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Clinical evaluation of the Nanoduct sweat test system in the diagnosis of cystic fibrosis after newborn screening

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European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

After a positive newborn screening test for cystic fibrosis (CF), a sweat test is performed to confirm the diagnosis. The success rate of the generally acknowledged methods (Macroduct/Gibson and Cooke) in newborns varies between 73 and 99 %. The Nanoduct sweat test system is easier to perform and less sweat is needed. The main aim of this study was to measure the success rate of the Nanoduct compared to current approved sweat test methods in a newborn population. After informed consent of the parents, newborns with a positive screening test for CF were included. The Macroduct or Gibson and Cooke and Nanoduct were performed in all infants, during the same appointment. The chloride concentration was determined by standard coulorimetry; conductivity was measured directly and converted to a NaCl molarity. One hundred eight newborns were included: 17 with CF, 7 with cystic fibrosis transmembrane regulator (CFTR)-related metabolic syndrome (CRMS), and 84 healthy children. The success rate of the Nanoduct was 93 % and for the Macroduct/Gibson and Cooke 79 % (McNemar, p = 0.002). The Nanoduct detected the same CF patients as the Macroduct/Gibson and Cooke; one CF patient had an equivocal result for both tests, and no patients were missed. The area under the receiver operating characteristic curve for detection of CF with the Nanoduct was 0.999, with ideal cutoff levels of 91 and 66 mmol/l, comparable to former studies.

Conclusion: The success rate of the Nanoduct to collect sufficient sweat in infants was higher compared to the Macroduct and Gibson and Cooke.

What is known:

• The internationally accepted methods for collecting and determining NaCl values in sweat, the Gibson and Cooke method and Macroduct, are difficult to perform and require well-trained and experienced personnel. The test often fails in newborns. As yet there is insufficient evidence to recommend the use of the Nanoduct which fails less often, requires less sweat, and is much easier to perform.

What is new:

• This study provides further evidence that the Nanoduct fails less often in newborns than the Gibson and Cooke/Macroduct and can be used to exclude or confirm the diagnosis CF in infants with a positive newborn screening test for CF.

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Abbreviations

AUC:

Area under the curve

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane regulator

CHOPIN:

Cystic fibrosis heel prick among a newborn population in The Netherlands

CRMS:

CFTR-related metabolic syndrome

DNA:

Desoxyribonucleic acid

IRT:

Immunoreactive trypsinogen

NBS:

Newborn screening

NBSCF:

Newborn screening for cystic fibrosis

PAP:

Pancreatitis-associated protein

ROC:

Receiver operating characteristic curve

QPIT:

Quantitative pilocapine ionthophoresis test

QNS:

Quantity not sufficient

References

  1. Barben J, Ammann RA, Metlagel A, Schoeni MH (2005) Conductivity determined by a new sweat analyzer compared with chloride concentrations for the diagnosis of cystic fibrosis. J Pediatr 146:183–188

    Article  CAS  PubMed  Google Scholar 

  2. Barben J, Rüegg CS, Gallatti S, Kuehni CE, Baumgartner M, Torresani T, Schöni M (2013) Comparison of two sweat test systems (Macroduct versus Nanoduct) for the diagnosis of cystic fibrosis in the newborn screening program in Switzerland. J Cyst Fibros 12(Abstract 37):S57

    Article  Google Scholar 

  3. De Boeck K, Wilschanski M, Castellani C, Taylor C, Cuppens H, Dodge JA, Sinaasappel M (2006) Cystic fibrosis: terminology and diagnostic algorithms. Thorax 61:627–635

    Article  PubMed Central  PubMed  Google Scholar 

  4. Desax MC, Ammann RA, Hammer J, Schoeni MH, Barben J (2007) Nanoduct(R) sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis. Eur J Pediatr

  5. Eng W, LeGrys VA, Schechter MS, Laughon MM, Barker PM (2005) Sweat-testing in preterm and full-term infants less than 6 weeks of age. Pediatr Pulmonol 40:64–67

    Article  PubMed  Google Scholar 

  6. Farrell PM, Koscik RE (1996) Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics 97:524–528

    CAS  PubMed  Google Scholar 

  7. Funk MJ, LeGrys VA (2005) Testing diagnostic tests: why size matters. J Pediatr 146:159–162

    Article  PubMed  Google Scholar 

  8. Hammond KB, Turcios NL, Gibson LE (1994) Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis. J Pediatr 124:255–260

    Article  CAS  PubMed  Google Scholar 

  9. Heeley ME (2000) Indirect measurements of sweat electrolyte concentration in the laboratory diagnosis of cystic fibrosis. Arch Dis Child 82:420–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kleyn M, Korzeniewski S, Grigorescu V, Young W, Homnick D, Goldstein-Filbrun A, Schuen J, Nasr S. Predictors of insufficient sweat production during confirmatory testing for cystic fibrosis. Pediatr Pulmonol;46:23–30

  11. LeGrys VA (2001) Assessment of sweat-testing practices for the diagnosis of cystic fibrosis. Arch Pathol Lab Med 125:1420–1424

    CAS  PubMed  Google Scholar 

  12. LeGrys VA, Rosenstein BJ, Doumas BT, Miller WG, D’Orazio P, Eckfeld JH, Evans SA, Graham GA, Myers GL, Parsons PJ, Stanton NV (2000) Sweat Testing: Sample Collection and Quantative Analysis; Approved Guideline-Second Edition. NCCLS;20

  13. Lezana JL, Vargas MH, Karam-Bechara J, Aldana RS, Furuya ME (2003) Sweat conductivity and chloride titration for cystic fibrosis diagnosis in 3834 subjects. J Cyst Fibros 2:1–7

    Article  CAS  PubMed  Google Scholar 

  14. Losty HC (2006) The evaluation of a novel conductometric device for the diagnosis of cystic fibrosis. Ann Clin Biochem 43:375–381

    Article  PubMed  Google Scholar 

  15. Mastella G, Di Cesare G, Borruso A, Menin L, Zanolla L (2000) Reliability of sweat-testing by the Macroduct collection method combined with conductivity analysis in comparison with the classic Gibson and Cooke technique. Acta Paediatr 89:933–937

    Article  CAS  PubMed  Google Scholar 

  16. Mayell SJ, Munck A, Craig JV, Sermet I, Brownlee KG, Schwarz MJ, Castellani C, Southern KW (2009) A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis. J Cyst Fibros 8:71–78

    Article  CAS  PubMed  Google Scholar 

  17. Moran J, Quirk K, Duff AJ, Brownlee KG (2007) Newborn screening for CF in a regional paediatric centre: the psychosocial effects of false-positive IRT results on parents. J Cyst Fibros 6:250–254

    Article  PubMed  Google Scholar 

  18. Parad RB, Comeau AM, Dorkin HL, Dovey M, Gerstle R, Martin T, O’Sullivan BP (2005) Sweat testing infants detected by cystic fibrosis newborn screening. J Pediatr 147:S69–72

    Article  PubMed  Google Scholar 

  19. Sands D, Oltarzewski M, Nowakowska A, Zybert K. Bilateral sweat tests with two different methods as a part of cystic fibrosis newborn screening (CF NBS) protocol and additional quality control. Folia Histochem Cytobiol 48:358–365

  20. Sezer RG, Aydemir G, Akcan AB, Paketci C, Karaoglu A, Aydinoz S, Bozaykut A. Nanoduct sweat conductivity measurements in 2664 patients: relationship to age, arterial blood gas, serum electrolyte profiles and clinical diagnosis. J Clin Med Res5:34–41

  21. Sims EJ, Clark A, McCormick J, Mehta G, Connett G, Mehta A (2007) Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and requires more therapy. Pediatrics 119:19–28

    Article  PubMed  Google Scholar 

  22. Slieker MG, Uiterwaal CS, Sinaasappel M, Heijerman HG, van der Laag J, van der Ent CK (2005) Birth prevalence and survival in cystic fibrosis: a national cohort study in The Netherlands. Chest 128:2309–2315

    Article  PubMed  Google Scholar 

  23. Tluczek A, Koscik RL, Farrell PM, Rock MJ (2005) Psychosocial risk associated with newborn screening for cystic fibrosis: parents’ experience while awaiting the sweat-test appointment. Pediatrics 115:1692–1703

    Article  PubMed  Google Scholar 

  24. Vernooij-van Langen AM, Loeber JG, Elvers B, Triepels RH, Gille JJ, Van der Ploeg CP, Reijntjens S, Dompeling E, Dankert-Roelse JE (2012) Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study. Thorax 67:289–295

    Article  PubMed  Google Scholar 

  25. Williams SN, Nussbaum E, Chin TW, Do PC, Singh KE, Randhawa I (2014) Diagnosis of cystic fibrosis in the kindred of an infant with CFTR-related metabolic syndrome: importance of follow-up that includes monitoring sweat chloride concentrations over time. Pediatr Pulmonol 49:E103–108

    Article  PubMed  Google Scholar 

  26. www.STARD-statement.org. In; 2013

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Conflict of interest

None

Ethics committee approval

The Central Committee on Research inv. Human Subjects (CCMO) and the ethical committees of the participating CF centers approved the performance of the Nanoduct study according to the Good Clinical Practice guidelines and privacy statements.

Funding

At our request, the Elitech group, Wescor Biomedicals, provided the materials needed for performance of the Nanoduct; they also instructed the personnel that performed the sweat tests. Wescor Biomedicals had in no way influence on the data collection, analysis, or interpretation of the results nor did they say anything about the writing or the decision for submission.

Author’s contributions

AV and JD develop the study design, which was approved by BA, ED, HT and JYand the METC in each of the participating CF centers. JD, ED and GL supported the analysis andinterpretation of the results, and the writing. AV coordinated the study, collected the results and analyzed and interpreted the results and wrote the article. BA, ED, HT and JY coordinated the performance of the sweat test in the participating CF centers, and collected and reported the results. BA, ED, HT and JY also informed the parents about the diagnosis and results of the sweat test and were involved in the treatment and follow-up of the infants diagnosed with CF. All authors participated in the study, worked on the study design and read the article extensively. All authors approved the final version to be published.

Author information

Authors and Affiliations

  1. Department of Paediatrics, St Jansdal Hospital, PO box 138, 3840 AC, Harderwijk, The Netherlands

    Annette Vernooij-van Langen

  2. Department of Paediatric Pulmonology, Maastricht University Medical Centre, P. Debeyelaan 25, 6229 HX, Maastricht, The Netherlands

    Edward Dompeling

  3. Department of Paediatric Pulmonology, University Medical Centre Nijmegen-St Radboud, PO box 9101, 6500 HB, Nijmegen, The Netherlands

    Jan-Bart Yntema

  4. Department of Paediatric Pulmonology, University Medical Centre Utrecht-Wilhelmina’s Children’s Hospital, PO box 85090, 3508 BA, Utrecht, The Netherlands

    Bert Arets

  5. Department of Paediatric Pulmonology, Erasmus Medical Centre, Sophia Children’s Hospital, PO box 2060, 3000 CB, Rotterdam, The Netherlands

    Harm Tiddens

  6. Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), PO box 1, 3720 BA, Bilthoven, The Netherlands

    Gerard Loeber

  7. Department of Paediatrics, Atrium Medical Centre, PO box 4446, 6401 CX, Heerlen, The Netherlands

    Jeannette Dankert-Roelse

Authors
  1. Annette Vernooij-van Langen
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  2. Edward Dompeling
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  3. Jan-Bart Yntema
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  4. Bert Arets
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  5. Harm Tiddens
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  6. Gerard Loeber
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  7. Jeannette Dankert-Roelse
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Corresponding author

Correspondence to Annette Vernooij-van Langen.

Additional information

Communicated by Peter de Winter

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Langen, A.Vv., Dompeling, E., Yntema, JB. et al. Clinical evaluation of the Nanoduct sweat test system in the diagnosis of cystic fibrosis after newborn screening. Eur J Pediatr 174, 1025–1034 (2015). https://doi.org/10.1007/s00431-015-2501-0

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  • DOI: https://doi.org/10.1007/s00431-015-2501-0

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