Optimum Predictors of Childhood Asthma: Persistent Wheeze or the Asthma Predictive Index?

Abstract

Background The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed asthma. Objective To determine whether the University of Cincinnati API (ucAPI) and/or persistent wheezing at age three can accurately predict objectively confirmed asthma at age seven. Methods Data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a high risk prospective birth cohort, was used. Asthma was defined as: parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ≥ 12% post bronchodilator or a positive methacholine challenge (PC20 ≤ 4 mg/ml); or prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age seven and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age three. Results At age seven, 103 of 589 (17.5%) children satisfied the criteria for asthma. Confirmed asthma at age seven was significantly associated with a positive ucAPI (adjusted [a]OR=13.3; 95% CI [7.0–25.2]; p<0.01) and the persistent wheezing phenotype (aOR = 9.8 [4.9–19.5]; p <0.01) at age three. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR = 10.4 [4.1–26.0]; p<0.01) than non-allergic persistent wheezing (aOR = 5.4 [2.04–14.06]; p <0.01). Conclusions Both a positive ucAPI and persistent wheeze at age 3 years were associated with objectively confirmed asthma at age seven; however the highest risk was associated with ucAPI. These results demonstrate that the ucAPI as a clinically useful tool for predicting future asthma in school-age children.

Factors predicting persistence of early wheezing through childhood and adolescence: a systematic review of the literature

“…Parental history of physician-diagnosed asthma was one of the two major criteria in the API 3. Modifications of the first API that resulted in the modified Asthma Predictive Index (mAPI),8 the University of Cincinnati Asthma Predictive Index (ucAPI),9 and the Asthma Detection and Monitoring (ADEM) API9 also included parental history of physician-diagnosed asthma as a major criterion. Hafkamp-de Groen et al performed an external validation of a modified version of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) risk score in a population of 2877 preschoolers.…”

“…The mAPI also included a medical diagnosis of eczema as a major criterion, although it changed allergic rhinitis to sensitization to milk, egg, or peanut as a minor criterion 22. The ucAPI also included a medical diagnosis of eczema and physician-diagnosed allergic rhinitis as a major and a minor criterion, respectively 9. Medical diagnosis of eczema as a major and allergic rhinitis as a minor criterion were used in the ADEM API 23.…”

“…Likewise, the ucAPI also included allergic sensitization to one aeroallergen as a major criterion and allergic sensitization to milk or eggs as a minor criterion 9. In this same study, allergic persistent wheezing (defined as having persistent wheezing with one or more skin prick tests (SPTs) positive for 15 of the local common aeroallergens) was associated with a significantly higher risk of asthma (OR=10.4; 95% CI: 4.1–26.0; p <0.01) compared to non-allergic persistent wheezing (OR=5.4; 95% CI: 2.04–14.06; p <0.01) 9. In the MAS cohort, perennial sensitization to indoor (mites, cat, and dog) allergens was a strong predictor of wheezing at 11–13 years in the multivariate analysis among early wheezers (OR=6.23; 95% CI: 2.41–16.09; p <0.001) 12.…”

“…They reported that persistent early frequent wheeze, the strictest prediction rule, had the highest OR (9.5 at the age of 7 years; 12.0 at the age of 10 years), specificity (99% at both the ages), and positive predictive value (51%, 55%), but the lowest sensitivity (12% at both the ages) and poor discriminative ability (c statistic <0.6) 29. Amin et al confirmed that asthma at age 7 was significantly associated with the persistent wheezing phenotype (defined as two or more episodes of wheezing in the previous 12 months at both the 2- and 3-year clinic visits, or if the parent reported a history of physician-diagnosed asthma in the past 12 months at the 3-year clinic visit) at age 3 (OR=9.8; 95% CI: 4.9–19.5; p <0.01) 9. Devulapalli et al, using a simple scoring system (based on the frequency and the persistence of episodes of bronchial obstruction and on hospitalizations for bronchial obstruction), determined that severe obstructive airway disease by the age of 2 years was a substantial risk factor for predicting asthma at 10 years of age (OR=8.0; 95% CI: 4.8–13.2) 30.…”

Predicting asthma outcomes

“…20 Among children followed in the Cincinnati Childhood Allergy and Air Pollution study, those with allergic persistent wheezing has a higher risk of asthma at age 7 years than those with nonallergic persistent wheezing (aOR, 10.4; 95% CI, 4.1-26.0 vs aOR, 5.4; 95% CI, 2.0-14.1; P <.01). 6 Follow-up of the Tasmanian Asthma Study cohort to age 44 years identified that childhood allergic rhinitis was not only associated with a 2-to 7-fold increased risk of incident asthma in preadolescence, adolescence, or adult life but also was associated with a 3-fold increased risk of childhood asthma persisting rather than remitting by middle age. 24 Early sensitization and sensitization to multiple allergens are more strongly predictive of persistence throughout childhood and into adulthood.…”