Introduction
Cystic fibrosis (CF), stemming from mutations in the CF transmembrane conductance regulator (CFTR) gene, presents ongoing challenges in diagnosis. The advent of newborn screening and a deeper understanding of CF genetics have necessitated a critical review and refinement of diagnostic criteria. To address these evolving complexities, the Cystic Fibrosis Foundation convened a global panel of experts to establish clear and actionable clinical care guidelines for CF diagnosis and related disorders. This initiative aims to standardize diagnostic approaches worldwide, ensuring consistent and accurate identification of CF across diverse populations and age groups.
Expert Consensus for Diagnostic Clarity
Recognizing the critical need for standardized definitions in CF diagnosis, the CF Foundation assembled a committee of 32 leading experts from 9 countries. This expert panel was tasked with developing consensus guidelines to enhance the precision and consistency of CF diagnosis. Their work focused on clarifying diagnostic criteria and terminology, particularly for conditions associated with CFTR mutations beyond classic CF. The rigorous consensus process required a high threshold of agreement, with at least 80% of affirmative votes needed for each recommendation to be accepted, ensuring robust and widely supported guidelines.
Key Recommendations for CF Diagnosis
Through a comprehensive review of existing literature and clinical cases, the expert committee formulated a series of consensus statements. These statements, developed by an executive subcommittee, underwent a thorough voting process by the entire panel. Ultimately, 27 out of 28 statements were approved, highlighting a strong consensus on key aspects of CF diagnosis. A central recommendation emphasizes the importance of evaluating CFTR function using the sweat chloride test for all individuals, from newborns to adults, suspected of having a CFTR-related disorder. Furthermore, the guidelines advocate for the use of the most current CFTR mutation classifications provided by the Clinical and Functional Translation of CFTR project (CFTR2, accessible at http://www.cftr2.org/index.php). This resource is crucial for interpreting genetic testing results and informing diagnostic decisions.
Refined Terminology and Classification
The consensus guidelines also address the complexities of newborn screening results. For newborns exhibiting a high immunoreactive trypsinogen level alongside inconclusive CFTR functional and genetic testing, the term CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis has been refined. These terms are now considered merged and equivalent, with CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis being the recommended terminology. This clarification aims to streamline communication and ensure consistent classification in newborn screening follow-up. To further standardize diagnostic reporting, the guidelines include International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for diagnoses associated with CFTR mutations, facilitating accurate record-keeping and data analysis.
Conclusion
These newly established clinical care guidelines represent a significant step forward in standardizing CF diagnosis worldwide. By emphasizing functional CFTR assessment, utilizing updated mutation classifications, and refining diagnostic terminology, these guidelines promise to enhance diagnostic accuracy and ensure consistent, evidence-based care for individuals with CF and CFTR-related disorders. The widespread adoption of these Cf Diagnosis Clinical Care Guidelines is crucial for improving patient outcomes and advancing research in the field of cystic fibrosis.
