Different management approaches and outcome for infants with an inconclusive diagnosis following newborn screening for cystic fibrosis (CRMS/CFSPID) and Pseudomonas aeruginosa isolation

Dolce, Daniela; Claut, Laura; Colombo, Carla; Tosco, Antonella; Castaldo, Alice; Padoan, Rita; Timpano, Silviana; Fabrizzi, Benedetta; Bonomi, Paolo; Taccetti, Giovanni; Terlizzi, Vito

doi:10.1016/j.jcf.2022.07.007

Cited by 15 publications

(17 citation statements)

References 27 publications

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“…Our results suggest greater overlap in HNE assay results between children who reclassified to CF and those who retained the CRMS/CFSPID designation compared to sw[Cl − ] values in these two groups (Figure 3). On the other hand, HNE assays show a greater distinction between the CRMS/CFSPID group and healthy controls than sw[Cl − ], as healthy controls and carriers may have sw[Cl − ] from <30 to >60 mmol/l 32 . However, the small number of assays and the small ( n = 2) subset that progressed to a diagnosis of CF limits the interpretation of these results.…”

Section: Discussionmentioning

confidence: 99%

“…One CRMS/CFSPID child with two positive cultures in the previous 12 months was placed in the chronic category; in this case, the second positive culture was immediately after 28 days of inhaled tobramycin (Tobi®), which triggered a second course of treatment. Per California standard of practice, sites collect throat cultures with annual visits in the CRMS/CFSPID population; however, there is no consensus on how to proceed when a culture is positive for PSA, as clearance is not shown to rely upon treatment 32 …”

Section: Discussionmentioning

confidence: 99%

“…The short follow‐up may be attributed to the young age of this population, early discharge per physician's decision, and high lost‐to‐follow‐up rates 40,41 . The second challenge for defining prognosis in this population is high variability in the duration of follow‐up, care practices, and CF reclassification criteria despite improved guidelines 32,42 …”

Section: Discussionmentioning

confidence: 99%

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Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification

Salinas

Ginsburg

Wee

et al. 2023

Pediatric Pulmonology

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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), with limited guidance regarding prognosis and standardized care. Rates of reclassification from CFSPID to CF vary and risk factors for reclassification are not well established. We investigated whether clinical characteristics are associated with the 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 CF transmembrane conductance regulator (CFTR) functional assessment. Multivariate logistic regression was used to assess the risk of 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 (wtCFTR) function in those who reclassified and 27%–67% of wtCFTR 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 a history of PSA colonization are associated with the risk of reclassification from CFSPID to CF in a population with high IRT and two CFTR variants. A close follow‐up to monitor phenotypic changes remains critical in this population. The role of CFTR functional assays in this population requires further exploration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification

Salinas

Ginsburg

Wee

et al. 2023

Pediatric Pulmonology

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“…Among the advantages of this study is the fact that this is one of the few studies that has described the phenotype of children with CFSPID [ 24 , 49 , 50 ]. The obtained data suggest that in asymptomatic children with CFSPID, despite the lack of routine vitamin supplementation, we did not observe significant deficits in this area.…”

Section: Discussionmentioning

confidence: 99%

Vitamin Status in Children with Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation

et al. 2022

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Background: The issue of vitamin metabolism in children with cystic fibrosis screen positive, inconclusive diagnosis (CFSPID) is not well known. The aim of this study was to determine the status of vitamins A, D, E, and C in the blood of a group of children with CFSPID. Material and Methods: A total of 89 children were enrolled in the study (Me: 3.6 years, 52.8% boys), as follows: 28 with CFSPID, 31 with CF (cystic fibrosis), and 30 HC (healthy children). Their blood concentrations of vitamins A, D, E, and C, and their dietary intake of these vitamins were analysed in the study groups on the basis of a three-day food diary. Results: The patients with CFSPID had significantly higher serum vitamin D (p = 0.01) and E (p = 0.04) concentrations, compared to the children with CF. None of the children with CFSPID revealed vitamin A or E deficiencies. Patients with CF had been consuming significantly higher vitamin D and E amounts (p = 0.01). The vitamin concentrations did not depend either on the pancreatic/liver function or on anthropometric parameters. In total, 32.14% of patients with CF did not cover the baseline recommended calorie intake, and 53.6% and 36% did not take the recommended vitamin E and vitamin A intake, respectively. Conclusion: Children with CF and CFSPID did not fully cover the dietary recommendations for vitamin supply, but vitamin deficiency was found only in CF.

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“…Advent of the NBS has led to the identification of asymptomatic infants found to have a positive NBS with at least one mutation and a SC concentration between 30 and 59 mmol/L, who are considered to have an inconclusive diagnosis and may be designated to have CF Screen Positive, Inconclusive Diagnosis (CFSPID), also known as CFTR-related metabolic syndrome (CRMS) (8)(9)(10)(11)(12)(13)(14)(15). Repeated SCT in the diagnostic range or identification of two known CF disease-causing mutations can subsequently confirm the diagnosis of CF (15,16).…”

Section: Introductionmentioning

confidence: 99%

Outcomes of children with cystic fibrosis screen positive, inconclusive diagnosis/CFTR related metabolic syndrome

et al. 2023

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BackgroundSome infants undergoing newborn screening (NBS) tests have inconclusive sweat chloride test (SCT) results that lead to the designation of Cystic Fibrosis Screen Positive, Inconclusive Diagnosis/CFTR-related metabolic syndrome (CFSPID/CRMS). Some proportion of them transition to a CF diagnosis, but no predictive markers can stratify which are at risk for this transition. We report single-center outcomes of children with CRMS.MethodsWe retrospectively identified all infants born in Alabama from 2008 through 2020 referred to our CF Center with an elevated immunoreactive trypsinogen level (IRT) associated with a cystic fibrosis transmembrane conductance regulator (CFTR) mutation (IRT+/DNA+) who had at least one SCT result documented. Infants were classified per established guidelines as Carrier, CRMS, or CF based on the IRT+/DNA+ and SCT results. The electronic health record was reviewed for follow-up visits until the children received a definitive diagnosis (to carrier or CF) according to current diagnostic guidelines for CF, or through the end of the 2020 year.ResultsOf the 1,346 infants with IRT+ and at least 1 CFTR mutation identified (IRT+/DNA+), 63 (4.7%) were designated as CRMS. Of these infants, 12 (19.1%) transitioned to Carrier status (CRMS-Carrier), 40 (63.5%) of them remained CRMS status (CRMS-Persistent) and 11 (17.5%) of them transitioned to a diagnosis of CF (CRMS-CF). Of the 11 children in the CRMS-CF group, 4 (36%) had an initial SCT 30–39 mmol/L, 4 (36%) had an initial SCT 40–49 mmol/L and 3 (27%) had an initial SCT 50–59 mmol/L. These children also had higher initial sweat tests and greater yearly increases in sweat chloride values than others with CRMS. We found that in comparison to children in the CRMS-P group, a greater proportion of children in the CRMS-CF group cultured bacteria like methicillin-resistant Staphylococcus aureus, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa, had smaller weight-for-height percentiles and remained smaller over time despite slightly greater growth.ConclusionInfants with an inconclusive diagnosis of CF should continue to receive annual care and management given their potential risk of transition to CF. Further research is needed to assess whether certain phenotypic patterns, clinical symptoms, diagnostic tests or biomarkers could better stratify these children.

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Different management approaches and outcome for infants with an inconclusive diagnosis following newborn screening for cystic fibrosis (CRMS/CFSPID) and Pseudomonas aeruginosa isolation

Cited by 15 publications

References 27 publications

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification

Gradual increase in sweat chloride concentration is associated with a higher risk of CRMS/CFSPID to CF reclassification

Vitamin Status in Children with Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation

Outcomes of children with cystic fibrosis screen positive, inconclusive diagnosis/CFTR related metabolic syndrome

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