How Does Mild Asthma Differ Phenotypically from Difficult-to-Treat Asthma?

Abstract

Background

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

Abbreviations

• A. fumigatus, Aspergillus fumigatus; ABPA, Allergic bronchopulmonary aspergillosis; ACQ-6, Asthma control questionnaire-6; BD, Bronchodilator; BDP equiv., Beclomethasone dipropionate equivalent/day; BEC, Blood eosinophil count; BMI, Body mass index; BRC, Biomedical Research Centre; BTS, British Thoracic Society; DHAAC, David Hide Asthma & Allergy Centre; COPD, Chronic obstructive pulmonary disease; EOSA, Epigenetics of Severe Asthma; EQ5D-5L, EuroQoL 5D-5L questionnaire; FeNO, Fractional exhaled nitrogen oxide; FEF_25-75%, Forced expiratory flow between 25 and 75% exhalation; FEV₁, Forced expiratory volume in 1 s; FVC, Forced vital capacity; GINA, Global Initiative for Asthma; GORD, Gastro-oesophageal reflux disease; HADS-A, Hospital anxiety and depression scale – anxiety subscale; HADS-D, Hospital anxiety and depression scale – depression subscale; HRQoL, Health-related quality of life; ICS, Inhaled corticosteroid; ICU, Intensive care unit; IgE, Immunoglobulin E; IOW, Isle of Wight; IOWBC, Isle of Wight Whole Population Birth Cohort; LABA, Long-acting beta-agonist; mOCS, Maintenance oral corticosteroid; NIHR, National Institute for Health and Care Research https://www.nihr.ac.uk/; NRAD, National Review of Asthma Deaths; OCS, Oral corticosteroid; ppb, Parts per billion; SAFS, Severe asthma with fungal sensitisation; SGRQ, St George’s respiratory questionnaire; SNOT22, Sino-nasal outcome test-22; SPT, Skin prick test; T2, Type 2; UHSFT, University Hospital Southampton NHS Foundation Trust; VAS, Visual analogue scale; WATCH, Wessex AsThma CoHort of difficult asthma.

Data Sharing Statement

We confirm that data accessed complied with relevant data protection and privacy regulations with reference to the General Data Protection Regulations 2018.

Acknowledgments

The authors wish to thank the patients who are participating in this study. They also wish to acknowledge the contributions of the wider WATCH study team including Matthew Harvey, Mae Felongco, Yvette Thirlwall, Kim Bentley, Laura Presland, Yueqing Cheng, Josune Olza Meneses, Adnan Azim, Anna Freeman, Kerry Day, David Hill and Peter Howarth. The authors also wish to acknowledge the support of Southampton NIHR BRC and Clinical Research Facility. Southampton Clinical Research Facility and BRC are funded by NIHR and are a partnership between the University of Southampton and University Hospital Southampton NHS Foundation Trust. The authors also acknowledge funding support from Novartis, NIH and the AAIR Charity.

Disclosure

The authors, JN, HM, FM, JB, MAK, CB, HMH, PD, RD, GS, PV, SHA, RJK, declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Since completion of this work, CB now works for Aztra Zeneca. Professor Ratko Djukanovic reports personal fees, has shares in the company and is a consultant to Synairgen, and personal fees from GlaxoSmithKline and Kymab, outside the submitted work.

Additional information

Funding

The Wessex AsThma CoHort of difficult asthma (WATCH) study has been supported by the NIHR Southampton Biomedical Research Centre (BRC) and Clinical Research Facility at University Hospital Southampton NHS Foundation Trust (UHSFT), UK. The WATCH study itself is not externally funded. Funding assistance for database support for the WATCH study was initially obtained from a non-promotional grant from Novartis (£35,000). Funding assistance for patient costs (eg parking) was initially provided by a charitable grant (£3500) from the Asthma, Allergy & Inflammation Research (AAIR) Charity. Lastly, funding assistance for the Epigenetics of Severe Asthma (EOSA) study was obtained from a National Institutes of Health (NIH) grant (£400,000) in collaboration with La Jolla Institute of Immunology, La Jolla, California, USA.