Chronic Bronchitis: Coughers and Spitters Die Young
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a retained consultant for Cephalon and Ventus, and serves on the speakers bureaus for Cephalon and Boehringer Ingelheim.
Synopsis: People younger than age 50 who have cough and sputum production have increased all-cause mortality, risk of development of abnormal pulmonary function, and higher IL-8 and CRP levels, even if they have normal spirometry.
Source: Guerra S, et al. Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk. Thorax 2009;64:894-900.
This analysis comes from the Tucson Epidemilogical Study of Airway Obstructive Disease (TESAOD). TESAOD is a population-based prospective cohort study that has been ongoing for more than three decades. At enrollment and every 2 years afterward, participants completed a standard respiratory questionnaire and underwent spirometry. The current report is based on those who, at the time of enrollment, were 21-80 years old, were not asthmatic, were not pregnant, had never had chest surgery, and had normal pulmonary function. Normal pulmonary function was defined as a forced expired volume in 1 second/forced vital capacity ratio (FEV1/FVC) of at least 70%. Chronic bronchitis was defined as cough and sputum production on most days for at least 3 months in at least 2 consecutive years. The investigators also recorded smoking history, performed skin prick tests, and measured serum immunoglobulin E (IgE), IL-8, CRP, and blood eosinophil counts at enrollment. Incident airflow limitation was defined as an FEV1/FVC ratio < 70% in any of the follow-up surveys. The vital status of TESAOD participants as of January 2005 was determined through direct contact with the family or designated next of kin of the participant, linkage with the Social Security Death Index, and linkage with the National Death Index.
Of the 1412 subjects eligible for analysis in this study, 97 (6.9%) reported chronic bronchitis (cough and sputum production on most days for at least 3 months in at least 2 consecutive years) at the time of entry into the study. As compared with subjects with no chronic bronchitis, those with chronic bronchitis at baseline were more likely to be males and smokers, had fewer years of formal education and slightly lower FEV1/FVC ratio at enrollment. There were no significant differences between the two groups in terms of age, body mass index, skin tests, total IgE levels, or eosinophilia.
With regard to mortality risk, 63% of the subjects who had chronic bronchitis at enrollment had died by2005 as compared with 50% of the subjects with no chronic bronchitis (P = 0.02), despite the similar age distribution of the two groups at enrollment. The risk for all-cause mortality associated with chronic bronchitis was strongest among smokers and among subjects younger than 50 years of age. During follow-up, 42% of subjects with chronic bronchitis at the beginning of the study developed airflow limitation (FEV1/FVC < 70%) vs 23% of those without chronic bronchitis (P < 0.001). Those with chronic bronchitis at baseline had a more than two-fold higher risk of developing airflow limitation if they were younger than 50 years of age, but the risk was not increased for those older than age 50.
The analysis of serum samples demonstrated that 66% of subjects with chronic bronchitis had elevated serum IL-8 vs 49% of subjects without chronic bronchitis at baseline. Similarly, serum CRP levels were higher among subjects with chronic bronchitis than in subjects with no chronic bronchitis, although this association was no longer significant after adjusting for covariates.
Not surprisingly, chronic bronchitis was strongly associated with cigarette smoking in this study, and its effects on incident airflow limitation, mortality risk, and systemic inflammation appeared stronger among smokers than never-smokers. In fact, there was no significant association between chronic bronchitis and any outcome in the never-smokers.
Commentary
This is the first study to address by age the risk of death and disability posed by chronic bronchitis within the same population. The implication of this work is that those smokers who already have cough and sputum by the age of 50 have a markedly increased risk of death and declining pulmonary function. The authors speculate that the onset of symptoms is an early marker of susceptibility to the effects of cigarette smoking. This suggests that asking younger smokers about cough and sputum may allow identification and intervention in those at greatest risk.
The association between chronic cough and sputum is intriguing, and could represent a cost-effective screen for mortality. The biologic rationale for this finding may be that the airway inflammation in COPD may extend beyond the lung to systemic inflammation,1-4 which has been implicated in the systemic manifestations and excess mortality of COPD. The authors hypothesize that early development of chronic bronchitis represents an early marker of susceptibility to both the proinflammatory effects and the long-term health consequences of cigarette smoking, which will affect the risk for incident COPD and mortality.
References
1. Gan WQ, et al. Association between chronic obstructive pulmonary disease and systemic inflammation: A systematic review and a meta-analysis. Thorax 2004;59:574-580.
2. Walter RE, et al. Systemic inflammation and COPD: The Framingham Heart Study. Chest 2008;133:19-25.
3. Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet 2007;370:797-799.
4. Sin DD, Man SF. Systemic inflammation and mortality in chronic obstructive pulmonary disease. Can J Physiol Pharmacol 2007;85:141-147.