

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

**1.3 Results of a research**

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

#### **1.3 Results of a research**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

**1.2 Materials and methods of research**

and papillomatosis—4 were revealed.

FBS and morphology according to the results of surgery.

3D reconstruction of the tracheobronchial system (TBS) with the ability to view its inner surface in real-time virtual bronchoscopy (VB) [2–16]. In addition to VB methods such as minimum and maximum intensity (MinIP, MIP) images, the mode of shaded surfaces—VTR allow to assess the state of the outer wall of the TBS, the relationship with adjacent organs and tissues [4, 5, 8, 16]. Comparison of the data of FBS and VB of the zone of interest showed their coincidence in the evaluation of the macrostructure of the bronchial lumen, the presence of intrabronchial tumor masses, and their type and localization [4, 9, 12]. In addition, the study of the bronchus distal to the stenosis at bronchoscopy is difficult and VB is the only method giving the possibility to evaluate the macrostructure of the bronchus beyond the area of narrowing [2, 5, 16]. The restrained attitude to VB of radiologists of foreign countries at the initial stage of data accumulation was replaced by a wide application of the method in clinical practice, as indicated by a significant increase in publications in recent years [2, 3, 7–13]. The purpose of the study is to clarify the concept of VB techniques and their role in improving the diagnostic information content of CT in the diagnosis and prevalence of neoplastic lesions of TBS.

The MSCT data of 26 patients with tracheal tumor lesions were analyzed. Adenoid cystic cancer of the trachea was observed in 10 (32, 25%) patients, squamous cell in 6 (of 19.35%) patients, and neoplastic lesions of the trachea in 5 patients; the process has spread outside the body wall infiltrating the surrounding tissue. Of 10 (32, 25%) patients who had benign tumor, 4 had adenoma of the trachea, 3 had polyp, and 3 had papillomatosis. We analyzed patients' data of 61 MSCT with a neoplastic lesion of the bronchi of primary and secondary origin and hyperplastic lymph nodes. Lung cancer took place in 35 (57.37%) patients, metastatic lung damage and lymph nodes were observed in 5 (8.19%), and postinflammatory hyperplasia of the lymph node adjacent to the bronchus in 4 (6.55%). In 17 (27, 86%) patients, benign bronchial formations of adenoma—8, polyposis—5

The diagnosis was verified in all patients in the process of material sampling in

MSCT was performed on 128-slice computed tomography company "GE Healthcare", model "Optima CT 660". Post-processing data processing, obtaining virtual bronchograms, and 3D imaging were performed at the workstation"Optima

CT 660". Постпроцессинговая обработка данных, получение виртуальных бронхограмм. 3D изображений проводилась на рабочей станции Advantage Workstation (GE). Toshiba Aquilion 16 (16-slice) and Aquilion ONE (320-slice) according to the previously described method [4–6, 26]. A comparative analysis of the value of different methods of MSCT VB in determining the lesion of TBS showed the need to use them in a complex for the full characteristics of both the intraluminal part of the trachea, сarina, the main bronchi, and the outer wall in the images of the minimum (MinIP) and maximum intensity (MIP). For the reconstruction of 3D data in the images of virtual bronchoscopy, the technique of three-dimensional modeling was used, which produced a three-dimensional array with the display of the inner and the outer surface of the bronchi. Based on these data, a VB examination of the tracheobronchial tree was performed using VB fly-through method and volumetric reconstruction of the lung and its structures. In order to obtain the outer surface of the lung, trachea, or bronchi, the technique of obtaining an image of shaded surfaces and volume conversion was used. The complex analysis necessarily includes the data of native MSCT, the results of which allow avoiding false positive and negative conclusions in the presence of mucus and scar changes in the TBS.

**38**

Data of CT VB of 16 patients with cancer of the trachea were analyzed. At VB tumor mass spreading inside the body lumen was multinodular masses presented heterogeneous density and narrowing the lumen of the organ. The tumor was localized on the wall of the trachea with a wide base, spreading along it or circularly. The tracheal rings of the affected area were not visualized. Followed by multiplanar image reconstruction in MinIP mode, shaded surfaces and volume data transformations allowed visualizing the distribution of neoplastic lesions in the wall of the trachea, the length and volume of the lesion, and the degree of overlap of the organ lumen (**Figure 1**). In 11 patients, the tumor was localized within the tissues of the organ, without infiltrating the surrounding tissue, and in 5 patients, the tracheal wall sprouted and spread to the mediastinal tissue and esophagus (1 patient). In 6 out of 11 patients, the outer edge of the wall had a flat surface and the tumor process spread mainly along the inner surface of the organ, without infiltrating the wall. Thickening of the tracheal wall was observed in five patients, indicating its tumor infiltration. The nonorgan part of the tumor was heterogeneous and multi-nodular, without clear contours with the surrounding tissue. Tumors of the trachea chaotically accumulated a contrast material during bolus contrast enhancement. Followed by multiplanar reconstruction in MIP and MinIP modes, an unorganized component of the trachea cancer was clearly identified. Signs of esophageal germination were compression, overlapping of its lumen, and dilation above the site of infiltration (one patient). Increased regional lymph nodes (diameter 13–17 mm) were additionally determined in five patients, indicating a high degree of probability of metastatic lesions. This MSCT VB did not allow determining the morphological variant of malignant lesions and the state of the tracheal mucosa of the affected area and intact areas.

#### **Figure 1.**

*AQ-Adenocystic cancer of a trachea – On the right – MSCT – on the right – a sidewall of a trachea is defined the tumor on the wide basis (sagittal section), uneven, hilly contours sprouting the right – a trachea sidewall (an axial cut). At the left below – VB – the hilly tumor on the wide basis stenoses a trachea lumen (carrying out BFS is impossible); at the left above – VB – distalny tumors a wall of a trachea of an intact.*

The MSCT data of 10 patients with benign tracheal formations were analyzed. Benign formations were characterized by a smooth surface, homogeneous internal structure, no infiltration of the wall, and the destruction of the cartilage of the trachea. Benign tumor of the trachea performed into the lumen of it making its lumen narrowed (**Figure 2a, b**). Focal changes emanating from the exterior pushed them to the opposite side without narrowing of lumen and signs of infiltration of the exterior wall.

**Figure 2.**

*a. Carina adenoma of a trachea – MIP, axial cut – deformation of a carina of a trachea due to formation of uniform structure. b. VB – in the field of a carina is defined the correct form, a smooth surface tumor.*

**41**

**Figure 3.**

*right-tracheas of a sidewall.*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

side from the formation, without signs of infiltration of the wall.

With growth in the direction of the esophagus, the latter was also pushed aside by the formation without signs of its infiltration. Papillomatosis, polyps manifested by visualization of smooth, on the peduncle, the correct form coming from the mucous linear structures localized on the side wall of the trachea (**Figure 3**). As shown by the combined analysis of native MSCT data and VB techniques (fly-through, MinIP, MIP, and 3D reconstruction), this approach is highly effective in the predictive test of the nature of both primary and secondary organ damage. Benign formations (adenoma, polyp, and others) were characterized by the presence of peduncles, linking the formation and mucous trachea, the wall of which was not thickened or infiltrated. The benign one went out into the lumen of the trachea. It had the right shape, smooth surface, and homogeneous structure. Secondary displacements of the trachea by benign processes emanating from the mediastinum and the esophagus are manifested by the displacement of the organ to the opposite

Thus, the signs of malignancy tumors of the trachea were wide base and destraction of the adjacent cartilage structures, a rough bumpy surface, infiltration of the wall of the trachea in length, the output of the process beyond the body with tissue infiltration in the mediastinum, spreading to the esophagus. Additional signs of malignancy of changes were visualizations of enlargement of regional lymph nodes. The data of MSCT VB in 35 patients with lung cancer were analyzed. Three variant neoplastic lesions of the bronchi, mostly peribronchial, intrabronchial, and a combined form of infiltration were observed. As a result of the study, according to the methods of VB fly-through, the leading method of determining the macrostructure and the border of the intrabronchial lesion that were inside the lumen of the bronchus, multinodal, polypoid masses were visualized, usually located on a wide base, narrowing the bronchus down to complete obstruction (**Figure 4a, b**).

The cartilaginous structures of the bronchus in the affected area were not visualized. The distribution of the lesions in the area of the branching of the bronchi last

*Trachea papillomatosis, MSCT, an axial cut, processing of MIP the mode – visualization of papilloma up to* 

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

#### *Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

The MSCT data of 10 patients with benign tracheal formations were analyzed. Benign formations were characterized by a smooth surface, homogeneous internal structure, no infiltration of the wall, and the destruction of the cartilage of the trachea. Benign tumor of the trachea performed into the lumen of it making its lumen narrowed (**Figure 2a, b**). Focal changes emanating from the exterior pushed them to the opposite side without narrowing of lumen and signs of infiltration of the exterior wall.

*a. Carina adenoma of a trachea – MIP, axial cut – deformation of a carina of a trachea due to formation of uniform structure. b. VB – in the field of a carina is defined the correct form, a smooth surface tumor.*

**40**

**Figure 2.**

With growth in the direction of the esophagus, the latter was also pushed aside by the formation without signs of its infiltration. Papillomatosis, polyps manifested by visualization of smooth, on the peduncle, the correct form coming from the mucous linear structures localized on the side wall of the trachea (**Figure 3**).

As shown by the combined analysis of native MSCT data and VB techniques (fly-through, MinIP, MIP, and 3D reconstruction), this approach is highly effective in the predictive test of the nature of both primary and secondary organ damage. Benign formations (adenoma, polyp, and others) were characterized by the presence of peduncles, linking the formation and mucous trachea, the wall of which was not thickened or infiltrated. The benign one went out into the lumen of the trachea. It had the right shape, smooth surface, and homogeneous structure. Secondary displacements of the trachea by benign processes emanating from the mediastinum and the esophagus are manifested by the displacement of the organ to the opposite side from the formation, without signs of infiltration of the wall.

Thus, the signs of malignancy tumors of the trachea were wide base and destraction of the adjacent cartilage structures, a rough bumpy surface, infiltration of the wall of the trachea in length, the output of the process beyond the body with tissue infiltration in the mediastinum, spreading to the esophagus. Additional signs of malignancy of changes were visualizations of enlargement of regional lymph nodes.

The data of MSCT VB in 35 patients with lung cancer were analyzed. Three variant neoplastic lesions of the bronchi, mostly peribronchial, intrabronchial, and a combined form of infiltration were observed. As a result of the study, according to the methods of VB fly-through, the leading method of determining the macrostructure and the border of the intrabronchial lesion that were inside the lumen of the bronchus, multinodal, polypoid masses were visualized, usually located on a wide base, narrowing the bronchus down to complete obstruction (**Figure 4a, b**).

The cartilaginous structures of the bronchus in the affected area were not visualized. The distribution of the lesions in the area of the branching of the bronchi last

#### **Figure 3.**

*Trachea papillomatosis, MSCT, an axial cut, processing of MIP the mode – visualization of papilloma up to right-tracheas of a sidewall.*

#### *Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

#### **Figure 4.**

*a. Cancer of a lower lobe bronchial tube on the right – MinIP, frontal reconstruction, in a gleam of a lower lobe bronchial tube – the hilly masses, hypoventilation of the lower lung lobe on the right. b. VB – the hilly tumor on the wide basis stenoses a lumen of a lower lobe bronchial tube the right lung lower than an until the discharge of a midlobar bronchial tube.*

lost "pointed" appearance and grew deformed. Carina of the trachea with peribronchial spread the tumor from smooth and it turned into tumor growths covered with shapeless structure. Image of the trachea and bronchi in MIP and MinIP modes and 3D volumetric reconstructions completed the picture WB flythrough, allowing to evaluate the association of intrabronchial mass with pulmonary part of the tumor, and thus, to obtain a holistic view of the prevalence of lung cancer (**Figure 5a, b**).

In peribronchial infiltration (four patients with central cancer), semiotic signs in the mode of MinIP were visualized with varying degrees of local narrowing of the bronchial lumen. The transition of a changed plot of pathologically unchanged tissue of the bronchus was a border infiltration and was a "bayonet-like" extension of the lumen. The analysis showed the presence of sub-variants of peribronchial

**43**

**Figure 5.**

*bronchial tube tumoral masses.*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

tumor growth—circular, when they infiltrated all the walls of the bronchi and focal-segmental, in which the tumor struck one of the walls of the bronchus. Method VB fly-through was detected in this group of patients, along with narrowing of the lumen of the bronchus and the disappearance of the rosary-like structure

*a. Peripheral cancer of the right lung with centralization a) MIP, frontal reconstruction of 20 mm, a tumor grows up to a superlobar and intermediate bronchial tube. b. VB – in a proximal part of an intermediate* 

The mixed variant of TBS infiltration was characterized by a combination of symptoms of one and two variants of VB (six patients with central and two peripheral cancer). In addition to intrabronchial component of the tumor, peribronchial growth was determined in the direction of the main, lobar bronchi, trachea.

of the bronchi due to infiltration of the cartilaginous structures.

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

**Figure 5.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

lost "pointed" appearance and grew deformed. Carina of the trachea with peribronchial spread the tumor from smooth and it turned into tumor growths covered with shapeless structure. Image of the trachea and bronchi in MIP and MinIP modes and 3D volumetric reconstructions completed the picture WB flythrough, allowing to evaluate the association of intrabronchial mass with pulmonary part of the tumor, and thus, to obtain a holistic view of the prevalence of lung cancer (**Figure 5a, b**). In peribronchial infiltration (four patients with central cancer), semiotic signs in the mode of MinIP were visualized with varying degrees of local narrowing of the bronchial lumen. The transition of a changed plot of pathologically unchanged tissue of the bronchus was a border infiltration and was a "bayonet-like" extension of the lumen. The analysis showed the presence of sub-variants of peribronchial

*a. Cancer of a lower lobe bronchial tube on the right – MinIP, frontal reconstruction, in a gleam of a lower lobe bronchial tube – the hilly masses, hypoventilation of the lower lung lobe on the right. b. VB – the hilly tumor on the wide basis stenoses a lumen of a lower lobe bronchial tube the right lung lower than an until the* 

**42**

**Figure 4.**

*discharge of a midlobar bronchial tube.*

*a. Peripheral cancer of the right lung with centralization a) MIP, frontal reconstruction of 20 mm, a tumor grows up to a superlobar and intermediate bronchial tube. b. VB – in a proximal part of an intermediate bronchial tube tumoral masses.*

tumor growth—circular, when they infiltrated all the walls of the bronchi and focal-segmental, in which the tumor struck one of the walls of the bronchus. Method VB fly-through was detected in this group of patients, along with narrowing of the lumen of the bronchus and the disappearance of the rosary-like structure of the bronchi due to infiltration of the cartilaginous structures.

The mixed variant of TBS infiltration was characterized by a combination of symptoms of one and two variants of VB (six patients with central and two peripheral cancer). In addition to intrabronchial component of the tumor, peribronchial growth was determined in the direction of the main, lobar bronchi, trachea.

One of the tasks of MSCT in lung cancer is to determine the boundaries of tumor infiltration and its prevalence in the proximal TBS, which is essential for the planning of the operation. This is due to the close connection in the area of the gates of the lungs and bronchi, large arterial and venous vessels, lymph nodes, and fibrous changes as a result of previous inflammatory processes, which make it difficult to detect tumor infiltration of the main bronchi and trachea according to native CT; however, it is essential for the planning of surgery [17]. Data native MSCT are not always enough to fully answer the question of the defeat of the trachea in lung cancer. Tumor infiltration can be observed in both central and peripheral cancer with centralization. Signs of infiltration at fly-through VB main bronchus, the trachea was narrowing of the lumen, no visualization of cartilage structures: bronchi become deformed tubular structure. The area of preserved cartilage structures indicated the edge of tumor infiltration. According to MSCT VB, three options of neoplastic lesions of the trachea with lung cancer were allocated—predominantly paratracheal (two patients), mainly intrabronchial (three patients), and combined form of infiltration (one patient). In the first variant—peritracheal infiltration—the leading technique was the analysis of images of MinIP, which allowed to clarify the data of the primary MSCT. Semiotic signs in the MinIP mode of infiltration of the external part of the trachea by the tumor were local narrowing of the tracheal lumen. The boundary of the infiltrated tissues, as in the case of bronchial lesions, was determined by the place of visualization of cartilaginous rings and the expansion of the tracheal lumen. With mainly intra-tracheal tumor growth, the leading technique for determining the macrostructure and the lesion boundary was VB and images in MinIP and MIP mode. When this cartilage structure was not visualized, the lumen bumpy, polyp-like mass. Cartilaginous structures of the affected area were not visualized (**Figure 6a–c**).

3D reconstructions in the mode of semitransparent or shaded surfaces were auxiliary in nature, giving a volumetric representation of the extent of changes and supplementing the data of both methods, both in the presence of changes and the boundaries of infiltrative changes. Construction of 3D reconstructions made it possible to obtain a three-dimensional image of the pathology zone and surrounding tissues, including vessels, comparing them with the tumor array, which allows for virtual reconstruction of the surgical intervention zone for optimal choice of surgical tactics.

In five patients, metastatic lesions of the lungs and lymph nodes of the organ gate were revealed (primary kidney cancer in three and colon cancer in two patients). Part of the foci infiltrated segmental, lobar bronchi, enlarged lymph node packages caused their compression, which led to a violation of ventilation of the affected segments and lung lobes up to the development of atelectasis. In VB fly-through of affected bronchi, narrowing lumen nodules and changes in the macrostructure of the bronchial wall in the infiltration zone were clearly identified as secondary foci when compared with the results of the analysis of MinIP images of the zone of interest and data of the native MSCT. When compression of the bronchus of the affected package metastatic lymph nodes were detected luminal narrowing without signs of the wall infiltration (**Figure 7**).

The MSCT data of 17 patients with benign tracheal formations (adenoma, polyp, and others) were analyzed. Benign tumors were characterized by the correct form, a smooth surface, a homogeneous internal structure, the absence of infiltration of the wall, and destruction of the cartilage of the bronchial wall. The localization in the mucous membrane of the tumor was visualized in the lumen of the bronchus, causing narrowing (**Figure 8**).

**45**

bronchus part.

**Figure 6.**

*and a carina.*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

mucosa. In some cases, the external pressure of the adjacent single enlarged lymph node can simulate a benign tumor (four patients). Comprehensive data analysis of native MSCT and fly-through VB allowed to determine that the deformation and narrowing of the lumen of the bronchus was associated with the presence of external pressure adjacent to the bronchial lymph node (**Figure 9**). The presence of visual information made it possible to develop a "road map" to perform FBS in order to determine the optimal place for the collection of material for cytological examination, to calculate the depth of the puncture of the wall of the affected

*a. Central cancer of the top share of the right lung, an atelectasis of the top share, spread of a tumor on a primary bronchus, a trachea – MinIP, frontal reconstruction. b. MSCT – an axial cut – the right primary bronchus is narrowed due to tumoral infiltration, suspicion on tumoral damage of a trachea. c. VB – the view from a trachea – the right primary bronchus is narrowed, the tumor extends to the right semi-circle of a trachea* 

As shown by the combined analysis of native MSCT data and VB techniques, this approach is highly effective in predictive testing of the nature of both primary and secondary TBS lesions. In benign formations (adenoma, polyp, and others), the macrostructure of cartilage structures was preserved, and there was no infiltration of the surrounding tissues. The benign one was protruded into the lumen of the trachea and had the right shape, smooth surface, and homogeneous structure.

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

Papillomatosis, polyps manifested by the visualization of smooth, on the peduncle, the correct form of the structures emanating from the bronchial

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

#### **Figure 6.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

One of the tasks of MSCT in lung cancer is to determine the boundaries of tumor infiltration and its prevalence in the proximal TBS, which is essential for the planning of the operation. This is due to the close connection in the area of the gates of the lungs and bronchi, large arterial and venous vessels, lymph nodes, and fibrous changes as a result of previous inflammatory processes, which make it difficult to detect tumor infiltration of the main bronchi and trachea according to native CT; however, it is essential for the planning of surgery [17]. Data native MSCT are not always enough to fully answer the question of the defeat of the trachea in lung cancer. Tumor infiltration can be observed in both central and peripheral cancer with centralization. Signs of infiltration at fly-through VB main bronchus, the trachea was narrowing of the lumen, no visualization of cartilage structures: bronchi become deformed tubular structure. The area of preserved cartilage structures indicated the edge of tumor infiltration. According to MSCT VB, three options of neoplastic lesions of the trachea with lung cancer were allocated—predominantly paratracheal (two patients), mainly intrabronchial (three patients), and combined form of infiltration (one patient). In the first variant—peritracheal infiltration—the leading technique was the analysis of images of MinIP, which allowed to clarify the data of the primary MSCT. Semiotic signs in the MinIP mode of infiltration of the external part of the trachea by the tumor were local narrowing of the tracheal lumen. The boundary of the infiltrated tissues, as in the case of bronchial lesions, was determined by the place of visualization of cartilaginous rings and the expansion of the tracheal lumen. With mainly intra-tracheal tumor growth, the leading technique for determining the macrostructure and the lesion boundary was VB and images in MinIP and MIP mode. When this cartilage structure was not visualized, the lumen bumpy, polyp-like mass. Cartilaginous structures of the affected area

3D reconstructions in the mode of semitransparent or shaded surfaces were auxiliary in nature, giving a volumetric representation of the extent of changes and supplementing the data of both methods, both in the presence of changes and the boundaries of infiltrative changes. Construction of 3D reconstructions made it possible to obtain a three-dimensional image of the pathology zone and surrounding tissues, including vessels, comparing them with the tumor array, which allows for virtual reconstruction of the surgical intervention zone for optimal choice of

In five patients, metastatic lesions of the lungs and lymph nodes of the organ

The MSCT data of 17 patients with benign tracheal formations (adenoma, polyp, and others) were analyzed. Benign tumors were characterized by the correct form, a smooth surface, a homogeneous internal structure, the absence of infiltration of the wall, and destruction of the cartilage of the bronchial wall. The localization in the mucous membrane of the tumor was visualized in the lumen of the bronchus,

Papillomatosis, polyps manifested by the visualization of smooth, on the peduncle, the correct form of the structures emanating from the bronchial

gate were revealed (primary kidney cancer in three and colon cancer in two patients). Part of the foci infiltrated segmental, lobar bronchi, enlarged lymph node packages caused their compression, which led to a violation of ventilation of the affected segments and lung lobes up to the development of atelectasis. In VB fly-through of affected bronchi, narrowing lumen nodules and changes in the macrostructure of the bronchial wall in the infiltration zone were clearly identified as secondary foci when compared with the results of the analysis of MinIP images of the zone of interest and data of the native MSCT. When compression of the bronchus of the affected package metastatic lymph nodes were detected luminal

narrowing without signs of the wall infiltration (**Figure 7**).

**44**

were not visualized (**Figure 6a–c**).

causing narrowing (**Figure 8**).

surgical tactics.

*a. Central cancer of the top share of the right lung, an atelectasis of the top share, spread of a tumor on a primary bronchus, a trachea – MinIP, frontal reconstruction. b. MSCT – an axial cut – the right primary bronchus is narrowed due to tumoral infiltration, suspicion on tumoral damage of a trachea. c. VB – the view from a trachea – the right primary bronchus is narrowed, the tumor extends to the right semi-circle of a trachea and a carina.*

mucosa. In some cases, the external pressure of the adjacent single enlarged lymph node can simulate a benign tumor (four patients). Comprehensive data analysis of native MSCT and fly-through VB allowed to determine that the deformation and narrowing of the lumen of the bronchus was associated with the presence of external pressure adjacent to the bronchial lymph node (**Figure 9**). The presence of visual information made it possible to develop a "road map" to perform FBS in order to determine the optimal place for the collection of material for cytological examination, to calculate the depth of the puncture of the wall of the affected bronchus part.

As shown by the combined analysis of native MSCT data and VB techniques, this approach is highly effective in predictive testing of the nature of both primary and secondary TBS lesions. In benign formations (adenoma, polyp, and others), the macrostructure of cartilage structures was preserved, and there was no infiltration of the surrounding tissues. The benign one was protruded into the lumen of the trachea and had the right shape, smooth surface, and homogeneous structure.

#### **Figure 7.**

*Kidney cancer, secondary damage of lungs, lymph nodes, narrowing deformation of bronchial tubes, hypoventilation of the top share of the right lung – VB – tumoral masses stenose a superlobar bronchial tube of the right lung.*

#### **Figure 8.**

*Adenoma of the right intermediate bronchial tube – on native CT (the right part of fig.) in a lumen of the right intermediate bronchial tube is defined tumor which on the VB proceeds from a mucous wall of a bronchial tube, equal accurate contours, the macrostructure of a bronchial tube is kept.*

Malignant lesions were characterized by the presence in the lumen of lumpy tumor masses and the disappearance of the annular structure due to the destruction of cartilage. Peribronchial, paratracheal growth was determined by the narrowing of the lumen with the disappearance of the ring-shaped cartilaginous structures.

**47**

**1.4 Discussion**

**Figure 9.**

**1.5 Conclusion**

appeared in recent years [11, 13, 15].

valuable information for the planning of radical treatment.

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

The study showed that complex analysis of VB, post-processing images, and native MSCT data allowed obtaining additional information about TBS in lung cancer, secondary lesions, and benign tumors. In contrast to the previous studies, when only the method of VB fly-through was used, it does not allow to agree with the opinion of the authors about the limited possibilities of VB in lung pathology [9, 10]. Most of the studies on VB are based on individual clinical observations and literature data [10, 11, 14, 15]. Our study was conducted on the basis of the analysis of significant clinical material with the development of semiotic signs of TBS lesions and assessment of the diagnostic value of VB methods of their combined analysis with the results of native MSCT. Overall, our opinion about the necessity of wide application in clinical practice CT VB coincides with the result of the work

*Deformation of a wall of a bronchial tube under external influence – in distal department of the left lower lobe bronchial tube is defined the lymph node, adjacent to a bronchial tube, deforming a bronchial tube* 

*without destruction of cartilages. According to morphology (FBS) – in a lymph node signs of.*

Virtual bronchoscopy of multispiral computed tomography has the possibilities of multiplanar and volumetric reconstructions, post-processing image processing optimal method of diagnosis, determining the probable nature of tumor lesions of the trachea, the prevalence of the process, both outside the body and secondary invasions. In some cases, in stenotic lesions of the trachea, MSCT VB becomes the method of choice in assessing the prevalence of the process. Virtual modeling of intraluminal tracheal tumor, with the data about the surrounding tissues, provides

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

#### **Figure 9.**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

*Kidney cancer, secondary damage of lungs, lymph nodes, narrowing deformation of bronchial tubes, hypoventilation of the top share of the right lung – VB – tumoral masses stenose a superlobar bronchial tube of* 

Malignant lesions were characterized by the presence in the lumen of lumpy tumor masses and the disappearance of the annular structure due to the destruction of cartilage. Peribronchial, paratracheal growth was determined by the narrowing of the lumen with the disappearance of the ring-shaped cartilaginous structures.

*Adenoma of the right intermediate bronchial tube – on native CT (the right part of fig.) in a lumen of the right intermediate bronchial tube is defined tumor which on the VB proceeds from a mucous wall of a* 

*bronchial tube, equal accurate contours, the macrostructure of a bronchial tube is kept.*

**46**

**Figure 8.**

**Figure 7.**

*the right lung.*

*Deformation of a wall of a bronchial tube under external influence – in distal department of the left lower lobe bronchial tube is defined the lymph node, adjacent to a bronchial tube, deforming a bronchial tube without destruction of cartilages. According to morphology (FBS) – in a lymph node signs of.*

#### **1.4 Discussion**

The study showed that complex analysis of VB, post-processing images, and native MSCT data allowed obtaining additional information about TBS in lung cancer, secondary lesions, and benign tumors. In contrast to the previous studies, when only the method of VB fly-through was used, it does not allow to agree with the opinion of the authors about the limited possibilities of VB in lung pathology [9, 10]. Most of the studies on VB are based on individual clinical observations and literature data [10, 11, 14, 15]. Our study was conducted on the basis of the analysis of significant clinical material with the development of semiotic signs of TBS lesions and assessment of the diagnostic value of VB methods of their combined analysis with the results of native MSCT. Overall, our opinion about the necessity of wide application in clinical practice CT VB coincides with the result of the work appeared in recent years [11, 13, 15].

#### **1.5 Conclusion**

Virtual bronchoscopy of multispiral computed tomography has the possibilities of multiplanar and volumetric reconstructions, post-processing image processing optimal method of diagnosis, determining the probable nature of tumor lesions of the trachea, the prevalence of the process, both outside the body and secondary invasions. In some cases, in stenotic lesions of the trachea, MSCT VB becomes the method of choice in assessing the prevalence of the process. Virtual modeling of intraluminal tracheal tumor, with the data about the surrounding tissues, provides valuable information for the planning of radical treatment.

#### **2. Virtual bronchoscopy multislice computer tomography at traumatic damage of a primary bronchus**

#### **2.1 Introduction**

Injuries of main bronchi (MB) result from traumatic injury of lungs, as a rule, are combined with injuries of bones of a thorax area. The full separation MB rather rare complication at a thorax injury can be met in 1–3% of cases. In 80% of patients, the rupture comes at the level of bifurcation of a trachea or within 4–2.5 cm from bifurcation of a trachea. Ruptures of MB tubes are met more often on the right. Depending on the severity of the injury, various degrees of damage to the main bronchus are observed—from a small tear to a complete rupture with a divergence of its fragments (partial or complete rupture) are observed [18–20]. The most common clinical manifestations of rupture are chest pain and cough, often accompanied by hemoptysis, shortness of breath, cyanosis due to intense pneumothorax with lung collapse and mediastinal displacement, possible presence of emphysema of the soft tissues of the chest wall and in the neck, and retraction of intercostal spaces. In complicated cases, the presence of intense mediastinal emphysema with extrapericardial cardiac tamponade is noted [21]. Existence or absence of pneumothorax and emphysema generally depends on character and localization of a wound MB. In cases of intrapleural ruptures of the primary and lobar bronchi, there is a tension pneumothorax. At a rupture of a primary bronchus, the lung is switched off from function of breath [22].

Diagnosis of traumatic damages of MB in patients with a thorax injury is a task of tactics of patient treatment; prevention of heavy complications depends on early identification of a rupture of bronchial tubes and a trachea [23]. A MSCT with intravenous administration of a contrast agent the leading noninvasive diagnostic method of consequences of blunt injury of thorax, including their traumatic damage (separation) of a bronchial tube [24–26]. In available literature, studies about the role of the VB of MSCT at traumatic injuries of MB are not found.

#### **2.2 Materials and methods of the research**

Data of the VB of MSCT of 10 patients with traumatic injuries of MB as a result of the combined injuries of a thorax—falling from height—3 patients, car accidents—4 patients, and motorcycle—2 patients were analyzed. All patients were brought to the clinic of institute for carrying out reconstructive operations on a primary bronchus from ambulance where they were brought directly after a trauma and received primary medical care and anti-shock therapy.

In seven patients, the rupture was right, and in three, left MB took place (RMB; LMB). The closed pneumothorax took place in eight and opened in two patients. At physical checkup, the expressed dyspnea amplifying at loading, percussion - obtusion of a pulmonary sound, lack of breath. When conducting pneumoscintigraphy with TC-99 m-Makrotekh, a decrease in the size of the lung reduced diffuse inhomogeneous accumulation of the radiotracer at the affected side. The total function of the affected lung was 17–21% and left 82–87%; the difference was 65–66% and violation of 3–4 violation stage capillary blood flow. Capillary blood flow in the intact lung was not disturbed. Traumatic rupture of the MB in all patients is accompanied by fractures of the ribs with displacement on the side of the lesion and hemopneumothorax. All patients underwent reconstructive surgery-isolated resection of the damaged main bronchus with the imposition of tracheobronchial anastomosis. CT with bolus gain of 80–100 ml of the radiopaque medium was carried out on AquilionONE CT scanner (320-slice). Data of native MSCT were

**49**

**Figure 10.**

*cavity, hypodermic emphysema on the right.*

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

supplemented with 3D-volume, multiplanar reconstruction, MinIP mode, and the VB of fly-through at the earlier described technique [4–6, 26]. Controls were carried out in 14–15 days after the transfer from resuscitation to chamber and 40 and more days after operation. Data of the VB of fly-through were compared with results of a

Native MSCT revealed a collapsed lung and a stump MB was defined. Shift of a mediastinum towards the injured lung and existence in a pleural cavity of nonuniform liquid content (with a density up to 45 HU) were noted. The break of MB was defined at distance of 4–30 mm from bifurcation of a trachea—at this length below a carina, the stump of MB tied from tracheas, distal lumen MB, and lobar and segmental bronchi were not visualized. There was hemo, pheumothorax, fractures of ribs, a humeral bone, in 3 - hypodermic emphysema. MSCT with contrast enhancement—the vascular peduncle of the affected lung was safe (**Figure 10**). VB fly-through in all patients revealed various localization break of a primary bronchus through which the pleural cavity with the collapsed lung and existence of level of liquid in a hemithorax were seen. In the area of a rupture, all patients had an uneven bronchial tube stump perimeter because of the "fragmentary" nature of damage

At survey of a trachea, a carina, a contralateral MB, and its branching of data for pathological changes were not revealed. According to FBS data localization, the extent and the nature of the line of a rupture of MB coincided with results of the VB (**Figure 11c**). 3D volume, multiplanar reconstruction, and the image of TBS in MinIP mode significantly supplemented the localizations given by MSCT and VB fly-through in identification, prevalence of traumatic damages, and planning of

Thus, a complex of techniques of the MSCT and VB allowed giving full information about a condition of a trachea, macrostructural changes of the injured MB, and secondary complications of a lung, to receive virtual model of a zone of interest for planning of an operation. Data of MSCT with contrast enhancement and

*The fallen-down lung are visualized his safe vascular leg, mediastinum shift to the right, liquid in a pleural* 

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

bronchofibroscopy (BFS).

**2.3 Results of the research**

(**Figure 11a, b**).

operation.

supplemented with 3D-volume, multiplanar reconstruction, MinIP mode, and the VB of fly-through at the earlier described technique [4–6, 26]. Controls were carried out in 14–15 days after the transfer from resuscitation to chamber and 40 and more days after operation. Data of the VB of fly-through were compared with results of a bronchofibroscopy (BFS).

#### **2.3 Results of the research**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

**damage of a primary bronchus**

**2.1 Introduction**

from function of breath [22].

**2.2 Materials and methods of the research**

**2. Virtual bronchoscopy multislice computer tomography at traumatic** 

Injuries of main bronchi (MB) result from traumatic injury of lungs, as a rule, are combined with injuries of bones of a thorax area. The full separation MB rather rare complication at a thorax injury can be met in 1–3% of cases. In 80% of patients, the rupture comes at the level of bifurcation of a trachea or within 4–2.5 cm from bifurcation of a trachea. Ruptures of MB tubes are met more often on the right. Depending on the severity of the injury, various degrees of damage to the main bronchus are observed—from a small tear to a complete rupture with a divergence of its fragments (partial or complete rupture) are observed [18–20]. The most common clinical manifestations of rupture are chest pain and cough, often accompanied by hemoptysis, shortness of breath, cyanosis due to intense pneumothorax with lung collapse and mediastinal displacement, possible presence of emphysema of the soft tissues of the chest wall and in the neck, and retraction of intercostal spaces. In complicated cases, the presence of intense mediastinal emphysema with extrapericardial cardiac tamponade is noted [21]. Existence or absence of pneumothorax and emphysema generally depends on character and localization of a wound MB. In cases of intrapleural ruptures of the primary and lobar bronchi, there is a tension pneumothorax. At a rupture of a primary bronchus, the lung is switched off

Diagnosis of traumatic damages of MB in patients with a thorax injury is a task of tactics of patient treatment; prevention of heavy complications depends on early identification of a rupture of bronchial tubes and a trachea [23]. A MSCT with intravenous administration of a contrast agent the leading noninvasive diagnostic method of consequences of blunt injury of thorax, including their traumatic damage (separation) of a bronchial tube [24–26]. In available literature, studies about

Data of the VB of MSCT of 10 patients with traumatic injuries of MB as a result of the combined injuries of a thorax—falling from height—3 patients, car accidents—4 patients, and motorcycle—2 patients were analyzed. All patients were brought to the clinic of institute for carrying out reconstructive operations on a primary bronchus from ambulance where they were brought directly after a trauma

In seven patients, the rupture was right, and in three, left MB took place (RMB; LMB). The closed pneumothorax took place in eight and opened in two patients. At physical checkup, the expressed dyspnea amplifying at loading, percussion - obtusion of a pulmonary sound, lack of breath. When conducting pneumoscintigraphy with TC-99 m-Makrotekh, a decrease in the size of the lung reduced diffuse inhomogeneous accumulation of the radiotracer at the affected side. The total function of the affected lung was 17–21% and left 82–87%; the difference was 65–66% and violation of 3–4 violation stage capillary blood flow. Capillary blood flow in the intact lung was not disturbed. Traumatic rupture of the MB in all patients is accompanied by fractures of the ribs with displacement on the side of the lesion and hemopneumothorax. All patients underwent reconstructive surgery-isolated resection of the damaged main bronchus with the imposition of tracheobronchial anastomosis. CT with bolus gain of 80–100 ml of the radiopaque medium was carried out on AquilionONE CT scanner (320-slice). Data of native MSCT were

the role of the VB of MSCT at traumatic injuries of MB are not found.

and received primary medical care and anti-shock therapy.

**48**

Native MSCT revealed a collapsed lung and a stump MB was defined. Shift of a mediastinum towards the injured lung and existence in a pleural cavity of nonuniform liquid content (with a density up to 45 HU) were noted. The break of MB was defined at distance of 4–30 mm from bifurcation of a trachea—at this length below a carina, the stump of MB tied from tracheas, distal lumen MB, and lobar and segmental bronchi were not visualized. There was hemo, pheumothorax, fractures of ribs, a humeral bone, in 3 - hypodermic emphysema. MSCT with contrast enhancement—the vascular peduncle of the affected lung was safe (**Figure 10**). VB fly-through in all patients revealed various localization break of a primary bronchus through which the pleural cavity with the collapsed lung and existence of level of liquid in a hemithorax were seen. In the area of a rupture, all patients had an uneven bronchial tube stump perimeter because of the "fragmentary" nature of damage (**Figure 11a, b**).

At survey of a trachea, a carina, a contralateral MB, and its branching of data for pathological changes were not revealed. According to FBS data localization, the extent and the nature of the line of a rupture of MB coincided with results of the VB (**Figure 11c**). 3D volume, multiplanar reconstruction, and the image of TBS in MinIP mode significantly supplemented the localizations given by MSCT and VB fly-through in identification, prevalence of traumatic damages, and planning of operation.

Thus, a complex of techniques of the MSCT and VB allowed giving full information about a condition of a trachea, macrostructural changes of the injured MB, and secondary complications of a lung, to receive virtual model of a zone of interest for planning of an operation. Data of MSCT with contrast enhancement and

#### **Figure 10.**

*The fallen-down lung are visualized his safe vascular leg, mediastinum shift to the right, liquid in a pleural cavity, hypodermic emphysema on the right.*

#### **Figure 11.**

*a. VB of fly-through – break of the right main bronchial tube, liquid level in the right hemithorax, the "fragmentary" nature of the line of a rupture of a bronchial tube (shooter). b. The same patient close-up, the edge of the collapsed lung (arrow) (A). The trachea, carina is not damaged (B). Navigator (C). c. FBS – data on an internal macrosturcture of a stump of a bronchial tube, area of a gap is distinctly traced, a condition of tracheas and LMB coincide with results of the VB.*

**51**

**Figure 12.**

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

liquid in a pleural cavity, and pneumothorax options.

multiplanar reconstruction specified a condition of a vascular lung peduncle on the party of defeat, a complication from a bone skeleton of a thorax, availability of

ture of a zone of an anastomosis were obtained at FBS (**Figure 13a, b**).

As shown, the conducted research of the VB of MSCT gives the chance of a visual estimation of a macrostructure of area of a posttraumatic rupture of MB and assessment of a condition of a trachea and bronchial tubes of a contralateral lung. The comparison of data of FBS and VB showed their full identity in visualization of anatomy of an internal surface of TBS that allows in believing that the VB of MSCT can be a method of choice in monitoring of dynamics of post-operational changes of the reconstructed MB. Combined analysis of the reconstruction of native CT and 3D images in MinIP mode allows studying also an external wall of a bronchial tube that is inaccessible to FBS. VB allows creating a virtual model of area of reconstructive intervention that plays an important role in its planning. As we noted in the introduction, studies on VB traumatic damage to the main bronchi of the lung us were not found in available literature (except the clinical observation published by us) [27, 28].

*14 day after reconstructive operation on RMB. MSCT, the frontal plane, MinIP the mode – the right lung is straightened, in the right pleural cavity a small amount of air, the formed fibrous ring in RMB (shooter).*

In 14–20 days after surgical treatment patient control MSCT at an operated lung was carried out; a small amount of air was found in a pleural cavity. At MSCT, it was defined that the lumen of the reconstructed MB was shortened, narrowed, and deformed in the area of an anastomosis. Air filling the lung, MB, and segmental bronchi was restored, the lung completely filling hemithorax. The lumen of the reconstructed bronchial tube was narrowed in the area of reconstruction (**Figure 12**). MSCT control in four and more months after operation in all patients revealed that the lung was completely normalized, and air and liquid in a pleural cavity were absent. The VB stated restoration of a lumen of a main bronchus with existence of deformation of a lumen in the area of an anastomosis. Similar data on a macrostruc-

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

**2.4 Discussion**

#### *Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

multiplanar reconstruction specified a condition of a vascular lung peduncle on the party of defeat, a complication from a bone skeleton of a thorax, availability of liquid in a pleural cavity, and pneumothorax options.

In 14–20 days after surgical treatment patient control MSCT at an operated lung was carried out; a small amount of air was found in a pleural cavity. At MSCT, it was defined that the lumen of the reconstructed MB was shortened, narrowed, and deformed in the area of an anastomosis. Air filling the lung, MB, and segmental bronchi was restored, the lung completely filling hemithorax. The lumen of the reconstructed bronchial tube was narrowed in the area of reconstruction (**Figure 12**).

MSCT control in four and more months after operation in all patients revealed that the lung was completely normalized, and air and liquid in a pleural cavity were absent. The VB stated restoration of a lumen of a main bronchus with existence of deformation of a lumen in the area of an anastomosis. Similar data on a macrostructure of a zone of an anastomosis were obtained at FBS (**Figure 13a, b**).

#### **2.4 Discussion**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

*a. VB of fly-through – break of the right main bronchial tube, liquid level in the right hemithorax, the "fragmentary" nature of the line of a rupture of a bronchial tube (shooter). b. The same patient close-up, the edge of the collapsed lung (arrow) (A). The trachea, carina is not damaged (B). Navigator (C). c. FBS – data on an internal macrosturcture of a stump of a bronchial tube, area of a gap is distinctly traced, a condition of* 

**50**

**Figure 11.**

*tracheas and LMB coincide with results of the VB.*

As shown, the conducted research of the VB of MSCT gives the chance of a visual estimation of a macrostructure of area of a posttraumatic rupture of MB and assessment of a condition of a trachea and bronchial tubes of a contralateral lung. The comparison of data of FBS and VB showed their full identity in visualization of anatomy of an internal surface of TBS that allows in believing that the VB of MSCT can be a method of choice in monitoring of dynamics of post-operational changes of the reconstructed MB. Combined analysis of the reconstruction of native CT and 3D images in MinIP mode allows studying also an external wall of a bronchial tube that is inaccessible to FBS. VB allows creating a virtual model of area of reconstructive intervention that plays an important role in its planning. As we noted in the introduction, studies on VB traumatic damage to the main bronchi of the lung us were not found in available literature (except the clinical observation published by us) [27, 28].

#### **Figure 12.**

*14 day after reconstructive operation on RMB. MSCT, the frontal plane, MinIP the mode – the right lung is straightened, in the right pleural cavity a small amount of air, the formed fibrous ring in RMB (shooter).*

#### **Figure 13.**

*a. 3 months after reconstructive operation on RMB – VB of fly-through – the lumen of RMB is restored, narrowed due to fibrous changes. b. FBS – given bronchofibroscopy coincide with results of a VB on a macrostructure of an internal surface of a bronchial tube.*

#### **2.5 Conclusion**

At traumatic damages of TBS techniques of the VB MSCT allow to define damages of primary bronchi with high precision, to carry out monitoring of efficiency of reconstructive operations. The combined analysis of multiplanar reconstruction, post-processing, 3D images, and the VB of fly-through allows estimating both internal and external walls of a bronchial tube, to receive the virtual image of reconstructive intervention zone.

**53**

provided the original work is properly cited.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Research Department of New Technologies and Semiotics Beam Diagnostics of Diseases of Organs and Systems of Russian Scientific Center of Roengenordiology

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

I would like to express my deep gratitude to Chernichenko Natalia Vasilievna MD, Scientific Research Department of Surgery and Surgical Technologies in Oncology, Russian Scientific Center of Roengenordiology (RSCRR), Moscow, **an** endoscopist and a specialist in the field of diseases of the chest and abdominal

The author declares no conflict of interest and sponsorship when performing this work. The work was performed within the scientific subject of RSCRR Russian

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

**Acknowledgements**

cavity for cooperation.

**Conflict of interest**

Ministry of Health.

**Author details**

Kotlyarov Peter Mikhaylovich

(RSCRR), Moscow, Russian Federation

\*Address all correspondence to: marnad@list.ru

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

#### **Acknowledgements**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

At traumatic damages of TBS techniques of the VB MSCT allow to define damages of primary bronchi with high precision, to carry out monitoring of efficiency of reconstructive operations. The combined analysis of multiplanar reconstruction, post-processing, 3D images, and the VB of fly-through allows estimating both internal and external walls of a bronchial tube, to receive the virtual image of

*a. 3 months after reconstructive operation on RMB – VB of fly-through – the lumen of RMB is restored, narrowed due to fibrous changes. b. FBS – given bronchofibroscopy coincide with results of a VB on a* 

**52**

**2.5 Conclusion**

**Figure 13.**

reconstructive intervention zone.

*macrostructure of an internal surface of a bronchial tube.*

I would like to express my deep gratitude to Chernichenko Natalia Vasilievna MD, Scientific Research Department of Surgery and Surgical Technologies in Oncology, Russian Scientific Center of Roengenordiology (RSCRR), Moscow, **an** endoscopist and a specialist in the field of diseases of the chest and abdominal cavity for cooperation.

#### **Conflict of interest**

The author declares no conflict of interest and sponsorship when performing this work. The work was performed within the scientific subject of RSCRR Russian Ministry of Health.

### **Author details**

Kotlyarov Peter Mikhaylovich Research Department of New Technologies and Semiotics Beam Diagnostics of Diseases of Organs and Systems of Russian Scientific Center of Roengenordiology (RSCRR), Moscow, Russian Federation

\*Address all correspondence to: marnad@list.ru

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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трахео – бронхиальной системы по данным мультисрезовой компьютерной томографии. Лучевая диагностика и терапия. 2011. №2. (2) С. 50-55)

[6] Kotlyarov PM, Nudnov NV, Egorova EV. Multidetector computed tomography virtual bronchoscopy in bronchiectasis and osteochondroplasty of bronchopathy. Pulmonology. 2014, No. 4. pp. 68-72. In Russian. (Котляров ПМ, Нуднов НВ, Егорова ЕВ. Мультиспиральная компьютерно– томографическая виртуальная бронхоскопия при бронхоэктатической болезни и остеохондропластической бронхопатии. Пульмонология, 2014, № 4, С. 68-72)

[7] Sdvizcov AM, Yudin AL, Kozhanov LG et al. Multislice computed tomographywith threedimensional modeling indiagnosing and treatingcancer patients. Bulletin of Moscowcancer Society. 2009. No. 3. pp. 1-4. In Russian. (Cдвижков АМ, Юдин АЛ, Кожанов ЛГидр. Мультиспиральная компьютерная томография с трехмерным моделированием в диагностике и лечении онкологических больных. Вестник Московского онкологического общества. 2009. № 3. С. 1-4)

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*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways*

http://vestnik.rncrr.ru/vestnik/v3/

[18] Velly JF, Martigne C, Moreau JM, et al. Post traumatic tracheobronchial lesions. A follow-up study of 47 cases. European Journal of Cardio-Thoracic

[19] Scognamiglio G, Solli P, Benni M, et al. Less is more: lung-sparing direct repair of a traumatic rupture of the bronchus intermedius. Journal of Visualized Surgery. 2017;**3**:109. DOI: 10.21037/jovs.2017.06.07. e Collection

papers/harch14\_v3.htm))

Surgery. 1991;**5**(7):352-355

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[21] Krawczyk L, Byrczek TP,

Łuczyk АM, et al. Traumatic tension pneumopericardium and amputation of the left main bronchus. Polish Journal of Cardio-Thoracic Surgery. 2017;**1**(1): 63-65. DOI: 10.5114/kitp.2017.66935

[22] Nishiumi N, Inokuchi S, Oiwa K, et al. Diagnosis and treatment of deep pulmonary laceration with intrathoracic hemorrhage from blunt trauma. The Annals of Thoracic

Surgery. 2010;**9**:232-238. DOI: 10.1016/j.

[23] Kummer C, Netto FS, Rizoli S, et al. A review of traumatic airway injuries: potential implications for airway assessment and management. Injury. 2007;**38**:27-33. DOI: 10.1016/j.injury

[24] Kotlyarov PM. Multislice computed tomography: A new stage of development of radiodiagnostics of diseases of the lungs. Medical Imaging. 2011. No. 4. pp. 14-20. In Russian. (Котляров ПМ, Мультисрезовая КТ. новый этап развития лучевой диагностики заболеваний легких. Медицинская визуализация.

athoracsur.2009.09.041

2011. №4. С. 14-20)

thorsurg.2007.03.005

2017

*DOI: http://dx.doi.org/10.5772/intechopen.84562*

[11] Das KM, Lababidi H, Al Dandan S,

virtualbronchoscopy: Normal variants, pitfalls, and spectrum of common and rare pathology. Canadian Association of Radiologists Journal. 2015;**66**(1):58-70

[12] Gutiérrez R, Rodríguez SD, Ros Lucas JA. Torsion of middle lobe after lobectomy. correlation between optical bronchoscopy-computed tomography virtual bronchoscopy. Archivos de Bronconeumología. 2015;**51**(7):355-359

virtualbronchoscopy in the evaluation of bronchial lesions: A pictorial essay. Current Problems in Diagnostic Radiology. 2013;**42**(2):33-39

[15] Osiri X, Sano A, Tsuchiya TJ. Virtual bronchoscopy using OsiriX. Journal of Bronchology and Interventional Pulmonology. 2014;**21**(2):113-116

Güven K et al. The diagnostic efficiency of multislice CT virtual bronchoscopy in detecting endobronchial tumors.

[17] Kharchenko VP, Gvarishvili AA, Eltishev N et al. Examination and treatment of patients with multiple primary malignant tumors of the respiratory system. Bulletin RSCRR Ministry of Health of Russia. 2004. (URL: http://vestnik.rncrr.ru/vestnik/ v3/papers/harch14\_v3.htm. In Russian). (Харченко ВП, Гваришвили АА, Елтышев НА и др. Обследование и лечение больных с первичномножественными злокачественными опухолями органов дыхания. Вестник РНЦРР Минздрава России. 2004. (URL:

[16] Terzibaşioğlu E, Dursun M,

Tuberk Toraks

[14] Luo M, Duan C, Qiu J, et al. Diagnostic value of multidetector CT and its multiplanar reformation, volume rendering and virtual bronchoscopy postprocessing techniques for primary trachea and main bronchus tumors. PLoS One. 2015;**10**(9):e0137329

[13] Hussein SR. Role of

et al. Computed tomography

*Virtual Bronchoscopy for Tumors and Traumatic Lesions of the Airways DOI: http://dx.doi.org/10.5772/intechopen.84562*

[11] Das KM, Lababidi H, Al Dandan S, et al. Computed tomography virtualbronchoscopy: Normal variants, pitfalls, and spectrum of common and rare pathology. Canadian Association of Radiologists Journal. 2015;**66**(1):58-70

[12] Gutiérrez R, Rodríguez SD, Ros Lucas JA. Torsion of middle lobe after lobectomy. correlation between optical bronchoscopy-computed tomography virtual bronchoscopy. Archivos de Bronconeumología. 2015;**51**(7):355-359

[13] Hussein SR. Role of virtualbronchoscopy in the evaluation of bronchial lesions: A pictorial essay. Current Problems in Diagnostic Radiology. 2013;**42**(2):33-39

[14] Luo M, Duan C, Qiu J, et al. Diagnostic value of multidetector CT and its multiplanar reformation, volume rendering and virtual bronchoscopy postprocessing techniques for primary trachea and main bronchus tumors. PLoS One. 2015;**10**(9):e0137329

[15] Osiri X, Sano A, Tsuchiya TJ. Virtual bronchoscopy using OsiriX. Journal of Bronchology and Interventional Pulmonology. 2014;**21**(2):113-116

[16] Terzibaşioğlu E, Dursun M, Güven K et al. The diagnostic efficiency of multislice CT virtual bronchoscopy in detecting endobronchial tumors. Tuberk Toraks

[17] Kharchenko VP, Gvarishvili AA, Eltishev N et al. Examination and treatment of patients with multiple primary malignant tumors of the respiratory system. Bulletin RSCRR Ministry of Health of Russia. 2004. (URL: http://vestnik.rncrr.ru/vestnik/ v3/papers/harch14\_v3.htm. In Russian). (Харченко ВП, Гваришвили АА, Елтышев НА и др. Обследование и лечение больных с первичномножественными злокачественными опухолями органов дыхания. Вестник РНЦРР Минздрава России. 2004. (URL: http://vestnik.rncrr.ru/vestnik/v3/ papers/harch14\_v3.htm))

[18] Velly JF, Martigne C, Moreau JM, et al. Post traumatic tracheobronchial lesions. A follow-up study of 47 cases. European Journal of Cardio-Thoracic Surgery. 1991;**5**(7):352-355

[19] Scognamiglio G, Solli P, Benni M, et al. Less is more: lung-sparing direct repair of a traumatic rupture of the bronchus intermedius. Journal of Visualized Surgery. 2017;**3**:109. DOI: 10.21037/jovs.2017.06.07. e Collection 2017

[20] Karmy-Jones R, Wood DE. Traumatic injury to the trachea and bronchus. Thoracic Surgery Clinics. 2007;**17**:35-46. DOI: 10.1016/j. thorsurg.2007.03.005

[21] Krawczyk L, Byrczek TP, Łuczyk АM, et al. Traumatic tension pneumopericardium and amputation of the left main bronchus. Polish Journal of Cardio-Thoracic Surgery. 2017;**1**(1): 63-65. DOI: 10.5114/kitp.2017.66935

[22] Nishiumi N, Inokuchi S, Oiwa K, et al. Diagnosis and treatment of deep pulmonary laceration with intrathoracic hemorrhage from blunt trauma. The Annals of Thoracic Surgery. 2010;**9**:232-238. DOI: 10.1016/j. athoracsur.2009.09.041

[23] Kummer C, Netto FS, Rizoli S, et al. A review of traumatic airway injuries: potential implications for airway assessment and management. Injury. 2007;**38**:27-33. DOI: 10.1016/j.injury

[24] Kotlyarov PM. Multislice computed tomography: A new stage of development of radiodiagnostics of diseases of the lungs. Medical Imaging. 2011. No. 4. pp. 14-20. In Russian. (Котляров ПМ, Мультисрезовая КТ. новый этап развития лучевой диагностики заболеваний легких. Медицинская визуализация. 2011. №4. С. 14-20)

**54**

*Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics*

трахео – бронхиальной системы по данным мультисрезовой компьютерной томографии. Лучевая диагностика и терапия. 2011. №2. (2) С. 50-55)

[6] Kotlyarov PM, Nudnov NV, Egorova EV. Multidetector computed tomography virtual bronchoscopy in bronchiectasis and osteochondroplasty of bronchopathy. Pulmonology. 2014, No. 4. pp. 68-72. In Russian. (Котляров ПМ, Нуднов НВ, Егорова ЕВ. Мультиспиральная компьютерно– томографическая виртуальная

бронхоскопия при бронхоэктатической болезни и остеохондропластической бронхопатии. Пульмонология, 2014, №

[7] Sdvizcov AM, Yudin AL, Kozhanov LG et al. Multislice computed tomographywith threedimensional modeling indiagnosing and treatingcancer patients. Bulletin of Moscowcancer Society. 2009. No. 3. pp. 1-4. In Russian. (Cдвижков АМ, Юдин АЛ, Кожанов ЛГидр. Мультиспиральная компьютерная томография с трехмерным моделированием в диагностике и лечении онкологических больных. Вестник Московского онкологического

общества. 2009. № 3. С. 1-4)

Radiology. 2013;**78**(1):30-41

2015;**41**(7):1613-1615

[9] Aliannejad R. Comment on

[10] Bauer TL, Steiner KV. Virtual bronchoscopy: clinical applications and limitations. Surgical Oncology Clinics of North America. 2007;**16**(2):323-328

[8] Adamczyk M, Tomaszewski G, Naumczyk P, et al. Usefulness of computed tomography

virtualbronchoscopy in the evaluation of bronchi divisions. Polish Journal of

"Comparison of virtualbronchoscopy to fiber-optic bronchoscopy for assessment of inhalation injury severity". Burns.

4, С. 68-72)

**References**

С.250)

Russian

2013;**69**(3):305-310

flerov\_v13.htm))

econstruction and

[1] Malignant neoplasms Russia in 2014. edited by Kaprin AD,

StarostinVV, Petrova GVM. 2016. p. 250. (Злокачественныеновобразования России в 2014г. под ред. Каприна АД. Старостина ВВ, Петровой ГВМ. 2016.

[2] Jugpal TS, Garg A, Sethi GR, et al. Multi-detector computed tomography imaging of large airway pathology: A pictorial review. World Journal of Radiology. 2015;**7**(12):459-474. In

[3] Debnath J, George RA, Satija L, et al. Virtual bronchoscopy in the era of multi-detector computed tomography: Is there any reality? Medical Journal Armed Forces India.

[4] Kotlyarov P. Temirhanov Z, Flerov E. et al. Virtual bronchoscopy in the diagnosis of lung cancer and its

prevalence, monitoring of postoperative changes. Bulletin RSCRR Ministry of Health of Russia. 2013. (URL: http://vestnik.rncrr.ru/vestnik/v13/ papers/flerov\_v13.htm). In Russian. (Котляров ПМ, Темирханов СЗ, Флеров КЕидр. Виртуальная бронхоскопия в диагностике рака легкого и его распространенности, мониторинге послеоперационных изменений. Вестник РНЦРР. 2013. (URL: http:// vestnik.rncrr.ru/vestnik/v13/papers/

[5] Kotlyarov PM, Temirkhanov ZS,

virtualbronchoscopyin the evaluation of the statetracheo – bronchial system according Multidetector computed tomography. Radiation Diagnostics and Therapy. 2011. No.2. (2) pp. 50-55. In Russian. (Котляров ПМ, Темирханов ЗС, Щербахина ЕВ. Мультипланарные

Serbahina EV. Multiplanarr

реконструкции и виртуальная бронхоскопия в оценке состояния [25] Cui Y, Ma D-q, Liu W-h. Value of multiplanar reconstruction in MSCT in demonstrating the relationship between solitary pulmonary nodule and bronchus. Clinical Imaging. 2009;**33**:15-21

[26] Kotlyarov PM. Virtual bronchoscopy in the diagnosis of lung cancer. Radiation Diagnosis and Therapy. 2015. № 1. pp. 56-63. In Russian. (Котляров ПМ. Виртуальная бронхоскопия в диагностике рака легкого. Лучевая диагностика и терапия. 2015. № 1. С. 56-63)

[27] Kharchenko VP, Kotlyarov PM, Vinikovetskaya AV et al. Trauma of the right main bronchus (clinical observation). Medical Imaging. 2011. N 4. pp. 76-81. In Russian. (Харченко ВП, Котляров ПМ, Виниковецкая АВ и др. Травматический отрыв правого главного бронха (клиническое наблюдение). Медицинская визуализация. 2011. N 4. С. 76-81)

[28] Kotlyarov PM, Chernichenko NV. Virtual bronchoscopy multislice tomography in traumatic injuries of the main bronchi. Journal of Medical Imaging and Case Reports. 2018. Proceedings of the First International Conference on Medical Imaging and Case Reports (MICR-2018);**2**(2):S25-S26. DOI: 10.17756/ micr.2018-suppl 1

**57**

Section 3

Pulmonary Hypertention

Section 3
