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Increase in Sweat Chloride Concentration Is Associated with a Higher Risk of CFSPID to CF Reclassification
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  • Danieli Salinas,
  • Daniella Ginsburg,
  • Choo Phei Wee,
  • Muhammad Saeed,
  • John Brewington
Danieli Salinas
University of Southern California Keck School of Medicine

Corresponding Author:[email protected]

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Daniella Ginsburg
University of Southern California Keck School of Medicine
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Choo Phei Wee
University of Southern California Southern California Clinical and Translational Science Institute
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Muhammad Saeed
Kaiser Permanente Los Angeles Medical Center
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John Brewington
University of Cincinnati Department of Pediatrics
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Objectives: Universal implementation of cystic fibrosis (CF) newborn screening (NBS) has led to the diagnostic dilemma of infants with CF screen positive, inconclusive diagnosis (CFSPID), for which there is limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are unknown. We investigated whether clinical characteristics are associated with risk of reclassification from CFSPID to a CF diagnosis. Methods: Children with a positive CF NBS were recruited from two sites in California. Retrospective, longitudinal, and cross-sectional data were collected. A subset of subjects had nasal epithelial cells collected for CFTR functional assessment. Multivariate logistic regression was used to assess the risk of CFSPID-to-CF reclassification. Results: A total of 112 children completed the study (CF=53, CFSPID=59). Phenotypic characteristics between groups showed differences in pancreatic insufficiency prevalence, immunoreactive trypsinogen (IRT) levels, and Pseudomonas aeruginosa (PSA) colonization. Spirometry measures were not different between groups. Nasal epithelial cells from 10 subjects showed 7-30% of wild type (WT)-CFTR function in those who reclassified and 27-67% of WT-CFTR function in those who retained the CFSPID designation. Modeling revealed that increasing sweat chloride concentration (sw[Cl -]) and PSA colonization were independent risk factors for reclassification to CF. Conclusion: Increasing sw[Cl -] and history of PSA colonization are associated with risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. Close follow-up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration.
20 Jul 2022Submitted to Pediatric Pulmonology
22 Jul 2022Submission Checks Completed
22 Jul 2022Assigned to Editor
22 Jul 2022Reviewer(s) Assigned
09 Aug 2022Review(s) Completed, Editorial Evaluation Pending
28 Aug 2022Editorial Decision: Revise Major
16 Oct 20221st Revision Received
26 Oct 2022Assigned to Editor
26 Oct 2022Review(s) Completed, Editorial Evaluation Pending
26 Oct 2022Submission Checks Completed
26 Oct 2022Reviewer(s) Assigned
26 Nov 2022Editorial Decision: Revise Minor
11 Dec 20222nd Revision Received
12 Dec 2022Assigned to Editor
12 Dec 2022Submission Checks Completed
12 Dec 2022Reviewer(s) Assigned
12 Dec 2022Review(s) Completed, Editorial Evaluation Pending
24 Dec 2022Editorial Decision: Accept