**11.2.5 Supportive management**

#### i. Oxygen therapy:

Chronic hypoxemia may develop in patients with severe stable COPD (GOLD stage IV). Two landmark trials, the British Medical Research Council (MRC) study and the National Heart, Lung, Blood Institute's Nocturnal Oxygen Therapy Trial (NOTT) showed that longterm oxygen therapy improves survival by 2-fold or more in hypoxemic patients with COPD(Kvalle,1980;Medical Research Council Working Party,1981). Improved quality of life is also achieved likely due to reduced dyspnea during exercise, which improves performance of activities of daily living. Other benefits include reduction in hematocrit, modest neuropsychological improvement, and some improvement in pulmonary hemodynamics(Heaton et al,1983;Kvalle,1980;Timms et al,1985 as cited in Shapiro SD,2010).

Hypoxemia which is defined as a PaO2 of <55 mmHg or oxygen saturation of ˂90%. For those whose resting arterial Po2 is between 56 and 59 mmHg, long-term oxygen therapy is indicated if they demonstrate erythrocytosis (hematocrit ≥ 55%) or evidence of cor pulmonale. Stable ambulatory patients should meet these criteria after being on an optimal treatment regimen for at least 30 days (Petty, 1990;Petty & Snider,1988;Tiep,1990 as cited in Shapiro SD,2010). Exercise-induced hypoxemia is also an accepted indication for supplemental oxygen because it improves exercise performance (Cotes & Gilson,1956;Woodcock et al,1981 as cited in Shapiro SD,2010). Supplementary oxygen during air travel is recommended for only those individuals whose in-flight PaO2 is expected to fall below 50 mmHg since all commercial airline cabins are not always pressurized to sea level(Gong,1984;Schwartz et al,1984 as cited in Shapiro SD,2010). Patients with major bullous disease run a high risk of life-threatening pneumothorax and hence, probably should not fly. Studies have failed to show any benefit arising from nocturnal oxygen supplementation targeted at correcting hypoxemic episodes during sleep (Chaouat et al,1999,2001; Zanchet & Viegas,2006 as cited in Shapiro SD,2010).

The continuous-flow nasal cannula is the standard means of oxygen delivery for stable hypoxemic patients. The cannula is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fraction of inspired oxygen (FiO2). Oxygen-conserving devices function by delivering all of the oxygen during early inhalation. Three distinct oxygen-conserving devices are available, and they include reservoir cannulas, demandpulse delivery devices, and transtracheal oxygen delivery.

ii. Nutrition:

Patients with advanced COPD and a predominance of emphysema often experience progressive weight loss. The weight loss is multifactorial including a 15% to 25% increase in resting energy expenditure from elevated work of breathing and increased circulatory inflammatory cytokines, higher energy cost of daily activities and a reduced caloric intake(Barnes,2009;Di Francia et al,1994 as cited in Shapiro SD,2010). This leads to reduced muscle strength including weakness of respiratory muscles thus worsening the dyspnea. Improved nutrition can restore respiratory and general muscle strength and endurance (Wilson,1986,Whittaker et al,1990 as cited in Shapiro SD,2010).

iii. Pulmonary Rehabilitation:

144 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

with COPD who are ≥65 years old, or who are younger than 65 years with a forced expiratory volume in one second (FEV1) less than 40 percent. An annual influenza vaccine

Chronic hypoxemia may develop in patients with severe stable COPD (GOLD stage IV). Two landmark trials, the British Medical Research Council (MRC) study and the National Heart, Lung, Blood Institute's Nocturnal Oxygen Therapy Trial (NOTT) showed that longterm oxygen therapy improves survival by 2-fold or more in hypoxemic patients with COPD(Kvalle,1980;Medical Research Council Working Party,1981). Improved quality of life is also achieved likely due to reduced dyspnea during exercise, which improves performance of activities of daily living. Other benefits include reduction in hematocrit, modest neuropsychological improvement, and some improvement in pulmonary hemodynamics(Heaton et al,1983;Kvalle,1980;Timms et al,1985 as cited in Shapiro SD,2010). Hypoxemia which is defined as a PaO2 of <55 mmHg or oxygen saturation of ˂90%. For those whose resting arterial Po2 is between 56 and 59 mmHg, long-term oxygen therapy is indicated if they demonstrate erythrocytosis (hematocrit ≥ 55%) or evidence of cor pulmonale. Stable ambulatory patients should meet these criteria after being on an optimal treatment regimen for at least 30 days (Petty, 1990;Petty & Snider,1988;Tiep,1990 as cited in Shapiro SD,2010). Exercise-induced hypoxemia is also an accepted indication for supplemental oxygen because it improves exercise performance (Cotes & Gilson,1956;Woodcock et al,1981 as cited in Shapiro SD,2010). Supplementary oxygen during air travel is recommended for only those individuals whose in-flight PaO2 is expected to fall below 50 mmHg since all commercial airline cabins are not always pressurized to sea level(Gong,1984;Schwartz et al,1984 as cited in Shapiro SD,2010). Patients with major bullous disease run a high risk of life-threatening pneumothorax and hence, probably should not fly. Studies have failed to show any benefit arising from nocturnal oxygen supplementation targeted at correcting hypoxemic episodes during sleep (Chaouat

et al,1999,2001; Zanchet & Viegas,2006 as cited in Shapiro SD,2010).

pulse delivery devices, and transtracheal oxygen delivery.

The continuous-flow nasal cannula is the standard means of oxygen delivery for stable hypoxemic patients. The cannula is simple, reliable, and generally well tolerated. Each liter of oxygen flow adds 3-4% to the fraction of inspired oxygen (FiO2). Oxygen-conserving devices function by delivering all of the oxygen during early inhalation. Three distinct oxygen-conserving devices are available, and they include reservoir cannulas, demand-

Patients with advanced COPD and a predominance of emphysema often experience progressive weight loss. The weight loss is multifactorial including a 15% to 25% increase in resting energy expenditure from elevated work of breathing and increased circulatory inflammatory cytokines, higher energy cost of daily activities and a reduced caloric intake(Barnes,2009;Di Francia et al,1994 as cited in Shapiro SD,2010). This leads to reduced muscle strength including weakness of respiratory muscles thus worsening the dyspnea.

should be given to all patients with COPD.

**11.2.5 Supportive management** 

i. Oxygen therapy:

ii. Nutrition:

Comprehensive pulmonary rehabilitation has been shown to improve exercise capacity, improve independence quality of life, decrease dyspnea, and decrease health care utilization and it may also reduce mortality (Celli et al.,1995 as cited in Shapiro SD,2010). Although airflow obstruction ( FEV1) is not improved, the effects of rehabilitation on health status ("quality of life") are generally much greater than seen with pharmacologic treatments (Finnerty et al,2001 as cited in Shapiro SD,2010). Pulmonary rehabilitation should be considered as an addition to medication therapy for symptomatic patients who have GOLD Stage II, III, or IV COPD.

Pulmonary rehabilitation program usually requires a team approach, including physicians, nurses, dietitians, respiratory therapists, exercise physiologists, physical therapists, occupational therapists, recreational therapists, cardiorespiratory technicians, pharmacists, and psychosocial professionals. This multidisciplinary approach emphasizes on patient and family education, smoking cessation, medical management (including oxygen and immunization), respiratory and chest physiotherapy, physical therapy with bronchopulmonary hygiene, exercise, and vocational rehabilitation and psychosocial support.

Exercise conditioning is the single most important aspect of rehabilitation and comprises of aerobic lower extremity endurance exercises and upper extremity exercise training to improve dyspnea and allow increased activities of daily life(ATS,1987). Breathing retraining techniques (eg, diaphragmatic and pursed-lip breathing) may improve the ventilatory pattern and may prevent dynamic airway compression (Celli,1991;Lotters,2002 as cited in Shapiro SD,2010).

#### **11.2.6 Treatment of respiratory failure**

i. Chronic Ventilatory Failure - Intermittent Noninvasive Ventilation :

The use of noninvasive mechanical ventilators is based on the concept that, in patients with severe COPD, the respiratory muscles are at the fatigue threshold. Resting the muscles provides time for "recovery" and prevents small increases in respiratory requirements from precipitating fatigue and perhaps acute respiratory failure. Due to lack of evidence of clinical benefit in several studies, the routine use of this form of support for COPD patients is not recommended at present(GOLD,2006).

	- a. Almitrine bismesylate a peripheral chemoreceptor agonist, significantly improves resting room air arterial pO2 in about 80% of stable COPD patients mainly from improved ventilation-perfusion relationships because almitrine enhances hypoxic pulmonary vasoconstriction by way of sympathetic efferent pathways(Bury et al.,1989;Romaldini et al.,1983;Weitzenblum et al.,1991 as cited in Shapiro SD,2010). Further evidence is needed in its support before it can be recommended for regular use in COPD (GOLD,2006).
	- b. Analeptic agents: The benefit of the analeptic agents, like acetazolamide, which stimulates respiration by acidifying plasma and cerebrospinal fluid(Skatruc &

Current Overview of COPD with Special Reference to Emphysema 147

Variable decrease in pulmonary function, and tachypnea are typical in acute exacerbations however, severe cases can lead to respiratory failure and death. Higher exacerbation frequency is associated with more loss of FEV1, impairment in quality of life and increase in

AECOPDs occur in clusters and patients with an AECOPD were at an increased risk of another attack in the 8 weeks following their initial episode(Hurst et al.,2009 as cited in Shapiro SD,2010). Viral and bacterial infections and environmental pollutants incite most of the acute exacerbations. The single best predictor of exacerbations was a history of exacerbations. Other predictors of frequent exacerbations were chronic cough and phlegm production, episodic wheezing, pneumonia, active smoking, exertional dyspnoea, lower lung function, advanced age, duration of COPD, history of antibiotic therapy, COPD-related hospitalization within the previous year and having one or more comorbidities (eg, ischemic heart disease, chronic heart failure, diabetes mellitus or gastroesophageal reflux)(Foreman et al.,2007 as cited in Shapiro SD,2010). Important differential diagnosis are

AECOPDs are a major reason for hospital admission for failure of outpatient treatment, marked increase in dyspnea, altered mental status, and increase in hypoxemia or hypercapnia and respiratory acidosis. Mild episodes may be managed as out-patient. Supplemental oxygen is a critical component of acute therapy. It should target an arterial oxygen tension (PaO2) of 60 to 70 mmHg(GOLD,2006). If the episode is severe, the patient may require ventilatory support in the form of either noninvasive or invasive positivepressure ventilation(GOLD,2006). A Cochrane review showed NIPPV reduces mortality, avoids endotracheal intubation, and decreased treatment failure(Lightowler et al.,2003 as

Pharmacological treatment of COPD includes bronchodilators, antibiotics, and steroids. Short-acting bronchodilators are the mainstay of therapy. Oral or parenteral steroids are indicated in the treatment of AECOPD and have been shown to shorten recovery time and improve outcome and reduce hospital stay. Most exacerbations are treated with full dose therapy (eg, prednisone 30 to 40 mg daily) for 7 to 10 days. Antibiotics have been shown to provide benefit in patients who present with dyspnea, increased purulence, and increased volume of sputum(Fagon et al,1990; Iyer & Murphy,2009 as cited in Shapiro SD,2010).

Several parameters correlate with prognosis in COPD, including forced expiratory volume in 1 second (FEV1), diffusion capacity for carbon monoxide (DLCO), blood gas measurements, body mass index (BMI), exercise capacity, clinical status and radiographic findings on CT scan. A widely used simple prognostication tool is the BODE index, which is based on the BMI, obstruction (FEV1), dyspnea (using Medical Research Council Dyspnea

The 6-min walk test (6MWT) remains the most popular test for the evaluation of exercise tolerance in COPD patients. It is simple and well standardised, but its interpretation criteria remain controversial. A distance of <361m also predicted mortality in patients with FEV1, 50% predicted. The 6MWT is currently used to evaluate the impact of treatment. The classical 54 m is defined as the minimal significant difference to detect benefit of treatment

heart failure, pulmonary thromboembolism, and pneumonia.

dyspnea with time.

cited in Shapiro SD,2010).

**12. Prognosis and follow-up** 

Scale), and exercise capacity (ie, 6-minute walk distance).

Dempsey,1983 as cited in Shapiro SD,2010), and medroxyprogesterone acetate, which directly acts on brainstem respiratory neurons, is not established for COPD patients. Clinical benefits are not established for these medications and their use to stimulate ventilation in COPD is not recommended(GOLD,2006).

### **11.2.7 Surgical intervention**

i. Lung Volume Reduction Surgery:

Various surgical approaches to improve symptoms and restore function in patients with emphysema have been described. Dr. Otto Brantigan pioneered resectional surgery in 1950s, but it was Cooper et al's work showing remarkable improvement in physical measures and quality of life measures in patients of COPD who underwent lung volume reduction surgery, generated tremendous interest in the procedure and led eventually to the National Emphysema Treatment Trial (NETT,1999). The NETT study found a substantial reduction in mortality and improvements in HRQOL and exercise capacity as a result of lung volume reduction surgery (LVRS) in properly selected patients(Pinto-Plata et al.,2007 as cited in Shapiro SD,2010). Caution is recommended in proper selection of patients as individuals with an FEV1 less than 20% predicted and either homogenous disease or a diffusion capacity of less than 20% predicted were at very high risk for mortality if treated surgically.

ii. Bullectomy:

Removal of giant bullae has been a standard approach in selected patients for many years. Giant bullae may compress adjacent lung tissue, reducing the blood flow and ventilation to the relatively healthy lung. Giant bullectomy can produce subjective and objective improvement in selected patients, ie, those who have bullae that occupy at least 30%—and preferably 50%—of the hemithorax that compress adjacent lung, with an FEV1 of less than 50% of predicted and relatively preserved lung function otherwise(Kinnear & Tattersfield,1990;Nickoladze,1992 as cited in Shapiro SD,2010).

iii. Lung transplantation:

Despite multiple difficulties and obstacles, single-lung transplant has become most common procedure of choice when transplantation is performed for emphysema. Available data suggest that lung transplantation offers improved function and HRQOL to patients with advanced COPD, but it is not clear that it offers any survival benefit(Marulli & Rea,2008;Stavem,2006 as cited in Shapiro SD,2010). Worldwide, COPD is the most common reason for lung transplantation. Current guidelines by the International Society of Heart and Lung Transplantation recommends referring A1PI individuals with COPD for transplantation in a scenario with the BODE index greater than 5, post-bronchodilator FEV1 <25 percent of predicted, resting hypoxemia(PaO2 <55 to 60 mmHg), hypercapnia, secondary pulmonary hypertension or accelerated decline in FEV1 (Orens et al.,2006 as cited in Shapiro SD,2010).

#### **11.2.8 Management of acute exacerbations of COPD (AECOPD)**

GOLD and WHO defines an exacerbation of COPD as an acute increase in symptoms beyond normal day-to-day variation which includes worsening of cough, increase in phlegm production, change in phlegm quality, and increase in dyspnea(GOLD,2006).

Various surgical approaches to improve symptoms and restore function in patients with emphysema have been described. Dr. Otto Brantigan pioneered resectional surgery in 1950s, but it was Cooper et al's work showing remarkable improvement in physical measures and quality of life measures in patients of COPD who underwent lung volume reduction surgery, generated tremendous interest in the procedure and led eventually to the National Emphysema Treatment Trial (NETT,1999). The NETT study found a substantial reduction in mortality and improvements in HRQOL and exercise capacity as a result of lung volume reduction surgery (LVRS) in properly selected patients(Pinto-Plata et al.,2007 as cited in Shapiro SD,2010). Caution is recommended in proper selection of patients as individuals with an FEV1 less than 20% predicted and either homogenous disease or a diffusion capacity

stimulate ventilation in COPD is not recommended(GOLD,2006).

of less than 20% predicted were at very high risk for mortality if treated surgically.

Tattersfield,1990;Nickoladze,1992 as cited in Shapiro SD,2010).

**11.2.8 Management of acute exacerbations of COPD (AECOPD)** 

Removal of giant bullae has been a standard approach in selected patients for many years. Giant bullae may compress adjacent lung tissue, reducing the blood flow and ventilation to the relatively healthy lung. Giant bullectomy can produce subjective and objective improvement in selected patients, ie, those who have bullae that occupy at least 30%—and preferably 50%—of the hemithorax that compress adjacent lung, with an FEV1 of less than 50% of predicted and relatively preserved lung function otherwise(Kinnear &

Despite multiple difficulties and obstacles, single-lung transplant has become most common procedure of choice when transplantation is performed for emphysema. Available data suggest that lung transplantation offers improved function and HRQOL to patients with advanced COPD, but it is not clear that it offers any survival benefit(Marulli & Rea,2008;Stavem,2006 as cited in Shapiro SD,2010). Worldwide, COPD is the most common reason for lung transplantation. Current guidelines by the International Society of Heart and Lung Transplantation recommends referring A1PI individuals with COPD for transplantation in a scenario with the BODE index greater than 5, post-bronchodilator FEV1 <25 percent of predicted, resting hypoxemia(PaO2 <55 to 60 mmHg), hypercapnia, secondary pulmonary hypertension or accelerated decline in FEV1 (Orens et al.,2006 as cited

GOLD and WHO defines an exacerbation of COPD as an acute increase in symptoms beyond normal day-to-day variation which includes worsening of cough, increase in phlegm production, change in phlegm quality, and increase in dyspnea(GOLD,2006).

**11.2.7 Surgical intervention** 

ii. Bullectomy:

iii. Lung transplantation:

in Shapiro SD,2010).

i. Lung Volume Reduction Surgery:

Dempsey,1983 as cited in Shapiro SD,2010), and medroxyprogesterone acetate, which directly acts on brainstem respiratory neurons, is not established for COPD patients. Clinical benefits are not established for these medications and their use to Variable decrease in pulmonary function, and tachypnea are typical in acute exacerbations however, severe cases can lead to respiratory failure and death. Higher exacerbation frequency is associated with more loss of FEV1, impairment in quality of life and increase in dyspnea with time.

AECOPDs occur in clusters and patients with an AECOPD were at an increased risk of another attack in the 8 weeks following their initial episode(Hurst et al.,2009 as cited in Shapiro SD,2010). Viral and bacterial infections and environmental pollutants incite most of the acute exacerbations. The single best predictor of exacerbations was a history of exacerbations. Other predictors of frequent exacerbations were chronic cough and phlegm production, episodic wheezing, pneumonia, active smoking, exertional dyspnoea, lower lung function, advanced age, duration of COPD, history of antibiotic therapy, COPD-related hospitalization within the previous year and having one or more comorbidities (eg, ischemic heart disease, chronic heart failure, diabetes mellitus or gastroesophageal reflux)(Foreman et al.,2007 as cited in Shapiro SD,2010). Important differential diagnosis are heart failure, pulmonary thromboembolism, and pneumonia.

AECOPDs are a major reason for hospital admission for failure of outpatient treatment, marked increase in dyspnea, altered mental status, and increase in hypoxemia or hypercapnia and respiratory acidosis. Mild episodes may be managed as out-patient. Supplemental oxygen is a critical component of acute therapy. It should target an arterial oxygen tension (PaO2) of 60 to 70 mmHg(GOLD,2006). If the episode is severe, the patient may require ventilatory support in the form of either noninvasive or invasive positivepressure ventilation(GOLD,2006). A Cochrane review showed NIPPV reduces mortality, avoids endotracheal intubation, and decreased treatment failure(Lightowler et al.,2003 as cited in Shapiro SD,2010).

Pharmacological treatment of COPD includes bronchodilators, antibiotics, and steroids. Short-acting bronchodilators are the mainstay of therapy. Oral or parenteral steroids are indicated in the treatment of AECOPD and have been shown to shorten recovery time and improve outcome and reduce hospital stay. Most exacerbations are treated with full dose therapy (eg, prednisone 30 to 40 mg daily) for 7 to 10 days. Antibiotics have been shown to provide benefit in patients who present with dyspnea, increased purulence, and increased volume of sputum(Fagon et al,1990; Iyer & Murphy,2009 as cited in Shapiro SD,2010).
