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Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood.In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years.Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models.We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years.We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

ImportanceDespite advances in asthma therapeutics, the burden remains highest in preschool children; therefore, it is critical to identify primary care tools that distinguish preschool children at high risk for burdensome disease for further evaluation. Current asthma prediction tools, such as the modified Asthma Predictive Index (mAPI), require invasive tests, limiting their applicability in primary care and low-resource settings.ObjectiveTo develop and evaluate the use of a symptom-based screening tool to detect children at high risk of asthma, persistent wheeze symptoms, and health care burden.Design, Setting, and ParticipantsThe cohort for this diagnostic study included participants from the CHILD Study (n = 2511) from January 1, 2008, to December 31, 2012, the Raine Study from January 1, 1989, to December 31, 2012 (n = 2185), and the Canadian Asthma Primary Prevention Study (CAPPS) from January 1, 1989, to December 31, 1995 (n = 349), with active follow-up to date. Data analysis was performed from November 1, 2019, to May 31, 2022.ExposuresThe CHILDhood Asthma Risk Tool (CHART) identified factors associated with asthma in patients at 3 years of age (timing and number of wheeze or cough episodes, use of asthma medications, and emergency department visits or hospitalizations for asthma or wheeze) to identify children with asthma or persistent symptoms at 5 years of age.Main Outcomes and MeasuresWithin the CHILD Study cohort, CHART was evaluated against specialist clinician diagnosis and the mAPI. External validation was performed in both a general population cohort (Raine Study [Australia]) and a high-risk cohort (CAPPS [Canada]). Predictive accuracy was measured by sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and positive and negative predicted values.ResultsAmong 2511 children (mean [SD] age at 3-year clinic visit, 3.08 [0.17] years; 1324 [52.7%] male; 1608 of 2476 [64.9%] White) with sufficient questionnaire data to apply CHART at 3 years of age, 2354 (93.7%) had available outcome data at 5 years of age. CHART applied in the CHILD Study at 3 years of age outperformed physician assessments and the mAPI in predicting persistent wheeze (AUROC, 0.94; 95% CI, 0.90-0.97), asthma diagnosis (AUROC, 0.73; 95% CI, 0.69-0.77), and health care use (emergency department visits or hospitalization for wheeze or asthma) (AUROC, 0.70; 95% CI, 0.61-0.78). CHART had a similar predictive performance for persistent wheeze in the Raine Study (N = 2185) in children at 5 years of age (AUROC, 0.82; 95% CI, 0.79-0.86) and CAPPS (N = 349) at 7 years of age (AUROC, 0.87; 95% CI, 0.80-0.94).Conclusions and RelevanceIn this diagnostic study, CHART was able to identify children at high risk of asthma at as early as 3 years of age. CHART could be easily incorporated as a routine screening tool in primary care to identify children who need monitoring, timely symptom control, and introduction of preventive therapies.

New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.

Background Persisting atopic dermatitis (AD) is known to be associated with more serious allergic diseases at later ages; however, making an accurate diagnosis during infancy is challenging. We assessed the diagnostic performance of questionnaire-based AD measures with criteria-based in-person clinical assessments at age 1 year and evaluated the ability of these diagnostic methods to predict asthma, allergic rhinitis and food allergies at age 5 years. Methods Data relate to 3014 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study who were directly observed in a clinical assessment by an experienced healthcare professional using the UK Working Party criteria. The majority (2221; 73.7%) of these children also provided multiple other methods of AD ascertainment: a parent reporting a characteristic rash on a questionnaire, a parent reporting the diagnosis provided by an external physician and a combination of these two reports. Results Relative to the direct clinical assessment, the area under the Receiver Operating Characteristic curve for a parental report of a characteristic rash, reported physician diagnosis and a combination of both were, respectively, 0.60, 0.69 and 0.70. The strongest predictor of asthma at 5 years was AD determined by criteria-based in-person clinical assessment followed by the combination of parental and physician report. Conclusions These findings suggest that questionnaire data cannot accurately substitute for assessment by experienced healthcare professionals using validated criteria for diagnosis of atopic dermatitis. Combining the parental report with diagnosis by a family physician might sometimes be appropriate (eg to avoid costs of a clinical assessment).

Background The atopic march describes the progression from atopic dermatitis during infancy to asthma and allergic rhinitis in later childhood. In a Canadian birth cohort we investigated whether concomitant allergic sensitization enhances subsequent development of these allergic diseases at age 3 years. Methods Children completed skin prick testing at age 1 year. Children were considered sensitized if they produced a wheal 2 mm or larger than that elicited by the negative control to any of 10 inhalant or food allergens. Children were also assessed for atopic dermatitis by using the diagnostic criteria of the UK Working Party. At age 3 years, children were assessed for asthma, allergic rhinitis, food allergy, and atopic dermatitis. Data from 2311 children were available. Results Atopic dermatitis without allergic sensitization was not associated with an increased risk of asthma at age 3 years after adjusting for common confounders (relative risk [RR], 0.46; 95% CI, 0.11-1.93). Conversely, atopic dermatitis with allergic sensitization increased the risk of asthma more than 7-fold (RR, 7.04; 95% CI, 4.13-11.99). Atopic dermatitis and allergic sensitization had significant interactions on both the additive (relative excess risk due to interaction, 5.06; 95% CI, 1.33-11.04) and multiplicative (ratio of RRs, 5.80; 95% CI, 1.20-27.83) scales in association with asthma risk. There was also a positive additive interaction between atopic dermatitis and allergic sensitization in their effects on food allergy risk (relative excess risk due to interaction, 15.11; 95% CI, 4.19-35.36). Conclusions Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years.

Background: In the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, early introductions of egg, cow9s milk products and peanut were associated with reduced sensitization to these foods at 1 year. We investigated whether these effects differed by specific parental atopy and child sex. Methods: We analyzed feeding patterns in 2284 children in relation to food sensitization at 1 year, stratified by paternal and maternal atopy independently and child sex. Results: In male infants with atopic fathers/non-atopic mothers (n=215), using introduction after 12 months as reference, introduction of cow9s milk products by 6 months reduced sensitization to egg (OR 0.13, 95% CI 0.02,0.91) and peanut (OR 0.08, 95%CI 0.01,0.63); introduction of peanut between 7-12 months reduced sensitization to egg (OR 0.31, 95%CI 0.08,0.94); and introduction of milk between 7-12 months reduced peanut sensitization (OR 0.05, 95%CI 0.01,0.44). Sensitization to any of these 3 foods was reduced by 87% by milk products and 67% by peanut introduction before 12 months. In contrast, among males with atopic mothers/non-atopic fathers (n=110), egg introduction by 6 months reduced the risk of sensitization to any of these 3 foods but no other associations were significant. Female infants with only atopic fathers (n=125) had less milk sensitization if introduced to cow9s milk by 6 months (OR 0.04, 95%CI 0.0,0.69) or between 7-12 months (OR 0.03, 95%CI 0.0,0.77), but among females with only atopic mothers (n=127), no effect of timing of food introduction was evident. Conclusions: Early introduction of allergenic foods was more protective against food sensitization in male infants with atopic fathers.

A1 Role of fibrocytes in allergic rhinitis Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet A2 Patterns of aeroallergens sensitization in Northern Alberta Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA) Sara F. Johnson, Roberta L. Woodgate A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum A6 Detection of regulatory B cells in the airways of subjects with asthma John-Paul Oliveria, Stephanie Phan, Mark W. 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