title: Cystic Fibrosis Diagnostic Challenges over 4 Decades: Historical Perspectives and Lessons Learned.
abstract: OBJECTIVE
  Because cystic fibrosis (CF) can be difficult to diagnose, and because information about the genetic complexities and pathologic basis of the disease has grown so rapidly over the decades, several consensus conferences have been held by the US CF Foundation, and a variety of other efforts to improve diagnostic practices have been organized by the European CF Society. Despite these efforts, the application of diagnostic criteria has been variable and caused confusion.
  
  
  METHODS
  To improve diagnosis and achieve standardization in terms and definitions worldwide, the CF Foundation in 2015 convened a committee of 32 experts in the diagnosis of CF from 9 countries. As part of the process, all previous consensus-seeking exercises sponsored by the CF Foundation, along with the important efforts of the European CF Society, were comprehensively and critically reviewed. The goal was to better understand why consensus conferences and their publications have not led to the desired results.
  
  
  RESULTS
  Lessons learned from previous diagnosis consensus processes and products were identified. It was decided that participation in developing a consensus was generally not inclusive enough for global impact. It was also found that many efforts to address sweat test issues were valuable but did not always improve clinical practices as CF diagnostic testing evolved. It also became clear from this review that premature applications of potential diagnostic tests such as nasal potential difference and intestinal current measurement should be avoided until validation and standardization occur. Finally, we have learned that due to the significant and growing number of cases that are challenging to diagnose, an associated continuing medical education program is both desirable and necessary.
  
  
  CONCLUSIONS
  It is necessary but not sufficient to organize and publish CF diagnosis consensus processes. Follow-up implementation efforts and monitoring practices seem essential.
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: Cystic Fibrosis Foundation, Bethesda, MD.
authors.forename: Terry B
authors.initials: TB
authors.lastname: White
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: Cystic Fibrosis Center, Ospedale Civile Maggiore, Verona, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castellani
authors.affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
authors.forename: Beryl J
authors.initials: BJ
authors.lastname: Rosenstein
mesh_terms: D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics / Q000266:history*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005820:Genetic Testing; D049673:History, 20th Century; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D017410:Practice Guidelines as Topic
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CF screen positive; CFSPID; CFTR; CFTR-related metabolic syndrome; CRMS; ICD-10; ICM; IRT; immunoreactive trypsinogen; inconclusive diagnosis; intestinal current measurement; nasal potential difference; newborn screening; sweat test