Does integration of various ion channel measurements improve diagnostic performance in cystic fibrosis?
BACKGROUND
The diagnosis of cystic fibrosis (CF) may remain inconclusive despite comprehensive evaluation.


OBJECTIVE
Determine whether combined ion channel measurements (C-ICMs) obtained from different end-organ epithelia can help diagnose CF.


METHODS
Prospective enrollment of (1) a training sample of 156 non-CF subjects and 107 patients with CF, and (2) a validation cohort of 202 patients with single-organ CF-like phenotypes. All subjects had genotyping, sweat test, and nasal potential difference (NPD). Principal components analysis was applied to derive various candidate C-ICMs by combining sweat chloride plus every one or two combination(s) of four NPD parameters (maximal potential difference [MaxPD], change in potential difference in response to perfusion with amiloride [ΔAmil], change after chloride-free and isoproterenol perfusion [ΔCl-free+Iso], and total change in potential difference [ΔAmil+Cl-free+Iso]).


RESULTS
The best of the 10 candidate C-ICMs, which combined sweat chloride and two NPD parameters (ΔCl-free+Iso and ΔAmil+Cl-free+Iso), diagnosed CF in the training sample with 100% sensitivity and specificity (CF cutoff > 0). In the validation cohort, C-ICM was normal in all subjects with normal sweat test and normal/borderline NPD, with the exception of one subject. C-ICM was abnormal in all subjects when the sweat test was abnormal and the NPD was abnormal/borderline, and when the sweat test was borderline and the NPD was abnormal. C-ICM was abnormal in 75 and 85.7% of subjects with normal sweat chloride plus abnormal NPD, and those with abnormal sweat test plus normal NPD, respectively. In borderline sweat test cases, 23.5, 90, and 100% of subjects had abnormal C-ICM with normal, borderline, and abnormal NPD, respectively.


CONCLUSIONS
The concept of combining different measures of cystic fibrosis transmembrane conductance regulator function into a single composite score is feasible. The C-ICM may be useful for diagnostic determination of patients with questionable CF.
1 Physiology and Experimental Medicine, Research Institute.
Chee Y
CY
Ooi
Annie
A
Dupuis
Tanja
T
Gonska
Lynda
L
Ellis
Andy
A
Ni
Keith
K
Jarvi
Sheelagh
S
Martin
Peter
P
Ray
Leslie
L
Steele
Paul
P
Kortan
Ruslan
R
Dorfman
Melinda
M
Solomon
Julian
J
Zielenski
Mary
M
Corey
Elizabeth
E
Tullis
Peter
P
Durie
D000293:Adolescent; D000328:Adult; D053713:Azoospermia / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D010195:Pancreatitis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D010254:Paranasal Sinus Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D010641:Phenotype; D025341:Principal Component Analysis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013542:Sweat / Q000737:chemistry*; D055815:Young Adult
D019005:Cystic Fibrosis Transmembrane Conductance Regulator