The Detrimental Clinical Associations Of Anxiety and Depression with Difficult Asthma Outcomes

Wei Chern Gavin Fong, Ishmail Rafiq, Matt Harvey, Sabina Stanescu, Ben Ainsworth, Judit Varkonyi-Sepp, Heena Mistry, Aref Kyyaly, Clair Barber, Mae Felongco, Tom Wilkinson, Ratko Djukanovic, Paddy Dennison, Ramesh Kurukulaaratchy

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4 Citations (SciVal)


Difficult asthma describes asthma in which comorbidities, inadequate treatment, subop-timal inhaler technique and/or poor adherence impede good asthma control. The association of anxiety and depression with difficult asthma outcomes (exacerbations, hospital admissions, asthma control, etc.) is unclear. This study assessed the clinical associations of anxiety and depression with difficult asthma outcomes in patients with a specialist diagnosis of difficult asthma. Using real-world data, we retrospectively phenotyped patients from the Wessex Asthma Cohort of Difficult Asthma (N = 441) using clinical diagnoses of anxiety and depression against those without anxiety or depression (controls). Additionally, we stratified patients by severity of psychological distress using the Hospital Anxiety and Depression Scale (HADS). We found that depression and/or anxiety were reported in 43.1% of subjects and were associated with worse disease-related questionnaire scores. Each psychological comorbidity group showed differential associations with difficult asthma outcomes. Anxiety alone (7.9%) was associated with dysfunctional breathing and more hospitalisa-tions [anxiety, median (IQR): 0 (2) vs. controls: 0 (0)], while depression alone (11.6%) was associated with obesity and obstructive sleep apnoea. The dual anxiety and depression group (23.6%) displayed multimorbidity, worse asthma outcomes, female predominance and earlier asthma onset. Worse HADS-A scores in patients with anxiety were associated with worse subjective outcomes (ques-tionnaire scores), while worse HADS-D scores in patients with depression were associated with worse objective (ICU admissions and maintenance oral corticosteroid requirements) and subjective outcomes. In conclusion, anxiety and depression are common in difficult asthma but exert differential detrimental effects. Difficult asthma patients with dual anxiety and depression experience worse asthma outcomes alongside worse measures of psychological distress. There is a severity-gradient association of HADS scores with worse difficult asthma outcomes. Collectively, our findings highlight the need for holistic, multidisciplinary approaches that promote early identification and management of anxiety and depression in difficult asthma patients.

Original languageEnglish
Article number686
JournalJournal of Personalized Medicine
Issue number5
Early online date26 Apr 2022
Publication statusPublished - 31 May 2022

Bibliographical note

Funding Information:
Funding: The WATCH study received a non-promotional grant from Novartis (35,000 GBP) and initial assistance through a charitable grant (3500 GBP) for relevant patient costs (e.g., parking) from the Asthma, Allergy and Inflammation Research Charity. The WATCH study itself is not externally funded.

Funding Information:
Acknowledgments: We would like to extend our heartfelt gratitude to the WATCH patients and the wider WATCH study team: Yvette Thirlwall, Kimberley Bennett, Karen Long, Deborah Knight, Colin Newell, Yueqing Cheng, Kerry Day, Mae Felongco, David Hill, Adnan Azim, and Peter Howarth. We also wish to acknowledge the support of the Southampton NIHR Biomedical Research Centre and the Southampton NIHR Clinical Research Facility, which are funded by the NIHR and are a partnership between the University of Southampton and the University Hospital Southampton NHS Foundation Trust.

Funding Information:
Conflicts of Interest: W.C.G.F. reports ownership of Sanofi, AstraZeneca, G.S.K., Synairgen and BioNTech stocks. B.A. reports personal fees from AstraZeneca and personal fees from Roche. T.W. reports personal fees and other fees from M.M.H., grants and personal fees from G.S.K., grants and personal fees from AstraZeneca, personal fees from B.I. and grants and personal fees from Synairgen. J.V.S. reports grants from Glaxo SmithKline, grants from Asthma Allergy and Inflammation Research Trust Ltd., outside the submitted work. R.D. reports consultancy fees from Sanofi, Boehringer, Novartis and TEVA Pharmaceuticals; speaker fees from Novartis and TEVA Pharmaceuticals; grants from Novartis, I.M.I. and M.R.C.; and ownership of Synairgen stocks. R.D. also sits on the Urgent Public Health committee and is one of the co-founders of Synairgen. No relevant conflicts of interest exist for I.R., M.H., S.S., H.M., M.A.K., C.B., M.F., P.D., H.M.H. or R.J.K.


  • anxiety disorders
  • asthma
  • cohort studies
  • mental health
  • mood disorders

ASJC Scopus subject areas

  • Medicine (miscellaneous)


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