**1. Introduction**

102 Practical Applications in Biomedical Engineering

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[3] Pillai, J., Sperling, M.R. Interictal EEG and the Diagnosis of Epilepsy, Epilepsia (Vol. 47).

[4] Lüders, H.O., Noachtar, S. Atlas and Classification of Electroencephalography: Introduction to the Evaluation of the Electroencephalogram. São Paulo: Lemos

[5] Wilson, S. B., & Emerson, R. Spike Detection: a review and comparison of algorithms.

[7] Addison, P.S. The Illustrated Wavelet Transform Handbook: Introductory Theory and Applications in Science, Engineering, Medicine and Finance. New York: Taylor &

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[6] Mallat, S. A Wavelet Tour of Signal Processing. USA: Academic Press; 1999

Asthma is an inflammatory condition of the airways resulting in their hyper-reactivity, generating increased mucus, mucosal swelling and airway smooth muscle contraction all of which contribute to (partial) airway obstruction. The symptoms include chest tightness, coughing and wheezing, and in severe cases shortness of breath and low blood oxygen (1). According to Dorland's medical dictionary small airway impairment (SAI) is a chronic obstructive bronchitis with narrowing of the bronchioles and small bronchi. The term small airways refer to about 7th to 19th generation of airways with an inner diameter of about 2 to 0.5 mm. These airways are considered to be an important site of inflammation in asthma and chronic obstructive pulmonary disease (COPD). The atopic manifestation just prior to asthma could be early small airway disease (SAD) and then if inflammation persists, asthma would appear. SAD includes a spectrum of inflammatory and fibrotic pulmonary diseases centered on the small conducting airways.

According to the American Academy of Allergy Asthma & Immunology, Asthma and allergies stroke 1 out of 12 Americans and approximately 25 million Americans (8% of the U.S. population) had asthma in 2009. About 1 in 10 children (10%) had asthma and 1 in 12 adults (8%) had asthma in 2009. For the period 2008-2010, asthma prevalence was higher among children than adults. For the period 2008-2010, asthma prevalence was higher among multiplerace, black, and American Indian or Alaska Native persons than white persons. Asthma costs in the US grew from about \$53 billion in 2002 to about \$56 billion in 2007, about a 6% increase. Compared with adults, children had higher rates for asthma primary care and emergency department visits, similar hospitalization rates, and lower death rates. Asthma was linked to

© 2012 Merez et al., licensee InTech. This is an open access chapter 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. © 2012 Merez et al., licensee InTech. This is a paper 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.

3,447 deaths (about 9 per day) in 2007. Internationally asthma has a rising prevalence in low and middle income countries and it is reaching a steady level in high income countries. An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths attributed to the disease; almost all of these deaths are avoidable (2).

Impulse Oscillometric Features and Respiratory System Models Track Small Airway Function in Children 105

Lung Capacity **(TLC)"** in which it was mentioned that reference values play an important role in establishing whether the measured volumes fall within an expected range for healthy individuals of the same sex, similar stature, age, and other characteristics. They also point out that comparing reference with measured values is fraught with difficulties, as this may result in disease being undetected and as a consequence untreated. It is also mentioned that FRC is the only lung volume that can be measured routinely with accuracy and reliability, and in addition it is stated that attempts have been made to evaluate TLC and RV. In this report reference values (values for healthy subjects) and prediction equations for lung volumes for children and adults are obtained using different techniques like helium dilution and body plethysmography. These values are presented for different heights. However, this report does not include reference values and prediction equations based on the FOT or IOS. Few studies have been developed to obtain Reference Values for healthy children using the FOT and IOS (35-42). It is essential to have IOS Reference Values for children, as this technique has been shown to be very effective in the detection of lung abnormalities. Therefore, here we intend to make an effort towards establishing normal IOS Reference Values in North American Anglo and Hispanic children 5 to 19 years old. We also aim to present baseline (pre-) and postbronchodilation IOS parameters for Anglo and Hispanic children with Probable Small Airway

IOS data generate frequency-dependent curves of respiratory impedance (resistance and reactance) that are visually analyzed to recognize changes in their shape and magnitude and distinguish healthy respiratory function from dysfunction. The IOS data can be deployed to develop mechanical and equivalent electrical circuit models of the respiratory impedance to evaluate and quantify lung mechanics. In these equivalent models, electrical components analogous to mechanical resistance, compliance, and inertance inherent in the respiratory system are used. Therefore, estimates for these Model Parameters based on IOS measurements could be used as baseline measures for better detection, diagnosis, and

Previous work by our research group for more than a decade has focused on development and analysis of different equivalent electrical circuit models for human respiratory impedance. This effort to date has demonstrated that the performance of extended Resistance Inductance Capacitance (eRIC) model and the augmented RIC (aRIC) model (an improvement of the eRIC model) ranked in the middle of a series of conventional models developed over the past several decades in terms of total cumulative error. However, they provide parameter estimates that are physiologically more realistic and in line with expected values in normal subjects and those suffering from pulmonary diseases (43-51),

The IOS data collected from children for this study were partially analyzed and presented in several publications (52-61), the latest results of this research are presented in this chapter.

Here we determine the eRIC and aRIC model parameter estimates in addition to sensitive IOS measures of lung function in Normal (N) or Healthy (H), PSAI, SAI and Asthmatic (A), Anglo and Hispanic children. We further evaluate the performance of these models in

Impairment (PSAI), Small Airway Impairment (SAI) and Asthma.

treatment of different respiratory diseases (43).

than previous models.

In Mexico, 10% (approximately 10 million people), of the population suffer from asthma. It is the most common cause of chronic illnesses and emergency hospitalizations in children according to the Mexican College of Allergy, Asthma and Pediatric Pulmonology (3).

Assessment of respiratory function is important in diagnosis and monitoring of asthma and other respiratory diseases in children (4). The pulmonary function test most commonly used to detect asthma is spirometry, which measures the volume of air that can be moved in or out of the lungs as a function of time with rapid and maximal inspiratory and expiratory efforts. This requires a considerable degree of cooperation from the subject, which is difficult to achieve in older children and almost impossible to achieve by younger children. This makes the diagnosis of asthma difficult owing to the lack of objective measurements for younger children (5). Furthermore, it has been reported that some asthmatic patients do not improve spirometrically, despite clinical improvement with treatment (6). This is of concern because if asthma is not appropriately controlled, it can lead to permanent airway damage.

In contrast to forced spirometry, the Forced Oscillation Technique (FOT) superimposes small air pressure perturbations on the natural breathing of a subject to measure lungs mechanics (respiratory impedance). The Impulse Oscillometry System (IOS) measures respiratory impedance by using short pulses (impulses) of air pressure. It has been developed as a patientfriendly lung function test that minimizes demands on the patient and requires only passive cooperation of the patient wearing a nose clip, keeping lips tightly closed about a mouthpiece and breathing normally through the mouth. IOS has been used with success to assess lung function in healthy and asthmatic children and adolescents (4-32). In infants and children, reversible airway obstruction and bronchial hyperresponsiveness (BHR) are significant components contributing to the diagnosis of bronchial asthma (27). All this evidence, which will be described in detail, confirms that lung function in children and adolescents is sensitively and accurately assessed by the IOS, before and after bronchodilation. To build upon this evidence and demonstrate the potential enhancements in the clinical utility of IOS, here we present respiratory system Model Parameters and selected IOS features derived from Pre- and Post-bronchodilation data acquired from Anglo and Hispanic children, that offer significant improvements in quantitative evaluation of small airway impairments and assessment of asthma in this population.

In 1991, the American Thoracic Society published guidelines focusing on spirometry as the most widely used lung function test, where they presented Reference Values for spirometric parameters for Caucasian and Black men and women. They also mentioned that it is common practice to interpret the results of lung function tests in relation to Reference Values and in terms of whether or not they are considered to be within the "normal" range (33).

The European Respiratory Society in 1995 published a workshop report (34) about "Reference Values for Residual Volume (RV), Functional Residual Capacity (FRC) and Total Lung Capacity **(TLC)"** in which it was mentioned that reference values play an important role in establishing whether the measured volumes fall within an expected range for healthy individuals of the same sex, similar stature, age, and other characteristics. They also point out that comparing reference with measured values is fraught with difficulties, as this may result in disease being undetected and as a consequence untreated. It is also mentioned that FRC is the only lung volume that can be measured routinely with accuracy and reliability, and in addition it is stated that attempts have been made to evaluate TLC and RV. In this report reference values (values for healthy subjects) and prediction equations for lung volumes for children and adults are obtained using different techniques like helium dilution and body plethysmography. These values are presented for different heights. However, this report does not include reference values and prediction equations based on the FOT or IOS.

104 Practical Applications in Biomedical Engineering

assessment of asthma in this population.

3,447 deaths (about 9 per day) in 2007. Internationally asthma has a rising prevalence in low and middle income countries and it is reaching a steady level in high income countries. An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths

In Mexico, 10% (approximately 10 million people), of the population suffer from asthma. It is the most common cause of chronic illnesses and emergency hospitalizations in children

Assessment of respiratory function is important in diagnosis and monitoring of asthma and other respiratory diseases in children (4). The pulmonary function test most commonly used to detect asthma is spirometry, which measures the volume of air that can be moved in or out of the lungs as a function of time with rapid and maximal inspiratory and expiratory efforts. This requires a considerable degree of cooperation from the subject, which is difficult to achieve in older children and almost impossible to achieve by younger children. This makes the diagnosis of asthma difficult owing to the lack of objective measurements for younger children (5). Furthermore, it has been reported that some asthmatic patients do not improve spirometrically, despite clinical improvement with treatment (6). This is of concern because if asthma is not appropriately controlled, it can lead to permanent airway damage. In contrast to forced spirometry, the Forced Oscillation Technique (FOT) superimposes small air pressure perturbations on the natural breathing of a subject to measure lungs mechanics (respiratory impedance). The Impulse Oscillometry System (IOS) measures respiratory impedance by using short pulses (impulses) of air pressure. It has been developed as a patientfriendly lung function test that minimizes demands on the patient and requires only passive cooperation of the patient wearing a nose clip, keeping lips tightly closed about a mouthpiece and breathing normally through the mouth. IOS has been used with success to assess lung function in healthy and asthmatic children and adolescents (4-32). In infants and children, reversible airway obstruction and bronchial hyperresponsiveness (BHR) are significant components contributing to the diagnosis of bronchial asthma (27). All this evidence, which will be described in detail, confirms that lung function in children and adolescents is sensitively and accurately assessed by the IOS, before and after bronchodilation. To build upon this evidence and demonstrate the potential enhancements in the clinical utility of IOS, here we present respiratory system Model Parameters and selected IOS features derived from Pre- and Post-bronchodilation data acquired from Anglo and Hispanic children, that offer significant improvements in quantitative evaluation of small airway impairments and

In 1991, the American Thoracic Society published guidelines focusing on spirometry as the most widely used lung function test, where they presented Reference Values for spirometric parameters for Caucasian and Black men and women. They also mentioned that it is common practice to interpret the results of lung function tests in relation to Reference Values and in

The European Respiratory Society in 1995 published a workshop report (34) about "Reference Values for Residual Volume (RV), Functional Residual Capacity (FRC) and Total

terms of whether or not they are considered to be within the "normal" range (33).

according to the Mexican College of Allergy, Asthma and Pediatric Pulmonology (3).

attributed to the disease; almost all of these deaths are avoidable (2).

Few studies have been developed to obtain Reference Values for healthy children using the FOT and IOS (35-42). It is essential to have IOS Reference Values for children, as this technique has been shown to be very effective in the detection of lung abnormalities. Therefore, here we intend to make an effort towards establishing normal IOS Reference Values in North American Anglo and Hispanic children 5 to 19 years old. We also aim to present baseline (pre-) and postbronchodilation IOS parameters for Anglo and Hispanic children with Probable Small Airway Impairment (PSAI), Small Airway Impairment (SAI) and Asthma.

IOS data generate frequency-dependent curves of respiratory impedance (resistance and reactance) that are visually analyzed to recognize changes in their shape and magnitude and distinguish healthy respiratory function from dysfunction. The IOS data can be deployed to develop mechanical and equivalent electrical circuit models of the respiratory impedance to evaluate and quantify lung mechanics. In these equivalent models, electrical components analogous to mechanical resistance, compliance, and inertance inherent in the respiratory system are used. Therefore, estimates for these Model Parameters based on IOS measurements could be used as baseline measures for better detection, diagnosis, and treatment of different respiratory diseases (43).

Previous work by our research group for more than a decade has focused on development and analysis of different equivalent electrical circuit models for human respiratory impedance. This effort to date has demonstrated that the performance of extended Resistance Inductance Capacitance (eRIC) model and the augmented RIC (aRIC) model (an improvement of the eRIC model) ranked in the middle of a series of conventional models developed over the past several decades in terms of total cumulative error. However, they provide parameter estimates that are physiologically more realistic and in line with expected values in normal subjects and those suffering from pulmonary diseases (43-51), than previous models.

The IOS data collected from children for this study were partially analyzed and presented in several publications (52-61), the latest results of this research are presented in this chapter.

Here we determine the eRIC and aRIC model parameter estimates in addition to sensitive IOS measures of lung function in Normal (N) or Healthy (H), PSAI, SAI and Asthmatic (A), Anglo and Hispanic children. We further evaluate the performance of these models in

quantifying lung function in this population and analyze the correlation of these Model Parameters with sensitive IOS measures of lung function.

Impulse Oscillometric Features and Respiratory System Models Track Small Airway Function in Children 107

breathing (66). Therefore, FOT superimposes small external pressure signals on the natural breathing to determine a subject's breathing mechanics. FOT measures respiratory impedance to this applied forced pressure oscillations produced by a loud speaker (67). FOT is indicated as a reliable diagnostic tool to obtain tidal breathing analysis. One of the great advantages of FOT over other pulmonary function tests is that the results measured are independent of the subject respiratory pattern, therefore it is effort independent; it requires only passive cooperation from the subject breathing normally through a mouth piece, keeping lips airtight closed around it, while wearing a nose clips occluding the nares (68). FOT has been used in humans for more than 50 years; it has been used in children with

1. To characterize the lung function abnormalities of chronic respiratory diseases in

FOT applied at oscillation frequencies between 3 and 35 Hz can provide helpful information to help distinguish between large and small airways. The use of multiple oscillation frequencies in FOT allows a separation of large airways from small airways. Frequencies below 15 Hz, low oscillation frequencies, have been shown to be transmitted more distally (peripherally) in the lungs, whilst frequencies higher than 20 Hz, high oscillation frequencies, can reach only the intermediate size airways. As a result low oscillation frequencies reflect small and large airways, while high oscillation frequencies merely reflect large airways. Therefore, changes in large airway resistance cause uniform changes in resistance at all oscillation frequencies (3-35 Hz), whereas changes in small airway resistance result in noticeable changes in low frequency (3-15 Hz) resistance with small or no change in high frequency resistance. Peripheral airways include all airways with a diameter less than

One of the most remarkable features of FOT in relation to spirometry is that it has a relatively greater sensitivity to peripheral airways disease; due to the fact that spirometry does not provide a clear indication of peripheral airway obstruction regardless of the information contained in the flow-volume curve and the values of mid-flow rates

In 1956 Dubois presented the first study on FOT; in this study FOT was applied using sinusoidal oscillations with multiple single frequencies between 2 and 18 Hz. After this study several modifications of FOT were developed, until 1993 when the pulse technique was improved and commercially produced by the German company Jaeger. It was named Impulse Oscillometry System (IOS), as an easier to use method to measure respiratory resistance (R) and reactance (X). The advantages of IOS include good time resolution. It measures 5 pulses per second, with continuous resolution in the frequency domain using a

2. As a diagnostic tool, especially to recognize asthma and bronchial responsiveness 3. To study the physiological mechanisms and pathophysiology of diverse conditions

involving and/or threatening the respiratory system

2mm, and large airways are those with diameters greater than 4 mm (66).

three major clinical aims (69):

children

(FEF25%-75%) (68).

**2.3. Impulse Oscillometry System (IOS)** 
