Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease: Risk to relatives for airflow obstruction and chronic bronchitis

• Published in: American journal of respiratory and critical care medicine 1998-06, Vol.157 (6), p.1770-1778
• Main Authors: SILVERMAN, E. K, CHAPMAN, H. A, WAIN, J, SPEIZER, F. E, DRAZEN, J. M, WEISS, S. T, ROSNER, B, CAMPBELL, E. J, O'DONNELL, W. J, REILLY, J. J, GINNS, L, MENTZER, S
• Format: Article
• Language: English
• Subjects: alpha 1-Antitrypsin Deficiency - complications; Biological and medical sciences; Bronchitis - etiology; Bronchitis - genetics; Chronic Disease; Chronic obstructive pulmonary disease, asthma; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive - etiology; Lung Diseases, Obstructive - genetics; Lung Diseases, Obstructive - physiopathology; Male; Medical sciences; Middle Aged; Pneumology; Risk Factors; Smoking - adverse effects; Vital Capacity
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.157.6.9706014

Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.