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Abnormal Lung Clearance Index in Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Children with Otherwise Normal FEV1

Abstract

In preschool children with cystic fibrosis (CF), lung clearance index (LCI) is a sensitive test to detect early lung disease. Some children with CF screen positive, inconclusive diagnosis (CFSPID) may in time develop clinical features of CF. LCI has not been studied in CFSPID children. LCI and spirometry were performed in preschool age children with CF, CFSPID, and non-CF healthy controls (HCs) during two visits. Fifty-four preschool age children (HC n = 18, CFSPID n = 17, and CF n = 19) were tested. Mean LCI from the CFSPID group was not statistically different from HC (p = 0.49), but significantly different when compared to CF (p = 0.04). LCI was abnormal in 2 CFSPID children who carried potentially deleterious CFTR variants. Mean forced expiratory volume in 1 s (FEV1) was not statistically different between CFSPID and CF (p = 0.26). LCI can potentially detect early lung disease in CFSPID individuals as part of assessing their risk for reclassification to CF diagnosis.

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Notes

  1. 1.

    Newborn screening for CF in California uses a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens, (2) testing of 40 pre-selected CFTR mutations in specimens with immunoreactive trypsinogen values ≥ 62 ng/mL (top 1.6%), and (3) performing CFTR-DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with ≥ 2 mutations/variants are screen positive and referred to CF care centers for diagnostic evaluation and follow-up [23].

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Acknowledgements

The authors thank Dr. Sally L. Davidson Ward and the Cystic Fibrosis Team at Children’s Hospital Los Angeles for supporting this study. The authors thank Whitney Gore, Cynthia Leyva, Monique Margetis, Alejandra Franquez, Amy Deblaise-Kasai, Maria Carmen Reyes, and Cathleen Salata for their help with patient recruitment. They also thank the children and families who participated in this study.

Funding

This project was supported by the Webb Family and National Institute of Health (NIH)/National Center for Research Resources Southern California Clinical and Translational Science Institute (NCRR SC-CTSI), Grant Number UL1 TR000130. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Correspondence to Ajay S. Kasi.

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Kasi, A.S., Wee, C.P., Keens, T.G. et al. Abnormal Lung Clearance Index in Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Children with Otherwise Normal FEV1. Lung 198, 163–167 (2020). https://doi.org/10.1007/s00408-019-00307-3

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Keywords

  • Cystic fibrosis
  • CFTR-related metabolic syndrome
  • CRMS
  • CFSPID
  • Lung clearance index
  • Early lung disease