REBUTTAL FROM DR. CALVERLEY

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It is clear that Peter Barnes and I have very similar views about this topic although his long clinical experience of bronchial asthma may lead him to expect more dramatic spirometric improvements. The inability of inhaled corticosteroids to reduce some inflammatory markers of neutrophil activity may explain why inhaled corticosteroids do not affect the rate of decline in FEV₁. However, one set of mediators, no matter how plausible, cannot adequately describe all the inflammatory processes occurring in COPD particularly during exacerbations where other cellular components may be more important (1).

It is convenient but optimistic to assume that any patient having a bronchodilator response exceeding an arbitrary threshold has coexisting asthma. As we and others (2, 3) have shown, treating corticosteroid-responsive patients produces worthwhile clinical benefits but still leaves them with significant persistent airflow limitation. These patients are likely to be diagnosed as COPD initially, and omitting inhaled corticosteroids would be a disservice.

Exacerbations of COPD are distressing for the patient and expensive to treat; their reduction is a desirable treatment endpoint. They occurred in significant numbers in only two trials of inhaled corticosteroids (4, 5) and in both treatments reduced their severity and frequency of exacerbations. This was important in explaining how treatment reduced the impact of the illness on the patients' general health. Whether the financial cost of doing this is thought to be worthwhile in a condition in which other ways of improving patient well-being are limited, is something for physicians, third party payers, governments and the pharmaceutical industry to resolve together.

Arguments about adverse effects will need firmer data than speculation about potential risks to patients where experience with these agents over many years in older people has not suggested any particular hazard.

Studying the effects of inhaled corticosteroids in COPD has provided important new knowledge about this disease and its impact on patients. Now we have data about who is likely to benefit and who is not. The task ahead is to ensure that this therapy is given rationally and that better treatments are developed and studied in this common and serious illness.

	References

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1. Saetta, M., A. DiStefano, P. Maestrelli, G. Turato, M. P. Ruggieri, A. Roggeri, P. Calcagni, C. E. Mapp, A. Ciaccia, and L. M. Fabbri. 1994. Airway eosinophilia in chronic bronchitis during exacerbations. Am. J. Respir. Crit. Care Med. 150: 1646-1652 [Abstract].

2. Nisar, M., M. Walshaw, J. E. Earis, M. G. Pearson, and P. M. Calverley. 1990. Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease. Thorax 45: 190-194 [Abstract/Free Full Text].

3. Davies, L., M. Nisar, M. G. Pearson, R. W. Costello, J. E. Earis, and P. M. A. Calverley. 1999. Oral corticosteroid trials in the management of stable chronic obstructive pulmonary disease. Quart. J. Med. 92: 395-400 .

4. Burge, P. S.. 1999. EUROSCOP, ISOLDE and the Copenhagen City Lung Study. Thorax 54: 287-288 [Free Full Text].

5. Paggiaro, P. L., R. Dahle, I. Bakran, L. Frith, K. Hollingworth, and J. Efthimiou. 1998. Multicentre randomized placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. Lancet 351: 773-780 [Medline].