TY - JOUR
T1 - A prospective study of the effects of sex hormones on lung function and inflammation in women with cystic fibrosis
AU - Holtrop, Melanie
AU - Heltshe, Sonya
AU - Shabanova, Veronika
AU - Keller, Ashley
AU - Schumacher, Lauren
AU - Fernandez, Lynn
AU - Jain, Raksha
N1 - Funding Information:
Supported by the Cystic Fibrosis Foundation Harry Shwachman Cystic Fibrosis Clinical Investigator Award (JAINR15A0), Clinical Research Scholars Program (CRSP) Award (JAIN18Y5), and the StatNet Award (Egan 605017).
Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/7
Y1 - 2021/7
N2 - Rationale: Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations after puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences. Objectives: We sought to explore whether natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers. Methods: We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded with menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (loestrin), and reevaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone concentrations, and sputum for inflammatory markers, bacterial density, and cytology. Results: Twenty-three women participated in this study. Hormone concentrations were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum proinflammatory cytokines (neutrophil-free elastase) and a corresponding pattern of decrease in lung function. Proinflammatory cytokines (IL-8, TNF-a, and neutrophil-free elastase) improved when placed on hormone contraception. Conclusions: Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses.
AB - Rationale: Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations after puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences. Objectives: We sought to explore whether natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers. Methods: We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded with menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (loestrin), and reevaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone concentrations, and sputum for inflammatory markers, bacterial density, and cytology. Results: Twenty-three women participated in this study. Hormone concentrations were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum proinflammatory cytokines (neutrophil-free elastase) and a corresponding pattern of decrease in lung function. Proinflammatory cytokines (IL-8, TNF-a, and neutrophil-free elastase) improved when placed on hormone contraception. Conclusions: Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses.
KW - Cystic fibrosis
KW - Estrogen
KW - Inflammation
KW - Sex
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U2 - 10.1513/AnnalsATS.202008-1064OC
DO - 10.1513/AnnalsATS.202008-1064OC
M3 - Article
C2 - 33544657
AN - SCOPUS:85106200872
SN - 2325-6621
VL - 18
SP - 1158
EP - 1166
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 7
ER -