High rate of pulmonary exacerbations and neutrophilic airway inflammation in children with repaired esophageal atresia with or without tracheoesophageal fistula

BACKGROUND: Children with repaired esophageal atresia with or without tracheoesophageal fistula (EA/TEF) frequently have chronic respiratory morbidity, but airway inflammation is poorly defined. We described bronchoalveolar lavage (BAL) cell patterns in symptomatic EA/TEF and compared them with primary ciliary dyskinesia (PCD), protracted bacterial bronchitis (PBB), and healthy controls (HC). METHODS: BAL profiles from symptomatic EA/TEF patients (n = 44) were analyzed against PCD (n = 10), PBB (n = 21), and HC (n = 16). Endoscopic bronchitis severity was assessed using the BScore. Associations between BScore and BAL profiles were assessed using multivariable modeling. RESULTS: All EA/TEF patients had pulmonary exacerbations. BAL neutrophils were higher in EA TEF than HC (median 8.0%, IQR 3-25 vs 1.0%, IQR 0-2, p < 0.001) and similarly elevated in PBB and PCD. BScore correlated with neutrophils (Spearman rho 0.69, p < 0.001) and independently predicted neutrophilic inflammation (beta 4.53, 95% CI 1.78-7.28, p = 0.002). Pathogenic bacteria were cultured in 61%, most commonly Haemophilus influenzae (29.5%) and Staphylococcus aureus (25.0%). CONCLUSIONS: This is the first study to systematically demonstrate neutrophil-driven airway inflammation in symptomatic children with repaired EA/TEF. These findings underscore the need for structured pulmonary follow up and the evaluation of anti inflammatory strategies in EA/TEF patients. IMPACT: Children with repaired EA/TEF and respiratory symptoms show frequent pulmonary exacerbations and neutrophil driven BAL inflammation. Neutrophil levels resemble protracted bacterial bronchitis and primary ciliary dyskinesia and track bronchoscopic bronchitis severity. Bronchoscopic bronchitis severity tracks neutrophilic inflammation and independently predicts it. Bacterial pathogens are common in BAL of EA/TEF children, supporting infection related airway injury risk. Results inform phenotype driven care pathways to reduce exacerbations and long term airway damage in EA/TEF children.