Melanie Holtrop1,2, Sonya Heltshe3, Veronika Shabanova4, Ashley Keller1, Lauren Schumacher1, Lynn Fernandez1, Raksha Jain1. 1. Department of Internal Medicine and. 2. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. 3. Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington School of Medicine, Cystic Fibrosis Foundation Therapeutics Development Network, Seattle Children's Research Institute, Seattle, Washington; and. 4. Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut.
Abstract
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-α, 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.
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-α, 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.
Entities:
Keywords:
cystic fibrosis; estrogen; inflammation; sex
Authors: Natalie E West; Traci M Kazmerski; Jennifer L Taylor-Cousar; Vin Tangpricha; Kelsie Pearson; Moira L Aitken; Raksha Jain Journal: Pediatr Pulmonol Date: 2021-10-08