**11.2.4 Adjuvant pharmacologic agents**

142 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

Inhaled corticosteroids are only minimally absorbed and therefore systemic adverse effects are limited. Local effects include oral candidiasis and dysphonia(Pauwels et al,1999 as cited in Shapiro SD,2010). Systemic effects include increased bruising and reduced bone density, and possible susceptibility for pneumonia(Calverley et al.,2007 as cited in Shapiro SD,2010). Appropriate caution and monitoring is recommended although the clinical importance of

Systemic steroids have been widely used in the treatment of acute exacerbation of COPD. A meta-analysis concluded that systemic corticosteroids significantly reduced treatment failure and need for additional medical treatment and increased the rate of improvement in lung function and dyspnea over the first 72 hours(Rice et al,2000 as cited in Shapiro SD,2010). The use of oral steroids in persons with chronic stable COPD is not recommended given the adverse effect profile, which includes hypertension, glucose intolerance, osteoporosis, fractures, and cataracts, among others(Burge et al,2003 as cited in Shapiro

Inhaled glucocorticoids are typically used in combination with a long-acting bronchodilator for patients in GOLD stage III-IV, who have significant symptoms or repeated exacerbations, despite an optimal bronchodilator regimen. Steroids may be introduced earlier if there are signs of inflammation or an asthmatic component to the COPD(Ferguson et al.,2008 as cited in Shapiro SD,2010). In the TORCH (Toward a Revolution in COPD Health) trial involving patients with moderate to severe COPD, salmeterol plus fluticasone significantly improved the lung function, health status, and the rate of exacerbations compared to placebo, salmeterol alone, or fluticasone alone(Calverley et al.,2007). It also minimally decreased mortality compared to placebo (10.3 versus 12.6 percent, hazard ratio 0.81, 95% CI, 0.67-0.98). The Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) trial included 1323 patients with stable, mostly severe COPD and results failed to show significant benefits of combining inhaled steroids with

"Triple inhaler therapy" - with a long-acting beta agonist plus an inhaled glucocorticoid plus a long-acting anticholinergic is often used in refractory COPD patients. This approach is supported by some studies(Tashkin et al.,2008). These data are insufficient to warrant a change in the current guidelines in which the first step is initiation of a long-acting bronchodilator alone and then if response is inadequate or disease advances, to introduce a

Phosphodiesterase-4 (PDE-4) inhibition decreases inflammation and promotes airway smooth muscle relaxation. Cilomilast and roflumilast are highly specific, oral, secondgeneration PDE-4 inhibitors being considered for use in patients with asthma and COPD(Gamble et al.,2003;Profita et al.,2003 as cited in Shapiro SD,2010). Recent trials have supported their inclusion in COPD combination treatment plans(Calverly et al.,2009;Chong et al.,2011as cited in Shapiro SD,2010). Several randomized, double-blind, placebocontrolled multicenter trials revealed increased FEV1 (*P* < .0001) and the rate of COPD exacerbations was reduced by 17% (*P* <.0003) in patients who received roflumilast compared with placebo. Additional studies are necessary before PDE-4 inhibitors can be recommended

combination of long-acting beta agonist plus an inhaled glucocorticoid.

these effects remains uncertain.

LABAs(Wedzicha et al.,2008).

ii. Phosphodiesterase inhibitors :

for routine use in patients with stable COPD.

SD,2010).

i. Augmentation therapy for A1PI deficiency:

The treatment strategies for A1PI deficiency involve reducing the neutrophil elastase burden, primarily by smoking cessation, and augmenting the levels of A1PI. Available augmentation strategies include pharmacologic attempts to increase endogenous production of A1PI by the liver (ie, danazol, tamoxifen) or administration of purified A1PI by periodic intravenous infusion or by inhalation. Tamoxifen can increase endogenous production of A1PI to a limited extent, so this may be beneficial in persons with the PISZ phenotype.

Intravenous augmentation therapy is the only available approach that can increase serum levels to greater than 11 mmol/L, the protective threshold. Studies show that the infusions can maintain levels of more than 11 mmol/L, and replacement is administered weekly (60 mg/kg), biweekly (120 mg/kg), or monthly (250 mg/kg) (Buist et al,1989;Sandhaus,2009 as cited in Shapiro SD,2010). Uncontrolled observations of patients suggest that the FEV1 may fall at a slower rate in patients who receive A1PI replacement. It seems reasonable to weigh carefully the advantages and disadvantages of augmentation therapy and to reach a decision jointly with elderly persons or with those with severe lung function impairment (FEV1 values < 0.8 L)(Buist et al,1989 as cited in Shapiro SD,2010).

ii. Mucoactive and expectorant agents:

Mucolytic agents like acetylcysteine, dornase(DNAse), guaifenesin reduce sputum viscosity and improve secretion clearance. however, studies have failed to justify a role for these medications in management of COPD(Decramer et al,2005 as cited in Shapiro SD,2010). The role of oral expectorants like guaifenesin in promoting mucous clearance in COPD patients remains controversial.

iii. Antibiotic therapy:

Chronic infection or colonization of the lower airways with *S pneumoniae, H influenzae,* and/or *Moraxella catarrhalis* is common and in later stage disease, with Gram-negative organisms such as *Pseudomonas*. Macrolides like erythromycin, may have additional antiinflammatory effects. Patients whose COPD is associated with, bronchiectasis may benefit from chronic antibiotic therapy. However, at present, chronic antibiotics are not recommended for stable COPD management.

The use of antibiotics for the treatment of acute COPD exacerbations and pneumonias is well supported (Adams et al.,2008). The patients who benefited most from antibiotic therapy were those with exacerbations that were characterized by at least 2 of the following: increases in dyspnea, sputum production, and sputum purulence (The Winnipeg criteria).

iv. Vaccine prophylaxis:

Infection is a common cause of COPD exacerbation and vaccination is the most effective way of prophylaxis. Pneumococcal polysaccharide vaccine should be offered to patients

Current Overview of COPD with Special Reference to Emphysema 145

Improved nutrition can restore respiratory and general muscle strength and endurance

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

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

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

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

b. Analeptic agents: The benefit of the analeptic agents, like acetazolamide, which stimulates respiration by acidifying plasma and cerebrospinal fluid(Skatruc &

(Wilson,1986,Whittaker et al,1990 as cited in Shapiro SD,2010).

iii. Pulmonary Rehabilitation:

Stage II, III, or IV COPD.

Shapiro SD,2010).

**11.2.6 Treatment of respiratory failure** 

is not recommended at present(GOLD,2006).

use in COPD (GOLD,2006).

ii. Altering Ventilatory Control

i. Chronic Ventilatory Failure - Intermittent Noninvasive Ventilation :

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 should be given to all patients with COPD.
