Hollian Richardson,Daniela Alferes De Lima Headley,Clare Clarke,Abirami Veluchamy,Petra Rauchhaus,Jennifer Pollock,Thomas Pembridge,Diane Cassidy,Holly R Keir,Simon Finch,Furrah Hussain,Margaret Band,Andrew Smith,Manish Patel,Mohammad Paracha,Gourab Choudhury,Devesh Dhasmana,Rekha Chaudhuri,Philip M Short,James D Chalmers
{"title":"不同吸入皮质类固醇和长效支气管扩张剂组合对严重慢性阻塞性肺疾病患者气道微生物组的影响:一项随机试验(MUSIC)","authors":"Hollian Richardson,Daniela Alferes De Lima Headley,Clare Clarke,Abirami Veluchamy,Petra Rauchhaus,Jennifer Pollock,Thomas Pembridge,Diane Cassidy,Holly R Keir,Simon Finch,Furrah Hussain,Margaret Band,Andrew Smith,Manish Patel,Mohammad Paracha,Gourab Choudhury,Devesh Dhasmana,Rekha Chaudhuri,Philip M Short,James D Chalmers","doi":"10.1183/13993003.00287-2025","DOIUrl":null,"url":null,"abstract":"INTRODUCTION\r\nThe microbiome is associated with exacerbation risk, quality of life and mortality in COPD. Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence. How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated. The aim of the MUSIC trial was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD.\r\n\r\nMETHODS\r\nMulticentre randomized controlled trial. After a four-week washout period during which they withdrew from ICS, patients with COPD (FEV1 <50% predicted at baseline and/or a history of 2 or more exacerbations per year) were randomized to one of 4 treatments (budesonide/formoterol 400/12 mcg, fluticasone/salmeterol 500 mcg, fluticasone/salmeterol 250 mcg or aclidinium/formoterol 340/12 mcg, twice daily). Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S rRNA sequencing to characterise the microbiome. Inflammatory markers were measured in sputum and blood. The primary outcome was bacterial load in oropharyngeal swabs comparing budesonide/formoterol versus fluticasone/salmeterol 500, with sputum bacterial load the key secondary endpoint.\r\n\r\nRESULTS\r\n122 participants started the washout period. ICS withdrawal was poorly tolerated, 61 participants withdrew before randomization with 45 experiencing an exacerbation. 61 patients were randomized. No statistically significant differences were observed for the primary comparison of budesonide/formoterol versus fluticasone/salmeterol 500 in oropharyngeal bacterial load. There was however a significant increase in sputum bacterial load with fluticasone/salmeterol 500 compared to budesonide/formoterol by month 3. This difference was not seen with fluticasone/salmeterol 250. No significant differences in microbiome alpha diversity were observed over time. Adverse events were similar between the groups.\r\n\r\nCONCLUSION\r\nFluticasone/salmeterol 500 increased sputum but not upper airway bacterial loads. ICS withdrawal was poorly tolerated in severe COPD.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"32 1","pages":""},"PeriodicalIF":21.0000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe chronic obstructive pulmonary disease: A randomized trial (MUSIC).\",\"authors\":\"Hollian Richardson,Daniela Alferes De Lima Headley,Clare Clarke,Abirami Veluchamy,Petra Rauchhaus,Jennifer Pollock,Thomas Pembridge,Diane Cassidy,Holly R Keir,Simon Finch,Furrah Hussain,Margaret Band,Andrew Smith,Manish Patel,Mohammad Paracha,Gourab Choudhury,Devesh Dhasmana,Rekha Chaudhuri,Philip M Short,James D Chalmers\",\"doi\":\"10.1183/13993003.00287-2025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"INTRODUCTION\\r\\nThe microbiome is associated with exacerbation risk, quality of life and mortality in COPD. Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence. How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated. The aim of the MUSIC trial was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD.\\r\\n\\r\\nMETHODS\\r\\nMulticentre randomized controlled trial. After a four-week washout period during which they withdrew from ICS, patients with COPD (FEV1 <50% predicted at baseline and/or a history of 2 or more exacerbations per year) were randomized to one of 4 treatments (budesonide/formoterol 400/12 mcg, fluticasone/salmeterol 500 mcg, fluticasone/salmeterol 250 mcg or aclidinium/formoterol 340/12 mcg, twice daily). Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S rRNA sequencing to characterise the microbiome. Inflammatory markers were measured in sputum and blood. The primary outcome was bacterial load in oropharyngeal swabs comparing budesonide/formoterol versus fluticasone/salmeterol 500, with sputum bacterial load the key secondary endpoint.\\r\\n\\r\\nRESULTS\\r\\n122 participants started the washout period. ICS withdrawal was poorly tolerated, 61 participants withdrew before randomization with 45 experiencing an exacerbation. 61 patients were randomized. No statistically significant differences were observed for the primary comparison of budesonide/formoterol versus fluticasone/salmeterol 500 in oropharyngeal bacterial load. There was however a significant increase in sputum bacterial load with fluticasone/salmeterol 500 compared to budesonide/formoterol by month 3. This difference was not seen with fluticasone/salmeterol 250. No significant differences in microbiome alpha diversity were observed over time. Adverse events were similar between the groups.\\r\\n\\r\\nCONCLUSION\\r\\nFluticasone/salmeterol 500 increased sputum but not upper airway bacterial loads. ICS withdrawal was poorly tolerated in severe COPD.\",\"PeriodicalId\":12265,\"journal\":{\"name\":\"European Respiratory Journal\",\"volume\":\"32 1\",\"pages\":\"\"},\"PeriodicalIF\":21.0000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Respiratory Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1183/13993003.00287-2025\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Respiratory Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/13993003.00287-2025","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe chronic obstructive pulmonary disease: A randomized trial (MUSIC).
INTRODUCTION
The microbiome is associated with exacerbation risk, quality of life and mortality in COPD. Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence. How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated. The aim of the MUSIC trial was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD.
METHODS
Multicentre randomized controlled trial. After a four-week washout period during which they withdrew from ICS, patients with COPD (FEV1 <50% predicted at baseline and/or a history of 2 or more exacerbations per year) were randomized to one of 4 treatments (budesonide/formoterol 400/12 mcg, fluticasone/salmeterol 500 mcg, fluticasone/salmeterol 250 mcg or aclidinium/formoterol 340/12 mcg, twice daily). Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S rRNA sequencing to characterise the microbiome. Inflammatory markers were measured in sputum and blood. The primary outcome was bacterial load in oropharyngeal swabs comparing budesonide/formoterol versus fluticasone/salmeterol 500, with sputum bacterial load the key secondary endpoint.
RESULTS
122 participants started the washout period. ICS withdrawal was poorly tolerated, 61 participants withdrew before randomization with 45 experiencing an exacerbation. 61 patients were randomized. No statistically significant differences were observed for the primary comparison of budesonide/formoterol versus fluticasone/salmeterol 500 in oropharyngeal bacterial load. There was however a significant increase in sputum bacterial load with fluticasone/salmeterol 500 compared to budesonide/formoterol by month 3. This difference was not seen with fluticasone/salmeterol 250. No significant differences in microbiome alpha diversity were observed over time. Adverse events were similar between the groups.
CONCLUSION
Fluticasone/salmeterol 500 increased sputum but not upper airway bacterial loads. ICS withdrawal was poorly tolerated in severe COPD.
期刊介绍:
The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.