COPD: Pathogenesis, Epidemiology, and the Role of Cigarette Smoke

The diagnosis of COPD is based on pulmonary function testing. All smokers with dyspnea or symptoms of chronic bronchitis should undergo pre- and post-brochodilator pulmonary function testing. A reduction in expired airflow is the sina qua non for the diagnosis of COPD. Hence, pulmonary function testing is the cornerstone of establishing the diagnosis and is fundamental in assessing its severity and in predicting mortality. The spirometric standard for COPD is a persistent or permanent reduction of FEV₁/FVC below a fixed ratio of 0.7. A growing consensus is that, since patients with severe airflow obstruction may be unable to achieve complete exhalation during a forced expiratory maneuver, measurement of FEV₆(forced expiratory volume at six seconds) may be an adequate surrogate for FEV₁/FVC.

Severity of COPD is determined by the magnitude of the reduction in FEV₁ compared with normative values based on height, gender, race, and age. Since aging results in a disproportionate decrease of FEV₁ relative to FVC, spirometrically defined COPD becomes prevalent in healthy non-smokers who live long enough. Accordingly, some have suggested using the lower limit of normal (LLN) for FEV₁/FVC, defining values that comprise the lowest 5 percent of the population as abnormal.

However, this approach does not appear to improve markedly the diagnosis of COPD in otherwise asymptomatic individuals. In fact, evaluation of a population-based cohort indicated that prediction of the rate of subsequent hospitalization for respiratory reasons was higher using the fixed-ratio method than it was using the LLN-based approach. (Presumably, the latter approach is more reflective of indolent disease in asymptomatic individuals.) In addition, post-bronchodilator measurements are preferred in defining obstruction in order to prevent misclassification of reversible disease. Many older, population-based studies did not assess post-bronchodilator measures.

Current guidelines from the Global Initiative on Obstructive Lung Disease (GOLD), which use the fixed-ratio method (FEV₁/FVC <0.7) to define airway obstruction, stress the use of post-bronchodilator measurements. Although, in order to avoid overlap with asthma, studies of COPD commonly exclude patients with significant reversibility, those with significant airflow obstruction despite partial reversibility have COPD. In fact, patients with fixed expiratory airflow obstruction commonly demonstrate some reversibility that varies between physician visits. Furthermore, a significant response to methacholine following development of fixed airflow obstruction in COPD is common despite absence of a history of childhood asthma. However, a positive methacholine challenge test or documentation of reversible airflow obstruction does not reliably predict who among asymptomatic smokers will develop COPD with continued smoking.

Since pulmonary fibrosis is more prevalent in smokers, combined pulmonary fibrosis and emphysema (CPFE) may sometimes be present with attendant "pseudo-normalization" of spirometry and lung volumes. For this reason, further work-up of a low DLCO noted in the absence of clear obstructive lung disease may be an indication of the need for a high-resolution chest CT scan.

Once the diagnosis of COPD has been established, patients with severe disease (GOLD Stage IV, FEV₁< 30% predicted; see below) may benefit from a test for exercise-associated desaturation or a six-minute walk test. The BODE index, a tool that incorporates measurements of body mass index (B), airflow obstruction (O), dyspnea (D), and exercise capacity (E), utilizes the six-minute walk distance, in conjunction with other common measurements (FEV₁, body mass index, and Medical Research Council Dyspnea Score), to predict survival in COPD.

_{Reposted with permission from Decision Support in Medicine, LLC.}