REBUTTAL FROM DR. WEDZICHA

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Dr. MacNee provides an interesting account of his reasons why airway infection does not affect decline of lung function in COPD. However, his arguments are based on studies that are now rather dated and performed in the 1950s to 1970s. Central to the debate is the landmark study of Fletcher and colleagues, who suggested that chronic mucous hypersecretion and progressive airflow obstruction were separate entities and there was no relation observed between exacerbations and decline in lung function (1).

Airway infection can affect lung function decline either through airway bacterial colonization increasing airway inflammation in the stable state (2) or by infective exacerbations not recovering to baseline function (3). However, the study reported by Fletcher and colleagues was performed in patients with relatively mild COPD, who would not be expected to have frequent bacterial colonization, despite being sputum producers. Thus this study was unlikely to show a relation between airway infection and decline in lung function (1). Exacerbation rates also increase with worsening lung function and thus exacerbations are relatively few in this patient group. In this study, as in most studies of COPD exacerbations previously reported, exacerbation rates were obtained from patients' recall or from questionnaires and not rigorously defined, and few studies have prospectively measured exacerbation frequency. Only 50% of COPD exacerbations are reported to healthcare professionals and thus retrospective information collected on exacerbations will underestimate their frequency (4). Dr. MacNee also states that only a minority of patients with COPD exacerbations do not recover, although we have shown that in 25% of exacerbations, peak flow measured on a daily basis did not recover at 35 days and thus this nonrecovery may contribute to decline in lung function (3).

However, we both agree on the important issue that carefully designed studies of appropriate patients with more severe disease are required to evaluate the role of airway infection in lung function decline, especially as inhaled steroids have failed to show an effect (5). Although prophylactic antibiotics were not effective in the 1950s, antibiotics are now available that are specifically active against airway bacteria and the subject requires revisiting. With the increased understanding of the mechanisms responsible for decline in lung function, we may at last find new therapies to improve the prognosis of patients with COPD.

	References

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1. Fletcher CM, Peto R, Tinker CM, Speizer FE. The natural history of chronic bronchitis and emphysema. Oxford: Oxford University Press; 1976.

2. Hill AT, Campbell EJ, Hill SL, Bayley DL, Stockley RA. Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med 2000; 109: 288-295 [Medline].

3. Seemungal TAR, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with COPD. Am J Respir Crit Care Med 2000; 161: 1608-1613 [Abstract/Free Full Text].

4. Seemungal TAR, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157: 1418-1422 [Abstract/Free Full Text].

5. Burge PS, Calverley PMA, Jones PW, Spencer S, Anderson UA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. Br Med J 2000; 320: 1297-1303 [Abstract/Free Full Text].