title: Biomarkers for cystic fibrosis drug development.
abstract: To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs.
  
  
  
  Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation.
  
  
  
  Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa) are commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments.
  
  
  
  Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with 'omics-based technologies, are needed to accelerate CF drug development.
authors.affiliation: Division of Pulmonology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address: marianne_muhlebach@med.unc.edu.
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Muhlebach
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: J P
authors.initials: JP
authors.lastname: Clancy
authors.affiliation: Division of Pulmonary, Department of Pediatrics, University of Washington, Seattle, WA, United States.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Assem
authors.initials: A
authors.lastname: Ziady
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Kelley
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, United States.
authors.forename: Frank
authors.initials: F
authors.lastname: Accurso
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pilewski
authors.affiliation: Division of Pulmonary, Department of Pediatrics, University of Washington, Seattle, WA, United States; Division of Pulmonology, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer-Hamblett
authors.affiliation: Cystic Fibrosis Foundation, Bethesda, MD, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joseloff
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, United States.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Sagel
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans
chemical_list: D015415:Biomarkers; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Advanced technologies; Biomarker; Electrophysiology; Infection; Inflammation; Microbiome