使用一项新评分（MiDAS）评估多病共存对难治性哮喘的影响：一项多国哮喘队列研究
2025/08/01
摘要
背景：多病共存（即同时存在两种或以上健康状况）在难治性哮喘患者中高度普遍。然而，目前尚不清楚多病共存与此类患者的疾病严重程度及不良健康结局之间的关系，以及哪些合并疾病最为重要。我们旨在通过开发一个以患者为中心、具有临床描述性的难治性哮喘多病共存评分（MiDAS），以填补这一知识空白。
方法：本研究使用来自英国Wessex难治性哮喘队列（WATCH，n=500，数据收集时间：2015年4月22日至2020年4月1日）的数据开发了“难治性哮喘多病共存评分”（MiDAS）。首先，我们在WATCH队列中建立了改良版哮喘严重度评分系统（m-ASSESS），随后进行单变量相关性分析，以检验WATCH队列中最常见的13种合并疾病与m-ASSESS之间的关联，并采用分枝定界法筛选最相关的合并疾病纳入MiDAS评分。我们对WATCH中资料完整的患者（n=319）计算了MiDAS值，并评估其与m-ASSESS各组成部分、促炎性生物标志物及圣乔治呼吸问卷（SGRQ，生活质量测量工具）得分的相关性。我们还在四个国际队列（澳大利亚两队列：n=236 [2014年6月14日至2022年4月1日]，n=140 [2012年8月6日至2016年10月18日]；东南亚队列：n=151 [2017年3月21日至2024年1月16日]；美国队列：n=100 [2021年7月9日至2023年12月14日]）中评估了MiDAS与多项临床结局之间的关联。
结果：基于分枝定界分析，我们选定了七种常见合并疾病（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道疾病以及阻塞性睡眠呼吸暂停）纳入MiDAS评分，并通过多元线性回归将其与WATCH队列中的m-ASSESS相关联，建立了MiDAS模型。MiDAS得分范围为9.6–16.2。在WATCH患者中，MiDAS平均值为11.97（标准差1.21），且MiDAS与m-ASSESS中哮喘控制不良（τ=0.31 [95% CI 0.24–0.38]）及加重发作（τ=0.16 [0.08–0.24]）组成部分呈名义相关性。MiDAS还与更差的SGRQ总分（r=0.39 [95% CI 0.28–0.49]，p<0.0001）及促炎性血浆细胞因子（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；瘦蛋白: r=0.29 [0.17–0.40], p<0.0001）呈相关。在四个国际队列中，MiDAS平均值与WATCH（英国队列）相似，澳大利亚两个队列的平均值分别为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均与较差的哮喘控制、较差的生活质量、焦虑、抑郁及炎症水平升高呈相关。
结论：MiDAS揭示了多病共存与难治性哮喘最不良结局的共同存在。这一发现强烈表明，单纯以气道为中心的治疗方法是不足够的，全面且多学科的管理是必要的。该临床评分有助于临床医生识别多病共存风险最高的患者。
Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts
Kurukulaaratchy, R. J., Freeman, A., Bansal, A. T., Kadalayil, L., Denton, E., Clark, V., Gibson, P. G., Varkonyi-Sepp, J., Ainsworth, B., Hudson-Colby, J. J., Lewis, A., Eames, C., Wei, L., Fong, W. C. G., Djukanovic, R., Hromis, S., Tay, T. R., Lugogo, N., McDonald, V. M., Hew, M., … Haitchi, H. M. (2025)
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. 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：多病共存（即同时存在两种或以上健康状况）在难治性哮喘患者中高度普遍。然而，目前尚不清楚多病共存与此类患者的疾病严重程度及不良健康结局之间的关系，以及哪些合并疾病最为重要。我们旨在通过开发一个以患者为中心、具有临床描述性的难治性哮喘多病共存评分（MiDAS），以填补这一知识空白。
方法：本研究使用来自英国Wessex难治性哮喘队列（WATCH，n=500，数据收集时间：2015年4月22日至2020年4月1日）的数据开发了“难治性哮喘多病共存评分”（MiDAS）。首先，我们在WATCH队列中建立了改良版哮喘严重度评分系统（m-ASSESS），随后进行单变量相关性分析，以检验WATCH队列中最常见的13种合并疾病与m-ASSESS之间的关联，并采用分枝定界法筛选最相关的合并疾病纳入MiDAS评分。我们对WATCH中资料完整的患者（n=319）计算了MiDAS值，并评估其与m-ASSESS各组成部分、促炎性生物标志物及圣乔治呼吸问卷（SGRQ，生活质量测量工具）得分的相关性。我们还在四个国际队列（澳大利亚两队列：n=236 [2014年6月14日至2022年4月1日]，n=140 [2012年8月6日至2016年10月18日]；东南亚队列：n=151 [2017年3月21日至2024年1月16日]；美国队列：n=100 [2021年7月9日至2023年12月14日]）中评估了MiDAS与多项临床结局之间的关联。
结果：基于分枝定界分析，我们选定了七种常见合并疾病（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道疾病以及阻塞性睡眠呼吸暂停）纳入MiDAS评分，并通过多元线性回归将其与WATCH队列中的m-ASSESS相关联，建立了MiDAS模型。MiDAS得分范围为9.6–16.2。在WATCH患者中，MiDAS平均值为11.97（标准差1.21），且MiDAS与m-ASSESS中哮喘控制不良（τ=0.31 [95% CI 0.24–0.38]）及加重发作（τ=0.16 [0.08–0.24]）组成部分呈名义相关性。MiDAS还与更差的SGRQ总分（r=0.39 [95% CI 0.28–0.49]，p<0.0001）及促炎性血浆细胞因子（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；瘦蛋白: r=0.29 [0.17–0.40], p<0.0001）呈相关。在四个国际队列中，MiDAS平均值与WATCH（英国队列）相似，澳大利亚两个队列的平均值分别为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均与较差的哮喘控制、较差的生活质量、焦虑、抑郁及炎症水平升高呈相关。
结论：MiDAS揭示了多病共存与难治性哮喘最不良结局的共同存在。这一发现强烈表明，单纯以气道为中心的治疗方法是不足够的，全面且多学科的管理是必要的。该临床评分有助于临床医生识别多病共存风险最高的患者。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
（Lancet Respir Med. 2025 Jul 8; DOI: 10.1016/S2213-2600(25)00135-3 ）
Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts
Kurukulaaratchy, R. J., Freeman, A., Bansal, A. T., Kadalayil, L., Denton, E., Clark, V., Gibson, P. G., Varkonyi-Sepp, J., Ainsworth, B., Hudson-Colby, J. J., Lewis, A., Eames, C., Wei, L., Fong, W. C. G., Djukanovic, R., Hromis, S., Tay, T. R., Lugogo, N., McDonald, V. M., Hew, M., … Haitchi, H. M. (2025)
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. 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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