Gender-related differences in severe, early-onset chronic obstructive pulmonary disease

Men have higher prevalence rates of chronic obstructive pulmonary disease ( COPD) than women, which has been attributed to the historically higher rate s of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated wit h steadily Increasing rates of COPD in women. As part of a study of the gen etics 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 preva lence (71.4%) of females among the early-onset COPD probands. Among the ent ire group of first-degree relatives of early-onset COPD probands, univariat e analysis demonstrated similar spirometric values and bronchodilator respo nsiveness in males and females; however, among current or ex-smokers, femal e 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 gre ater 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 = 0.0 02). Female smoking first-degree relatives were significantly more likely t o demonstrate profound reductions in FEV1 (< 40% pred) than male smoking fi rst-degree relatives (p = 0.03). Multivariate analysis, performed with gene ralized estimating equations, demonstrated that current or ex-smoking femal e 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 t o the development of severe COPD.