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Background: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50‐>80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool‐aged children with LCI and determine its utility in predicting persistent wheeze. Methods: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6 multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). Results: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z‐score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p <.01), IS (mean (SD): −0.14 (0.59), p <.01), and NCS (mean (SD): −0.08 (1.06), p <.01). LCI z‐score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). Conclusions: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5. [ABSTRACT FROM AUTHOR]

Background: The "old friends" hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the "old friends" hypothesized to help prevent allergic diseases. We sought to elucidate whether early‐life CMV infection is associated with childhood atopy via perturbations of the gut microbiota. Methods: Participants were recruited from a population‐based birth cohort (CHILD study) and followed prospectively until age 5 years in four Canadian cities. A total of 928 participants provided stool microbiome data, urine for CMV testing, skin prick tests, and questionnaire‐based detailed environmental exposures. Cytomegalovirus infection was assessed in the first year of life while the main outcome was defined by persistent sensitization to any allergen at ages 1, 3, and 5 years. Results: Early CMV infection was associated with increased beta and decreased alpha diversity of the gut microbiota. Both changes in diversity measures and early CMV infection were associated with persistent allergic sensitization at age 5 years (aOR = 2.08; 95% CI: 1, 4.33). Mediation analysis demonstrated that perturbation of gut microbial composition explains 30% of the association. Conclusions: Early‐life CMV infection is associated with an alteration in the intestinal microbiota, which mediates the effect of the infection on childhood atopy. This work indicates that preventing CMV infection would not put children at increased risk of developing atopy. Rather, a CMV vaccine, in addition to preventing CMV‐associated morbidity and mortality, might reduce the risk of childhood allergic diseases. [ABSTRACT FROM AUTHOR]

Overall, children below 3 years of age incurred 3.6 times higher asthma costs and in particular 9.3 times higher asthma-related hospitalization costs than those aged 4 and older. The substantially higher costs in the first 3 years of life reflect the challenge of managing asthma in young children because, despite the early diagnosis, they were frequently hospitalized for asthma and other respiratory conditions. Right panel, direct medical costs related to other respiratory conditions, total and by components gl Figures S3 and S4 respectively present the sex- and SES-stratified age trends of costs related to asthma and other respiratory conditions. Between 4 and 18 years of age, per child-year asthma-related costs steadily declined, but at a slower rate of -14.1%, while hospitalization costs declined by -30.0% every year. [Extracted from the article]

Background: Polyunsaturated fatty acids (PUFAs) may influence immune development. We examined the association of PUFAs in human milk with food sensitization and atopic dermatitis among breastfed infants. Methods: In a selected subgroup of 1109 mother‐infant dyads from the CHILD Cohort Study, human milk was analyzed by gas‐liquid chromatography to quantify PUFAs including arachidonic acid (ARA) and docosahexaenoic acid (DHA). At 1 year of age, food sensitization was determined by skin‐prick testing for egg, peanut, cow's milk, and soybean, and atopic dermatitis was diagnosed by pediatricians. Logistic regression analyses controlled for breastfeeding exclusivity, family history of atopy, and other potential confounders. Results: Overall, 184 infants (17%) were sensitized to one or more food allergens and 160 (14%) had atopic dermatitis. Sex‐specific associations were observed between these conditions and milk PUFAs. Girls receiving human milk with lower proportions of DHA had lower odds of food sensitization (aOR 0.35; 95% CI 0.12, 0.99 for lowest vs highest quintile), and a clear dose‐dependent association was observed for the ARA/DHA ratio (aOR 2.98; 95% CI 1.10, 8.06 for lowest vs highest quintile). These associations were not seen in boys. Similar sex‐specific tendencies were observed for atopic dermatitis. Conclusions: Human milk PUFA proportions and their ratios are associated with infant atopic conditions in a sex‐specific manner. In female infants, a higher ratio of ARA/DHA may reduce the risk of food sensitization and atopic dermatitis. Further research is needed to determine the underlying mechanisms and clinical relevance of this sex‐specific association. [ABSTRACT FROM AUTHOR]

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. FEV0.75z‐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. [ABSTRACT FROM AUTHOR]

Here, using data from the Canadian CHILD Cohort Study, we performed a sex-stratified analysis of human milk adiponectin, leptin, and insulin concentrations and their association with possible or probable asthma development by 3 years of age. For this analysis, asthma was classified as "possible or probable asthma" or "no asthma." Milk hormone concentrations did not differ in milk produced for sons vs. daughters (Table, Figure A); however, sex-specific associations were observed between milk hormone concentrations and child asthma (Table, Figure B). It is known that circulating leptin can stimulate the production of pro-inflammatory cytokines, potentially mediating the asthma-obesity axis; however, it is not known whether leptin in human milk can trigger similar responses. [Extracted from the article]

Background The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development ( CHILD) birth cohort study. Methods Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18, and 24 months were used to determine timing of introduction of cow's milk products, egg, and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white, and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort. Results Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg, and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adj OR 3.69, 95% CI 1.37-9.08; egg adj OR 1.89, 95% CI 1.25-2.80; peanut adj OR 1.76, 95% CI 1.07-3.01). Latent class analysis produced a three-class model: early, usual, and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adj OR 1.78, 95% CI 1.26-2.49). Conclusions Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods. [ABSTRACT FROM AUTHOR]