Association of lower airway inflammation with physiologic findings in young children with cystic fibrosis.
BACKGROUND: The relationship between lower airway markers of inflammation and infection with physiologic findings is poorly understood in young children with cystic fibrosis (CF). The goal of this study was to evaluate the association of bronchoalveolar lavage fluid (BALF) markers of infection and inflammation, including mediators linked to airway remodeling, to infant lung function values in young children with CF undergoing clinically indicated bronchoscopy. METHODS: Plethysmography and the raised volume rapid thoracoabdominal compression (RVRTC) technique were performed in 16 sedated infants and young children with CF prior to bronchoscopy. BALF was collected and analyzed for pathogen density, cell count, % neutrophils, transforming growth factor beta 1 (TGF-beta(1)), matrix metalloproteinases (MMP), and interleukin-8 (IL-8). RESULTS: There was a significant direct correlation between functional residual capacity (FRC), the ratio of residual volume to total lung capacity (RV/TLC) and FRC/TLC with % neutrophils (P < 0.05). Forced expiratory flows were inversely correlated to % neutrophils (P < 0.01). Lung function parameters did not differentiate those with and without lower airway infection; however, pathogen density directly correlated with FRC and inversely correlated with flows (P < 0.05). In a subset of the population, MMP-2 directly correlated with RV/TLC and inversely correlated with flows (P < 0.05) and TGF-beta(1) directly correlated with FRC (P < 0.05). CONCLUSIONS: Results from this study suggest that lower airway inflammation as well as mediators linked to airway remodeling play an active role in pulmonary deterioration in CF infants and young children undergoing clinically indicated bronchoscopy.
Peterson-Carmichael, SL; Harris, WT; Goel, R; Noah, TL; Johnson, R; Leigh, MW; Davis, SD
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