Fernando Sergio Leitao Filho1,2, Hiroto Takiguchi1,2,3, Kentaro Akata1,2,4, Seung Won Ra1,2,5, Ji-Yong Moon1,2,6, Hyun Kuk Kim1,2,7, Yuji Cho1,2,8, Kei Yamasaki1,2,9, Stephen Milne1,2,10, Julia Yang1,2, Cheng Wei Tony Yang1,2, Xuan Li1,2, Corey Nislow11, Stephan F van Eeden1,2, Tawimas Shaipanich1,2, Stephen Lam1,2,12, Janice M Leung1,2, Don D Sin1,2. 1. Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada. 2. Division of Respiratory Medicine, Department of Medicine, and. 3. Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan. 4. Division of Infection Control and Prevention, University of Occupational and Environmental Health, Kitakyushu City, Fukuoka, Japan. 5. Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. 6. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea. 7. Department of Internal Medicine, College of Medicine, Inje University Haeundae Paik Hospital, Busan, South Korea. 8. Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea. 9. Department of Respiratory Medicine, University of Occupational and Environmental Health Japan, Fukuoka, Japan. 10. Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; and. 11. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 12. British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Abstract
Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in α-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov (NCT02833480).
Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in α-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov (NCT02833480).
Authors: William Yip; Xuan Li; Graeme J Koelwyn; Stephen Milne; Fernando Sergio Leitao Filho; Chen Xi Yang; Ana I Hernández Cordero; Julia Yang; Cheng Wei Tony Yang; Tawimas Shaipanich; Stephan F van Eeden; Janice M Leung; Stephen Lam; Kelly M McNagny; Don D Sin Journal: Biomedicines Date: 2022-05-11
Authors: Chunman Germain Ho; Stephen Milne; Xuan Li; Chen Xi Yang; Fernando Sergio Leitao Filho; Chung Yan Cheung; Julia Shun Wei Yang; Ana I Hernández Cordero; Cheng Wei Tony Yang; Tawimas Shaipanich; Stephan F van Eeden; Janice M Leung; Stephen Lam; Don D Sin Journal: Biomedicines Date: 2022-06-15