RESUMO
BACKGROUND: There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants. METHODS: Urine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers. RESULTS: Urinary cathepsin B was significantly higher in CF infants compared to healthy infants (p = 0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p = 0.002 & p = 0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p < 0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p = 0.046). BALF CCSP was negatively associated with IL-8 (p = 0.017). There was no correlation between biomarker concentration and FEV0.5. CONCLUSIONS: Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.
Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/metabolismo , Triagem Neonatal/tendências , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/diagnóstico , Inflamação/metabolismo , Estudos Longitudinais , Masculino , Neutrófilos/metabolismo , Estudos Prospectivos , Escarro/metabolismoRESUMO
BACKGROUND: Cystic fibrosis (CF) patients exhibit a progressive decline in lung function accelerated by intermittent pulmonary exacerbations. There are urgent needs for clinically relevant biomarkers to aid in the diagnosis and management of a CF pulmonary exacerbation, in addition to providing insight into its pathophysiology. Club cell secretory protein (CCSP) is produced by bronchial epithelial cells, known to have anti-inflammatory properties and may play a role in CF pulmonary exacerbations. Our objective was to measure sputum CCSP concentration during hospitalizations for CF pulmonary exacerbation and during quarterly outpatient clinic visits for 2 years. We explored the correlations between CCSP concentration, lung function and markers of inflammation and infection. METHODS: In this prospective, longitudinal cohort study, expectorated sputum, blood and lung function data were collected from 45 CF patients during 68 hospitalizations for pulmonary exacerbation and 193 clinic visits. Sputum CCSP concentration was measured and sputum and blood were assayed with a panel of inflammatory cytokines. We used a repeated measures model to compare log transformed sputum CCSP concentrations across multiple time points and to correlate those concentrations with related clinical variables. RESULTS: Our population had a mean age of 29 (16-58 years), and a median FEV(1) %predicted of 60% (18-105%). Sputum CCSP concentration was significantly lower in the initial, interim and final exacerbation samples (p=0.0021, p=0.0005 and p=0.0274, respectively) compared to outpatient visits. Sputum CCSP concentration was negatively associated with sputum neutrophil elastase concentration (p=0.0373). Patients with Pseudomonas aeruginosa mucoid had a significantly lower sputum CCSP concentration (p=0.0129). CONCLUSION: Sputum CCSP concentration is associated with CF pulmonary exacerbation.