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Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
Philip M Farrell1, Terry B White2, Clement L Ren3
1Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Insights
New guidelines recommend sweat chloride testing for diagnosing cystic fibrosis (CF) in all ages. Updated CFTR mutation classifications and terminology for CFTR-related metabolic syndrome aid diagnosis.
Area of Science:
- Medical Genetics
- Pulmonology
- Diagnostic Medicine
Background:
- Cystic fibrosis (CF) diagnosis is challenging due to genetic complexities and evolving screening methods.
- Current diagnostic criteria require updates to reflect advancements in CFTR gene understanding and newborn screening.
- Standardized global definitions for CF and related disorders are needed.
Purpose of the Study:
- To develop consensus guidelines for diagnosing CF and related CFTR disorders.
- To establish clear, actionable diagnostic criteria and terminology for CFTR-related conditions.
- To standardize CF diagnosis worldwide.
Main Methods:
- A 32-expert international committee was convened by the CF Foundation.
- Systematic literature review and case evidence analysis were performed.
- Consensus statements were developed and approved via voting, requiring ≥80% affirmative votes.
Main Results:
- 27 out of 28 consensus statements were approved by the committee.
- Seven statements required revisions and a second round of voting.
- Guidelines address diagnosis from newborn to adult stages.
Conclusions:
- Sweat chloride testing is recommended for CFTR mutation-associated diagnoses in all individuals.
- Utilize the latest CFTR mutation classifications from the CFTR2 project.
- Standardized terminology for inconclusive newborn screening results (CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis) is established.
Objective:
Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria.
Study Design:
To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement.
Results:
After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting.
Conclusions:
It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included.