Chronic Cough, Phlegm in Young Adults Predict Increased Risk of Developing COPD


COPDJanuary 8, 2006 — Independent of smoking, chronic cough and phlegm in young adults are strong predictors of increased risk of developing chronic obstructive pulmonary disease (COPD), according to the results of a study reported in the January 1 issue of the American Journal of Respiratory and Critical Care Medicine.

"The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results," write Roberto de Marco, MD, of the University of Verona in Italy, and colleagues. "The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have introduced a stage 0 (normal spirometry, but presence of chronic cough or phlegm) in the COPD staging system as a tool to identify subjects at risk of developing the disease later in life."

From 1991 to 2002, the investigators followed up an international cohort of 5002 subjects without asthma enrolled in the European Community Respiratory Health Survey II (ECRHS II). Age range was 20 to 44 years, and subjects had normal lung function, defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of 70% or greater. Incident cases of COPD were defined as those with an FEV1/FVC ratio of less than 70% at the end of follow-up, but who did not report a clinician diagnosis of asthma during follow-up.

The incidence rate of COPD was 2.8 cases/1000 per year (95% confidence interval [CI], 2.3 - 3.3). After adjustment for smoking habits and other potential confounders, chronic cough with phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17 - 2.93). However, dyspnea did not predict COPD (IRR, 0.98; 95% CI, 0.64 - 1.50). Compared with asymptomatic subjects, those who reported chronic cough with phlegm both at baseline and at follow-up had a nearly 3-fold increased risk of developing COPD (IRR, 2.88; 95% CI, 1.44 - 5.79).

"The incidence of COPD is substantial even in young adults," the authors write. "The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits."

Study limitations include the use of prebronchodilator spirometric values for defining COPD instead of postbronchodilator values, as suggested by the GOLD guidelines; only 2 measurements of lung function during the 9-year study period; and the GOLD definition for airflow obstruction rather than the new American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines definition and participation rate being quite low in some centers.

"In our large, international cohort of young adults, the incidence of COPD is substantial," the authors conclude. "The presence of chronic cough/phlegm is an early marker of COPD in a nonignorable proportion of patients, independently of smoking habits. In clinical practice, the persistence of chronic symptoms should be accurately investigated."

The European Commission supported this study. The authors have disclosed financial relationships with Novartis, AstraZeneca, Pfizer, and/or GlaxoSmithKline.

In an accompanying editorial, Jørgen Vestbo, MD, of the Hvidovre University Hospital in Denmark, notes that the moderately high incidence rates of COPD in young adults are "hardly surprising."

"As recently reported in the AJRCCM [American Journal of Respiratory and Critical Care Medicine], our understanding of COPD has gradually developed over more than a century," Dr. Vestbo writes. "It has taken the respiratory community a painstakingly long time to do properly sized studies in young adults with sound methodology and state-of-the-art data analysis. With COPD epidemiology growing in the European Community Respiratory Health Survey and other cohorts of young adults, we may get a better picture of early events in COPD — although our colleagues in pediatric epidemiology will probably continue to claim that we are still only looking at 'the elderly'!"

Dr. Vestbo has disclosed no relevant financial relationships.

Am J Respir Crit Care Med. 2007;175:2-3, 32-39.

Clinical Context

The GOLD guidelines, published by the National Heart, Lung, and Blood Institute in April 2001, include chronic cough or phlegm as stage 0 of the COPD staging system to identify those at risk of developing COPD. Subsequently, as noted by Celli and MacNee in the June 2004 issue of The European Respiratory Journal, the ATS and ERS recommended the addition of dyspnea to stage 0 symptoms. Depending on the percentage of subjects aged 65 years or older, the incidence of COPD, based on the GOLD guidelines, was 6.1%, according to Johannessen and colleagues in the August 2005 issue of The International Journal of Tuberculosis and Lung Disease. And, the incidence of COPD was 13.5%, according to Lindberg and colleagues in the May 2005 issue of Chest.

In the May 2004 issue of The European Respiratory Journal, Toren and colleagues reported on the 1991-1993 ECRHS I, an international multicenter study of adults aged 20 to 44 years. The 1999-2002 ECRHS II was a follow-up study of a random sample of 20% of ECRHS I respondents who underwent further evaluation.

The current prospective study uses the ECRHS II database to evaluate the incidence of COPD and the roles of chronic cough or phlegm and dyspnea as predictors of COPD.

source Medscape