The Value of Fractional Exhaled Nitric Oxide and Impulse Oscillometric and Spirometric Parameters for Predicting Bronchial Hyperresponsiveness in Adults with Chronic Cough

Figures & data

Table 1 Demographics of the Patients with Positive or Negative Bronchial Provocation Tests

Demographics	Positive Bronchial Provocation (n=29)	Negative Bronchial Provocation (n=83)	p
Age (year)	36.55 (12.10)	39.87 (11.42)	0.188
Male/female (n)	11/18	39/44	0.398
Height (cm)	160.07 (8.23)	162.35 (8.34)	0.206
Weight (kg)	56.83 (9.81)	61.43(12.41)	0.074
Symptom duration (month)	6 (2–36)	4 (2–96)	0.670
Never smoker/Ex-smoker	23/6	72/11	0.372
Rhinitis (n [%])	14[48.3]	15[18.1]	0.001*
Rhinosinusitis (n [%])	0[0.00]	2[0.02]	—
History of GRED or gastrointestinal symptoms such as heartburn and dyspepsia	3[0.103]	6[0.072]	0.693

Notes: Data are expressed as mean (SD) or median (range), unless indicated otherwise. *Statistical significance.

Abbreviation: GRED, gastroesophageal reflux disease.

Table 2 Parameters of the Patients with Positive or Negative Bronchial Provocation Tests

Parameters	Positive Bronchial Provocation (n=29)	Negative Bronchial Provocation (n=83)	p
FeNO (ppb)	43 (5–97)	10 (5–48)	<0.001*
IOS
Z5 (kpa·L^−1·s^−1)	0.44 (0.12)	0.41 (0.97)	0.091
Fres (Hz)	14.45 (4.25)	12.32 (3.17)	0.005*
R5 (kpa·L^−1·s^−1)	0.42 (0.11)	0.39 (0.10)	0.169
R20 (kpa·L^−1·s^−1)	0.34 (0.20–0.49)	0.32 (0.23–0.62)	0.400
R5-R20 (kpa·L^−1·s^−1)	0.06 (0.00–0.19)	0.04 (0.00–0.22)	0.109
X5 (kpa·L^−1·s^−1)	−0.13 (0.05)	−0.10 (0.04)	0.001*
AX	0.44 (0.13–2.22)	0.30 (0.02–1.51)	0.010*
Spirometry
FVC (% predicted)	99.79 (13.30)	102.41 (13.40)	0.365
FEV1 (% predicted)	94.05 (11.09)	100.17 (12.46)	0.021*
FEV1/FVC (% predicted)	80.33 (6.26)	82.69 (5.99)	0.074
PEF (% predicted)	82.32 (15.07)	92.77 (15.68)	0.002*
MEF75 (% predicted)	83.51(15.08)	97.34 (17.81)	<0.001*
MEF50 (% predicted)	74.54 (16.62)	92.93(23.69)	<0.001*
MEF25 (% predicted)	63.04 (21.40)	75.38 (28.30)	0.034*
MMEF (% predicted)	67.21 (16.49)	83.47 (20.85)	<0.001*

Notes: Data are expressed as mean (SD) or median (range), unless indicated otherwise. *Statistical significance.

Abbreviations: FeNO, fractional exhaled nitric oxide; ppb, parts per billion; IOS, impulse oscillometry; Z5, impedance at 5 Hz; Fres, resonant frequency; R5, resistance at 5 Hz; R20, resistance at 20 Hz; R5-R20, the difference between R5 and R20; X5, reactance at 5 Hz; AX, integrated area of low-frequency X; FVC, forced vital capacity; FEV1, forced expiratory volume in 1s; PEF, peak expiratory flow; MEF₇₅, forced expiratory flow at 75% of the FVC; MEF₅₀, forced expiratory flow at 50% of the FVC; MEF₂₅, forced expiratory flow at 25% of the FVC; MMEF, forced expiratory flow between 25 and 75%.

Figure 1 Enrollment flow chart of the study.

Figure 2 ROC curves of (A) FeNO and IOS parameters, (B) spirometric parameters and (C) FeNO combined with Fres, FeNO combined with MMEF, or a combination of FeNO, Fres and MMEF in predicting a positive bronchial provocation test.

Table 3 Univariate Logistic Regression Analyses of Parameters from Chronic Cough to Predict Positive Bronchial Provocation Tests

Variable	β	OR(95% CI)	p
FeNO	0.097	1.102 (1.062–1.144)	<0.000
Allergic rhinitis	−1.442	0.236 (0.094–0.592)	0.002
Fres	0.163	1.177 (1.043–1.328)	0.008
X5	−19.202	0.000 (0.000–0.002)	0.003
AX	1.709	5.525 (1.695–18.003)	0.005
FEV1 (% predicted)	−0.043	0.958 (0.922–0.994)	0.024
PEF (% predicted)	−0.046	0.955 (0.926–0.985)	0.003
MEF75 (% predicted)	−0.051	0.951 (0.923–0.979)	0.001
MEF50 (% predicted)	−0.041	0.960 (0.937–0.983)	0.001
MEF25 (% predicted)	−0.019	0.981 (0.963–0.999)	0.038
MMEF (% predicted)	−0.043	0.958 (0.934–0.982)	0.001

Notes: Method: Enter; Dependent Y: BHR; Enter Variable < 0.05; Remove Variable > 0.1.

Abbreviations: OR, odds ratio; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; Fres, resonant frequency; X5, reactance at 5 Hz; AX, integrated area of low-frequency X; FEV1, forced expiratory volume in 1s; PEF, peak expiratory flow; MEF₇₅, forced expiratory flow at 75% of the FVC; MEF₅₀, forced expiratory flow at 50% of the FVC; MEF₂₅, forced expiratory flow at 25% of the FVC; MMEF, forced expiratory flow between 25 and 75%.

Table 4 Multivariate Analyses of Characteristics, FeNO, IOS and Spirometric Parameters from Chronic Cough to Predict Positive Bronchial Provocation Tests

Multivariate Analysis of FeNO and Allergic Rhinitis
Variable	β	OR(95% CI)	p
FeNO	0.094	1.099 (1.057–1.142)	<0.001
Multivariate analysis of FeNO, Allergic rhinitis and IOS parameters
Variable	β	OR(95% CI)	p
FeNO	0.135	1.144 (1.084–1.208)	<0.000
Fres	0.395	1.484 (1.191–1.849)	0.000
Multivariate analysis of FeNO, Allergic rhinitis and Spirometric parameters
Variable	β	OR(95% CI)	p
FeNO	0.109	1.115 (1.066–1.166)	0.000
MMEF (% predicted)	−0.057	0.945 (0.913–0.977)	0.001
Multivariate analysis of FeNO, Allergic rhinitis and IOS and Spirometric parameters
Variable	β	OR(95% CI)	p
FeNO	0.134	1.143 (1.080–1.210)	0.000
Fres	0.331	1.393 (1.097–1.768)	0.007
MMEF (% predicted)	−0.044	0.957 (0.922–0.994)	0.022

Notes: Method: Backward LR; Dependent Y: BHR; Enter Variable < 0.05; Remove Variable > 0.1.

Abbreviations: OR, odds ratio; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; Fres, resonant frequency; MMEF, forced expiratory flow between 25 and 75%.

Figure 3 Calibration curves of (A) FeNO combined with Fres (model 1), (B) FeNO combined with MMEF (model 2) and (C) the combination of FeNO, Fres, and MMEF (model 3) in predicting a positive bronchial provocation test.

Notes: The x-axis represents the predicted risk of BHR. The y-axis represents the actual diagnosed BHR. The diagonal dotted line represents a perfect prediction by an ideal model.