Paediatric Respiratory Reviews
Volume 10, Issue 4 , Pages 220-226 , December 2009

Physiological Measurements Confirming the Diagnosis of Cystic Fibrosis: the Sweat Test and Measurements of Transepithelial Potential Difference

  • C.J. Taylor

      Affiliations

    • Sheffield Paediatric Cystic Fibrosis Centre, Sheffield, Academic Unit of Child Health, University of Sheffield, UK
    • Corresponding Author InformationCorresponding author. Academic Unit Child Health, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH.
    • ,
  • J. Hardcastle

      Affiliations

    • Sheffield Paediatric Cystic Fibrosis Centre, Sheffield, Academic Unit of Child Health, University of Sheffield, UK
    • ,
  • K.W. Southern

      Affiliations

    • Royal Liverpool Children's Hospital, Institute of Child Health, University of Liverpool, Liverpool, UK

References 

  1. Di Sant’ Agnese PA, Darling RC, Perera GA, Shea E. Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas. Pediatrics. 1953;12:549–563
  2. Gibson LE, Cooke RE. A test for the concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics. 1959;23:545–549
  3. Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr. 1998;132:589–595
  4. Schwartz IL, Thaysen JH, Haysen , Dole VP. Sodium and potassium excretion in human sweat. Am. J. Physiol. 1954;179:671
  5. Quinton PM. Physiological Basis of Cystic Fibrosis: A Historical Perspective. Physiological Reviews. 1999;79(No. 1):S3–S22
  6. Quinton PM, Reddy MM. Regulation of absorption by phosphorylation of CFTR. Jpn J Physiol. 1994;44(Suppl 2):S207–S213
  7. Tarran R, Button B, Boucher RC. Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress. Annu Rev Physiol. 2006;68:543–561
  8. Reddy MM, Quinton PM. Functional interaction of CFTR and ENaC in sweat glands. Pflugers Arch. 2003;445:499–503Epub 2002 Nov 21
  9. Gleeson M, Henry RL. Sweat sodium or chloride?. Clin Chem. 1991;37:112
  10. Slegers JFG. The Secretion and Reabsorption of Salt and Water in the Sweat Gland: a Comparative Study Between Normal Subjects and Patients Suffering From Fibrocystic Disease. Pflügers Arch. 1966;290:231–236
  11. Augarten A, Hacham S, Kerem E, et al. The significance of sweat Cl/Na ratio in patients with borderline sweat test. Pediatr Pulmonol. 1995;20:369–371
  12. di SAnt’Agnese PA, Powell GF. The eccrine sweat defect in cystic fibrosis of the pancreas. Ann NY Acad Sci. 1962;93:555–599
  13. Shamsuddin AK, Yanagimoto S, Kuwahara T, Zhang Y, Nomura C, Kondo N. Changes in the index of sweat ion concentration with increasing sweat during passive heat stress in humans. Eur J Appl Physiol. 2005;94:292–297Epub 2005 Mar 12
  14. Hodson ME, Beldon I, Power R, Duncan FR, Bamber M, Batten JC. Sweat tests to diagnose cystic fibrosis in adults. Br Med J (Clin Res Ed). 1983;286:1381–1383
  15. Hardy JD, Davison SH, Higgins MU, Polycarpou PN. Sweat tests in the newborn period. Arch Dis Child. 1973;48:316–318
  16. Parad RB, Comeau AM, Dorkin HL, et al. Sweat testing infants detected by cystic fibrosis newborn screening. J Pediatr. 2005;147(3 Suppl):S69–72
  17. Eng W, LeGrys VA, Schechter MS, Laughon MM, Barker PM. Sweat-testing in preterm and full-term infants less than 6 weeks of age. Pediatr Pulmonol. 2005;40:64–67
  18. Eisenhut M, Sidaras D, Barton P, Newland P, Southern KW. Elevated sweat sodium associated with pulmonary oedema in meningococcal sepsis. Eur J Clin Invest. 2004;34:576–579
  19. Rubin BK, MacLeod PM, Sturgess J, King M. Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport?. Pediatr Pulmonol. 1991;10:304–309
  20. Lobeck BB, Barta RA, Mangos JA. Study of sweat in pitressin-resistant diabetes insipidus. J Pediatr. 1963;62:868–875
  21. Walpole IR, Goldblatt J. Rapp-Hodgkin hypohidrotic ectodermal dysplasia syndrome. Clin Genet. 1991;39:114–120
  22. Main K, Price DA, Savage MO, Skakkebaek NE. Decreased sweating in seven patients with Laron Syndrome. Journal of Clinical Endocrinology and Metabolism;. 1993;77:821–823
  23. Hillemeier AC, Hen J, Riely CA, Dolan TF, Gryboski JD. Meconium peritonitis and increasing sweat chloride determinations in a case of familial progressive intrahepatic cholestasis. Pediatrics. 1982;69:325–327
  24. Foulston C, Gall G, Mitchell I, Cooper DM, Scott RB. Transient neutral fat steatorrhea, elevated sweat chloride concentration, and hypoparathyroidism in a child with celiac disease. J Pediatr Gastroenterol Nutr. 1985;4:143–145
  25. Brand PL, Gerritsen J, van Aalderen WM. A baby with eczema and an abnormal sweat test. Lancet. 1996;348:932
  26. Silverman BL, Lloyd-Still JD, Hazinski TA, Hunt CE. Increased sweat chloride levels associated with prostaglandin E1 infusion. J Pediatr. 1985;106:953–954
  27. Beck R, Goldberg E, Durie PR, Levison H. Elevated sweat chloride levels in anorexia nervosa. J Pediatr. 1986;108:260–262
  28. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics. 1996;97:524–528
  29. Zielenski J, Tsui LC. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet. 1995;29:777–807
  30. Wilschanski M, Zielenski J, Markiewicz D, et al. Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations. J Pediatr. 1995;127:705–710
  31. Lording A, McGaw J, Dalton A, Beal G, Everard M, Taylor CJ. Pulmonary infection in mild variant cystic fibrosis: implications for care. J Cyst Fibros. 2006;5:101–104
  32. Roussey M, Le Bihannic A, Scotet V, et al. Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations. J Inherit Metab Dis. 2007;30:613
  33. Lebecque P, Leal T, De Boeck C, Jaspers M, Cuppens H, Cassiman JJ. Mutations of the cystic fibrosis gene and intermediate sweat chloride levels in children. Am J Respir Crit Care Med. 2002;165:757–761
  34. Desmarquest P, Feldmann D, Tamalat A, et al. Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results. Chest. 2000;118:1591–1597
  35. Padoan R, Bassotti A, Seia M, Corbetta C. Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations. Eur J Pediatr. 2002;161:212–215
  36. Multi-Disciplinary Working Group supported by the Cystic Fibrosis Trust. Evidence-based Guidelines for the Performance of the Sweat Test for the Investigation of Cystic Fibrosis in the UK.
  37. LeGrys VA, Yankaskas JR, Quittell LM, Marshall BC, Mogayzel PJ. Cystic Fibrosis Foundation. Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines. J Pediatr. 2007;151:85–89
  38. Price CP, Spencer K. Problems associated with measuring sweat chloride concentration with an ion specific electrode. Ann Clin Biochem. 1977;14:171–178
  39. Emrich HM, Stoll E, Friolet B, Colombo JP, Richterich R, Rossi E. Sweat composition in relation to rate of sweating in patients with cystic fibrosis of the pancreas. Pediatr Res. 1968;2:464–478
  40. Hammond KB, Turcios NL, Gibson LE. Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis. J Pediatr. 1994;124:255–260
  41. Mastella G, Di Cesare G, Borruso A, Menin L, Zanolla L. Reliability of sweat-testing by the Macroduct collection method combined with conductivity analysis in comparison with the classic Gibson and Cooke technique. Acta Paediatr. 2000;89:933–937
  42. Barben J, Casaulta C, Spinas R, Schoeni MH. Sweat testing practice in Swiss hospitals. Swiss Med Wkly. 2007;137:192–198
  43. Katherisan N, Gupta A, Mumfoed S, Cade A, Jones R. Sweat conductivity for the diagnosis of cystic fibrosis. J Cystic Fibrosis. 2004;3:205
  44. National Committee for Clinical Laboratory Standards (NCCLS). Sweat Testing: Sample Collection and Quantitative Analysis. Approved guideline C34-A2. Wayne, Pa: NCCLS; 2000.
  45. Webster HL, Quirante CG. Micro-flowcell conductometric sweat analysis for cystic fibrosis diagnosis. Ann Clin Biochem. 2000;37(Pt 3):399–407
  46. Desax MC, Ammann RA, Hammer J, Schoeni MH, Barben J On behalf of the Swiss Paediatric Respiratory Research Group. Nanoduct(R) sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis. Eur J Pediatr. 2008;167:299–304
  47. Barben J, Ammann RA, Metlagel A, Schoeni MH Swiss Paediatric Respiratory Research Group. Conductivity determined by a new sweat analyzer compared with chloride concentrations for the diagnosis of cystic fibrosis. J Pediatr. 2005;146:183–188
  48. Mishra A, Greaves R, Massie J. The Limitations of Sweat Electrolyte Reference Intervals for the Diagnosis of Cystic Fibrosis: A Systematic Review. Clin Biochem Rev. 2007;28:60–76
  49. Kirk JM, Keston M, McIntosh I, al Essa S. Variation of sweat sodium and chloride with age in cystic fibrosis and normal populations: further investigations in equivocal cases. Ann Clin Biochem. 1992;29(Pt 2):145–152
  50. Gilljam M, Ellis L, Corey M, Zielenski J, Durie P, Tullis DE. Clinical manifestations of cystic fibrosis among patients with diagnosis in adulthood. Chest. 2004;126:1215–1224
  51. Wilschanski M, Famini H, Strauss-Liviatan N, et al. Nasal potential difference measurements in patients with atypical cystic fibrosis. Eur Respir J. 2001;17:1208–1215
  52. Knowles MR, Carson JL, Collier AM, Gatzy JT, Boucher RC. Measurements of nasal transepithelial electric potential differences in normal human subjects in vivo. Am Rev Respir Dis. 1981;124:484–490
  53. Boyle MP, Diener-West M, Milgram L, Knowles M, Foy C, Zeitlin P, et al. A multicenter study of the effect of solution temperature on nasal potential difference measurements. Chest. 2003;124:482–489
  54. Knowles MR, Clarke LL, Boucher RC. Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med. 1991;25:533–538
  55. Mall M, Wissner A, Gonska T, et al. Inhibition of amiloride-sensitive epithelial Na(+) absorption by extracellular nucleotides in human normal and cystic fibrosis airways. Am J Respir Cell Mol Biol. 2000;23:755–761
  56. Höfmann T, Bohmer O, Hüls G, et al. Conventional and modified nasal potential-difference measurement in cystic fibrosis. Am J Respir Crit Care Med. 1997;155:1908–1913
  57. Wilson DC, Ellis L, Zielenski J, Corey M, Ip WF, Tsui LC, et al. Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements. J Pediatr. 1998;132:596–599
  58. Southern KW, Noone PG, Bosworth DG, Legrys VA, Knowles MR, Barker PM. A modified technique for measurement of nasal transepithelial potential difference in infants. The Journal of Pediatrics. 2001;139:353–358
  59. Munck A, Gerardin M, Godard A, Le Bourgeois M, Gaultier C, Navarro J et al. Nasal transepithelial potential difference in healthy young children. Ped Pulmonol 1999;suppl 19;215 (abstract 180).
  60. Schuler D, Sermet-Gaudelus I, Wilschanski M, Ballmann M, Dechaux M, Edelman A, et al. Basic protocol for transepithelial nasal potential difference measurements. J Cyst Fibros. 2004;(Suppl 2):151–155
  61. Standaert TA, Boitano L, Emerson J, Milgram LJ, Konstan MW, Hunter J, et al. Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trials. Pediatric pulmonology. 2004;37:385–392
  62. Hebestreit A, Kersting U, Basler B, Jeschke R, Hebestreit H. Exercise inhibits epithelial sodium channels in patients with cystic fibrosis. American journal of respiratory and critical care medicine. 2001;164:443–446
  63. Leal T, Lebacq J, Lebecque P, Cumps J, Wallemacq P. Modified method to measure nasal potential difference. Clin Chem Lab Med. 2003;41:61–67
  64. Jaron R, Yaakov Y, Rivlin J, et al. Nasal potential difference in non-classic cystic fibrosis-long term follow up. Pediatr Pulmonol. 2008;43:545–549
  65. Delmarco A, Pradal U, Cabrini G, Bonizzato A, Mastella G. Nasal potential difference in cystic fibrosis patients presenting borderline sweat test. Eur Respir J. 1997;10:1145–1149
  66. Lebecque P, Leal T, De Boeck C, Jaspers M, Cuppens H, Cassiman JJ. Mutations of the cystic fibrosis gene and intermediate sweat chloride levels in children. American journal of respiratory and critical care medicine. 2002;165:757–761
  67. Fajac I, Hubert D, Guillemot D, Honore I, Bienvenu T, Volter F, et al. Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult patients. Thorax. 2004;59:971–976
  68. Wallace HL, Barker PM, Southern KW. Nasal airway ion transport and lung function in young people with cystic fibrosis. American journal of respiratory and critical care medicine. 2003;168:594–600
  69. Crawford I, Maloney PC, Zeitlin PL, et al. Immunocytochemical localization of the cystic fibrosis gene product CFTR. Proc Natl Acad Sci. 1991;88:9262–9266
  70. O’Loughlin EV, Hunt DM, Bostrom TE, et al. X-ray microanalysis of cell elements in normal and cystic fibrosis jejunum: evidence for chloride secretion in villi. Gastroenterology. 1996;110:411–418
  71. Taylor CJ, Baxter PS, Hardcastle J, Hardcastle PT. Absence of secretory response in jejunal biopsy samples from children with cystic fibrosis. Lancet. 1987;II:107–108
  72. Taylor CJ, Baxter PS, Hardcastle J, Hardcastle PT. Failure to induce secretion in jejunal biopsy samples from children with cystic fibrosis. Gut. 1988;29:957–962
  73. Berschneider HM, Knowles MR, Azizkhan RG, Boucher RC, Tobey NA, Orlando RC, et al. Altered intestinal chloride transport in cystic fibrosis. FASEB J. 1988;2:2625–2629
  74. O’Loughlin EV, Hunt DM, Gaskin KJ, et al. Abnormal epithelial transport in cystic fibrosis jejunum. Am J Physiol. 1991;260:G758–G763
  75. Mall M, Bleich M, Kuehr J, Brandis M, Greger R, Kunzelmann K. CFTR-mediated inhibition of epithelial Na conductance is defective in cystic fibrosis. Am J Physiol. 1999;277:G709–G716
  76. Baxter PS, Goldhill J, Hardcastle J, Hardcastle PT, Taylor CJ. Enhanced intestinal glucose and alanine transport in cystic fibrosis. Gut. 1990;31:817–820
  77. Taylor CJ, Hughes H, Hardcastle PT, Hardcastle J. Genotype and secretory response in cystic fibrosis. Lancet. 1992;339:67–68
  78. Hirtz S, Gonska T, Seydewitz HH, et al. CFTR Cl− channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis. Gastroenterology. 2004;127:1085–1095

PII: S1526-0542(09)00041-4

doi: 10.1016/j.prrv.2009.05.002

Paediatric Respiratory Reviews
Volume 10, Issue 4 , Pages 220-226 , December 2009

Article Tools

* Image Usage & Resolution