title: Candidate markers associated with the probability of future pulmonary exacerbations in cystic fibrosis patients.
abstract: BACKGROUND
  Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE.
  
  
  METHODS
  We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment.
  
  
  RESULTS
  Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation.
  
  
  CONCLUSIONS
  Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Wojewodka
authors.affiliation: Institute of Immunology, Central University of Venezuela, Caracas, Venezuela.
authors.forename: Juan B
authors.initials: JB
authors.lastname: De Sanctis
authors.affiliation: Adult Cystic Fibrosis Clinic, Montreal Chest Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Joanie
authors.initials: J
authors.lastname: Bernier
authors.affiliation: McGill University Health Center Research Institute, Montreal, Quebec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bérubé
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Heather G
authors.initials: HG
authors.lastname: Ahlgren
authors.affiliation: Adult Cystic Fibrosis Clinic, Montreal Chest Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Jim
authors.initials: J
authors.lastname: Gruber
authors.affiliation: Adult Cystic Fibrosis Clinic, Montreal Chest Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Landry
authors.affiliation: Division of Pediatric Respiratory Medicine, Montreal Children's Hospital, McGill University Health Center Research Institute, Montreal, Quebec, Canada.
authors.forename: Larry C
authors.initials: LC
authors.lastname: Lands
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Dao
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Rousseau
authors.affiliation: Department of Medicine, McGill University, Montreal, Quebec, Canada ; Department of Epidemiology, Biostatistics and Occupational Health, Montreal Chest Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Benedetti
authors.affiliation: Adult Cystic Fibrosis Clinic, Montreal Chest Institute, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Elias
authors.initials: E
authors.lastname: Matouk
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada ; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003550:Cystic Fibrosis / Q000097:blood*; D018450:Disease Progression; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000097:blood; D053208:Kaplan-Meier Estimate; D015227:Lipid Peroxidation; D008137:Longitudinal Studies; D008171:Lung Diseases / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011788:Quality of Life; D012008:Recurrence; D012129:Respiratory Function Tests; D012307:Risk Factors; D013147:Spirometry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A