Risk of CFTR-related Disorders and Cystic Fibrosis in an Italian Cohort of CRMS/CFSPID Subjects in Preschool and School Age

Overview

Journal Eur J Pediatr

Specialty Pediatrics

Date 2023 Dec 6

PMID 38054992

Authors

C Fevola

D Dolce

A Tosco

R Padoan

V Dacco

L Claut

T Schgor

A Sepe

S Timpano

B Fabrizzi

P Piccinini

G Taccetti

P Bonomi

V Terlizzi

Affiliations

Soon will be listed here.

Abstract

Conclusion: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD.

What Is Known: • Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). • Over time a variable percentage of CFSPIDs will be diagnosed as CF. • Little data is available on CFSPIDs with a follow-up period of more than six years.

What Is New: • 80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. • Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. • Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC.

Citing Articles

Critical Issues in the Management of CRMS/CFSPID Children: A National Real-World Survey.

Terlizzi V, Fevola C, Presti S, Claut L, Ambroni M, Calderazzo M Pediatr Pulmonol. 2025; 60(1):e27483.

PMID: 39812351 PMC: 11734379. DOI: 10.1002/ppul.27483.

Cystic fibrosis year in review 2023.

Swetland D, Savant A Pediatr Pulmonol. 2024; 59(12):3106-3116.

PMID: 39056532 PMC: 11601032. DOI: 10.1002/ppul.27190.

References

Massie R, Curnow L, Glazner J, Armstrong D, Francis I . Lessons learned from 20 years of newborn screening for cystic fibrosis. Med J Aust. 2012; 196(1):67-70. DOI: 10.5694/mja11.10686. View

Hale J, Parad R, Dorkin H, Gerstle R, Lapey A, OSullivan B . Cystic fibrosis newborn screening: using experience to optimize the screening algorithm. J Inherit Metab Dis. 2010; 33(Suppl 2):S255-61. DOI: 10.1007/s10545-010-9117-3. View

Ren C, Borowitz D, Gonska T, Howenstine M, Levy H, Massie J . Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome and Cystic Fibrosis Screen Positive, Inconclusive Diagnosis. J Pediatr. 2017; 181S:S45-S51.e1. DOI: 10.1016/j.jpeds.2016.09.066. View

Terlizzi V, Claut L, Tosco A, Colombo C, Raia V, Fabrizzi B . A survey of the prevalence, management and outcome of infants with an inconclusive diagnosis following newborn bloodspot screening for cystic fibrosis (CRMS/CFSPID) in six Italian centres. J Cyst Fibros. 2021; 20(5):828-834. DOI: 10.1016/j.jcf.2021.03.015. View

Ooi C, Castellani C, Keenan K, Avolio J, Volpi S, Boland M . Inconclusive diagnosis of cystic fibrosis after newborn screening. Pediatrics. 2015; 135(6):e1377-85. DOI: 10.1542/peds.2014-2081. View

Bombieri C, Claustres M, De Boeck K, Derichs N, Dodge J, Girodon E . Recommendations for the classification of diseases as CFTR-related disorders. J Cyst Fibros. 2011; 10 Suppl 2:S86-102. DOI: 10.1016/S1569-1993(11)60014-3. View

Tosco A, Marino D, Polizzi S, Tradati V, Padoan R, Giust C . A Multicentre Italian Study on the Psychological Impact of an Inconclusive Cystic Fibrosis Diagnosis after Positive Neonatal Screening. Children (Basel). 2023; 10(2). PMC: 9955261. DOI: 10.3390/children10020177. View

Terlizzi V, Claut L, Colombo C, Tosco A, Castaldo A, Fabrizzi B . Outcomes of early repeat sweat testing in infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/CF screen-positive, inconclusive diagnosis. Pediatr Pulmonol. 2021; 56(12):3785-3791. DOI: 10.1002/ppul.25683. View

Scurati-Manzoni E, Fossali E, Agostoni C, Riva E, Simonetti G, Zanolari-Calderari M . Electrolyte abnormalities in cystic fibrosis: systematic review of the literature. Pediatr Nephrol. 2013; 29(6):1015-23. DOI: 10.1007/s00467-013-2712-4. View

10.

LeGrys V, Yankaskas J, Quittell L, Marshall B, Mogayzel Jr P . Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr. 2007; 151(1):85-9. DOI: 10.1016/j.jpeds.2007.03.002. View

11.

Anagnostopoulou P, Latzin P, Jensen R, Stahl M, Harper A, Yammine S . Normative data for multiple breath washout outcomes in school-aged Caucasian children. Eur Respir J. 2019; 55(4). DOI: 10.1183/13993003.01302-2019. View

12.

Oude Engberink E, Ratjen F, Davis S, Retsch-Bogart G, Amin R, Stanojevic S . Inter-test reproducibility of the lung clearance index measured by multiple breath washout. Eur Respir J. 2017; 50(4). PMC: 5898949. DOI: 10.1183/13993003.00433-2017. View

13.

Frey U, Stocks J, Coates A, Sly P, Bates J . Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society. Eur Respir J. 2000; 16(4):731-40. DOI: 10.1034/j.1399-3003.2000.16d28.x. View

14.

Terlizzi V, Parisi G, Ferrari B, Castellani C, Manti S, Leonardi S . Effect of Dornase Alfa on the Lung Clearance Index in Children with Cystic Fibrosis: A Lesson from a Case Series. Children (Basel). 2022; 9(11). PMC: 9688561. DOI: 10.3390/children9111625. View

15.

Flume P, Mogayzel Jr P, Robinson K, Goss C, Rosenblatt R, Kuhn R . Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009; 180(9):802-8. DOI: 10.1164/rccm.200812-1845PP. View

16.

Gunnett M, Baker E, Mims C, Self S, Gutierrez H, Guimbellot J . Outcomes of children with cystic fibrosis screen positive, inconclusive diagnosis/CFTR related metabolic syndrome. Front Pediatr. 2023; 11:1127659. PMC: 10034052. DOI: 10.3389/fped.2023.1127659. View

17.

Ginsburg D, Wee C, Reyes M, Brewington J, Salinas D . When CFSPID becomes CF. J Cyst Fibros. 2021; 21(1):e23-e27. DOI: 10.1016/j.jcf.2021.06.012. View

18.

Tosco A, Castaldo A, Colombo C, Claut L, Carnovale V, Iacotucci P . Clinical outcomes of a large cohort of individuals with the F508del/5T;TG12 CFTR genotype. J Cyst Fibros. 2022; 21(5):850-855. DOI: 10.1016/j.jcf.2022.04.020. View

19.

Terlizzi V, Padoan R, Claut L, Colombo C, Fabrizzi B, Lucarelli M . CRMS/CFSPID Subjects Carrying D1152H CFTR Variant: Can the Second Variant Be a Predictor of Disease Development?. Diagnostics (Basel). 2020; 10(12). PMC: 7764752. DOI: 10.3390/diagnostics10121080. View

20.

Terlizzi V, Mergni G, Centrone C, Festini F, Taccetti G . Trend of sweat chloride values in a cohort of patients carrying CFTR mutations of varying clinical consequence: Is there a risk of increasing sweat chloride over time?. Pediatr Pulmonol. 2020; 55(5):1089-1093. DOI: 10.1002/ppul.24721. View