Transforming growth factor‐β1 in bronchoalveolar lavage fluid from children with cystic fibrosis

AbstractRationaleTransforming factor β1 (TGF‐β1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF‐β1 protein levels and clinical markers of CF lung disease severity.ObjectivesTo determine the association between protein levels of TGF‐β1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity.MethodsTotal TGF‐β1 was measured in BALF from 30 pediatric CF patients and 12 non‐CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization.ResultsTGF‐β1 was elevated in CF BALF compared to non‐CF controls (135 ± 15 pg/ml vs. 57 ± 10 pg/ml, P < 0.01). In CF BALF, increased TGF‐β1 was associated with elevated BALF PMN % (r = 0.67, P < 0.01). BALF TGF‐β1 was increased in CF subjects whose FEV1 after the completion of antibiotic therapy remained below CF age‐normative median values (205.9 ± 20.5 pg/ml vs. 106.4 ± 24.0, P = 0.01). BALF TGF‐β1 was increased in CF children hospitalized in the previous year compared to those not recently hospitalized (169.9 ± 21.6 pg/ml vs. 107.5 ± 17.5 pg/ml, P = 0.04). Neither the presence of a bacterial pathogen nor bacterial quantity was associated with BALF TGF‐β1.ConclusionsIn CF, BALF TGF‐β1 is elevated compared to non‐CF controls. Increased BALF TGF‐β1 is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations. Pediatr Pulmonol. 2009; 44:1057–1064. ©2009 Wiley‐Liss, Inc.