title: Diagnosis of Cystic Fibrosis in Nonscreened Populations.
abstract: Although the majority of cases of cystic fibrosis (CF) are now diagnosed through newborn screening, there is still a need to standardize the diagnostic criteria for those diagnosed outside of the neonatal period. This is because newborn screening started relatively recently, it is not performed everywhere, and even for individuals who were screened, there is the possibility of a false negative. To limit irreversible organ pathology, a timely diagnosis of CF and institution of CF therapies can greatly benefit these patients.
  
  
  
  Experts on CF diagnosis were convened at the 2015 CF Foundation Diagnosis Consensus Conference. The participants reviewed and discussed published works and instructive cases of CF diagnosis in individuals presenting with signs, symptoms, or a family history of CF. Through a modified Delphi methodology, several consensus statements were agreed upon. These consensus statements were updates of prior CF diagnosis conferences and recommendations.
  
  
  
  CF diagnosis in individuals outside of newborn screening relies on the clinical evidence and on evidence of CF transmembrane conductance regulator (CFTR) dysfunction. Clinical evidence can include typical organ pathologies seen in CF such as bronchiectasis or pancreatic insufficiency but often represent a broad range of severity including mild cases. CFTR dysfunction can be demonstrated using sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests. On the basis of the large number of patients with bona fide CF currently followed in registries with sweat chloride levels between 30 and 40 mmol/L, the threshold considered "intermediate" was lowered from 40 mmol/L in the prior diagnostic guidelines to 30 mmol/L. The CF diagnosis was also discussed in the context of CFTR-related disorders in which CFTR dysfunction may be present, but the individual does not meet criteria for CF.
  
  
  
  CF diagnosis remains a rare but important condition that can be diagnosed when characteristic clinical features are seen in an individual with demonstrated CFTR dysfunction.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Sosnay
authors.affiliation: Cystic Fibrosis Foundation, Bethesda, MD.
authors.forename: Terry B
authors.initials: TB
authors.lastname: White
authors.affiliation: Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison WI.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Farrell
authors.affiliation: Section of Pediatric Pulmonology, Allergy, and Sleep Medicine, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN.
authors.forename: Clement L
authors.initials: CL
authors.lastname: Ren
authors.affiliation: CFTR Biomarker Center and Translational CF Research Group, CF Center, Pediatric Pulmonology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Derichs
authors.affiliation: Section of Pediatric Pulmonology, Allergy, and Sleep Medicine, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Howenstine
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO.
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Nick
authors.affiliation: Pediatric Pulmonology, University Hospital of Leuven, University of Leuven, Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015997:Neonatal Screening; D017410:Practice Guidelines as Topic
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR-related disorder; adult diagnosis of CF; atypical CF; cystic fibrosis; genotype; mutation; penetrance; variant