Factors Associated with Frequent Exacerbations in the UK Severe Asthma Registry

Freda Yang,John Busby,Liam G Heaney,Andrew Menzies-Gow,Paul E Pfeffer,David J Jackson,Adel H Mansur,Salman Siddiqui,Christopher E Brightling,Robert Niven,Neil C Thomson,Rekha Chaudhuri,Mitesh Patel,Robin Gore,Thomas Brown,Aashish Vyas,Deepak Subramanian

doi:10.1016/j.jaip.2020.12.062

Abstract

Frequent exacerbations are an important cause of morbidity in patients with severe asthma. Our aim was to identify factors associated with frequent exacerbations in a large well-characterized severe asthma population and determine whether factors differed in patients treated with and without maintenance oral corticosteroids (OCS). Adults with severe asthma from specialized asthma centers across the United Kingdom were recruited to the UK Severe Asthma Registry. Demography, comorbidities and physiological measurements were collected. We conducted univariable and multivariable logistic regression analyses to identify factors associated with frequent exacerbations, defined as 3 or more exacerbations treated with high-dose systemic corticosteroids in the past year. Of 1,592 patients with severe asthma from the UK Severe Asthma Registry, 1,137 (71%) were frequent exacerbators and 833 (52%) were on maintenance OCS. The frequent exacerbators were more likely to be ex-smokers, have gastroesophageal reflux disease, higher Asthma Control Questionnaire-6 (ACQ-6) score, and higher blood eosinophilia. Multivariable regression analyses showed ACQ-6 score greater than 1.5 (odds ratio [OR] 4.25; P < .001), past smoking history (OR 1.55; P= .024), and fractional exhaled nitric oxide greater than 50ppb (OR 1.54; P= .044) were independently associated with frequent exacerbations. Past smoking history correlated with frequent exacerbations only in patients on maintenance OCS (OR 2.25; P= .004), whereas ACQ-6 score greater than 1.5 was independently associated with frequent exacerbations in those treated with and without maintenance OCS (OR 2.74; P= .017 and OR 6.42; P < .001, respectively). Several factors were associated with frequent exacerbations in a large UK severe asthma registry population. High ACQ-6 score had the strongest association with frequent exacerbations irrespective of maintenance OCS status.

Highlights

Frequent exacerbations are an important cause of morbidity in patients with severe asthma
Frequent exacerbations are common in patients with severe asthma and are associated with poorer quality of life and higher health care costs.[1,2,3] Risk factors for exacerbations reported from studies of severe asthma include past history of severe exacerbations, high body mass index (BMI), chronic sinusitis, gastroesophageal reflux disease (GERD), psychological stress, a history of cigarette smoking, reduced lung function, blood or sputum eosinophilia and raised fractional exhaled nitric oxide (FeNO).(2, 4-10) It is uncertain whether risk factors identified from observational studies of participants recruited to clinical trials or cohorts of severe asthma, which have strict inclusion criteria, are generalizable to a population of adults with severe asthma managed in clinical practice
Replication of these findings in a well-characterized severe asthma population not recruited into clinical trials would support the use of Asthma Control Questionnaire (ACQ) in clinical practice to determine the risk of frequent exacerbations

Summary

Introduction

Frequent exacerbations are an important cause of morbidity in patients with severe asthma. The Asthma Control Questionnaire (ACQ) is a validated tool for assessing asthma control based on patient self-reported symptoms; a higher score indicates poorer control.[11] Post-hoc analysis of clinical trial data showed a positive correlation between ACQ score and exacerbation rates.[12, 13] The correlation between persistent symptoms and frequent exacerbations in patients with severe asthma is not well established. Replication of these findings in a well-characterized severe asthma population not recruited into clinical trials would support the use of ACQ in clinical practice to determine the risk of frequent exacerbations. This would, in turn, offer useful guidance for management planning

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Conclusion