BACKGROUND:Bronchiolitis obliterans syndrome (BOS) is the most common non-infectious complication of allogenic hematopoietic stem cell transplantation (HSCT) and is associated with poor outcomes. Hyperpolarized 129Xe MRI (Xe-MRI) holds promise for sensitive and non-ionizing imaging of lung ventilation in children and has been explored in the post-HSCT population. However, previous work was weighted towards children without BOS. In this pilot cross-sectional study, we hypothesize that ventilation abnormalities measured with Xe-MRI are increased in pediatric post-HSCT participants with BOS compared to those without. METHODS:Two groups of pediatric post-HSCT participants were recruited: those with a diagnosis or clinical findings consistent with BOS and those without. Xe-MRI was performed to calculate the ventilation defect percentage (VDP) and ventilation heterogeneity index (VHI) in all subjects. Group-wise differences were tested with Mann-Whitney U-test. Xe-MRI was compared to same-day spirometry and nitrogen multiple breath washout (MBW). RESULTS:Twelve (6 non-BOS and 6 BOS) participants aged 9-17 years (median 12.5 years) were recruited. VDP (median [range]) was elevated (p < 0.05) in participants with BOS (11.8 [4.3, 20.8]%) compared to those without BOS (4.0 [3.1, 4.9]%). A similar elevation (p < 0.01) in VHI was observed in those with BOS (12.1 [8.3, 16.3])%) compared to those without (7.4 [7.4, 8.1]%). Both VDP and VHI were correlated with forced expiratory volume in 1-second (FEV1) and the lung clearance index (LCI), while VDP also correlated with FEV1 over forced vital capacity ratio (FEV1/FVC). CONCLUSION:Xe-MRI ventilation measures were elevated in pediatric post-HSCT participants within the BOS group compared to those without BOS and correlated with same-day spirometry and MBW.
INTRODUCTION:Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to relevant clinical advances in people with cystic fibrosis (pwCF). However, its effects on aerobic fitness are unclear. OBJECTIVE:To evaluate the effects of CFTR modulator therapy on aerobic fitness in pwCF through a systematic review and meta-analysis. METHODS:This systematic review (CRD420251066602) was conducted by searching major databases without date or language restrictions. Analytical studies evaluating cardiopulmonary exercise testing outcomes before and after CFTR modulator therapy were included. The primary outcome was peak oxygen uptake (peak VO2). Secondary outcomes included peak VO2 (% predicted), VO2 at the first ventilatory threshold (VT1), breathing reserve, workload, forced expiratory volume in one second (FEV1), and body mass index. Meta-analyses were performed using a random-effects model with heterogeneity assessed by the I2 statistic, and sensitivity analyses conducted. RESULTS:Thirteen studies (n = 578 participants) were included, of which 11 were eligible for meta-analysis. The meta-analysis did not identify a significant improvement in peak VO2 (mL·kg-1·min-1) after CFTR modulator use (MD = -0.22; 95% CI: -2.10 to 1.65; p = 0.82). For submaximal outcomes, after sensitivity analysis, VO2 at VT1 was significantly lower in the post-intervention period (MD = -1.85; 95% CI: -2.61 to -1.10; p < 0.00001). Breathing reserve increased significantly (MD = 7.94; 95% CI: 2.15 to 13.73; p = 0.007), and workload also increased significantly (MD = 15.39; 95% CI: 2.20 to 28.58; p = 0.02). CONCLUSION:CFTR modulator therapy is not consistently associated with improvements in aerobic fitness, as assessed by peak VO2, although it appears to variably influence outcomes related to ventilatory response and exercise performance.
BACKGROUND:Congenital chylothorax is a rare pulmonary developmental disorder with high associated morbidity and mortality. A limited number of cases have been described, and clinical manifestations and outcomes vary. METHODS:This study aims to delineate the neonatal and long-term outcome of patients with congenital chylothorax by retrospective and prospective data collection at Ghent University Hospital in Belgium between 1992 and 2022. RESULTS:Eighteen patients with congenital chylothorax were included, seven of whom had a pathology-confirmed diagnosis of congenital pulmonary lymphangiectasia. Of 16 patients with prenatal diagnosis, four underwent an intra-uterine intervention. Thirteen patients were born prematurely. The most common comorbidities were hydrops (8/18), pulmonary hypertension (3/18), and reflux disease (6/18). One patient was diagnosed with Noonan syndrome. The majority of patients (14/18) required mechanical ventilation. Treatment included pleural drainage (15/18), total parenteral nutrition (14/18), medium-chain triglyceride diet (11/18), somatostatin (8/18), and surgical intervention (3/18), with a median hospital stay of 59 days. Three patients died during or after the neonatal period. Follow-up ranged from 6 months to 30 years, with most patients reporting good general health but variable respiratory complaints. Five out of eight respiratory function tests showed mild abnormalities. Follow-up chest CT showed persistent changes in all but two patients up to a maximum age of 16 years. Health-related quality of life was similar to healthy controls. CONCLUSION:Congenital chylothorax demonstrates a variable neonatal course. Long-term outcomes are generally favorable in patients without comorbidities, although mild pulmonary function and chest CT abnormalities persist in the majority of patients.
