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Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.

ABSTRACT: INTRODUCTION:Exacerbation-prone asthma subtype has been reported in studies using data-driven methodologies. However, patterns of severe exacerbations have not been studied. OBJECTIVE:To investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age. METHODS:We applied longitudinal k-means clustering to derive exacerbation trajectories among 887 participants from a population-based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early-life risk factors of the derived trajectories, and their asthma-related outcomes and lung function in adolescence. RESULTS:498/887 children (56%) had physician-confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two-cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: "Infrequent exacerbations (IE)" (n = 150, 93.7%) and "Early-onset frequent exacerbations (FE)" (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early-life risk factor for FE (weeks, median [IQR]: FE, 0 [0-1.75] vs. IE, 6 [0-20], P < .001). Specific airway resistance (sRaw ) was significantly higher in FE compared with IE trajectory throughout childhood. We then compared children in the two exacerbation trajectories with those who have never wheezed (NW, n = 389) or have wheezed but had no severe exacerbations (WNE, n = 338). At age 8 years, FEV1 /FVC was significantly lower and FeNO significantly higher among FE children compared with all other groups. By adolescence (age 16), subjects in FE trajectory were significantly more likely to have current asthma (67% FE vs. 30% IE vs. 13% WNE, P < .001) and use inhaled corticosteroids (77% FE vs. 15% IE vs. 18% WNE, P < .001). Lung function was significantly diminished in the FE trajectory (FEV1 /FVC, mean [95%CI]: 89.9% [89.3-90.5] vs. 88.1% [87.3-88.8] vs. 85.1% [83.4-86.7] vs. 74.7% [61.5-87.8], NW, WNE, IE, FE respectively, P < .001). CONCLUSION:We have identified two distinct trajectories of severe exacerbations during childhood with different early-life risk factors and asthma-related outcomes in adolescence.

SUBMITTER: Deliu M

PROVIDER: S-EPMC7065181 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.

Deliu Matea M Fontanella Sara S Haider Sadia S Sperrin Matthew M Geifman Nophar N Murray Clare C Simpson Angela A Custovic Adnan A

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20200121 3

<h4>Introduction</h4>Exacerbation-prone asthma subtype has been reported in studies using data-driven methodologies. However, patterns of severe exacerbations have not been studied.<h4>Objective</h4>To investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age.<h4>Methods</h4>We applied longitudinal k-means clustering to derive exacerbation trajectories among 887 participants from a population-based birth cohort with severe wheeze exacerbations confirmed in h ...[more]

PMID: 31876035

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Project description: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.

Dataset Information

Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.

Publications

Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes.

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