Clinical Determinants of Exacerbations in Severe, Early-onset COPD

¹ Channing Laboratory
² Channing Laboratory; and Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Brigham and Women's Hospital and Harvard Medical School
³ Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Brigham and Women's Hospital and Harvard Medical School

^* To whom correspondence should be addressed. E-mail: marilyn.foreman{at}channing.harvard.edu.

	Abstract

COPD exacerbations impair health. We analyzed participants in the Boston Early-Onset COPD Study for familial aggregation and propensity for COPD exacerbations.

Two exacerbation outcomes, episodes of cough and phlegm and frequent exacerbations, were analyzed with multivariable modeling and generalized estimating equations.

In early-onset probands, passive tobacco smoke exposure within the home strongly associated with episodes of cough and phlegm (p=0.002), OR 10.8 [95% CL 2.3, 49.9]. Chronic phlegm production associated with both exacerbation phenotypes in probands. In first-degree relatives, chronic bronchitis (p<0.0001), OR 5.2 [2.6, 10.4], episodic wheezing (p<0.0002), OR 3.1 [1.7, 5.7], pneumonia (p=0.006), OR 2.3 [1.3, 4.2] and active smoking (p=0.01), OR 2.1 [1.2, 3.9] were associated with the episodes of cough and phlegm phenotype. In relatives, identical characteristics plus exertional dyspnoea associated with frequent exacerbations. Exacerbation risk increased with declining lung function. Familial aggregation for episodes of cough and phlegm was observed in relatives with severe obstruction (p=0.005).

Passive smoke exposure increases morbidity in severe early-onset COPD probands. COPD exacerbations correlate with chronic sputum production in probands and relatives. Familial aggregation of exacerbations suggests a genetic basis for susceptibility to COPD exacerbations.

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