Repeatability and Diagnostic Value of Nasal Potential Difference in a Genetically Admixed Population

Abstract

Background: The genetic diversity of the Brazilian population results from three ethnic groups admixture: Europeans, Africans and Amerindians, thus increasing the difficulty of performing cystic fibrosis (CF) diagnosis. The nasal potential difference (NPD) evaluates the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. Despite being a useful CF diagnostic test and a biomarker of CFTR-modulator drugs, it is also highly operator dependent. Therefore, it may be difficult to get accurate results and to interpret them. Wilschanski and Sermet scores were proposed to address these issues. This study aimed to evaluate repeatability and diagnostic value of NPD parameters and Wilschanski and Sermet scores in a CF center in Rio de Janeiro.

Methods: NPD was performed in 78 subjects. Maximal PD, amiloride response, total chloride response, and Wilschanski and Sermet scores were explored as means (confidence interval, CI). One-way ANOVA was used to compare mean differences and Scheffe test was used to pair-wise comparisons. Repeatability was evaluated by scatter and Bland-Altman plots. The Ethics Committee of the CF Center has approved the study protocol. Parents and adult participants signed an informed consent form.

Results: Forty-eight healthy-volunteers, 19 non-CF and 11 CF patients were enrolled in this study. Significant differences were found when comparing CF patients' NPD parameters to the other two groups (P = 0.000). Moreover, no significant differences were found when parameters from non-CF patients were compared with those from healthy volunteers (P > 0.05). The means of NPD parameters and diagnostic scores of each group were in concordance with disease/non-disease conditions. The repeatability data - Wilschanski and Sermet and NPD - allow NPD to be performed in this Brazilian CF Center.

Conclusions: The present study gathered consistent data for Bland-Altman plots. The results of Wilschanski and Sermet diagnostic scores suggest that they were concordant with CF/non-CF conditions. More NPD tests should be performed in the Rio de Janeiro CF dynamic cohort to contribute to international NPD validation studies and to provide NPD as a biomarker in Brazil.

Keywords: Cystic fibrosis; Diagnostic test; Nasal potential difference; Repeatability; Sermet score; Wilschanski index.

Figure 1

Wilschanski index.

Figure 2

Sermet score.

Figure 3

Medians and interquartile intervals of NPD parameters and diagnostic indices among groups. (A) Box plots of PDmax (gray boxes), amiloride response - Δamil (white boxes) and total chloride response - TCR (dark gray boxes). (B) Box plots of Wilschanski index (white boxes) and Sermet score (dark gray boxes) obtained from NPD measurements performed in 11 CF patients, 19 non-CF patients and in 48 healthy-volunteers. The horizontal black line across each box indicates the sample median of the corresponding group. Upper and lower horizontal box lines illustrate the 25th and the 75th percentiles; extreme upper and lower lines represent the 0.5th and the 99.5th percentiles of the variable. The small dashed horizontal line represents the cut-off value for CF diagnosis according to Wilschanski index (> 0.7) and the large dashed horizontal line represents the cut-off value for CF diagnosis according to Sermet score (≤ 0.27).

Figure 4

Repeatability of NPD parameters: PDmax and TCR. Scatter and Bland-Altman plots of first and second measurements: (A) scatter plot of PDmax, (B) Bland-Altman of PDmax, (C) scatter plot of TCR and (D) Bland-Altman of TCR of each subject (n = 22), CF patients (black dots), non-CF patients (grey dots) and healthy volunteers (white dots), with the horizontal lines representing the perfect agreement (dotted line), the value of the mean difference (small dashed line) and limits of agreement of 95% CI (large dashed lines).

Figure 5

Repeatability of NPD parameters: NPD diagnostic indices: Wilschanski index and Sermet score. Scatter and Bland-Altman plots of first and second measurements: (A) scatter plot of Wilschanski index, (B) Bland-Altman of Wilschanski index, (C) scatter plot of Sermet score and (D) Bland-Altman of Sermet score of each subject (n = 22), CF patients (black dots), non-CF patients (grey dots) and healthy volunteers (white dots), with the horizontal lines representing the perfect agreement (dotted line), the value of the mean difference (small dashed line) and limits of agreement of 95% CI (large dashed lines).