Effects of Inhaled Corticosteroid/Long-Acting β2-Agonist Combination on the Airway Microbiome of Patients with Chronic Obstructive Pulmonary Disease : A Randomized Controlled Clinical Trial (DISARM)
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).
| Errataetall: |
CommentIn: Am J Respir Crit Care Med. 2021 Nov 15;204(10):1117-1119. - PMID 34554893 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:204 |
|---|---|
| Enthalten in: |
American journal of respiratory and critical care medicine - 204(2021), 10 vom: 15. Nov., Seite 1143-1152 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Leitao Filho, Fernando Sergio [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 06.12.2021 Date Revised 14.12.2021 published: Print ClinicalTrials.gov: NCT02833480 CommentIn: Am J Respir Crit Care Med. 2021 Nov 15;204(10):1117-1119. - PMID 34554893 Citation Status MEDLINE |
|---|
| doi: |
10.1164/rccm.202102-0289OC |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM330069330 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM330069330 | ||
| 003 | DE-627 | ||
| 005 | 20231225210512.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1164/rccm.202102-0289OC |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1100.xml |
| 035 | |a (DE-627)NLM330069330 | ||
| 035 | |a (NLM)34464242 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Leitao Filho, Fernando Sergio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of Inhaled Corticosteroid/Long-Acting β2-Agonist Combination on the Airway Microbiome of Patients with Chronic Obstructive Pulmonary Disease |b A Randomized Controlled Clinical Trial (DISARM) |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.12.2021 | ||
| 500 | |a Date Revised 14.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02833480 | ||
| 500 | |a CommentIn: Am J Respir Crit Care Med. 2021 Nov 15;204(10):1117-1119. - PMID 34554893 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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) | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 16S rRNA gene | |
| 650 | 4 | |a COPD | |
| 650 | 4 | |a airway microbiome | |
| 650 | 4 | |a inhaled corticosteroids | |
| 650 | 7 | |a Adrenal Cortex Hormones |2 NLM | |
| 650 | 7 | |a Adrenergic beta-2 Receptor Agonists |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a Receptors, Adrenergic, beta-2 |2 NLM | |
| 700 | 1 | |a Takiguchi, Hiroto |e verfasserin |4 aut | |
| 700 | 1 | |a Akata, Kentaro |e verfasserin |4 aut | |
| 700 | 1 | |a Ra, Seung Won |e verfasserin |4 aut | |
| 700 | 1 | |a Moon, Ji-Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyun Kuk |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Yuji |e verfasserin |4 aut | |
| 700 | 1 | |a Yamasaki, Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Milne, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Cheng Wei Tony |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Nislow, Corey |e verfasserin |4 aut | |
| 700 | 1 | |a van Eeden, Stephan F |e verfasserin |4 aut | |
| 700 | 1 | |a Shaipanich, Tawimas |e verfasserin |4 aut | |
| 700 | 1 | |a Lam, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Janice M |e verfasserin |4 aut | |
| 700 | 1 | |a Sin, Don D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of respiratory and critical care medicine |d 1994 |g 204(2021), 10 vom: 15. Nov., Seite 1143-1152 |w (DE-627)NLM074657305 |x 1535-4970 |7 nnns |
| 773 | 1 | 8 | |g volume:204 |g year:2021 |g number:10 |g day:15 |g month:11 |g pages:1143-1152 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1164/rccm.202102-0289OC |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 204 |j 2021 |e 10 |b 15 |c 11 |h 1143-1152 | ||