使用新评分（MiDAS）量表评估共患病对难治性哮喘的影响：一项针对哮喘队列的跨国研究
2025/10/11
摘要
背景：共患病（即两种或多种疾病状况共存）在难治性哮喘患者中非常普遍。然而，目前尚不清楚共患病与上述患者疾病的严重程度和不良预后之间的相关性，以及哪些共患病最重要。
目的：本研究旨在通过为难治性哮喘制定一个以患者为中心、具有临床描述性的共患病评分量表来填补这一知识空白。
方法：本研究采用来自英国威塞克斯难治性哮喘队列（WATCH；n=500，数据收集于2015年4月22日至2020年4月1日）的数据来制定难治性哮喘共患病评分（MiDAS）。首先，本研究在WATCH中创建了一个改进的哮喘严重程度评分系统（m-ASSESS）。然后，本研究通过单变量关联分析检验了WATCH中13种最常见的合并症与m-ASSESS之间的关联，并使用分支定界法选择最相关的合并症纳入MiDAS。本研究计算了WATCH中所有信息完整患者（n=319）的MiDAS值，并评估了它们与m-ASSESS、促炎生物标志物和圣乔治呼吸问卷（SGRQ）评分（一种生活质量指标）的相关性。同时本研究还评估了MiDAS与四个国际队列中多种临床结果的关联：两个来自澳大利亚（n=236，数据收集于2014年6月14日至2022年4月1日；n=140，数据收集于2012年8月6日至2016年10月18日），一个来自东南亚（n=151，数据收集于2017年3月21日至2024年1月16日），另一个来自美国（n=100，数据收集于2021年7月9日至2023年12月14日）。
结果：基于分支定界分析，本研究筛选出7种常见的合并症（即鼻炎、胃食管反流病、呼吸模式障碍、肥胖、支气管扩张、非甾体抗炎药加重的呼吸系统疾病和阻塞性睡眠呼吸暂停）纳入MiDAS，并使用多元线性回归将它们结合起来，得出与WATCH中m-ASSESS相关的MiDAS模型。MiDAS评分范围为9.6-16.2。在WATCH成员中，平均MiDAS值为11.97（SD 1.21），MiDAS与哮喘控制不良（τ=0.31[95%CI 0.24-0.38]）和急性加重（τ=0.16[0.08-0.24]）的m-ASSESS成分名义上相关。在WATCH中，MiDAS还与更差的SGRQ总评分（r=0.39[95%0.28-0.49]，p<0.0001）和促炎血浆细胞因子白细胞介素（IL）-4（r=0.19[95%CI 0.06-0.31]，p=0.0036）、IL-5（r=0.35[0.24-0.46]，p<0.00001）和瘦素（r=0.29[0.17-0.40]，p=0.0001）相关。四个国际队列的MiDAS值与WATCH（英国队列）相似，澳大利亚队列的平均值为12.33（SD 1.47）和12.31（1.37），美国队列为11.80（1.20），新加坡队列为11.55（1.23）。在这些队列中，MiDAS与较差的哮喘控制、较差的生活质量、焦虑、抑郁和炎症增加相关。
结论：MiDAS强调了难治性哮喘中共患病与最差预后共同发生。上述发现强烈表明，以气道为中心的评估方法是不够的，全面、多学科医疗护理至关重要。该临床评分可帮助临床医生识别共患病风险最大的患者。
Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts.
Kurukulaaratchy RJ, Freeman A, Bansal AT, Kadalayil L, Denton E, Clark V, Gibson PG, Varkonyi-Sepp J, Ainsworth B, Hudson-Colby JJ, Lewis A, Eames C, Wei L, Fong WCG, Djukanovic R, Hromis S, Tay TR, Lugogo N, McDonald VM, Hew M, Haitchi HM.
Abstract
BACKGROUND:Multimorbidity (ie, co-existence of two or more health conditions) is highly prevalent in patients with difficult-to-treat asthma. However, it remains unclear how multimorbidity correlates with disease severity and adverse health outcomes in these patients and which comorbidities are most important.
OBJECTIVES:We aimed to address this knowledge gap by developing a patient-centred, clinically descriptive multimorbidity score for difficult-to-treat asthma.
METHODS:We used data from the UK-based Wessex Asthma Cohort of Difficult Asthma (WATCH; n=500, data collected between April 22, 2015, and April 1, 2020) to develop the Multimorbidity in Difficult Asthma Score (MiDAS). Initially, we created a modified Asthma Severity Scoring System (m-ASSESS) in WATCH. We then conducted univariate association analysis to test the association between the 13 commonest comorbidities and m-ASSESS in WATCH and used a branch-and-bound approach to select the most relevant comorbidities for inclusion in MiDAS. We calculated MiDAS values for all patients with complete information in WATCH (n=319) and assessed them for correlation with components of m-ASSESS, proinflammatory biomarkers, and St George's Respiratory Questionnaire (SGRQ) score, a quality-of-life measure. We also assessed the association of MiDAS with multiple clinical outcomes in four international cohorts: two from Australia (n=236, data collected between June 14, 2014, and April 1, 2022; and n=140, Aug 6, 2012, to Oct 18, 2016), one from southeast Asia (n=151, March 21, 2017, to Jan 16, 2024), and one from the USA (n=100, July 9, 2021, to Dec 14, 2023).
RESULTS:We selected seven common comorbidities (ie, rhinitis, gastro-oesophageal reflux disease, breathing pattern disorder, obesity, bronchiectasis, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and obstructive sleep apnoea) for inclusion in MiDAS on the basis of the branch-and-bound analysis and combined them using multivariate linear regression to derive a MiDAS model associated with m-ASSESS in WATCH. The range of MiDAS scores was 9·6-16·2. In WATCH members, mean MiDAS value was 11·97 (SD 1·21) and MiDAS was nominally correlated with m-ASSESS components of poor asthma control (τ=0·31 [95% CI 0·24-0·38]) and exacerbations (τ=0·16 [0·08-0·24]). MiDAS was also correlated with worse total SGRQ score (r=0·39 [95% 0·28-0·49], p<0·0001) and with the proinflammatory plasma cytokines interleukin (IL)-4 (r=0·19 [95% CI 0·06-0·31], p=0·0036), IL-5 (r=0·35 [0·24-0·46], p<0·0001), and leptin (r=0·29 [0·17-0·40], p<0·0001) in WATCH. MiDAS values across the four international cohorts were similar to those of WATCH (UK cohort), with mean values of 12·33 (SD 1·47) and 12·31 (1·37) in the Australian cohorts, 11·80 (1·20) in the USA cohort, and 11·55 (1·23) in the Singapore cohort. In these cohorts, MiDAS correlated with worse asthma control, worse quality of life, anxiety, depression, and increased inflammation.
CONCLUSION: MiDAS highlights the co-occurrence of multimorbidity with the worst outcomes in difficult-to-treat asthma. These findings strongly indicate that an airway-centric approach is inadequate and that holistic and multidisciplinary care is imperative. This clinical score could help clinicians to identify patients most at risk from their multimorbidity.
背景：共患病（即两种或多种疾病状况共存）在难治性哮喘患者中非常普遍。然而，目前尚不清楚共患病与上述患者疾病的严重程度和不良预后之间的相关性，以及哪些共患病最重要。
目的：本研究旨在通过为难治性哮喘制定一个以患者为中心、具有临床描述性的共患病评分量表来填补这一知识空白。
方法：本研究采用来自英国威塞克斯难治性哮喘队列（WATCH；n=500，数据收集于2015年4月22日至2020年4月1日）的数据来制定难治性哮喘共患病评分（MiDAS）。首先，本研究在WATCH中创建了一个改进的哮喘严重程度评分系统（m-ASSESS）。然后，本研究通过单变量关联分析检验了WATCH中13种最常见的合并症与m-ASSESS之间的关联，并使用分支定界法选择最相关的合并症纳入MiDAS。本研究计算了WATCH中所有信息完整患者（n=319）的MiDAS值，并评估了它们与m-ASSESS、促炎生物标志物和圣乔治呼吸问卷（SGRQ）评分（一种生活质量指标）的相关性。同时本研究还评估了MiDAS与四个国际队列中多种临床结果的关联：两个来自澳大利亚（n=236，数据收集于2014年6月14日至2022年4月1日；n=140，数据收集于2012年8月6日至2016年10月18日），一个来自东南亚（n=151，数据收集于2017年3月21日至2024年1月16日），另一个来自美国（n=100，数据收集于2021年7月9日至2023年12月14日）。
结果：基于分支定界分析，本研究筛选出7种常见的合并症（即鼻炎、胃食管反流病、呼吸模式障碍、肥胖、支气管扩张、非甾体抗炎药加重的呼吸系统疾病和阻塞性睡眠呼吸暂停）纳入MiDAS，并使用多元线性回归将它们结合起来，得出与WATCH中m-ASSESS相关的MiDAS模型。MiDAS评分范围为9.6-16.2。在WATCH成员中，平均MiDAS值为11.97（SD 1.21），MiDAS与哮喘控制不良（τ=0.31[95%CI 0.24-0.38]）和急性加重（τ=0.16[0.08-0.24]）的m-ASSESS成分名义上相关。在WATCH中，MiDAS还与更差的SGRQ总评分（r=0.39[95%0.28-0.49]，p<0.0001）和促炎血浆细胞因子白细胞介素（IL）-4（r=0.19[95%CI 0.06-0.31]，p=0.0036）、IL-5（r=0.35[0.24-0.46]，p<0.00001）和瘦素（r=0.29[0.17-0.40]，p=0.0001）相关。四个国际队列的MiDAS值与WATCH（英国队列）相似，澳大利亚队列的平均值为12.33（SD 1.47）和12.31（1.37），美国队列为11.80（1.20），新加坡队列为11.55（1.23）。在这些队列中，MiDAS与较差的哮喘控制、较差的生活质量、焦虑、抑郁和炎症增加相关。
结论：MiDAS强调了难治性哮喘中共患病与最差预后共同发生。上述发现强烈表明，以气道为中心的评估方法是不够的，全面、多学科医疗护理至关重要。该临床评分可帮助临床医生识别共患病风险最大的患者。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Lancet Respir Med. 2025 Sep;13(9):821-832. doi: 10.1016/S2213-2600(25)00135-3. Epub 2025 Jul 8. PMID: 40645203.）
Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts.
Kurukulaaratchy RJ, Freeman A, Bansal AT, Kadalayil L, Denton E, Clark V, Gibson PG, Varkonyi-Sepp J, Ainsworth B, Hudson-Colby JJ, Lewis A, Eames C, Wei L, Fong WCG, Djukanovic R, Hromis S, Tay TR, Lugogo N, McDonald VM, Hew M, Haitchi HM.
Abstract
BACKGROUND:Multimorbidity (ie, co-existence of two or more health conditions) is highly prevalent in patients with difficult-to-treat asthma. However, it remains unclear how multimorbidity correlates with disease severity and adverse health outcomes in these patients and which comorbidities are most important.
OBJECTIVES:We aimed to address this knowledge gap by developing a patient-centred, clinically descriptive multimorbidity score for difficult-to-treat asthma.
METHODS:We used data from the UK-based Wessex Asthma Cohort of Difficult Asthma (WATCH; n=500, data collected between April 22, 2015, and April 1, 2020) to develop the Multimorbidity in Difficult Asthma Score (MiDAS). Initially, we created a modified Asthma Severity Scoring System (m-ASSESS) in WATCH. We then conducted univariate association analysis to test the association between the 13 commonest comorbidities and m-ASSESS in WATCH and used a branch-and-bound approach to select the most relevant comorbidities for inclusion in MiDAS. We calculated MiDAS values for all patients with complete information in WATCH (n=319) and assessed them for correlation with components of m-ASSESS, proinflammatory biomarkers, and St George's Respiratory Questionnaire (SGRQ) score, a quality-of-life measure. We also assessed the association of MiDAS with multiple clinical outcomes in four international cohorts: two from Australia (n=236, data collected between June 14, 2014, and April 1, 2022; and n=140, Aug 6, 2012, to Oct 18, 2016), one from southeast Asia (n=151, March 21, 2017, to Jan 16, 2024), and one from the USA (n=100, July 9, 2021, to Dec 14, 2023).
RESULTS:We selected seven common comorbidities (ie, rhinitis, gastro-oesophageal reflux disease, breathing pattern disorder, obesity, bronchiectasis, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and obstructive sleep apnoea) for inclusion in MiDAS on the basis of the branch-and-bound analysis and combined them using multivariate linear regression to derive a MiDAS model associated with m-ASSESS in WATCH. The range of MiDAS scores was 9·6-16·2. In WATCH members, mean MiDAS value was 11·97 (SD 1·21) and MiDAS was nominally correlated with m-ASSESS components of poor asthma control (τ=0·31 [95% CI 0·24-0·38]) and exacerbations (τ=0·16 [0·08-0·24]). MiDAS was also correlated with worse total SGRQ score (r=0·39 [95% 0·28-0·49], p<0·0001) and with the proinflammatory plasma cytokines interleukin (IL)-4 (r=0·19 [95% CI 0·06-0·31], p=0·0036), IL-5 (r=0·35 [0·24-0·46], p<0·0001), and leptin (r=0·29 [0·17-0·40], p<0·0001) in WATCH. MiDAS values across the four international cohorts were similar to those of WATCH (UK cohort), with mean values of 12·33 (SD 1·47) and 12·31 (1·37) in the Australian cohorts, 11·80 (1·20) in the USA cohort, and 11·55 (1·23) in the Singapore cohort. In these cohorts, MiDAS correlated with worse asthma control, worse quality of life, anxiety, depression, and increased inflammation.
CONCLUSION: MiDAS highlights the co-occurrence of multimorbidity with the worst outcomes in difficult-to-treat asthma. These findings strongly indicate that an airway-centric approach is inadequate and that holistic and multidisciplinary care is imperative. This clinical score could help clinicians to identify patients most at risk from their multimorbidity.
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