Detection of cystic fibrosis transmembrane conductance regulator activity in early-phase clinical trials

Proceedings of the American Thoracic Society

Volumn 4, Issue 4, 2007, Pages 387-398

  Rowe, Steven M ^a,b,c,d,f   Accurso, Frank ^e   Clancy, John P ^c,d  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c University of Alabama at Birmingham   (United States)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^e Children's Hospital Colorado   (United States)

^f UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Cystic fibrosis therapy; Cystic fibrosis transmembrane conductance regulator biomarkers; Ion transport; Nasal potential difference; Sweat chloride

Indexed keywords

CHLORIDE ION; GENTAMICIN; SODIUM ION; TRANSMEMBRANE CONDUCTANCE REGULATOR;

CELLULAR DISTRIBUTION; CHLORIDE TRANSPORT; CLINICAL TRIAL; CONFERENCE PAPER; CYSTIC FIBROSIS; DIAGNOSTIC APPROACH ROUTE; DRUG ABSORPTION; DRUG TOLERABILITY; FEASIBILITY STUDY; GENOTYPE PHENOTYPE CORRELATION; HUMAN; IMMUNOCYTOCHEMISTRY; OUTCOME ASSESSMENT; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REPRODUCIBILITY; SENSITIVITY AND SPECIFICITY; SODIUM ABSORPTION; SODIUM TRANSPORT; STATISTICAL ANALYSIS; SWEAT TEST; TREATMENT RESPONSE;

BIOLOGICAL MARKERS; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; FEASIBILITY STUDIES; HUMANS; NASAL MUCOSA; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; SWEAT;

EID: 34548286919     PISSN: 15463222     EISSN: None     Source Type: Journal    
DOI: 10.1513/pats.200703-043BR     Document Type: Conference Paper

References (115)

1. Rowe SM, Clancy JP. Advances in cystic fibrosis therapies. Curr Opin Pediatr 2006;18:604-613.
2. Knowles M, Gatzy J, Boucher R. Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. N Engl JMed 1981;305:1489-1495.
3. Schuler D, Sermet-Gaudelus I, Wilschanski M, Ballmann M, Dechaux M, Edelman A, Hug M, Leal T, Lebacq J, Lebecque P, et al. Basic protocol for transepithelial nasal potential difference measurements. J Cyst Fibros 2004;3:151-155.
4. Knowles M, Gatzy J, Boucher R. Relative ion permeability of normal and cystic fibrosis nasal epithelium. J Clin Invest 1983;71:1410-1417.
5. - secretion in human subjects by adenosine. Am J Respir Cell Mol Biol 2004;31:140-146.
6. Illek B, Zhang L, Lewis NC, Moss RB, Dong JY, Fischer H. Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am J Physiol 1999;277:C833-C839.
7. Middleton PG, Geddes DM, Alton EW. Protocols for in vivo measurement of the ion transport defects in cystic fibrosis nasal epithelium. Eur Respir J 1994;7:2050-2056.
8. Rosenstein BJ, Cutting GR; Cystic Fibrosis Foundation Consensus Panel. The diagnosis of cystic fibrosis: a consensus statement. J Pediatr 1998;132:589-595.
9. Knowles MR, Paradiso AM, Boucher RC. In vivo nasal potential difference: techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum Gene Ther 1995;6:445-455.
10. Wilschanski M, Dupuis A, Ellis L, Jarvi K, Zielenski J, Tullis E, Martin S, Corey M, Tsui LC, Durie P. Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials. Am J Respir Crit Care Med 2006;174:787-794.
11. Davies JC, Davies M, McShane D, Smith S, Chadwick S, Jaffe A, Farley R, Collins L, Bush A, Scallon M, et al. Potential difference measurements in the lower airway of children with and without cystic fibrosis. Am J Respir Crit Care Med 2005;171:1015-1019.
12. Bertrand CA, Frizzell RA. The role of regulated CFTR trafficking in epithelial secretion. Am J Physiol Cell Physiol 2003;285:C1-C18.
13. Amaral MD. Processing of CFTR: traversing the cellular maze - how much CFTR needs to go through to avoid cystic fibrosis? Pediatr Pulmonol 2005;39:479-491.
14. Ho LP, Samways JM, Porteous DJ, Dorin JR, Carothers A, Greening AP, Innes JA. Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis. Eur Respir J 1997;10:2018-2022.
15. Thomas SR, Jaffe A, Geddes DM, Hodson ME, Alton EW. Pulmonary disease severity in men with ΔF508 cystic fibrosis and residual chloride secretion. Lancet 1999;353:984-985.
16. Fajac I, Hubert D, Guillemot D, Honore I, Bienvenu T, Volter F, Dall'Ava-Santucci J, Dusser DJ. Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult patients. Thorax 2004;59:971-976.
17. Wallace HL, Barker PM, Southern KW. Nasal airway ion transport and lung function in young people with cystic fibrosis. Am J Respir Crit Care Med 2003;168:594-600.
18. Walker LC, Venglarik CJ, Aubin G, Weatherly MR, McCarty NA, Lesnick B, Ruiz F, Clancy JP, Sorscher EJ. Relationship between airway ion transport and amild pulmonary disease mutation in CFTR. Am J Respir Crit Care Med 1997;155:1684-1689.
19. Fajac I, Lacronique J, Lockhart A, Dall'Ava-Santucci J, Dusser DJ. Silver/silver chloride electrodes for measurement of potential difference in human bronchi. Thorax 1998;53:879-881.
20. Zabner J, Ramsey BW, Meeker DP, Aitken ML, Balfour RP, Gibson RL, Launspach J, Moscicki RA, Richards SM, Standaert TA, et al. Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis. J Clin Invest 1996;97:1504-1511.
21. Hay JG, McElvaney NG, Herena J, Crystal RG. Modification of nasal epithelial potential differences of individuals with cystic fibrosis consequent to local administration of a normal CFTR cDNA adenovirus gene transfer vector. Hum Gene Ther 1995;6:1487-1496.
22. Flotte TR, Zeitlin PL, Reynolds TC, Heald AE, Pedersen P, Beck S, Conrad CK, Brass-Ernst L, Humphries M, Sullivan K, et al. Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study. Hum Gene Ther 2003;14:1079-1088.
23. Knowles MR, Hohneker KW, Zhou Z, Olsen JC, Noah TL, Hu PC, Leigh MW, Engelhardt JF, Edwards LJ, Jones KR, et al. A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 1995;333:823-831.
24. Alton EW, Stern M, Farley R, Jaffe A, Chadwick SL, Phillips J, Davies J, Smith SN, Browning J, Davies MG, et al. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 1999;353:947-954.
25. Caplen NJ, Alton EW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery PK, Hodson ME, Coutelle C, et al. Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1995;1:39-46.
26. Zabner J, Cheng SH, Meeker D, Launspach J, Balfour R, Perricone MA, Morris JE, Marshall J, Fasbender A, Smith AE, et al. Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo. J Clin Invest 1997;100:1529-1537.
27. Gill DR, Southern KW, Mofford KA, Seddon T, Huang L, Sorgi F, Thomson A, MacVinish LJ, Ratcliff R, Bilton D, et al. A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 1997;4:199-209.
28. Porteous DJ, Dorin JR, McLachlan G, Davidson-Smith H, Davidson H, Stevenson BJ, Carothers AD, Wallace WA, Moralee S, Hoenes C, et al. Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 1997;4:210-218.
29. Noone PG, Hohneker KW, Zhou Z, Johnson LG, Foy C, Gipson C, Jones K, Noah TL, Leigh MW, Schwartzbach C, et al. Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis. Mol Ther 2000;1:105-114.
30. Tagawa T, Manvell M, Brown N, Keller M, Perouzel E, Murray KD, Harbottle RP, Tecle M, Booy F, Brahimi-Horn MC, et al. Characterisation of LMD virus-like nanoparticles self-assembled from cationic liposomes, adenovirus core peptide mu and plasmid DNA. Gene Ther 2002;9:564-576.
31. Alton EW. Use of nonviral vectors for cystic fibrosis gene therapy. Proc Am Thorac Soc 2004;1:296-301.
32. Stern M, Ulrich K, Geddes DM, Alton EW. Poly (D,L-lactide-co- glycolide)/ DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo. Gene Ther 2003;10:1282-1288.
33. Konstan MW, Davis PB, Wagener JS, Hilliard KA, Stern RC, Milgram LJ, Kowalczyk TH, Hyatt SL, Fink TL, Gedeon CR, et al. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum Gene Ther 2004;15:1255-1269.
34. Johnson LG, Olsen JC, Sarkadi B, Moore KL, Swanstrom R, Boucher RC. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet 1992;2:21-25.
35. Johnson LG, Boyles SE, Wilson J, Boucher RC. Normalization of raised sodium absorption and raised calcium-mediated chloride secretion by adenovirus-mediated expression of cystic fibrosis transmembrane conductance regulator in primary human cystic fibrosis airway epithelial cells. J Clin Invest 1995;95:1377-1382.
36. Goldman MJ, Yang Y, Wilson JM. Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect. Nat Genet 1995;9:126-131.
37. Wilschanski M, Yahav Y, Yaacov Y, Blau H, Bentur L, Rivlin J, Aviram M, Bdolah-Abram T, Bebok Z, Shushi L, et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N Engl J Med 2003;349:1433-1441.
38. Wilschanski M, Famini C, Blau H, Rivlin J, Augarten A, Avital A, Kerem B, Kerem E. A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations. Am J Respir Crit Care Med 2000;161:860-865.
39. Rodgers HC, Knox AJ. The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis. Eur Respir J 1999;14:693-696.
40. Zeitlin PL, Boyle MP, Guggino WB, Molina L. A phase I trial of intranasal Moli1901 for cystic fibrosis. Chest 2004;125:143-149.
41. Hofmann T, Stutts MJ, Ziersch A, Ruckes C, Weber WM, Knowles MR, Lindemann H, Boucher RC. Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis. Am J Respir Crit Care Med 1998;157:1844-1849.
42. Middleton PG, Pollard KA, Wheatley JR. Hypertonic saline alters ion transport across the human airway epithelium. Eur Respir J 2001;17:195-199.
43. 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;325:533-538.
44. Rubenstein RC, Propert KJ, Reenstra WW, Skotleski ML. A pilot trial of the combination of phenylbutyrate and genistein [abstract]. Pediatr Pulmonol Suppl 2006;41:248.
45. Goss CH, Genatossio A, Rowbotham RK, Hamblett N, McNamara S, Knowles M, Brass-Ernst L, Aitken ML, Zeitlin PL, Boyle MP. A phase I safety and dose finding study of orally administered curcuminoids in adult subjects with cystic fibrosis who are homozygous for ΔF508 cystic fibrosis transmembrane conductance regulator [abstract]. Pediatr Pulmonol Suppl 2006;41:247.
46. Clancy J, Rowe SM, Bebok Z, Aitken M, Gibson R, Zeitlin P, Berclaz PY, Knowles M, Avery Foy G, Davies Z, et al. No detectable improvements in CFTR associated with nasal aminoglycosides in CF patients heterozygous for stop mutations. Am J Respir Cell Mol Biol 2007;37:57-66.
47. McCarty NA, Standaert TA, Teresi M, Tuthill C, Launspach J, Kelley TJ, Milgram LJ, Hilliard KA, Regelmann WE, Weatherly MR, et al. A phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis. Pediatr Pulmonol 2002;33:90-98.
48. Clancy JP, Konstan MW, Rowe SM, Accurso F, Zeitlin P, Moss R, Bebok Z, Northcutt VJ, Elfring GL, Miller L, et al. A phase II study of PTC124 in CF patients harboring premature stop mutations [abstract]. Pediatr Pulmonol Suppl 2006;41:269.
49. Zabner J, Couture LA, Gregory RJ, Graham SM, Smith AE, Welsh MJ. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 1993;75:207-216.
50. Hyde SC, Southern KW, Gileadi U, Fitzjohn EM, Mofford KA, Waddell BE, Gooi HC, Goddard CA, Hannavy K, Smyth SE, et al. Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis. Gene Ther 2000;7:1156-1165.
51. Rubenstein RC, Zeitlin PL. A pilot clinical trial of oral sodium 4-phenylbutyrate (Buphenyl) in ΔF508-homozygous cystic fibrosis patients: partial restoration of nasal epithelial CFTR function. Am J Respir Crit Care Med 1998;157:484-490.
52. Clancy JP, Bebok Z, Ruiz F, King C, Jones J, Walker L, Greer H, Hong J, Wing L, Macaluso M, et al. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am J Respir Crit Care Med 2001;163:1683-1692.
53. Alton EW, Middleton PG, Caplen NJ, Smith SN, Steel DM, Munkonge FM, Jeffery PK, Geddes DM, Hart SL, Williamson R, et al. Noninvasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice. Nat Genet 1993;5:135-142.
54. Davies MG, Geddes DM, Alton EW. The effect of varying tonicity on nasal epithelial ion transport in cystic fibrosis. Am J Respir Crit Care Med 2005;171:760-763.
55. Illek B, Fischer H. Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo. Am J Physiol 1998;275:L902-L910.
56. Smith SN, Middleton PG, Chadwick S, Jaffe A, Bush KA, Rolleston S, Farley R, Delaney SJ, Wainwright B, Geddes DM, et al. The in vivo effects of milrinone on the airways of cystic fibrosis mice and human subjects. Am J Respir Cell Mol Biol 1999;20:129-134.
57. Knowles MR, Clarke LL, Boucher RC. Extracellular ATP and UTP induce chloride secretion in nasal epithelia of cystic fibrosis patients and normal subjects in vivo. Chest 1992;101:60S-63S.
58. Knowles MR, Stutts MJ, Spock A, Fischer N, Gatzy JT, Boucher RC. Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science 1983;221:1067-1070.
59. Miwa M, Matsunaga M, Nakajima N, Yamaguchi S, Watanabe K. Hypertonic saline alters electrical barrier of the airway epithelium. Otolaryngol Head Neck Surg 2007;136:62-66.
60. Cantin AM, Hanrahan JW, Bilodeau G, Ellis L, Dupuis A, Liao J, Zielenski J, Durie P. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am J Respir Crit Care Med 2006;173:1139-1144.
61. Ahrens RC, Standaert TA, Launspach J, Han SH, Teresi ME, Aitken ML, Kelley TJ, Hilliard KA, Milgram LJ, Konstan MW, et al. Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis. Pediatr Pulmonol 2002;33:142-150.
62. Standaert TA, Boitano L, Emerson J, Milgram LJ, Konstan MW, Hunter J, Berclaz PY, Brass L, Zeitlin PL, Hammond K, et al. Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trials. Pediatr Pulmonol 2004;37:385-392.
63. Boyle MP, Diener-West M, Milgram L, Knowles M, Foy C, Zeitlin P, Standaert T. A multicenter study of the effect of solution temperature on nasal potential difference measurements. Chest 2003;124:482-489.
64. Uwaifo O, Bamford P, Zeitlin PL, Blaisdell CJ. Acidic pH hyperpolarizes nasal potential difference. Pediatr Pulmonol 2006;41:151-157.
65. Mairbaurl H, Schwobel F, Hoschele S, Maggiorini M, Gibbs S, Swenson ER, Bartsch P. Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema. J Appl Physiol 2003;95:1843-1850.
66. Mairbaurl H, Weymann J, Mohrlein A, Swenson ER, Maggiorini M, Gibbs JS, Bartsch P. Nasal epithelium potential difference at high altitude (4,559 m): evidence for secretion. Am J Respir Crit Care Med 2003;167:862-867.
67. Mason NP, Petersen M, Melot C, Imanow B, Matveykine O, Gautier MT, Sarybaev A, Aldashev A, Mirrakhimov MM, Brown BH, et al. Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude. J Appl Physiol 2003;94:2043-2050.
68. Graham SM, Scott SN, Launspach J, Zabner J. The effects of fluticasone propionate on nasal epithelial potential difference. Am J Rhinol 2002;16:145-149.
69. Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med 2006;173:475-482.
70. Beckerman RC, Taussig LM. Hypoelectrolytemia and metabolic alkalosis in infants with cystic fibrosis. Pediatrics 1979;63:580-583.
71. Whitehead FJ, Couper RT, Moore L, Bourne AJ, Byard RW. Dehydration deaths in infants and young children. Am J Forensic Med Pathol 1996;17:73-78.
72. Quinton PM. Chloride impermeability in cystic fibrosis. Nature 1983;301:421-422.
73. Kerem E, Corey M, Kerem BS, Rommens J, Markiewicz D, Levison H, Tsui LC, Durie P. The relation between genotype and phenotype in cystic fibrosis: analysis of the most common mutation (ΔF508). N Engl J Med 1990;323:1517-1522.
74. Reddy MM, Quinton PM. Cytosolic potassium controls CFTR deactivation in human sweat duct. Am J Physiol Cell Physiol 2006;291:C122-C129.
75. Reddy MM, Quinton PM. Functional interaction of CFTR and ENaC in sweat glands. Pflugers Arch 2003;445:499-503.
76. Kartner N, Augustinas O, Jensen TJ, Naismith AL, Riordan JR. Mislocalization of ΔF508 CFTR in cystic fibrosis sweat gland. Nat Genet 1992;1:321-327.
77. Sorscher EJ, Kirk KL, Weaver ML, Jilling T, Blalock JE, LeBoeuf RD. Antisense oligodeoxynucleotide to the cystic fibrosis gene inhibits anion transport in normal cultured sweat duct cells. Proc Natl Acad Sci USA 1991;88:7759-7762.
78. Reddy MM, Quinton PM. Rapid regulation of electrolyte absorption in sweat duct. J Membr Biol 1994;140:57-67.
79. Davis PB, Schluchter MD, Konstan MW. Relation of sweat chloride concentration to severity of lung disease in cystic fibrosis. Pediatr Pulmonol 2004;38:204-209.
80. Kerem B, Kerem E. The molecular basis for disease variability in cystic fibrosis. Eur J Hum Genet 1996;4:65-73.
81. Cuppens H, Lin W, Jaspers M, Costes B, Teng H, Vankeerberghen A, Jorissen M, Droogmans G, Reynaert I, Goossens M, et al. Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes: the polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation. J Clin Invest 1998;101:487-496.
82. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics 1996;97:524-528.
83. 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;29:145-152.
84. Hardy JD, Davison SH, Higgins MU, Polycarpou PN. Sweat tests in the newborn period. Arch Dis Child 1973;48:316-318.
85. Shankle WR, Azen SP, Landing BH. Comparisons of eccrine sweat gland anatomy in genetic, chromosomal, and other diseases, and a suggested procedure for use of sweat gland measurements in differential diagnosis. Teratology 1982;25:239-245.
86. - conductance in both cell membranes of an absorptive epithelium. J Membr Biol 1992;130:49-62.
87. Frizzell RA, Halm DR, Rechkemmer G, Shoemaker RL. Chloride channel regulation in secretory epithelia. Fed Proc 1986;45:2727-2731.
88. - channel function. Nature 1999;402:301-304.
89. Stutts MJ, Rossier BC, Boucher RC. Cystic fibrosis transmembrane conductance regulator inverts protein kinase A-mediated regulation of epithelial sodium channel single channel kinetics. J Biol Chem 1997;272:14037- 14040.
90. Boucher RC. Human airway ion transport: part two. Am J Respir Crit Care Med 1994;150:581-593.
91. Knowles MR, Gatzy JT, Boucher RC. Aldosterone metabolism and transepithelial potential difference in normal and cystic fibrosis subjects. Pediatr Res 1985;19:676-679.
92. De Haller R, Siegenthaler P, Muller AF. [Influence of aldosterone on the concentration of sodium and chloride in sweat in mucoviscidosis and in the normal subject]. Helv Med Acta 1963;30:534-539.
93. Siegenthaler P, Haller J, Haller R, Hampai A, Muller AF. Effect of experimental salt depletion and aldosterone load on sodium and chloride concentration in the sweat of patients with cystic fibrosis of the pancreas and of normal children. Arch Dis Child 1964;39:61-65.
94. 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.
95. Grand RJ, Di Sant'Agnese PA, Talamo RC, Pallavicini JC. The effects of exogenous aldosterone on sweat electrolytes. II. Patients with cystic fibrosis of the pancreas. J Pediatr 1967;70:357-368.
96. Lobeck CC, McSherry NR. Response of sweat electrolyte concentrations to 9α-fluorohydrocortisone in patients with cystic fibrosis and their families. J Pediatr 1963;62:393-398.
97. Sato K, Sato F. Defective β adrenergic response of cystic fibrosis sweat glands in vivo and in vitro. J Clin Invest 1984;73:1763-1771.
98. Quinton PM, Bijman J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. N Engl J Med 1983;308:1185-1189.
99. LeGrys VA, Rosenstein BJ, Doumas BT, Miller WG, D'Orazio P, Eckfeldt JH, Evans SA, Graharn GA, Myers GL, Parsons PJ et al.; Clinical and Laboratory Standards Institute (formerly NCCLS). Sweat testing: sample collection and quantitative analysis; approved guideline, 2nd ed. Document C34-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2000. Available from: http://www.clsi.org/source/orders/free/c34-a2.pdf (accessed June 2007).
100. 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.
101. 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.
102. Anbar RD, Lapey A, Khaw KT, Spragg J, Strieder DJ, Shaw LF, Kelly DH, Shannon DC. Does lithium carbonate affect the ion transport abnormality in cystic fibrosis? Pediatr Pulmonol 1990;8:82-88.
103. Dodge JA, Custance JM, Goodchild MC, Laing SC, Vaughan M. Paradoxical effects of essential fatty acid supplementation on lipid profiles and sweat electrolytes in cystic fibrosis. Br J Nutr 1990;63:259-271.
104. van der Merwe DE, Ubbink JB, Delport R, Becker P, Dhatt GS, Vermaak WJ. Biological variation in sweat sodium chloride conductivity. Ann Clin Biochem 2002;39:39-43.
105. Moss RB, Rodman D, Spencer LT, Aitken ML, Zeitlin PL, Waltz D, Milla C, Brody AS, Clancy JP, Ramsey B, et al. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 2004;125:509-521.
106. Gerard CJ, Dell'Aringa J, Hale KA, Klump WM. A sensitive, real-time, RNA-specific PCR method for the detection of recombinant AAV-CFTR vector expression. Gene Ther 2003;10:1744-1753.
107. Bedwell DM, Kaenjak A, Benos DJ, Bebok Z, Bubien JK, Hong J, Tousson A, Clancy JP, Sorscher EJ. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med 1997;3:1280-1284.
108. Shushi L, Nissim-Rafinia M, Natan C, Kerem E, Wilschanski M, Yaacov Y, Rivlin J, Yahav Y, Blau H, Bentur L, et al. NMD pathway regulates the response to aminoglycoside treatment. Pediatr Pulmonol Suppl 2004;38:175-176.
109. Rose AC, Goddard CA, Colledge WH, Cheng SH, Gill DR, Hyde SC. Optimisation of real-time quantitative RT-PCR for the evaluation of non-viral mediated gene transfer to the airways. Gene Ther 2002;9:1312-1320.
110. Linde L, Boelz S, Nissim-Rafinia M, Oren YS, Wilschanski M, Yaacov Y, Virgilis D, Neu-Yilik G, Kulozik AE, Kerem E, et al. Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J Clin Invest 2007;117:683-692.
111. Harris CM, Mendes F, Dragomir A, Doull IJ, Carvalho-Oliveira I, Bebok Z, Clancy JP, Eubanks V, Sorscher EJ, Roomans GM, et al. Assessment of CFTR localisation in native airway epithelial cells obtained by nasal brushing. J Cyst Fibros 2004;3:43-48.
112. Mendes F, Doucet L, Hinzpeter A, Ferec C, Lipecka J, Fritsch J, Edelman A, Jorna H, Willemsen R, Bot AG, et al. Immunohistochemistry of CFTR in native tissues and primary epithelial cell cultures. J Cyst Fibros 2004;3:37-41.
113. Mendes F, Farinha CM, Roxo-Rosa M, Fanen P, Edelman A, Dormer R, McPherson M, Davidson H, Puchelle E, De Jonge H, et al. Antibodies for CFTR studies. J Cyst Fibros 2004;3:69-72.
114. Sermet-Gaudelus I, Dechaux M, Vallee B, Fajac A, Girodon E, Nguyen-Khoa T, Marianovski R, Hurbain I, Bresson JL, Lenoir G, et al. Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes. Am J Respir Crit Care Med 2005;171:1026-1031.
115. Munkonge F, Alton EW, Andersson C, Davidson H, Dragomir A, Edelman A, Farley R, Hjelte L, McLachlan G, Stern M, et al. Measurement of halide efflux from cultured and primary airway epithelial cells using fluorescence indicators. J Cyst Fibros 2004;3:171-176.