Pulmonary function characteristics in children with suspected asthma: implications for asthma diagnosis.

BACKGROUND: In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. However, there is no single gold standard test for diagnosing asthma. OBJECTIVE: This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). METHODS: We utilized 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 2019 and December 2019. RESULTS: Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. This group showed a significantly higher FeNO level and prevalence of allergic sensitization. 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 (2.05 [1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1(0.05 [0.01-0.19]),FEV1 /FVC (0.27 [0.18-0.41]), FEF25-75 (0.17 [0.11-0.28]), and FEF75 (0.14 [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. Repeated pulmonary function tests that closely monitor for subtle lung function impairments and active utilization of additional tests, such as allergic screening and FeNO, should be considered to close the gap in diagnosing asthma.

Predicting the Outcome of Pediatric Oral Food Challenges for Determining Tolerance Development.

PURPOSE: Despite the risk of anaphylaxis, oral food challenges (OFCs) are performed clinically for various indications, particularly to confirm tolerance development. This study aimed to assess OFCs by relevant indications and build an outcome prediction model to help determine when to perform OFCs in children who are likely to have developed immune tolerance. METHODS: In total, 432 pediatric OFCs were retrospectively analyzed according to indications. Clinical characteristics, serum total immunoglobulin (Ig) E, blood eosinophils, and specific IgE and IgG4 levels for food allergens were noted and compared. Machine learning was utilized to select the most important variables in determining the passage of the OFCs, and prediction models were constructed using the selected variables. RESULTS: OFCs were most commonly performed to confirm tolerance development (number, %; 267, 61.8%). The most common food allergens tested were egg (191, 44.2%) and milk (135, 31.3%). Children who passed the egg challenges for confirming tolerance acquisition had significantly lower egg white-specific IgE level (P = 0.008). Similarly, those who passed milk challenges had significantly lower cow's milk-specific IgE (P = 0.002) and casein-specific IgE levels (P = 0.005). We developed a nomogram to predict the outcome of OFCs to determine the tolerance acquisition with the selected variables; lower food-specific IgE, higher total IgE, and younger age indicated a higher probability of passage. The area under the curve (95% confidence interval) was 0.623 (0.503-0.743) for egg and 0.734 (0.628-0.840) for milk. CONCLUSIONS: Serum total IgE and food-specific IgE combined with age showed trends toward passing OFCs for confirming tolerance development. The constructed model may be used by clinicians as a practical guide for minimizing the risks of OFCs and a timely reintroduction for children with food allergies.

Radiologic Assessment of Lung Edema Score as a Predictor of Clinical Outcome in Children with Acute Respiratory Distress Syndrome.

PURPOSE: The radiographic assessment of lung edema (RALE) score enables objective quantification of lung edema and is a valuable prognostic marker of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the validity of RALE score in children with ARDS. MATERIALS AND METHODS: The RALE score was measured for its reliability and correlation to other ARDS severity indices. ARDS-specific mortality was defined as death from severe pulmonary dysfunction or the need for extracorporeal membrane oxygenation therapy. The C-index of the RALE score and other ARDS severity indices were compared via survival analyses. RESULTS: Among 296 children with ARDS, 88 did not survive, and there were 70 ARDS-specific non-survivors. The RALE score showed good reliability with an intraclass correlation coefficient of 0.809 [95% confidence interval (CI), 0.760-0.848]. In univariable analysis, the RALE score had a hazard ratio (HR) of 1.19 (95% CI, 1.18-3.11), and the significance was maintained in multivariable analysis adjusting with age, ARDS etiology, and comorbidity, with an HR of 1.77 (95% CI, 1.05-2.91). The RALE score was a good predictor of ARDS-specific mortality, with a C-index of 0.607 (95% CI, 0.519-0.695). CONCLUSION: The RALE score is a reliable measure for ARDS severity and a useful prognostic marker of mortality in children, especially for ARDS-specific mortality. This score provides information that clinicians can use to decide the proper time of aggressive therapy targeting severe lung injury and to appropriately manage the fluid balance of children with ARDS.

Efficacy of low dose and short duration defibrotide prophylaxis for hepatic veno-occlusive disease after autologous haematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a serious systemic endothelial complication after stem cell transplantation. Defibrotide is under investigation as a prophylactic agent for VOD; however, high costs limit its utility. We evaluated the prophylactic efficacy of a low-dose defibrotide regimen for VOD. We retrospectively enrolled 147 paediatric patients who underwent autologous haematopoietic stem cell transplantation (HSCT; 69 with defibrotide prophylaxis and 78 historical controls) at the Yonsei Cancer Center in Seoul, Korea, between March 2013 and Feb 2020. Low-dose defibrotide (12.5 mg/kg/day) was administered from D-3 to D+10 after HSCT. The most common diagnosis in the cohort was brain tumour (N = 86). VOD developed in 10 (12.8%) and 3 (4.3%) patients in the control and prophylaxis groups, respectively (P = 0.071). In the second HSCT group, VOD incidence was significantly lower in the prophylaxis group [2.9% (1/35)] than in the control group (28.6%, 6/21, P = 0.005). VOD severity was significantly higher in the control group than in the prophylaxis group (P = 0.006). Three VOD-related mortalities occurred in the control group, whereas no VOD-related mortality occurred in the prophylaxis group. In conclusion, low-dose defibrotide prophylaxis is a promising and economical strategy for preventing VOD, especially in second-round HSCT.