Background: In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). Methods: We utilised two separate real-world retrospective observational cohorts of children who underwent both spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2000 and December 2017. Results: Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. Baseline forced expiratory volume in 1 second (FEV 1), FEV 1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF 25-75), and FEF 75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients ( P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV 1/FVC (OR, 2.24 [95%CI, 1.43-3.52]) and FEF 25-75 (OR, 2.05 [95%CI, 1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV 1 (OR, 0.05 [95%CI, 0.01-0.19]), FEV 1/FVC (OR, 0.27 [95% CI, 0.18-0.41]), FEF 25-75 (OR, 0.17 [95%CI, 0.11-0.28]), and FEF 75 (OR, 0.14 [95%CI, 0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. Conclusions: We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR.

Background: The upper-airway microbiota may be associated with the pathogenesis of asthma and useful for predicting acute exacerbation. However, the relationship between the lower-airway microbiota and acute exacerbation in children with asthma is not well-understood. We evaluated the characteristics of the airway microbiome using induced sputum from children with asthma exacerbation and compared the microbiota-related differences of inflammatory cytokines with those in children with asthma. Methods: We analysed the microbiome using induced sputum during acute exacerbation of asthma in children. We identified microbial candidates that were prominent in children with asthma exacerbation and compared them with those in children with stable asthma using various analytical methods. The microbial candidates were analysed to determine their association with inflammatory cytokines. We also developed a predictive functional profile using PICRUSt. Results: Ninety-five children with allergic sensitisation including twenty-two with asthma exacerbation, sixty-seven with stable asthma, and six controls were evaluated. We selected 26 microbial candidates whose abundances were significantly increased, decreased, or correlated during acute exacerbation in children with asthma. Among the microbial candidates, Campylobacter, Capnocytophaga, Haemophilus, and Porphyromonas were associated with inflammatory cytokines including macrophage inflammatory protein (MIP)-1β, programmed death-ligand 1, and granzyme B. Both Campylobacter and MIP-1β levels were correlated with sputum eosinophils. Increased lipopolysaccharide biosynthesis and decreased glycan degradation were observed in children with asthma exacerbation. Conclusions: Gram-negative microbes in the lower airway were related to acute exacerbation in children with asthma. These microbes and associated cytokines may play a role in exacerbating asthma in children.

Background: The effect of prenatal secondhand smoke (SHS) exposure on childhood atopic dermatitis (AD) remains controversial. We aimed to investigate the association between prenatal SHS and childhood AD in a general population-based birth cohort. Methods: Patients included 2,360 mother–child pairs from the Cohort for Childhood Origin of Asthma and Allergic diseases (COCOA), stratified into 0–3, 4–6, and 7–9 years age groups. Prenatal SHS exposure was assessed using questionnaires. AD diagnosis and symptom assessments were conducted through annual visits by pediatric allergists. Skin prick tests for 18 allergens were conducted. Serum total IgE and eosinophil levels were measured at birth and ages 3 and 7 years. Maternal urine cotinine concentrations were measured at week 36 of gestation. Multivariate logistic regression was performed. Results: Children aged 7–9 years exposed to prenatal SHS were significantly more likely to have an AD diagnosis (aOR 1.670, 95% CI: 0.995–2.804) and current AD (aOR 1.823, 95% CI: 1.051–3.161). This association in AD diagnosis was stronger in children with sensitization (aOR 2.205, 95% CI: 1.048–4.642). Higher maternal urine cotinine levels increased the risk of current AD at ages 4–6 (aOR 2.816, 95% CI: 1.053–7.529). Children exposed to prenatal SHS were more likely to have a late-onset phenotype of AD (aOR 1.663, 95% CI: 1.038–2.664). Conclusion: SHS exposure during pregnancy was associated with late childhood AD. Prevention of prenatal SHS exposure is necessary to reduce the risk of AD in schoolchildren.

Abstract Background: The level of pollen in Korea has increased over recent decades. Research suggests that pollen-food allergy syndrome (PFAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of PFAS in children aged 6–10 years from a general population-based birth cohort. Methods: We analyzed 930 children from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort. Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for children aged 3 and 7 years. Results: Of the 930 eligible children, 44 (4.7%) aged 6–10 years were diagnosed with. The mean age at onset was 6.74 years. PFAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. PFAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy before 3 years increased the risk of PFAS (aOR 2.971, 95% CI: 1.159–7.615). Conclusion: Food allergy and food sensitization in early childhood was associated with PFAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of PFAS.

Background: In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). Method: We utilised two separate retrospective observational cohorts of children who underwent spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2000 and December 2017. Result: Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. Baseline forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75), and FEF75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients (P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV1/FVC (OR, 2.24 [95%CI, 1.43-3.52]) and FEF25-75 (OR, 2.05 [95%CI, 1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1 (OR, 0.05 [95%CI, 0.01-0.19]), FEV1/FVC (OR, 0.27 [95% CI, 0.18-0.41]), FEF25-75 (OR, 0.17 [95%CI, 0.11-0.28]), and FEF75 (OR, 0.14 [95%CI, 0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. Conclusion: We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR.

Background: Although atopic dermatitis (AD) is associated with certain gene variants, the rapidly increasing incidence of AD suggests that environmental factors contribute to disease development. In this study, we investigated the association of AD incidence and phenotype with antibiotic exposure within 6 months of age, considering the dose administered and genetic risk. Methods: This study included 1,637 children from the COCOA birth cohort. Pediatric allergists assessed the presence of AD at each visit and obtained information about antibiotic exposure for more than 3 days. IL-13 (rs20541) polymorphism was genotyped by the TaqMan method. We stratified the AD phenotypes into 4 groups and used multinomial logistic regression models for analysis. Results: Antibiotic exposure within 6 months of age was found to increase the risk of AD within 3 years of life (aOR=1.40, 95%, CI 1.09–1.81) in dose-dependent manner. Antibiotic exposure more than twice increased the risk of the early-persistent AD phenotype (aOR=2.50, 95% CI 1.35–4.63). There was a weak interaction between genetic polymorphisms and environmental factors on the development of AD (p for interaction=0.06). Children with the IL-13 (rs20541) GA+ AA genotype have a higher risk of the early-persistent AD phenotype when exposed to antibiotics more than twice than those with the IL-13 (rs20541) GG genotype and without exposure to antibiotics (aOR=4.73, 2.01–11.14). Conclusion: Antibiotic exposure within 6 months was related to the incidence of early-persistent AD and a dose-dependent increase in the incidence of AD in childhood, whose effect was modified by the IL-13 (rs20541) genotype.