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
alpha(1)-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 FEV(1)/ 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 FEV(1)) (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 FEV(1) (< 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 FEV(1) < 80%
pred (OR 1.91, 95% CI 1.03- 3.54), FEV(1) < 40%
pred (OR 3.56, 95% CI 1.08-11.71), and
bronchodilator response greater than 10% of baseline FEV(1) (OR 4.74, 95% CI 1.91-11.75). These results suggest that women may be more susceptible to the development of severe
COPD.