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

Background: multimorbidity (co-existence of 2 or more health conditions) is highly prevalent in difficult-to-treat asthma. However, it remains unclear as to how multimorbidity correlates with disease severity and adverse health outcomes in such patients, and which comorbidities are most important. We aimed to develop a patient-centred, clinically descriptive Multimorbidity in Difficult Asthma Score (MiDAS) to address that knowledge gap.<br/><br/>Methods: we analysed data from the UK-based Wessex Asthma Cohort of Difficult Asthma (WATCH) (n=500; 2015-2020) to develop MiDAS, which we then sought to test in cohorts from Australia (two cohorts: n=236, 2014-2017; n=140, 2014-2017), South-East Asia (n=151, 2017-2024), and the USA (n=100, 2021-2023). Initially, we created a modified Asthma Severity Scoring System (m-ASSESS) in WATCH. We then conducted univariate association analysis between the 13 commonest comorbidities and m-ASSESS in WATCH, followed by a branch-and-bound approach to select relevant comorbidities associated with m-ASSESS for inclusion in MiDAS. We next assessed MiDAS and its association with multiple clinical outcomes in the other cohorts.<br/><br/>Findings: our study cohorts demonstrated some ethnicity differences but exhibited broadly similar clinical and comorbidity characteristics. By selecting and combining seven common comorbidities [rhinitis, gastro-oesophageal reflux disease (GORD), breathing pattern disorder (BPD), obesity, bronchiectasis, Nonsteroidal anti-inflammatory drug-Exacerbated Respiratory Disease (NERD), and obstructive sleep apnoea (OSA)] we calculated a MiDAS model associated with m-ASSESS in WATCH. MiDAS was correlated with adverse quality-of-life measures and pro-inflammatory plasma cytokines in WATCH. MiDAS was investigated in the independent cohorts, where it correlated with worse asthma control, worse quality of life, anxiety, depression, and increased inflammation.<br/><br/>Interpretation: MiDAS shines a spotlight on the co-occurrence of multimorbidity with the worst outcomes in difficult-to-treat asthma. There can now be no doubt that an airway-centric approach is inadequate: holistic and multi-disciplinary care is imperative. This clinical score could help clinicians to identify patients most in need.<br/><br/><br/>