Journal of Asthma and Allergy (Dec 2023)
How Does Mild Asthma Differ Phenotypically from Difficult-to-Treat Asthma?
Abstract
Jennifer Naftel,1,* Heena Mistry,1– 5,* Frances Ann Mitchell,4 Jane Belson,4 Mohammed Aref Kyyaly,2,4 Clair Barber,1,2 Hans Michael Haitchi,1– 3,6 Paddy Dennison,1– 3 Ratko Djukanovic,1– 3,6 Gregory Seumois,5 Pandurangan Vijayanand,2,5 Syed Hasan Arshad,1– 4,6 Ramesh J Kurukulaaratchy1– 4 1National Institute for Health Research (NIHR) Southampton Biomedical Research Centre at University Hospital Southampton NHS Foundation Trust, Southampton, UK; 2Clinical and Experimental Sciences Department, Faculty of Medicine, University of Southampton, Southampton, UK; 3Asthma, Allergy and Clinical Immunology Department, University Hospital Southampton NHS Foundation Trust, Southampton, UK; 4The David Hide Asthma & Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight, UK; 5Vijayanand Laboratory, La Jolla Institute of Immunology, San Diego, CA, 92037, USA; 6Institute for Life Sciences, University of Southampton, Southampton, UK*These authors contributed equally to this workCorrespondence: Ramesh J Kurukulaaratchy, Respiratory Medicine & Allergy, Clinical Experimental Sciences, Mailpoint 810, F-Level, South Academic Block, Southampton General Hospital, Tremona Road, Southampton, Hampshire, SO16 6YD, United Kingdom, Tel +442381 208790, Email [email protected]: Despite most of the asthma population having mild disease, the mild asthma phenotype is poorly understood. Here, we aim to address this gap in knowledge by extensively characterising the mild asthma phenotype and comparing this with difficult-to-treat asthma.Methods: We assessed two real-world adult cohorts from the South of England using an identical methodology: the Wessex AsThma CoHort of difficult asthma (WATCH) (n=498) and a mild asthma cohort from the comparator arm of the Epigenetics Of Severe Asthma (EOSA) study (n=67). Data acquisition included detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, plus biological samples (blood and sputum) in a subset.Results: Mild asthma is predominantly early-onset and is associated with type-2 (T2) inflammation (atopy, raised fractional exhaled nitric oxide (FeNO), blood/sputum eosinophilia) plus preserved lung function. A high prevalence of comorbidities and multimorbidity was observed in mild asthma, particularly depression (58.2%) and anxiety (56.7%). In comparison to difficult asthma, mild disease showed similar female predominance (> 60%), T2-high inflammation and atopy prevalence, but lower peripheral blood/airway neutrophil counts and preserved lung function. Mild asthma was also associated with a greater prevalence of current smokers (20.9%). A multi-component T2-high inflammatory measure was comparable between the cohorts; T2-high status 88.1% in mild asthma and 93.5% in difficult asthma.Conclusion: Phenotypic characterisation of mild asthma identified early-onset disease with high prevalence of current smokers, T2-high inflammation and significant multimorbidity burden. Early comprehensive assessment of mild asthma patients could help prevent potential later progression to more complex severe disease.Keywords: mild asthma, difficult asthma, multimorbidity, type 2 inflammation