Although familial clustering has been described, few studies have quantified the risk of airflow obstruction in siblings of patients with chronic obstructive pulmonary disease (COPD). One hundred fifty-two subjects with airflow obstruction and a low gas transfer factor (but without PiZ alpha(1)-antitrypsin deficiency) were identified and 150 were enrolled in the study. Complete data were obtained from 173 of 221 siblings of these subjects. Forty-four of 126 current or ex-smoking siblings had airflow obstruction (FEV(1)/FVC < 0.7) and 36 also had a FEV(1) < 80% predicted, in keeping with COPD. One hundred eleven current or ex-smoking siblings were matched for age, sex, and smoking history with 419 subjects, without a known family history of COPD, from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. The prevalence of COPD was much lower in the EPIC group (9.3%) when compared with the siblings (31.5%; odds ratio, 4.70; 95% confidence interval, 2.63 to 8.41). The odds ratio for COPD in siblings with less than a 30 pack-year smoking history was 5.39 (95% confidence interval, 2.49 to 11.67) when compared with matched control subjects. Taken together these results demonstrate a significant familial risk of airflow obstruction in smoking siblings of patients with severe COPD.
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