© 2007 American Thoracic Society doi: 10.1164/rccm.200610-1458ED
Chronic Cough and Phlegm in Young AdultsShould We Worry?Hvidovre University Hospital, Hvidovre, Denmark and Wythenshawe Hospital/University of Manchester, Manchester, United Kingdom In this issue of the AJRCCM (pp. 32–39), de Marco and colleagues report their findings on incident chronic obstructive pulmonary disease (COPD) in the European Community Respiratory Health Survey (1). After studying 5,002 subjects aged 20 to 44 years and monitoring them for a median of 8.9 years, the authors found that a substantial number of subjects developed COPD and also that presence of chronic cough and phlegm almost doubled the risk of COPD after adjusting for risk factors for this disease. The findings of considerable incidence rates of COPD in young adults are hardly surprising. After all, COPD does not suddenly appear out of nowhere and in order for the disease to be a major health burden in the middle-aged and elderly, significant incidence rates in young adulthood are needed! The virtue of the study by de Marco and colleagues lies in its size and thus the ability to calculate estimates with acceptable reliability. In this respect, it adds to previous work from the same group (2) and indicates that the statement that "15% of smokers will develop COPD" is wrong (3), and that lifetime risk of COPD in smokers is significantly higher, probably about 35 to 50% (4–6). It is noteworthy, however, that even when studying more than 40,000 person-years, the numbers of incident cases of COPD and asthma are limited—that is, 123 and 22 cases, respectively. The predictive value of chronic cough and phlegm is probably more surprising given the fact that this cohort was young and had normal lung function at baseline. The predictive value of chronic mucus hypersecretion has been a topic of debate ever since the seminal study of Fletcher and colleagues (7), which tested—and refuted—the "British hypothesis." Although chronic mucus hypersecretion adds to the excess decline in lung function that determines progression in COPD (8), a recent analysis of the Copenhagen City Heart Study did not find any predictive value of chronic mucus hypersecretion in subjects with normal lung function at baseline (9). A lack of association between early chronic cough/phlegm and subsequent disease progression would fit with the assumption that, in COPD, inhaled gases and particles damage the lung's innate defense system and thus reduce mucociliary clearance. This could then produce an ineffective cough, disrupt the epithelial barrier, and initiate an acute-on-chronic inflammatory process in the airways and lung parenchyma (10). In this setting, mucus would be the result of the COPD disease process and not an early phenomenon initiating the pathology. For the findings reported by de Marco and colleagues in young adults to change our current understanding, we need to ensure that these associations cannot be explained by other mechanisms. In young adults, the most obvious bias would seem to be misclassification of asthma as COPD. In the current study, the authors relied on a doctor's diagnosis of asthma to identify individuals with asthma at follow-up. This may be a valid approach, but the incidence of asthma, 22 cases in 5,002 subjects over 8.9 years or approximately 0.5 cases per 1,000 per year is somewhat lower than previously reported in this age group (11–13), indicating potential diagnostic bias. In addition, the assessment of chronic cough/phlegm probably needs to be more critically evaluated. The questions used in most epidemiologic surveys have been thoroughly validated in working populations but the validation was done almost 50 years ago (14). It is perhaps timely to examine if the construct validity of these questionnaires is unchanged or if questions on cough and phlegm today actually measure something else than they did decades ago. Could difference in age of the subjects studied be the explanation for the seeming discrepancy between this study and previous findings? Possibly. Studying young adults provides a clear advantage when determining deviations from normal lung function over time. Exposures are likely to be more well defined and symptoms, such as cough or phlegm, could potentially be affected less by cumulative poorly characterized exposure. This could explain the associations found in this study—and potentially missed earlier in populations with more variable age at baseline (9). However, studying incidence of a chronic disease like COPD in a relatively young population also has the potential for methodologic problems. In the study by de Marco and colleagues, incident cases of COPD are defined according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines (15) as a ratio of FEV1 divided by VC less than 0.7. It is well accepted that in young adults this cutoff is likely to underestimate airflow obstruction and would lead to conservative incidence estimates in the study by de Marco and colleagues. However, it could also affect studies of predictors of COPD because "incident COPD" may in fact be "progression of COPD" in young subjects with mild airflow limitation being characterized as "normal" at baseline due to the crude cutoff of 0.7. How this has potentially influenced the findings of the current study is not possible to say on the basis of the data presented but should be the focus of attention in future epidemiologic investigations of young adults. How does the study by de Marco and colleagues impact on our understanding of the natural history of COPD? As recently reported in the AJRCCM, our understanding of COPD has gradually developed over more than a century (16). 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"! FOOTNOTES Conflict of Interest Statement: J. V. 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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