© 2003 American Thoracic Society
Stopping inhaling corticosteroids in COPDTo the Editor:We read with interest the COPE study, which determined that there is an increased COPD exacerbation rate when subjects are taken off of high-dose inhaled corticosteroids (1). The COPD subjects in the study all had an FEV1 between 25–80% predicted with a prebronchodilator FEV1/inspiratory vital capacity (IVC) ratio of 60% or less. Reversibility of FEV1 for inclusion in the COPE study needed to be less than 12% of predicted after 80 µg of ipratropium bromide via a metered dose inhaler with aerochamber. Traditionally, significant reversibility is defined using ß2-agonist inhalation and at least a 12% improvement in FEV1 from baseline and at least a 200 ml improvement in absolute FEV1 (2, 3). Using less than 12% of predicted as a bronchodilator response could include some subjects who would be greater than 12% of baseline using the American Thoracic Society guidelines (4). In addition, it is possible that some subjects would respond differently with the use of a ß2-agonist instead of an anticholinergic. This suggests that some of the COPE study patients probably have a significant degree of reversibility if classically defined. Therefore, it is possible that some of the patients had asthmatic characteristics that would predispose them toward an exacerbation of lung disease on withdrawal from inhaled corticosteroids as is seen in the asthmatic population. Given the above, we were wondering why reversibility was not determined with ß2-agonist therapy, since that is the traditional method. Are there studies validating that anticholinergic reversibility gives the same or similar information as ß2-agonist reversibility?
Harlem Hospital Center Columbia University New York, New York REFERENCES
From the Authors: We appreciate the comments of Drs. Pesola and Dogra regarding our article in the November 2002 issue of AJRCCM (1) and would like to address their concerns. Their first concern pertains to our use of a cut-off point for reversibility of 12% of predicted, compared with 12% of baseline, which they state is used in the American Thoracic Society (ATS) guidelines (2). Use of the first would lead to a higher probability to include patients with asthmatic characteristics.
The European Respiratory Society lung function guidelines (3) follow the study of Brand and colleagues (4), which compared different expressions of bronchodilator response with respect to dependence on initial FEV1. They conclude that the
Their second concern is related to the use of ipratropium bromide for testing reversibility, instead of a ß2-agonist. In a study by Hadcroft and Calverley (5), no significant differences were found in the magnitude of change in FEV1 after either salbutamol or ipratropium given singly or in combination in COPD patients. One recent study in patients with asthma (6) concluded that both salbutamol and ipratropium are effective bronchodilators in patients with asthma, although the overall response to salbutamol appears to be superior in asthma. However, in older patients there was less difference in the reaction to one or other of the two drugs. Since the patients in our study are relatively old (mean age 64), the type of bronchodilator seems to be less important. Furthermore, all our patients had a clinical diagnosis of stable COPD, as defined by ATS criteria without a history of asthma as checked in their hospital records. We choose to test reversibility after inhalation of a high dose of ipratropium bromide via a metered dose inhaler with aerochamber since ipratropium is the first bronchodilator of choice in COPD in the Netherlands because it is virtually without systemic side effects. As mentioned by Pesola and Dogra, it is possible that some subjects would respond differently to the use of a ß2-agonist compared with an anticholinergic, but this is also the case vice versa. Even when asthma is excluded, clinical COPD will always include some asthmatic features, which are hard to detect by simple reversibility testing.
Medisch Spectrum Twente Enschede, the Netherlands University Medical Centre Nijmegen, the Netherlands REFERENCES
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FEV1 predicted is the most useful method of expressing bronchodilator response, both for clinical and research purposes. Also, the ATS statement (