Sex differences in the clinical phenotype of difficult-to-treat asthma in adults.

Authors

Zoya Ahsan, Anna Freeman, Helen E Moyses, David Charles, Ben Ainsworth, Liuyu Wei, Hans Michael Haitchi, Chellan Eames, J J Hudson-Colby, Adam Lewis, Judit Varkonyi-Sepp, Hitasha Rupani, Patrick Dennison, Syed Hasan Arshad, Ratko Djukanovic, Elena Dabrio-Reina, Elena Vladimirovna Vorobeva, Ramesh Kurukulaaratchy

Published in

The journal of allergy and clinical immunology. In practice. Oct 30, 2026. Epub Oct 30, 2026.

Abstract

Sex disparity has been demonstrated within difficult-to-treat (difficult) asthma, with females reported to have greater disease severity and more comorbidities. Deeper understanding of these differences could help personalise management approaches.
To assess differences in disease characteristics between males and females with difficult asthma.
The Wessex AsThma CoHort study collected data from 500 patients across Southern England. Patient demographics, asthma and its treatment history, allergies, comorbidities, radiology, biological samples, lung function, and questionnaire data were subjected to univariable analyses to identify sex differences. Variables were then further assessed in multivariable regression models.
Males were older at disease onset and were more often ex-smokers. In multivariable regression models they had higher serum immunoglobulin E (ratio 1.95, 95% CI 1.19 to 3.20) and plasma inflammatory cytokine expression (interleukin-17, tumour necrosis factor - alpha, C-C motif ligands 3 and 11 and chitinase 3-like 1). Males had poorer lung function (forced expiratory volume in 1 second effect -9.98, 95% CI -15.21 to -4.74) and more frequently had nasal polyps. Females had higher Body Mass Index, and in multivariable regression higher plasma adipokine (ratio 1.25, 95% CI 1.12 to 1.37) and interleukin-5 expression (effect 3.52, 95% CI 2.65 to 4.39), multimorbidity burden (score effect 0.60, 95% CI 0.29 to 0.92), anxiety/depression, and inducible laryngeal obstruction (odds ratio 2.38, 95% CI 1.20 to 4.76). They self-reported worse Hull Cough Hypersensitivity, Nijmegen and Sino-Nasal Outcome Test scores. We observed no difference in treatment and healthcare utilisation, or composite asthma severity score.
Sex influences difficult asthma phenotype but contrasting factors are associated with similar overall disease severity in both sexes. Males have worse lung function and systemic inflammatory profiles, whilst females experience greater psychophysiological comorbidity and multimorbidity burden. Recognising differences and considering them clinically to fine-tune management may help improve difficult asthma outcomes.

PMID:
42962920
Bibliographic data and abstract were imported from PubMed on 31 Oct 2026.

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