Objectives
Cystic fibrosis (CF) & CFTR-related disorders (CFTR-RD) can be difficult to diagnose. NPD & extended CFTR genetics can improve the diagnostic yield when sweat Cl- and genotyping are inconclusive. We report the diagnostic outcomes of our DCFD service.
Methods
All patients referred (2017-2022) who had NPD were included in this retrospective study. Every patient was reviewed at a consensus meeting to assign them into diagnostic categories. We then explored the diagnostic discriminatory value of sweat Cl- & NPD using Kruskal-Wallis testing.
Results
122 patients (median[range] age 38.9y[7.3-75.1]) with a median sweat Cl- 39 (9.5-89.5)mmol/L. Diagnostic outcomes: CF, 24%(n=29); CFTR-RD, 22%(27); not-CF/CFTR-RD, 47%(58); inconclusive,7%(8). 2 CFTR variants were identified in 97% & 96% of CF & CFTR-RD patients, respectively. Of these, more were disease-causing in the CF(58%) v CFTR-RD(46%) group. Sweat Cl- could not discriminate between the groups whereas NPD could (table).
Conclusions
Our DCFD service clarified the diagnosis in 93% of patients. NPD played a pivotal role in discriminating between groups.
| Sweat Cl- (mmol/L); median(IQR) | Basal PD (mV) | ?Amiloride (mV) | ?Total Cl (mV) |
Wilschanski Index |
|
| CF;n=29 | 38(26.5;51) | -28(-34;-18) | 10(7;17) | -3.5(-8;-1) | 0.8(0.5;0.9) |
| CFTR-RD;n=27 | 35.5(29.5;44) | -20.8(-27.8;-16.5) | 11.5(7.3;20) | -14(-17;-7.5) | 0.3(0.2;0.5) |
| Inconclusive;n=8 | 45.7(34.5;56.5) | -18.8(-24.5;-17.3) | 3.3(1;12) | -1.9(-5.8;0) | 0.7(0.5;0.9) |
| Not-CF/CFTR-RD;n=58 | 42 (32;49) | -16(-22;-12) | 7(3.9;10) | -14.5(-20.8;-9.1) | 0.1(0.02;0.3) |
|
p value(all groups) CFvCFTR-RD |
NS
NS |
<0.001
NS |
0.002
NS |
<0.001 <0.001 |
<0.001 0.02 |