title: Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.
abstract: BACKGROUND
  Assessing 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.
  
  
  OBJECTIVE
  To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory.
  
  
  METHODS
  Severe 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.
  
  
  RESULTS
  Three 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.
  
  
  CONCLUSIONS
  Patients 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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: A C A
authors.initials: ACA
authors.lastname: Yii
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: J H Y
authors.initials: JHY
authors.lastname: Tan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Duke-National University Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: T S
authors.initials: TS
authors.lastname: Lapperre
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Allergy Centre, Singapore General Hospital, Singapore, Singapore.
authors.forename: A K W
authors.initials: AKW
authors.lastname: Chan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Duke-National University Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: S Y
authors.initials: SY
authors.lastname: Low
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Duke-National University Singapore Graduate Medical School, Singapore, Singapore.
authors.forename: T H
authors.initials: TH
authors.lastname: Ong
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Duke-National University Singapore Graduate Medical School, Singapore, Singapore.|Allergy Centre, Singapore General Hospital, Singapore, Singapore.
authors.forename: K L
authors.initials: KL
authors.lastname: Tan
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
authors.forename: S H
authors.identifier: http://orcid.org/0000-0003-0417-7607
authors.initials: SH
authors.lastname: Chotirmall
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.|Duke-National University Singapore Graduate Medical School, Singapore, Singapore.|Allergy Centre, Singapore General Hospital, Singapore, Singapore.
authors.forename: M S
authors.initials: MS
authors.lastname: Koh
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
keywords: asthma; asthma exacerbations; exacerbation risk; frequent exacerbations; recurrent exacerbations