COPD series: Dr Wilcox replies

Current evidence-based guidelines, including those of the Canadian Thoracic Society,[1] advocate long-acting bronchodilators for symptomatic COPD patients and the combination of inhaled corticost­eroids (ICS) and long-acting ß2 agonists (LABA) and long-acting anticholinergics (LAAC) for those with more advanced disease and more frequent exacerbations.

Dr Beever is correct to question the strength of these recommendations given that there has not been an unequivocal survival benefit yet demonstrated (17% relative risk or 2.6% absolute risk reduction for salmeterol/fluticasone,[2] not quite reaching the P<.05 level of significance) and the safety concerns raised. 

COPD patients receiving ICS do seem to have a higher pneumonia risk although, interestingly, not an increased exacerbation frequency or mortality. The larg­est study evaluating (a) ICS/LABA[2] reported reductions in exacerbation frequency and improved health status and lung function; and (b) ICS/ LAAC[3] found improved quality of life and lung function as well as reduced hospitalization rates. These represent the basis for the recommendations for these combination agents in COPD.

The data for monotherapy or combined LABA/LAAC in COPD are arguably less robust. That broncho­dilators might have a role in an airway disorder that is largely irreversible might not seem intuitive. Nevertheless, there is a body of evidence that LAAC improve exercise capacity and reduce dyspnea with exercise.[4]

Similar data exist for LABA for exercise; however, other studies have been contradictory as is summarized in the Canadian guidelines.[1] In our article we provide a physiological rationale for this symptomatic improvement, namely the reduction of air trapping and hyperinflation with exercise in COPD patients receiving these agents. 

The attenuation of the adverse mechanical effects of hyperinflation with consequent decreases in the work of breathing subtend the improvements in exercise capacity and dyspnea. Another benefit that defies easy explanation, but one that has clinical relevance, is the observation of re­duced exacerbation rates for LABA and LAAC.

Extrapolation from guidelines clearly is useful, but as Dr Beever alludes, one must make individual cost-benefit analyses when managing our patients. Benefits may not necessarily accrue to all patients and thus, particularly with less severe COPD patients, ongoing treatment should be prioritized for those who truly manifest functional benefit. Our patients are already routinely making these judgments.

—Pearce Wilcox, MD
Vancouver

References

1. O’Donnell DE, Aaron S, Bourbeau J, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease—2007 update. Can Respir J 2007;14:5B-32B.
2. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-789.
3. Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: A randomized trial. Ann Int Med 2007;146:545-555.
4. O’Donnell DE, Flüge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea, and exercise tolerance in COPD. Eur Respir J 2004;23:832-840.