清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

医学 慢性阻塞性肺病 肺活量 肺功能测试 内科学 肺活量测定 哮喘 气道阻塞 气道 扩散能力 外科 肺功能
作者
Giorgia Radicioni,Agathe Ceppe,Amina A. Ford,Neil E. Alexis,R. Graham Barr,Eugene R. Bleecker,Stephanie A. Christenson,Christopher B. Cooper,MeiLan K. Han,Nadia N. Hansel,Annette T. Hastie,Eric A. Hoffman,Richard E. Kanner,Fernando J. Martínez,Esin Özkan,Robert Paine,Prescott G. Woodruff,Wanda K. O’Neal,Richard C. Boucher,Mehmet Kesimer
出处
期刊:The Lancet Respiratory Medicine [Elsevier]
卷期号:9 (11): 1241-1254 被引量:108
标识
DOI:10.1016/s2213-2600(21)00079-5
摘要

Background We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD. Methods SPIROMICS was a multicentre, observational study in patients aged 40–80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV1, forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF25–75%). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344). Findings This analysis included 331 participants (mean age 63 years [SEM 9·40]), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV1 and FEF25–75%, and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04–1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV1, FEV1/FVC, FEF25–75%, and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years. Interpretation These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents. Funding National Institutes of Health; National Heart, Lung, and Blood Institute.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
fff发布了新的文献求助10
刚刚
空曲完成签到 ,获得积分10
6秒前
LELE完成签到 ,获得积分10
30秒前
王磊完成签到 ,获得积分10
54秒前
emxzemxz完成签到 ,获得积分10
57秒前
xun完成签到,获得积分10
1分钟前
焚心结完成签到 ,获得积分10
1分钟前
AUGKING27完成签到 ,获得积分10
1分钟前
秋子骞完成签到 ,获得积分10
1分钟前
su完成签到 ,获得积分10
1分钟前
大大蕾完成签到 ,获得积分10
1分钟前
Sophie发布了新的文献求助10
1分钟前
badgerwithfisher完成签到,获得积分10
1分钟前
深情安青应助fff采纳,获得10
1分钟前
小刘哥加油完成签到 ,获得积分10
1分钟前
spark810发布了新的文献求助10
2分钟前
Gary完成签到 ,获得积分10
2分钟前
飞天奶酪完成签到 ,获得积分10
2分钟前
文献搬运工完成签到 ,获得积分10
2分钟前
2分钟前
fff发布了新的文献求助10
2分钟前
SCINEXUS完成签到,获得积分0
2分钟前
蚂蚁踢大象完成签到 ,获得积分10
2分钟前
dream完成签到 ,获得积分10
2分钟前
简单幸福完成签到 ,获得积分10
3分钟前
Amic完成签到 ,获得积分10
3分钟前
Sino完成签到 ,获得积分10
3分钟前
梓歆完成签到 ,获得积分10
3分钟前
huazhangchina完成签到 ,获得积分10
3分钟前
Skywings完成签到,获得积分10
3分钟前
鹏程完成签到 ,获得积分10
3分钟前
janer完成签到 ,获得积分10
3分钟前
Karry完成签到 ,获得积分10
4分钟前
yujie完成签到 ,获得积分10
4分钟前
4分钟前
chi完成签到 ,获得积分10
4分钟前
Glory完成签到 ,获得积分10
4分钟前
小Q发布了新的文献求助20
4分钟前
Sophie完成签到,获得积分10
4分钟前
亘木完成签到,获得积分10
4分钟前
高分求助中
Sustainability in Tides Chemistry 1500
Handbook of the Mammals of the World – Volume 3: Primates 805
拟南芥模式识别受体参与调控抗病蛋白介导的ETI免疫反应的机制研究 550
Gerard de Lairesse : an artist between stage and studio 500
Digging and Dealing in Eighteenth-Century Rome 500
Queer Politics in Times of New Authoritarianisms: Popular Culture in South Asia 500
Manual of Sewer Condition Classification 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3068236
求助须知:如何正确求助?哪些是违规求助? 2722176
关于积分的说明 7476072
捐赠科研通 2369138
什么是DOI,文献DOI怎么找? 1256228
科研通“疑难数据库(出版商)”最低求助积分说明 609518
版权声明 596835