Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing

TY - JOUR

T1 - Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing

AU - Belgrave, Danielle C. M.

AU - Simpson, Angela

AU - Semic-Jusufagic, Aida

AU - Murray, Clare S.

AU - Buchan, Iain

AU - Pickles, Andrew

AU - Custovic, Adnan

PY - 2013/9

Y1 - 2013/9

N2 - 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).Conclusion: We identified a novel group of children with persistent troublesome wheezing, who have markedly different outcomes compared with persistent wheezers with controlled disease.

AB - 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).Conclusion: We identified a novel group of children with persistent troublesome wheezing, who have markedly different outcomes compared with persistent wheezers with controlled disease.

KW - Childhood asthma

KW - asthma endotypes

KW - wheeze phenotypes

KW - longitudinal analysis

KW - RESPIRATORY-SOCIETY STATEMENT

KW - PROBLEMATIC SEVERE ASTHMA

KW - 1ST 6 YEARS

KW - PRESCHOOL-CHILDREN

KW - LUNG-FUNCTION

KW - INHALED CORTICOSTEROIDS

KW - CHILDHOOD ASTHMA

KW - CLUSTER-ANALYSIS

KW - BIRTH COHORT

KW - PHENOTYPES

U2 - 10.1016/j.jaci.2013.05.041

DO - 10.1016/j.jaci.2013.05.041

M3 - Article

SN - 0091-6749

VL - 132

SP - 575-583.e12

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

M1 - N/A

ER -