J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 8, Number 1, January 2016, pages 15-24

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

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).

**Table 1.** Means (SD), 95% CI of NPD Parameters (mV), per Group and Pair-Wise Comparisons Between Groups
Groups (n)	PDmax^a	Δamil^b	TCR^c	Wilschanski index^d	Sermet score^e
^aPDmax: maximal basal PD; ^bΔamil: change in PD after amiloride solution infusion; ^cTCR: change in PD after zero chloride and isoproterenol solutions infusions; ^dWilschanski index = e^TCR/Δamil; ^eSermet score = -(0.11 × TCR) - (0.05 × Δamil).
CF patients (11)	-31.7 (9.5) (-38.1 to -25.3)	15 (7.2) (10.2 to 19.8)	-1.5 (5.8) (-5.4 to 2.5)	0.9 (0.4) (0.7 to 1.2)	-0.6 (0.7) (-1.1 to -0.1)
Non-CF patients (19)	-16.4 (6.9) (-19.7 to -13.1)	7.5 (4.2) (5.5 to 9.5)	-15.3 (5.7) (-18.0 to -12.5)	0.1 (0.1) (0.1 to 0.2)	1.3 (0.6) (1.0 to 1.6)
Healthy-volunteers (48)	-15.2 (7.6) (-17.4 to -13.0)	7.8 (4.7) (6.5 to 9.2)	-13.0 (6.7) (-15 to -11.1)	0.2 (0.2) (0.2 to 0.3)	1.0 (0.7) (0.8 to 1.2)
One way ANOVA (P-value)	0.000	0.000	0.000	0.000	0.000
Pair-wise comparison	Post hoc Scheffe (P-value)
CF × non-CF	0.000	0.001	0.000	0.000	0.000
CF × healthy-volunteers	0.000	0.000	0.000	0.000	0.000
Non-CF × healthy-volunteers	0.851	0.967	0.435	0.558	0.359

Table 1. Means (SD), 95% CI of NPD Parameters (mV), per Group and Pair-Wise Comparisons Between Groups

Groups (n)

PDmax^a

Δamil^b

TCR^c

Wilschanski index^d

Sermet score^e

^aPDmax: maximal basal PD; ^bΔamil: change in PD after amiloride solution infusion; ^cTCR: change in PD after zero chloride and isoproterenol solutions infusions; ^dWilschanski index = e^TCR/Δamil; ^eSermet score = -(0.11 × TCR) - (0.05 × Δamil).

CF patients (11)

-31.7 (9.5)
(-38.1 to -25.3)

15 (7.2)
(10.2 to 19.8)

-1.5 (5.8)
(-5.4 to 2.5)

0.9 (0.4)
(0.7 to 1.2)

-0.6 (0.7)
(-1.1 to -0.1)

Non-CF patients (19)

-16.4 (6.9)
(-19.7 to -13.1)

7.5 (4.2)
(5.5 to 9.5)

-15.3 (5.7)
(-18.0 to -12.5)

0.1 (0.1)
(0.1 to 0.2)

1.3 (0.6)
(1.0 to 1.6)

Healthy-volunteers (48)

-15.2 (7.6)
(-17.4 to -13.0)

7.8 (4.7)
(6.5 to 9.2)

-13.0 (6.7)
(-15 to -11.1)

0.2 (0.2)
(0.2 to 0.3)

1.0 (0.7)
(0.8 to 1.2)

One way ANOVA (P-value)

0.000

Pair-wise comparison

Post hoc Scheffe (P-value)

CF × non-CF

0.000

0.001

0.000

CF × healthy-volunteers

0.000

Non-CF × healthy-volunteers

0.851

0.967

0.435

0.558

0.359

**Table 2.** Clinical Data Diagnosis, Disease Status and Nasal Potential Difference Results From CF Patients (n = 11)
	Sex	Diagnostic data	Disease status	NPD parameters and diagnostic indices
^aQPIT sweat test; ^bNI: not identified; ^cFEV₁ = forced expiratory volume in the first second; ^dPa: Pseudomonas aeruginosa; ^ePDmax = maximum PD after Ringer’s solution perfusion; ^fΔamil = PD changes after amiloride solution perfusion; ^gTCR (total chloride response) = PD changes after perfusion with zero Cl^- and isoproterenol solutions; ^hWilschanski index: CF if > 0.7; ⁱSermet score: CF if ≤ 0.27.
1	M	2	100.7	F508del/F508del	II/II	81.4	No	-47	16	11	1.84	-2.11
2	F	4	96.0	F508del/F508del	II/II	76.7	Yes	-20	6	-5	0.43	0.25
3	M	9	82.5	F508del/F508del	II/II	103.0	Yes	-25	7	-1	0.87	-0.24
4	F	5	88.5	F508del/F508del	II/II	77.4	Yes	-30	16	-7	0.65	-0.03
5	M	80	78.6	F508del/F508del	II/II	50.7	Yes	-34	11	-7	0.53	0.22
6	M	14	59.0	F508del/W1282X	II/I	116.2	No	-29	15	4	1.31	-1.19
7	F	3	98.0	N1303K/G542X	II/I	45.8	Yes	-39	11	-2	0.83	-0.33
8	M	72	55.3	S4X/R334W	I/IV or V	124.0	No	-37	25	-8	0.73	-0.37
9	M	86	79.3	F508del/NI	II/-	64.9	Yes	-15	10	1	1.11	-0.61
10	M	144	52.9	F508del/NI	II/-	98.3	Yes	-40	21	3	1.15	-1.38
11	F	33	77.4	P205S/NI	IV/-	64.0	No	-30	19	-5	0.77	-0.40

Table 2. Clinical Data Diagnosis, Disease Status and Nasal Potential Difference Results From CF Patients (n = 11)

Sex

Diagnostic data

Disease status

NPD parameters and diagnostic indices

Age at diagnosis (months)

Sweat Cl^a (mmol/L)

Genotype^b

Class

FEV₁^c (% pred)

Chronic Pa^d

PDmax^e (mV)

Δamil^f (mV)

TCR^g (mV)

Wilschanski index^h

Sermet scoreⁱ

^aQPIT sweat test; ^bNI: not identified; ^cFEV₁ = forced expiratory volume in the first second; ^dPa: Pseudomonas aeruginosa; ^ePDmax = maximum PD after Ringer’s solution perfusion; ^fΔamil = PD changes after amiloride solution perfusion; ^gTCR (total chloride response) = PD changes after perfusion with zero Cl^- and isoproterenol solutions; ^hWilschanski index: CF if > 0.7; ⁱSermet score: CF if ≤ 0.27.

100.7

F508del/F508del

II/II

81.4

-47

1.84

-2.11

96.0

F508del/F508del

II/II

76.7

Yes

-20

-5

0.43

0.25

82.5

F508del/F508del

II/II

103.0

Yes

-25

-1

0.87

-0.24

88.5

F508del/F508del

II/II

77.4

Yes

-30

-7

0.65

-0.03

78.6

F508del/F508del

II/II

50.7

Yes

-34

-7

0.53

0.22

59.0

F508del/W1282X

II/I

116.2

-29

1.31

-1.19

98.0

N1303K/G542X

II/I

45.8

Yes

-39

-2

0.83

-0.33

55.3

S4X/R334W

I/IV or V

124.0

-37

-8

0.73

-0.37

79.3

F508del/NI

II/-

64.9

Yes

-15

1.11

-0.61

144

52.9

F508del/NI

II/-

98.3

Yes

-40

1.15

-1.38

77.4

P205S/NI

IV/-

64.0

-30

-5

0.77

-0.40