Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts

Ramesh J Kurukulaaratchy¹, Anna Freeman², Aruna T Bansal³, Latha Kadalayil⁴, Eve Denton⁵, Vanessa Clark⁶, Peter G Gibson⁷, Judit Varkonyi-Sepp⁸, Ben Ainsworth⁹, J J Hudson-Colby¹⁰, Adam Lewis¹¹, Chellan Eames¹², Liuyu Wei¹³, Wei Chern Gavin Fong¹⁴, Ratko Djukanovic², Sanja Hromis¹⁵, Tunn Ren Tay¹⁶, Njira Lugogo¹⁷, Vanessa M McDonald⁶, Mark Hew⁵, Hans Michael Haitchi¹⁸

Affiliations

¹ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; David Hide Asthma & Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address: rjk1s07@soton.ac.uk.
² School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³ Acclarogen, St John's Innovation Centre, Cambridge, UK.
⁴ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; School of Chemistry and Chemical Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.
⁵ Allergy, Asthma & Clinical Immunology, Alfred Hospital, Melbourne, VIC, Australia; Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ National Health and Medical Research Council Centre for Research Excellence in Severe Asthma, University of Newcastle, Newcastle, NSW, Australia; National Health and Medical Research Council Centre for Research Excellence in Treatable Traits, Hunter Medical Research Institute Asthma and Breathing Research Program, Newcastle, NSW, Australia; School of Nursing and Midwifery, University of Newcastle, Newcastle, NSW, Australia.
⁷ National Health and Medical Research Council Centre for Research Excellence in Severe Asthma, University of Newcastle, Newcastle, NSW, Australia; National Health and Medical Research Council Centre for Research Excellence in Treatable Traits, Hunter Medical Research Institute Asthma and Breathing Research Program, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, NSW, Australia.
⁸ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Health Psychology Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁹ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
¹⁰ Physiotherapy Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK; School of Health Sciences, University of Southampton, Southampton, UK.
¹¹ School of Health Sciences, University of Southampton, Southampton, UK.
¹² Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹³ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹⁴ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
¹⁵ Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
¹⁶ Duke-NUS Medical School, Singapore; Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore.
¹⁷ Michigan Medicine Asthma Program, University of Michigan, Ann Arbor, MI, USA.
¹⁸ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.

PMID: 40645203
DOI: 10.1016/S2213-2600(25)00135-3

Free article

Multicenter Study

Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts

Ramesh J Kurukulaaratchy et al. Lancet Respir Med. 2025 Sep.

Free article

. 2025 Sep;13(9):821-832.

doi: 10.1016/S2213-2600(25)00135-3. Epub 2025 Jul 8.

Authors

Affiliations

¹ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; David Hide Asthma & Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address: rjk1s07@soton.ac.uk.
² School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
³ Acclarogen, St John's Innovation Centre, Cambridge, UK.
⁴ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; School of Chemistry and Chemical Engineering, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK.
⁵ Allergy, Asthma & Clinical Immunology, Alfred Hospital, Melbourne, VIC, Australia; Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁶ National Health and Medical Research Council Centre for Research Excellence in Severe Asthma, University of Newcastle, Newcastle, NSW, Australia; National Health and Medical Research Council Centre for Research Excellence in Treatable Traits, Hunter Medical Research Institute Asthma and Breathing Research Program, Newcastle, NSW, Australia; School of Nursing and Midwifery, University of Newcastle, Newcastle, NSW, Australia.
⁷ National Health and Medical Research Council Centre for Research Excellence in Severe Asthma, University of Newcastle, Newcastle, NSW, Australia; National Health and Medical Research Council Centre for Research Excellence in Treatable Traits, Hunter Medical Research Institute Asthma and Breathing Research Program, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, NSW, Australia.
⁸ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Clinical Health Psychology Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁹ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
¹⁰ Physiotherapy Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK; School of Health Sciences, University of Southampton, Southampton, UK.
¹¹ School of Health Sciences, University of Southampton, Southampton, UK.
¹² Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹³ National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹⁴ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
¹⁵ Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
¹⁶ Duke-NUS Medical School, Singapore; Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore.
¹⁷ Michigan Medicine Asthma Program, University of Michigan, Ann Arbor, MI, USA.
¹⁸ School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Respiratory Medicine Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.

PMID: 40645203
DOI: 10.1016/S2213-2600(25)00135-3

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).

Findings: 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.

Interpretation: 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.

Funding: UK National Institute for Health and Care Research, Australian National Health and Medical Research Council, Hunter Medical Research Institute, University of Newcastle (Australia), and John Hunter Hospital Charitable Trust.

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Conflict of interest statement

Declaration of interests RJK co-holds a methods patent outside the submitted work on the cellular profiles of tissue resident memory T-cells and their use in asthma. BA is a member of the UK Taskforce for Lung Health, has received honoraria for educational talks from AstraZeneca, and sits on advisory boards for the Medito Foundation and earGym (all unrelated to this work). PGG reports personal fees from AstraZeneca, GSK, and Novartis and grants from AstraZeneca and GSK, outside the submitted work. VMM reports grants from GSK outside the submitted work, and advisory board and speaker fees from GSK, Menarini, and Boehringer-Ingelheim outside the submitted work. VC reports speakers fees from AstraZeneca, unrelated to the conduct of this study. MH has received grants and personal fees outside the submitted work from GSK, AstraZeneca, Sanofi, Novartis, Teva, and Chiesi, all paid to his employer Alfred Health. CE reports travel support from Chiesi and speaker fees from AstraZeneca outside the submitted work. RD is a co-founder of and consultant to Synairgen, has received funding for lectures from GSK, and has been on advisory boards of GSK, Celltrion, ALK Abello, and ZenasBio, all unrelated to this work. Unrelated to this work, NL has received consulting fees from Amgen, AstraZeneca, Avillion, Genentech, GSK, Niox, Novartis, Regeneron, Sanofi, and Teva; honoraria for non-speakers bureau presentations from GSK, Teva, and AstraZeneca; and travel support from AstraZeneca, Sanofi, Teva, Regeneron, and GSK; her institution received research support from Amgen, AstraZeneca, Avillion, Bellus, Evidera, Gossamer Bio, Genentech, GSK, Janssen, Niox, Regeneron, Sanofi, Novartis, and Teva. NL is an honorary faculty member of the Observational and Pragmatic Research Institute but does not receive compensation for this role. SH reports speakers fees from AstraZeneca, Berlin-Chemie Menarini, Takeda, Providens, and Amicus Therapeutics; support for attending meetings from AstraZeneca, Chiesi (Providens), and Hemofarm; and payment for advisory boards from AstraZeneca, Berlin-Chemie Menarini, and Providens, all unrelated to this work. WCGF declares stock ownership in relation to Sanofi, GSK, and AstraZeneca, unrelated to this work. HMH co-holds a method patent on anti-ADAM33 oligonucleotides and related methods, which is unrelated to the current work. All other authors declare no competing interests.

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Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts

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Evaluation of the effect of multimorbidity on difficult-to-treat asthma using a novel score (MiDAS): a multinational study of asthma cohorts

Authors

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Abstract

Conflict of interest statement

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