Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2152-2158

Gender-Related Differences in Severe, Early-Onset Chronic Obstructive Pulmonary Disease

EDWIN K. SILVERMAN, SCOTT T. WEISS, JEFFREY M. DRAZEN, HAROLD A. CHAPMAN, VINCENT CAREY, EDWARD J. CAMPBELL, PAUL DENISH, RACHEL A. SILVERMAN, JUAN C. CELEDON, JOHN J. REILLY, LEO C. GINNS, and FRANK E. SPEIZER

Channing Laboratory and Division of Pulmonary and Critical Medicine, Department of Medicine, Brigham and Women's Hospital, Boston; Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston; Harvard Medical School, Boston, Massachusetts; and Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah

Men have higher prevalence rates of chronic obstructive pulmonary disease (COPD) than women, which has been attributed to the historically higher rates of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated with steadily increasing rates of COPD in women. As part of a study of the genetics of severe, early-onset COPD, we assembled a group of 84 probands with severe, early-onset COPD (without severe alpha₁-antitrypsin deficiency) and 348 of their first-degree relatives. We found a markedly elevated prevalence (71.4%) of females among the early-onset COPD probands. Among the entire group of first-degree relatives of early-onset COPD probands, univariate analysis demonstrated similar spirometric values and bronchodilator responsiveness in males and females; however, among current or ex-smokers, female first-degree relatives had significantly lower FEV₁/ FVC (81.4 ± 17.2% in females versus 87.0 ± 12.9% in males, p = 0.009) and significantly greater bronchodilator responsiveness (expressed as percentage of baseline FEV₁) (7.7 ± 9.4% pred in females versus 4.1 ± 6.4% pred in males, p = 0.002). Female smoking first-degree relatives were significantly more likely to demonstrate profound reductions in FEV₁ (< 40% pred) than male smoking first-degree relatives (p = 0.03). Multivariate analysis, performed with generalized estimating equations, demonstrated that current or ex-smoking female first-degree relatives had significantly greater risk of FEV₁ < 80% pred (OR 1.91, 95% CI 1.03- 3.54), FEV₁ < 40% pred (OR 3.56, 95% CI 1.08-11.71), and bronchodilator response greater than 10% of baseline FEV₁ (OR 4.74, 95% CI 1.91-11.75). These results suggest that women may be more susceptible to the development of severe COPD.

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