title: Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model.
abstract: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management.
  
  
  
  We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes).
  
  
  
  80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer-Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.69 (95% CI 0.63 to 0.75; 0.63 to 0.75 and 0.63 to 0.75) for the three models, respectively; calibration was best for the spirometry ­model.
  
  
  
  A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of FeNO is modest. These models merit an implementation study in clinical practice to assess their utility.
  
  
  
  NTR 1756.
authors.affiliation: Department of General Practice, Academic Medical Center-University of Amsterdam (AMC), Amsterdam, The Netherlands.
authors.forename: Rik J B
authors.initials: RJ
authors.lastname: Loymans
authors.affiliation: LUMC Quality of Care Institute, Leiden University Medical Center (LUMC), Leiden, The Netherlands Department of Public Health and Primary Care, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Persijn J
authors.initials: PJ
authors.lastname: Honkoop
authors.affiliation: Department of Primary and Community Care, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
authors.forename: Evelien H
authors.initials: EH
authors.lastname: Termeer
authors.affiliation: LUMC Quality of Care Institute, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Jiska B
authors.initials: JB
authors.lastname: Snoeck-Stroband
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center (LUMC), Leiden, The Netherlands Department of Primary and Community Care, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
authors.forename: Willem J J
authors.initials: WJ
authors.lastname: Assendelft
authors.affiliation: Department of Primary and Community Care, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands.
authors.forename: Tjard R J
authors.initials: TR
authors.lastname: Schermer
authors.affiliation: Experimental Airway Disease, National Heart and Lung Institute, Imperial College London & Royal Brompton NIHR Biomedical Research Unit, London, UK.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Sousa
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center-University of Amsterdam (AMC), Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Clinical Management Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Reddel
authors.affiliation: LUMC Quality of Care Institute, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
authors.affiliation: Department of General Practice, Academic Medical Center-University of Amsterdam (AMC), Amsterdam, The Netherlands.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ter Riet
mesh_terms: D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry / Q000379:methods; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents
keywords: Asthma Epidemiology; Asthma in primary care