ABSTRACT
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.
Subject(s)
Bronchoalveolar Lavage Fluid/immunology , Cystic Fibrosis/immunology , Inflammation/immunology , Neutrophils/physiology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/microbiology , Child, Preschool , Cohort Studies , Colony Count, Microbial , Female , Forced Expiratory Flow Rates/immunology , Functional Residual Capacity/immunology , Humans , Infant , Interleukin-8/analysis , Leukocyte Count , Male , Metalloproteases/analysis , Plethysmography , Transforming Growth Factor beta1/analysisABSTRACT
A candidate chicken-protein hydrolysate was subjected to high-performance size-exclusion chromatography to characterize its molecular weight profile. An inhibition ELISA assay was developed to assess the residual antigenicity, using canine serum IgG produced by dogs sensitized to the intact protein. Finally, the hydrolysate was compared to the intact protein through electrophoresis and immunoblotting. The chicken hydrolysate had a suitable molecular weight profile with 96.9% reduced to less than 10 kDa peptides. The inhibition ELISA demonstrated a residual antigenic mass of 1.5% compared with the intact protein. Immunoblotting demonstrated a strong immunoreactive band at 68-70 kDa consistent with chicken serum albumin in the intact protein, which was absent in the hydrolysate. These results demonstrate the suitability of the chicken hydrolysate for use in a protein hydrolysate diet, and provide a basis for the future comparisons of the peptide components of hydrolyzed protein diets so that veterinarians may make more informed decisions in their dietary prescriptions.
Subject(s)
Diet/veterinary , Protein Hydrolysates/chemistry , Animals , Antibody Formation/immunology , Antigens/immunology , Blotting, Western/methods , Blotting, Western/veterinary , Chickens , Chromatography, Gel/methods , Chromatography, Gel/veterinary , Chromatography, High Pressure Liquid/methods , Chromatography, High Pressure Liquid/veterinary , Diet/statistics & numerical data , Electrophoresis, Polyacrylamide Gel/methods , Electrophoresis, Polyacrylamide Gel/veterinary , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/veterinary , Functional Residual Capacity/immunology , Molecular Weight , Protein Hydrolysates/immunologyABSTRACT
Obesity adversely affects lung function in humans often reducing arterial blood oxygenation. To determine if obesity adversely affects lung function in cynomolgus monkeys, which is a species that is often used for pulmonary research, pulmonary mechanics, ventilation, functional residual capacity (FRC), and arterial blood gases were measured using spontaneous respiration and on mechanical ventilation with room air or 100% O(2). Body fat percentage was measured by dual energy X-ray absorption. Blood leptin levels were measured by radioimmune assay. Obese monkeys breathed faster with lower tidal volume, but pulmonary resistance and dynamic lung compliance did not change with body fat. FRC and blood leptin were, respectively, negatively and positively correlated with percent body fat. FRC correlated moderately with ventilatory parameters and strongly with arterial oxygen tension, alveolar-arterial oxygen difference and venous admixture. Therefore, obesity in cynomolgus monkeys had marked, deleterious effects on FRC, ventilation and arterial oxygenation. Obesity may be an important confounding variable in lung function studies in primates.
