© 2004 American Thoracic Society
Does Early Treatment of Exacerbation Improve Outcome in Chronic Obstructive Pulmonary Disease?University of Pisa Pisa, Italy Chronic obstructive pulmonary disease (COPD) is characterized by chronic respiratory symptoms, progressive decline in pulmonary function, and recurrent acute exacerbations. Although a standardized definition is not available, an exacerbation of COPD is usually characterized by an increase in respiratory symptoms and deterioration of pulmonary function and gas exchange, which frequently cause respiratory failure (1). Depending on severity, exacerbations often lead to hospitalization and place the patient at increased risk of mortality. In severe COPD, inpatient mortality during an exacerbation reaches up to 11% (2). Exacerbations are considered a marker of disease severity, and have been the main outcome variable of many recent interventional studies (3, 4). Indeed, frequency and severity of exacerbations are associated with functional and biological markers of the disease, such as worse pulmonary function, more pronounced airway inflammation, and more frequent bacterial colonization (5, 6). Exacerbations contribute to a poor quality of life (7) and patients are at high risk of mortality in the year that follows a severe exacerbation (2). For all these reasons, prevention and prompt, aggressive treatment of each exacerbation are mandatory. The article by Wilkinson and coworkers (8) in this issue of the Journal (pp. 1298–1303) raises an important question: can early recognition, and prompt treatment, of an exacerbation of COPD lead to a better prognosis? To date, no consistent data have been reported about this issue. The authors collected data from a large database of patients with COPD, who recorded daily symptoms and peak expiratory flow to detect early signs of an exacerbation. They defined the beginning of acute exacerbation as the onset or the increase of two major, or one major and one minor, symptoms for two consecutive days. The duration of an exacerbation was computed as the number of days required to get back to the mean baseline daily symptom score. According to previous observations by the same (9) or by other authors (10), the average duration of an exacerbation was about 10 days. The article by Wilkinson and coworkers shows that a quicker recognition of exacerbation, with more rapid referral to the physician, and, consequently, earlier treatment, leads not only to a briefer exacerbation, but also to a lower rate of hospitalization and better quality of life. This observation has some potential consequences. First, the reduction in the duration of exacerbation and hospitalization rate is relevant in being associated with a better quality of life. Also, considering the risk of complications during exacerbations (2) and the high direct and indirect costs of exacerbations, particularly in terms of loss of number of active days and of consumption of health resources (11), reducing the duration and improving the prognosis of exacerbations can be considered as major outcomes in the treatment of COPD. The positive consequences on health status might even be greater if we extrapolate these data to more severe patients, in whom hospitalization rate and risk of acute respiratory failure and complications are usually higher. Wilkinson and coworkers evaluated mainly patients with mild to moderate exacerbations, and hospitalization rate in these well trained patients was thus rather low (6.7%). If these observations are confirmed for patients with more severe COPD, the impact would be more relevant. This study has other potential consequences. If each exacerbation causes persistent airway damage that may contribute to a more rapid decline in pulmonary function over time, then earlier treatment resulting in an exacerbation of shorter duration might slow the accelerated decline of FEV1 in these patients. The association between exacerbations of COPD and faster decline in FEV1 has been the subject of several studies, some with inconsistent results (12). Donaldson and coworkers recently demonstrated that a high number of exacerbations (greater than 2.9 episodes per year) were associated with a greater decrease in FEV1 over 3 years of follow-up (13). This observation can be explained by the fact that patients with faster decline in FEV1 are more susceptible to exacerbation of the disease. Another possible explanation is that every exacerbation may lead to further irreversible decrease in pulmonary function, thus contributing to progression of the disease. If both hypotheses are true, patients with COPD are located in a deep vicious circle. This issue cannot be clarified without a well-designed prospective study. Considering, however, that consistent results have not yet been obtained through the use of long-term regular pharmacological treatment in preventing FEV1 decline (14), the possibility of reducing the risk of disease progression by an early intervention for an exacerbation is particularly interesting. Long-term prognosis of patients who recovered more quickly from a severe exacerbation of COPD when treated with noninvasive mechanical ventilation, seems to support this hypothesis (15). The definition of exacerbation and assessment of its severity is poor in the article by Wilkinson and coworkers, as in other similar studies on exacerbations. Pulmonary function measurement and blood gas levels were not available in a large group of patients, and severity of exacerbation was evaluated only with a semiquantitative symptom score. The definition of the recovery time is incomplete in many studies (8–10) because only symptoms and peak flow, and not FEV1 or blood gases, have been evaluated. More objective data are required to assess whether early detection and treatment of exacerbation really lead to a reduction of persistent functional or structural airway impairment. A practical implication from the study of Wilkinson and coworkers is that patients with COPD should be trained in early recognition of an exacerbation, and that both general physicians and pulmonary specialists should promptly and aggressively treat each exacerbation. This point should be strongly emphasized in future guidelines (16). Moreover, prevention of an exacerbation by regular pharmacologic treatment can be useful and may indirectly halt progression of the disease. FOOTNOTES Conflict of Interest Statement: P.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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