title: Sputum club cell protein concentration is associated with pulmonary exacerbation in cystic fibrosis.
abstract: 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).
  
  
  CONCLUSIONS
  Sputum CCSP concentration is associated with CF pulmonary exacerbation.
authors.affiliation: Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States. Electronic address: lagun005@umn.edu.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Laguna
authors.affiliation: Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States.
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Williams
authors.affiliation: Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Brandy
authors.affiliation: Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States.
authors.forename: Cole
authors.initials: C
authors.lastname: Welchlin-Bradford
authors.affiliation: Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, United States.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Moen
authors.affiliation: School of Public Health, Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota and Veterans Administration Medical Center, Minneapolis, MN, United States.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wendt
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013183:Sputum / Q000378:metabolism*; D013997:Time Factors; D014598:Uteroglobin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D019272:Leukocyte Elastase
keywords: Biomarker; Cystic fibrosis; Cytokines; Infection; Inflammation; Lung function; Sputum