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: 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.