Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

BACKGROUND: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms. METHODS: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. RESULTS: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. CONCLUSION: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.

Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS: Seventy-four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P = .003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (P = .05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children.

Test for respiratory and asthma control in preschool kids in the emergency department as a predictor of wheezing exacerbations.

OBJECTIVE: The test for respiratory and asthma control in kids (TRACK score) is a standardized questionnaire tool validated to identify poor symptom control in children with stable preschool wheeze. This study determined if TRACK score measured within 5 days of an Emergency Department (ED) visit for acute wheezing predicts a subsequent wheezing exacerbation requiring an ED visit and/or treatment with systemic corticosteroids within 3 months. METHODS: This was a single-center prospective cohort study of children aged 36 to 71 months who presented to the ED with an acute episode of wheezing and had TRACK score measured at a clinic visit within 5 days of the index ED encounter, focused on information about symptoms occurring before the onset of the current acute episode. The outcomes were the independent association of a repeat wheezing exacerbation with the overall TRACK score (primary) and with mutually uncorrelated TRACK items (secondary), adjusted for sex and atopy. RESULTS: We enrolled 102 children; median age 52.3 (44.1, 59.9) months, 59% males. Of these, 33 (32.4%) had further wheezing exacerbations. For each 10 unit decrease in TRACK, the odds of a future exacerbation was 1.38 (95% CI, 1.10-1.75); male sex demonstrated OR, 5.13 (1.84-14.33). A model that included TRACK items reflecting more than equal to 1 awakenings for wheezing in the past 4 weeks, receipt of more than equal to 2 courses of corticosteroids in the last year and male sex was predictive of wheezing exacerbations: OR, 6.43 (2.18-19.00). CONCLUSION: In preschoolers with acute wheezing episodes in the ED, we have identified the TRACK score components which, together with male sex, can be used to identify children at risk of future exacerbations requiring referral for specialized care. These results need to be confirmed and validated in other populations enrolled at multiple sites before they can be implemented in practice.