Gender differences in outcomes of patients with cystic fibrosis

Abstract

Background: Cystic fibrosis (CF) is a common life-shortening genetic disease in which women have been described to have worse outcomes than males, particularly in response to respiratory infections with Pseudomonas aeruginosa. However, as advancements in therapies have improved life expectancy, this gender disparity has been challenged. The objective of this study is to examine whether a gender-based survival difference still exists in this population and determine the impact of common CF respiratory infections on outcomes in males versus females with CF.

Methods: We conducted a retrospective cohort analysis of 32,766 patients from the United States Cystic Fibrosis Foundation Patient Registry over a 13-year period. Kaplan-Meier and Cox proportional hazards models were used to compare overall mortality and pathogen based survival rates in males and females.

Results: Females demonstrated a decreased median life expectancy (36.0 years; 95% confidence interval [CI] 35.0-37.3) compared with men (38.7 years; 95% CI 37.8-39.6; p<0.001). Female gender proved to be a significant risk factor for death (hazard ratio 2.22, 95% CI 1.79-2.77), despite accounting for variables known to influence CF mortality. Women were also found to become colonized earlier with several bacteria and to have worse outcomes with common CF pathogens.

Conclusions: CF women continue to have a shortened life expectancy relative to men despite accounting for key CF-related comorbidities. Women also become colonized with certain common CF pathogens earlier than men and show a decreased life expectancy in the setting of respiratory infections. Explanations for this gender disparity are only beginning to be unraveled and further investigation into mechanisms is needed to help develop therapies that may narrow this gender gap.

FIG. 1.

Diagram of the study population of cystic fibrosis patients from the Cystic Fibrosis Foundation Patient Registry analyzed by gender. A total of 34,693 subjects were evaluated for this analysis. Subjects who received a lung transplant were excluded, resulting in 32,836 subjects. There were 70 patients whose survival lengths (SURV) were found to be less than zero and were therefore not included. There remained 32,766 subjects, of whom 17,174 were men and 15,592 were women.

FIG. 2.

Kaplan Meier estimate of survival comparing cystic fibrosis (CF) women with men seen at accredited U.S. CF care centers from 1995 to 2007. Females had poorer survival, with a median life expectancy of 36.0 years (95% CI 35.0–37.3) versus 38.7 years (95% CI 37.8–39.6) in men (p<0.001).