Association of Nasopharyngeal and Serum Glutathione Metabolism with Bronchiolitis Severity and Asthma Risk: A Prospective Multicenter Cohort Study.

Infants hospitalized for bronchiolitis are at high risk for asthma. Glutathione-related metabolites may antagonize oxidative stress, which induces airway injuries in respiratory infection and subsequent airway remodeling. However, little is known about the relationship of glutathione-related metabolites with bronchiolitis severity and the risk of asthma. In a multicenter prospective observational cohort study of infants hospitalized for bronchiolitis, we measured nasopharyngeal and serum glutathione-related metabolites by using liquid chromatography−tandem mass spectrometry. We then examined their association with bronchiolitis severity (defined by positive pressure ventilation (PPV) use). We also identified severity-related glutathione-related metabolite signatures and examined their association with asthma at age 6 years. In 1013 infants, we identified 12 nasopharyngeal and 10 serum glutathione-related metabolites. In the multivariable models, lower relative abundances of seven metabolites, e.g., substrates of glutathione, including cysteine (adjOR 0.21, 95%CI 0.06−0.76), glycine (adjOR 0.25, 95%CI 0.07−0.85), and glutamate (adjOR 0.25, 95%CI 0.07−0.88), were significantly associated with PPV use (all FDR < 0.05). These associations were consistent with serum glutathione-related metabolites. The nasopharyngeal glutathione-related metabolite signature was also associated with a significantly higher risk of asthma (adjOR 0.90, 95%CI 0.82−0.99, p = 0.04). In infants hospitalized for bronchiolitis, glutathione-related metabolites were associated with bronchiolitis severity and asthma risk.

Serum periostin among infants with severe bronchiolitis and risk of developing asthma: A prospective multicenter cohort study.

BACKGROUND: Infants hospitalized for bronchiolitis (severe bronchiolitis) are at high risk for developing childhood asthma. However, the pathobiological link between these conditions remains unclear. We examined the longitudinal relationship of periostin (an extracellular matrix protein upregulated in response to type 2 inflammation) during bronchiolitis with the subsequent development of asthma. METHODS: In a 17-center prospective cohort study of infants (aged <1 year) with severe bronchiolitis, we measured the serum periostin level at hospitalization and grouped infants into 3 groups: low, intermediate, and high levels. We examined their association with asthma development by age 6 years and investigated effect modification by allergic predisposition (eg, infant's IgE sensitization). RESULTS: The analytic cohort consists of 847 infants with severe bronchiolitis (median age, 3 months). Overall, 28% developed asthma by age 6 years. In the multivariable model adjusting for nine patient-level factors, compared to the low periostin group, the asthma risk was significantly higher among infants in the intermediate group (23% vs. 32%, OR 1.68, 95%CI 1.12-2.51, p = .01) and non-significantly higher in the high-level group (28%, OR 1.29, 95%CI 0.86-1.95, p = .22). In the stratified analysis, infants with IgE sensitization had a significantly higher risk for developing asthma (intermediate group, OR 4.76, 95%CI 1.70-13.3, p = .002; high group, OR 3.19, 95%CI 1.08-9.36, p = .04). By contrast, infants without IgE sensitization did not have a significantly higher risk (p > .15). CONCLUSIONS: In infants with severe bronchiolitis, serum periostin level at bronchiolitis hospitalization was associated with asthma risk by age 6 years, particularly among infants with an allergic predisposition.

Association of Growth Trajectory Profiles with Asthma Development in Infants Hospitalized with Bronchiolitis.

BACKGROUND: Little is known about the relationship of longitudinal growth trajectory in early life with asthma development, particularly in infants with bronchiolitis (a high-risk population). OBJECTIVE: Among infants with bronchiolitis, we aimed to identify growth trajectory profiles and determine their longitudinal relationship with the risk for developing childhood asthma. METHODS: A multicenter prospective study enrolled infants (aged <1 year) hospitalized for bronchiolitis. We identified growth trajectory profiles-derived from body mass index-for-age at ages 0, 6, 12, 15, 18, 24, and 36 months by using a longitudinal clustering method. We examined associations between growth trajectory profiles and asthma development by age 5 years. RESULTS: The analytic cohort consists of 880 infants hospitalized for bronchiolitis (median age, 3 months). Overall, 26% developed asthma by age 5 years. The longitudinal clustering identified 5 distinct profiles: persistent low growth (27%), normative growth (33%), transient overweight (21%), late-onset overweight (16%), and persistent obesity (3%) profiles. In multivariable model, compared with children with a normative profile, those with a persistent obesity profile had significantly higher risks of developing asthma (24% vs 38%, odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.07-6.09, P = .03). Among children with a persistent obesity profile, those without allergic predisposition had significantly higher risks of asthma (OR: 3.02, 95% CI: 1.05-8.64, P = .04 in the nonparental allergic history group; OR: 3.18, 95% CI: 1.02-9.92, P = .047 in the non-IgE sensitization group), whereas those with allergic predisposition were not at increased risk. CONCLUSIONS: This multicenter cohort study of infants with bronchiolitis demonstrated distinct growth trajectory profiles that have differential risks for developing asthma.

Association of Severe Bronchiolitis during Infancy with Childhood Asthma Development: An Analysis of the ECHO Consortium.

Objective: Many studies have shown that severe (hospitalized) bronchiolitis during infancy is a risk factor for developing childhood asthma. However, the population subgroups at the highest risk remain unclear. Using large nationwide pediatric cohort data, namely the NIH Environmental influences on Child Health Outcomes (ECHO) Program, we aimed to quantify the longitudinal relationship of bronchiolitis hospitalization during infancy with asthma in a generalizable dataset and to examine potential heterogeneity in terms of major demographics and clinical factors. Methods: We analyzed data from infants (age <12 months) enrolled in one of the 53 prospective cohort studies in the ECHO Program during 2001−2021. The exposure was bronchiolitis hospitalization during infancy. The outcome was a diagnosis of asthma by a physician by age 12 years. We examined their longitudinal association and determined the potential effect modifications of major demographic factors. Results: The analytic cohort consisted of 11,762 infants, 10% of whom had bronchiolitis hospitalization. Overall, 15% subsequently developed asthma. In the Cox proportional hazards model adjusting for 10 patient-level factors, compared with the no-bronchiolitis hospitalization group, the bronchiolitis hospitalization group had a significantly higher rate of asthma (14% vs. 24%, HR = 2.77, 95%CI = 2.24−3.43, p < 0.001). There was significant heterogeneity by race and ethnicity (Pinteraction = 0.02). The magnitude of the association was greater in non-Hispanic White (HR = 3.77, 95%CI = 2.74−5.18, p < 0.001) and non-Hispanic Black (HR = 2.39, 95%CI = 1.60−3.56; p < 0.001) infants, compared with Hispanic infants (HR = 1.51, 95%CI = 0.77−2.95, p = 0.23). Conclusions: According to the nationwide cohort data, infants hospitalized with bronchiolitis are at a higher risk for asthma, with quantitative heterogeneity in different racial and ethnic groups.

Hospital-Initiated Care Bundle, Posthospitalization Care, and Outcomes in Adults with Asthma Exacerbation.

BACKGROUND: Hospitalization for asthma exacerbation is an opportune setting for initiating preventive efforts. However, hospital-initiated preventive asthma care remains underdeveloped and its effectiveness is uncertain. OBJECTIVE: To examine the effectiveness of a hospital-initiated asthma care bundle on posthospitalization asthma care and clinical outcomes. METHODS: Prospective multicenter study of adults (18-54 years) hospitalized for asthma exacerbation in 2017 to 2019. During the hospitalization, we implemented an asthma-care bundle (inpatient laboratory testing, asthma education, and discharge care), and prospectively measured chronic asthma care (eg, immunoglobulin E testing, specialist care) and asthma exacerbation (ie, systemic corticosteroid use, emergency department [ED] visit, hospitalizations) outcomes. By applying a self-controlled case series method, we examined within-person changes in these outcomes before (2-year period) and after (1-year period) the bundle implementation. RESULTS: Of 103 adults hospitalized for asthma exacerbation, the median age was 40 years and 72% were female. Compared with the preimplementation period, the postimplementation period had improved posthospitalized asthma care, including serum specific immunoglobulin E testing (rate ratio [RR] 2.18; 95% confidence interval [95% CI] 0.99-4.84; P = .051) and evaluation by asthma specialist (RR 2.66; 95% CI 1.77-4.04; P < .001). Likewise, after care bundle implementation, patients had significantly lower annual rates of systemic corticosteroid use (4.2 vs 2.9 per person-year; RR 0.70; 95% CI 0.61-0.80; P < .001), ED visits (3.2 vs 2.7 per person-year; RR 0.83; 95% CI 0.72-0.95; P = .008), and hospitalizations (2.1 vs 1.8 per person-year; RR 0.82; 95% CI 0.69-0.97; P = .02). Stratified analyses by sex, race and ethnicity, and health insurance yielded consistent results. CONCLUSIONS: After hospital-initiated care bundle implementation, patients had improved posthospitalization care and reduced rates of asthma exacerbation.

Risk prediction of severe reaction to oral challenge test of cow's milk.

Cow's milk is one of the most common food allergens among children. Oral food challenge tests determine the threshold dose of allergens, but have not been standardized. To reduce the severe reactions, we developed a practical model of the test. We studied 111 high-risk patients who underwent a first milk oral food challenge on the risk-stratified dose between 2011 and 2017 for predicting the severe reaction risk. Severe reactions were defined as showing > 3 of Sampson's classification grade. Twenty-eight patients (25%) showed severe reactions without death. Prior to oral food challenge, severe reaction patients experienced milk avoidance (71% vs. 45%, p = 0.02) or bronchial asthma (61% vs. 28%, p = 0.003) more frequently and showed higher milk-specific IgE levels (median 28.3 vs. 7.7 UA/mL, p < 0.0001) than non-severe reaction patients. Multivariate logistic regression analyses established a formula including severe reaction-associated factors; increased levels of milk-specific IgE (odds ratio 11.61, p = 0.001), milk avoidance (odds ratio 3.88, p = 0.02), and bronchial asthma (odds ratio 3.75, p = 0.02). This model had 86% sensitivity and 56% specificity (cut-off 0.25) for risk. Five patients with < 25% probability developed severe reactions, which started in > 3 grade dyspnea up to 20 mL of challenge.Conclusion: This model could effectively reduce the severe reaction development on the first milk oral food challenge test according to the individual needs. What is Known: •Higher levels of milk-specific IgE values, bronchial asthma, and complete milk avoidance are independent risk factors of severe reactions during the cow's milk oral food challenge. What is New: •Statistical analyses of our milk oral food challenge records for 111 patients helped us develop a model formula predicting severe reactions at the first test with high specificity and sensitivity. •This simple risk-stratified protocol is useful for minimizing the adverse events in the first milk challenge.

[POLLEN FOOD ALLERGY SYNDROME IN A FIVE-YEAR-OLD BOY AFTER MOVING HOUSE AT THE FOOT OF THE MOUNTAIN: A CASE REPORT].

We report the case of a boy with a history of atopic dermatitis starting in infancy. At the age of four, his family moved into a newly built house at the foot of a mountain. One year later, he was diagnosed with Japanese Cedar pollinosis. During the same year, in March, he began to experience oral symptoms, hoarseness, and coughing, after eating multiple types of fruits and vegetables, like soybeans, apples, etc. His tests for Bet v1 and the pathogenesis-related protein-10 (PR-10) of the corresponding foods were positive; accordingly, he was diagnosed with Pollen Food Allergy Syndrome (PFAS). In order to investigate the relationship between pollen and food allergies, we counted the pollen grains dispersed at the patient's house during a period of one year and measured his specific IgE titers for pollen and food allergens every three months. We found a large amount of Japanese cedar, cypress, oak, and various other species of pollen dispersed at the patient's house. All counts were higher than the average pollen counts in the city of Fukuoka. After the seasonal dispersal of oak pollen, the patient's specific IgE antibody titers against Alder, Oak, Bet v1, Gly m4, and PR-10 protein group of fruits increased, although alder pollen was not detected. We thus inferred that the patient had developed PFAS by exposure to a large amount of Fagales species pollen, including oak.