Long‐term future risk of severe exacerbations: Distinct 5‐year trajectories of problematic asthma

Abstract

BackgroundAssessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short‐ but not long‐term risk. Problematic asthma patients with unfavorable long‐term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment.AimTo identify distinct trajectories of severe exacerbation rates among “problematic asthma” patients and develop a risk score to predict the most unfavorable trajectory.MethodsSevere exacerbation rates over five years for 177 “problematic asthma” patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group‐based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory.ResultsThree distinct trajectories were found: 58.5% had rare intermittent severe exacerbations (“infrequent”), 32.0% had frequent severe exacerbations at baseline but improved subsequently (“nonpersistently frequent”), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near‐fatal asthma (“persistently frequent”). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near‐fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the “persistently frequent” trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort.ConclusionsPatients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.

Multidimensional assessment of severe asthma: A systematic review and meta‐analysis

“…Psychological dysfunction was most frequently assessed (69.2% of Group 1), followed by sinusitis (nine studies) and gastro‐oesophageal reflux disease (GORD) (six studies) …”

“…Twenty-six studies were included, they were heterogeneous in their design and research questions. We allocated the studies into three groups based on their design: Group 1 'cohort studies/cross-sectional studies' (13 studies), [21][22][23][24][25][26][27][28][29][30][31][32][33][34] which included those that used MDA to examine the prevalence of co-morbidities and risk factors among selected groups of patients with severe asthma. Also included in this group were studies that used baseline variables to predict outcomes, such as exacerbations.…”

“…Bronchodilator reversibility (BDR) and airflow limitation were assessed 12 of 13 studies [22][23][24][25][27][28][29][30][32][33][34]42 (Table 2). Blood eosinophils were assessed in eight studies [21][22][23][24][25]30,[32][33][34] and airway inflammation (induced sputum and cell counts or fractional exhaled nitric oxide (FeNO) in fewer than half (six studies)). 23,25,27,30,32,33 Experimental/outcome studies.…”

Blood eosinophil count correlates with severity of respiratory failure in life‐threatening asthma and predicts risk of subsequent exacerbations

“…A blood eosinophil count is an easily acquired biomarker that correlates reasonably well with sputum eosinophilia, and elevated blood eosinophils have been shown to predict future exacerbation risk as well as treatment response to corticosteroids and anti‐IL‐5, anti‐IL‐5‐receptor‐alpha or anti‐IL‐4 receptor alpha antibodies . Most studies have investigated blood eosinophils when asthma is in stable state but not during an exacerbation of asthma . Blood eosinophil count varies between exacerbation and stable‐state, and the usefulness of measuring a spot blood eosinophil count during an exacerbation in relation to short‐term outcome of the exacerbation as well as the long‐term outcome of asthma is not known.…”

“…[9][10][11][12][13][14][15][16][17] Most studies have investigated blood eosinophils when asthma is in stable state but not during an exacerbation of asthma. 18 Blood eosinophil count varies between exacerbation and stable-state, [19][20][21] and the usefulness of measuring a spot blood eosinophil count during an exacerbation in relation to short-term outcome of the exacerbation as well as the long-term outcome of asthma is not known.…”