COPD Preferentially Takes Women's Breath Away

ANN ARBOR, Mich., Aug. 1 -- Chronic obstructive pulmonary disease (COPD) with severe emphysema strikes women harder than men on clinical and physiological measures, researchers affirmed.

In the first direct comparison study, women with advanced COPD reported greater breathlessness (P<0.0001) and depression than men (P=0.0001) at the same lung function and health status, found Fernando J. Martinez, M.D., of the University of Michigan here, and colleagues.

Anatomy and distribution of emphysema lesions also differed significantly between the sexes, they reported in the Aug. 1 issue of the American Journal of Respiratory and Critical Care Medicine.

The overall findings confirmed what has been suspected from prior indirect studies, they said.

In an accompanying editorial, Dawn L. DeMeo, M.D., M.P.H., of Brigham and Women's Hospital in Boston, said the reason for the differences and whether they are based culturally, genetically, or anatomically remains unknown.

But, what is not debatable, she said, is that these differences impact clinical care of patients, and notably so from a public health perspective, "because in 2000, the number of women dying of COPD surpassed the number of men."

For this study, the researchers retrospectively analyzed 1,053 patients (38.8% women) with severe emphysema who were extensively characterized during evaluation for lung volume reduction surgery as part of the National Emphysema Treatment Trial.

Women in the study reported significantly shorter smoking histories (54.8 versus 71.1, P=0.0001), younger age (65.4 versus 67.0, P=0.0001), and lower body mass index (24.4 versus 25.0 kg/m², P=0.007) than men.

On physiological testing, women had mixed results on lung function in comparison with men.

Their mean forced expiratory volume in one second (FEV₁) before bronchodilator use was 2.9% predicted higher compared with men (P=0.0001) regardless of adjustment for age, pack-years of smoking, and whole-lung emphysema proportion. Post-bronchodilator FEV₁ was similarly 3.1% predicted higher for women (P<0.0001).

But women had lower diffusing capacity (27.2% versus 29.3% predicted, P=0.0005) and inspiratory fraction (inspiratory-to-total lung capacity ratio (0.21 versus 0.23, P<0.0001).

Women also had decreased exercise capacity on the six-minute walk test compared with men (1,076.7 feet versus 1,185.5, P=0.0001).

Notably, women's reported symptom experience was also worse than men's.

They reported more dyspnea than men on the Shortness of Breath Questionnaire (5.03 higher adjusted score on average, P<0.0001) even controlling for age, FEV₁% predicted, whole-lung emphysema proportion, and pack-years.

Depressive symptoms were higher among women as measured by the Beck Depression Inventory (total score 10.4 versus 8.7, P=0.0001). Likewise, overall mental health component scores on the Short Form 36 survey were lower among women than men (51.6 versus 53.1, P=0.03), although physical health scores were similar (P=0.92).

The researchers cautioned that their data could not explain these differences, but they noted that "women might report greater respiratory symptoms and worse health status because they perceive a given physiological perturbation differently."

But if they reported worse symptoms, on radiological assessment with computed tomography (CT), women had less severe emphysema in multivariate analysis.

The proportion of moderate whole-lung emphysema was, on average, 3% less among women than men (95% CI 1.4% to 4.6% less, P=0.0002). The proportion of severe whole-lung emphysema was, on average, 16.4% less among women (95% CI 0.2 to 30.5% less, P=0.02).

Women also had a different distribution and amount of emphysematous lesions compared with men.

Women had proportionally more small lesions in both severe emphysema (P=0.001) and less severe emphysema (P=0.01) as measured by alpha value indicating radiological lung density.

They also had a lower proportion of peripheral emphysema in the "peel" of the lung (P=0.002) compared with men although a similar proportion of emphysema in the core of the lung (P=0.93).

In multivariate analysis, female sex was a significant predictor of modified BODE score (a composite measure of body mass index, airflow obstruction, dyspnea, and exercise capacity, P=0.0002), dyspnea (P<0.0001), depressive symptoms (P=0.007), mental health status (P=0.02), and quality of well-being score (P=0.02).

The study should be considered hypothesis generating, the researchers noted.

And, Dr. DeMeo said, it raises important questions, such as "are women more predisposed to have more airway disease?" and do they "do worse clinically because of the physiologic impact of having more airway disease? Or, is it that women have more systemic sequelae related to COPD."