From the Centre for Respiratory Medicine, University College London.
Correspondence to: Jadwiga A. Wedzicha, MD, Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill St, Hampstead, London, NW3 2PF, England; e-mail: email@example.com
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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COPD is a progressive, chronic inflammatory disorder caused by exposure to noxious agents. The condition is associated with considerable heterogeneity and progressive disability leading to increased mortality. Measurement of FEV1 is key in establishing the diagnosis of COPD and assessing its severity both as a single measure or in multidimensional tools. Decreasing FEV1 has been associated with increased respiratory and cardiovascular mortality.1,2 The classic definition of COPD describes progressive FEV1 decline over time, but we now know that this measure is variable3,4 and affected by the development of COPD exacerbations.5 Studies have shown that patients with COPD may, indeed, show rapid decline in FEV1, decline similar to the normal population, or even no actual FEV1 decline over time.4
Interventions used in COPD target symptoms and also prevent future risk, mainly by reducing the rate and severity of COPD exacerbations. However, these interventions are mainly aimed at patients with established disease; when patients present with symptoms, they already have considerable impairment of lung function. To date, no pharmacologic intervention has been shown to reduce disease progression in COPD. There is little information on the mechanisms of early development of COPD or lung function decline, especially during the asymptomatic phase or when smokers with normal lung function may just develop winter infections or chronic bronchitis. It is precisely at this stage that intervention with an appropriate antiinflammatory agent may be the most effective at preventing the progressive onset of COPD.
In this issue of CHEST (see page 695), Petersen and colleagues6 describe an analysis from the Lovelace Smokers Cohort (LSC) in 1,170 subjects without a spirometric diagnosis of COPD. Ever smokers were included if regular spirometric readings were taken over a minimum of 36 months. Patients were categorized as rapid decliners when the FEV1 decline was ≥ 30 mL/y; normal decliners, with FEV1 decline of 0 to 29.9 mL; or no decline, when there was improvement in FEV1 during the follow-up. The original LSC cohort included an intentional predominance of women, as the prevalence of COPD in women has increased, though generally there is little evidence of any effects on FEV1 decline by sex in previous longitudinal studies.3,4
The primary adjusted multivariable analyses show that the subjects who were rapid decliners were more likely to develop COPD after the 3-year period and, thus, smokers with normal FEV1 need to be observed and followed to obtain their personal pattern of FEV1 decline. Patients with normal or no decline were less likely to progress to classic COPD. However, the sample size from the LSC cohort was relatively small for this type of longitudinal analysis, and total follow-up time is not clear. Thus, the large size of the no decliner, ever-smoker group may be explained by a short initial follow-up of 3 years. The degree of smoking did not influence FEV1 decline or the ultimate development of COPD.
Patients who are rapid decliners must be targeted for therapies, though currently there is little information on the airway inflammatory mechanisms associated with ever smokers who have normal lung function and are showing rapid FEV1 decline. The study also evaluated the effect of concomitant medications on lung function, which were mainly for comorbid cardiovascular disease, hypertension, and diabetes.
The intriguing result from this study shows that the use of angiotensin-converting enzyme (ACE) inhibitors significantly reduced the rapid FEV1 decline. Thus, this suggests that an ACE inhibitor may actually protect against the development of COPD and also alter its natural history. This observation needs to be confirmed, however, in larger representative cohorts. The mechanisms for the observation need to be studied, especially as ACE inhibitors have actions ranging from those local to the lung to systemic actions. As the authors suggest, if this effect is correct, then the likely mechanism is an antiinflammatory action on the airways7 or some action on vascular endothelial dysfunction.8
The message from this article is that before the development and diagnosis of COPD, there is a period of rapid FEV1 decline in ever smokers. We need to further evaluate therapies that can reduce the rapid decline in lung function when smokers are still healthy. Thus, identification of these subjects is a key target for screening programs so we can reduce the significant morbidity and mortality associated with this common and disabling disease.
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