Rationale: Transforming factor beta(1) (TGF-beta(1)) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-beta(1) protein levels and clinical markers of CF lung disease severity.
Objectives: To determine the association between protein levels of TGF-beta(1) in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity.
Methods: Total TGF-beta(1) 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.
Results: TGF-beta(1) 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-beta(1) was associated with elevated BALF PMN % (r = 0.67, P < 0.01). BALF TGF-beta(1) was increased in CF subjects whose FEV(1) 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-beta(1) 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-beta(1).
Conclusions: In CF, BALF TGF-beta(1) is elevated compared to non-CF controls. Increased BALF TGF-beta(1) is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations.