title: Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing.
abstract: BACKGROUND
  Previous studies have suggested the presence of different childhood wheeze phenotypes through statistical modeling based on parentally reported wheezing.
  
  
  OBJECTIVE
  We sought to investigate whether joint modeling of observations from both medical records and parental reports helps to more accurately define wheezing disorders during childhood and whether incorporating information from medical records better characterizes severity.
  
  
  METHODS
  In a population-based birth cohort (n = 1184), we analyzed data from 2 sources (parentally reported current wheeze at 4 follow-ups and physician-confirmed wheeze from medical records in each year from birth to age 8 years) to determine classes of children who differ in wheeze trajectories. We tested the validity of these classes by examining their relationships with objective outcomes (lung function, airway hyperreactivity, and atopy), asthma medication, and severe exacerbations.
  
  
  RESULTS
  Longitudinal latent class modeling identified a 5-class model that best described the data. We assigned classes as follows: no wheezing (53.3%), transient early wheeze (13.7%), late-onset wheeze (16.7%), persistent controlled wheeze (13.1%), and persistent troublesome wheeze (PTW; 3.2%). Longitudinal trajectories of atopy and lung function differed significantly between classes. Patients in the PTW class had diminished lung function and more hyperreactive airways compared with all other classes. We observed striking differences in exacerbations, hospitalizations, and unscheduled visits, all of which were markedly higher in patients in the PTW class compared with those in the other classes. For example, the risk of exacerbation was much higher in patients in the PTW class compared with patients with persistent controlled wheeze (odds ratio [OR], 3.58; 95% CI, 1.27-10.09), late-onset wheeze (OR, 15.92; 95% CI, 5.61-45.15), and transient early wheeze (OR, 12.24; 95% CI, 4.28-35.03).
  
  
  CONCLUSIONS
  We identified a novel group of children with persistent troublesome wheezing, who have markedly different outcomes compared with persistent wheezers with controlled disease.
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom; Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, United Kingdom. Electronic address: danielle.belgrave@manchester.ac.uk.
authors.forename: Danielle C M
authors.initials: DCM
authors.lastname: Belgrave
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Aida
authors.initials: A
authors.lastname: Semic-Jusufagic
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Clare S
authors.initials: CS
authors.lastname: Murray
authors.affiliation: Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Iain
authors.initials: I
authors.lastname: Buchan
authors.affiliation: Department of Biostatistics, King's College London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pickles
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
mesh_terms: D000485:Allergens / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D008954:Models, Biological; D010290:Parents; D010820:Physicians; D012135:Respiratory Sounds / Q000145:classification* / Q000276:immunology / Q000503:physiopathology; D013147:Spirometry; D011795:Surveys and Questionnaires
chemical_list: D000485:Allergens; D007073:Immunoglobulin E
keywords: AHR; Airway hyperreactivity; Allergen-specific IgE; BIC; Bayesian information criteria; Childhood asthma; FVC; Forced vital capacity; GP; General practitioner; ICS; Inhaled corticosteroid; LOW; Late-onset wheeze; MWD; Mean wheal diameter; NW; No wheezing; OR; Odds ratio; PCW; PTW; Persistent controlled wheeze; Persistent troublesome wheeze; SPT; STRA; Severe therapy-resistant asthma; Skin prick test; Specific airway resistance; TEW; Transient early wheeze; asthma endotypes; longitudinal analysis; sIgE; sRaw; wheeze phenotypes