The Usefulness of FEF_25–75 in Predicting Airway Hyperresponsiveness to Mannitol

Figures & data

Table 1 The Baseline Characteristics of Overall Study Population

	ALL (n=428)	AHR (n=87)	Non-AHR (n=341)	p value*
Age	52.4 ± 18.3	49.1 ± 19.1	53.2 ± 18.1	0.057
Gender (male)	183 (42.8)	44 (50.6)	139 (40.8)	0.099
Height (meters)	1.62 ±0.09	1.63 ± 0.10	1.61 ± 0.09	0.347
Weight (kilograms)	62.8 ± 11.4	63.7 ± 11.9	62.5 ± 11.3	0.408
Body mass index	23.8 ± 3.5	23.8 ± 3.4	23.8 ±3.6	0.914
Cough	276 (64.5)	46 (52.9)	230 (67.4)	0.012
Sputum	207 (48.4)	38 (43.7)	169 (49.6)	0.339
Chest tightness	50 (11.7)	5 (5.7)	45 (13.2)	0.061
Wheezing	52 (12.1)	20 (23.0)	32 (9.4)	0.001
Dyspnea	142 (33.2)	47 (54.0)	95 (27.9)	<0.001
Smoking				0.470
Never smoker	242 (64.5)	43 (56.6)	199 (66.6)
Ex-smoker	63 (16.8)	18 (23.7)	45 (15.1)
Current smoker	70 (18.8)	15 (19.7)	55 (18.3)
Allergic sensitization	79 (18.5)	37 (42.5)	42 (12.3)	<0.001
Spirometric values
FEV1, L	2.69 ± 0.80	2.60 ± 0.80	2.71 ± 0.81	0.267
FEV1, % of predicted value	90.1 ± 14.1	84.1 ± 14.2	91.6 ± 13.6	<0.001
FVC, L	3.45 ± 0.97	3.63 ± 1.01	3.41 ± 0.96	0.053
FVC, % of predicted value	91.7 ± 14.3	94.4 ± 15.4	91.1 ± 13.9	0.048
FEV1/FVC	77.9 ± 8.48	71.5 ± 9.17	79.5 ± 7.50	<0.001
FEF25–75, L/sec	2.50 ± 1.16	1.97 ± 1.08	2.64 ± 1.14	<0.001
FEF25–75, % of predicted value	84.5 ± 30.6	62.4 ± 25.0	90.1 ± 29.4	<0.001

Notes: Data are presented as n (%) or mean ± SD. *P value was calculated by comparison of the AHR group and the non-AHR group.

Abbreviations: AHR, airway hyperresponsiveness; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF_25–75, forced expiratory flow between 25 and 75% of vital capacity.

Table 2 AUC Values of Typical Spirometric Indices Obtained Based on All Patients’ Spirometry

	AUC	SE	95% CI	Comparison with FEF25–75, % of Predicted Value
				Difference Between Area	SE	95% CI	Z Statistic	p value
FEF25–75, % of predicted value	0.772	0.029	0.729–0.811	–	–	–	–	–
FEF25–75/FVC	0.741	0.031	0.696 −0.782	0.031	0.016	0.001–0.061	1.997	0.046
FEV1, % of predicted value	0.666	0.034	0.619–0.710	0.106	0.026	0.056–0.156	4.129	<0.001
FEV1/FVC	0.741	0.032	0.697–0.782	0.030	0.015	0.000–0.060	1.987	0.047

Abbreviations: AUC, area under the curve; SE, standard error; 95% CI, 95% confidence interval; FEF_25–75, forced expiratory flow between 25 and 75% of vital capacity; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 1 ROC curves for predicting AHR to mannitol (total study population).

Abbreviations: ROC, receiver operating characteristic; AHR, airway hyperresponsiveness.

Figure 2 ROC curves for predicting AHR to mannitol (subjects with normal spirometry).

Abbreviations: ROC, receiver operating characteristic; AHR, airway hyperresponsiveness.

Table 3 AUC Values of Typical Spirometric Indices in Patients with Normal Spirometry (FEV₁ ≥ 80% and FEV₁/FVC ≥ 70)

	AUC	SE	95% CI	Comparison with FEF25–75, % of Predicted Value
				Difference Between Area	SE	95% CI	Z Statistics	p value
FEF25–75, % of predicted value	0.704	0.046	0.646–0.757	–	–	–	–	–
FEF25–75/FVC	0.665	0.049	0.606–0.720	0.039	0.032	−0.025–0.101	1.197	0.231
FEV1, % of predicted value	0.589	0.057	0.529–0.648	0.114	0.045	0.025–0.203	2.518	0.012
FEV1/FVC	0.644	0.051	0.584–0.700	0.060	0.030	0.001–0.119	1.986	0.047

Abbreviations: AUC, area under the curve; SE, standard error; 95% CI, 95% confidence interval; FEF_25–75, forced expiratory flow between 25 and 75% of vital capacity; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 3 AUC distributions in the total study population and subjects with normal spirometry.

Abbreviation: AUC, area under the curve.

Table 4 Criterion of FEF_25–75 for Predicting AHR to Mannitol

Patients’ Group	Criterion of FEF25–75	Number of Patients (% for Total Patients)	Number of Patients with AHR	Sensitivity (95% CI)	Specificity (95% CI)	Positive Predictive Value	Negative Predictive Value
All patients	≤90	254 (59.1)	75	86.2 (77.1–92.7)	47.8 (42.4–53.2)	29.6	93.1
	≤81	190 (44.4)	67	77.0 (66.8–85.4)	63.9 (58.6–69.0)	35.3	91.6
	≤80	185 (43.2)	65	74.7 (64.3–83.4)	64.8 (59.5–69.9)	35.1	90.9
	≤70	143 (33.4)	54	62.0 (51.0–72.3)	73.9 (68.9–78.5)	37.8	88.4
	≤60	97 (22.7)	46	52.8 (41.9–63.7)	85.0 (80.8–88.7)	47.4	87.6
	≤50	66 (15.4)	36	41.3 (30.9–52.4)	91.2 (87.7–94.0)	54.5	85.9
Patients with normal spirometry	≤90	139 (46.0)	29	72.5 (56.1–85.4)	61.0 (54.9–67.0)	22.1	93.6
	≤87	115 (38.1)	28	70.0 (53.5–83.4)	66.8 (60.7–72.5)	24.3	93.6
	≤80	78 (25.8)	20	50.0 (33.8–66.2)	77.8 (72.3–82.7)	25.6	91.1
	≤70	44 (14.6)	11	27.5 (14.6–43.9)	87.4 (82.8–91.2)	25.0	88.8
	≤60	16 (5.3)	6	15.0 (5.7–29.8)	96.1 (93.1–98.2)	37.5	88.1
	≤50	2 (0.7)	1	2.5 (0.1–13.2)	99.6 (97.9–99.9)	50.0	87.0

Abbreviations: AHR, airway hyperresponsiveness; 95% CI, 95% confidence interval; FEF_25–75, forced expiratory flow between 25 and 75% of vital capacity; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Table 5 Unadjusted or Adjusted or of FEF_25–75 ≤Optimal Cut-Off Values for AHR to Mannitol

Patients’ Group	Criterion of FEF25–75	Univariable Analysis		Multivariable Analysis*
		Unadjusted OR	95% CI	Adjusted OR	95% CI
All patients	≤81	5.93	3.43–10.25	9.57	4.88–18.74
Patients with normal spirometry	≤87	4.69	2.27–9.67	6.86	2.80–16.78

Note: *Adjusted for age, sex, BMI, and smoking status.