PURPOSE: Frequent exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality and decrease quality of life. We analyzed clinical characteristics that predict frequent exacerbations and assessed familial aggregation of COPD exacerbations.
METHODS: 139 eligible probands (age ≤ 52 years, FEV1 < 40% predicted without alpha 1-antitrypsin deficiency) and 465 first-degree relatives were studied. Two binary exacerbation outcomes, episodes of cough and phlegm and frequent exacerbations, were analyzed as qualitative phenotypes using regression models. The frequent exacerbation phenotype was dichotomized as ≥ 3 chest illnesses in 3 years. Generalized estimating equations were used to assess familial aggregation.
RESULTS: 73 probands (53%) reported a history of episodes of cough and phlegm. Predictors of episodes of cough and phlegm were exposure to other smokers in the home (p = 0.0023, OR 10.8 [95% CL 2.3, 50]) and chronic phlegm production (p < 0.007, OR 3.5 [95% CL 1.6, 7.7]). 86 probands (62%) reported a history of frequent exacerbations. Chronic phlegm production also predicted frequent exacerbations. 78 first-degree relatives (17%) reported a history of episodes of cough and phlegm and 43 (9%) reported frequent exacerbations. Predictors of both phenotypes in first-degree relatives included chronic bronchitis (p < 0.0001), attacks of wheezing with dyspnea (p = 0.0002), pneumonia (p = 0.006) and active smoking (p = 0.01). Familial aggregation for episodes of cough and phlegm was observed in the subset of first-degree relatives with FEV1 < 50% (p = 0.005). Familial aggregation was not demonstrated for frequent exacerbations.
CONCLUSION: Chronic phlegm production predicted both exacerbation phenotypes in probands, but the strongest predictor of cough and phlegm episodes was passive smoke exposure. Chronic bronchitis, wheezing, and pneumonia were associated with exacerbations and more frequent exacerbations in first-degree relatives. Familial aggregation of episodes of cough and phlegm lends support to the plausibility of a genetic basis for susceptibility to COPD exacerbations.
CLINICAL IMPLICATIONS: COPD exacerbations correlate with phlegm production in probands and their relatives. More importantly, passive exposure to tobacco smoke increases morbidity in individuals with severe COPD.
DISCLOSURE: Marilyn Foreman, None.