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 https://www.jocmr.org

Original Article

Volume 16, Number 5, May 2024, pages 220-231

Association of Small Airway Functional Indices With Respiratory Symptoms and Comorbidity in Asthmatics: A National Cross-Sectional Study

**Table 1.** Baseline Characteristics of Asthmatics Stratified by T2 Phenotype: NHANES 2007 - 2012
Baseline characteristics	All (N = 2,420)	T2 exposure	P-value^a
^aP-value is identified by ANOVA test for continuous variables and Chi-square test for categorical variables and stratified by T2 and non-T2 exposure. ANOVA: analysis of variance; BEC: blood eosinophil count; BMI: body mass index; CI: confidence interval; NHANES: National Health and Nutrition Examination Survey; FeNO: fractional exhaled nitric oxide.
Demographic characteristic
Age, mean (95% CI), years	33.5 (32.4, 34.6)	34.0 (32.9, 35.2)	32.3 (30.3, 34.2)	0.0315
Female sex, n (%)	1,229 (54.3)	782 (49.8)	447 (64.4)	< 0.0001
BMI group, n (%)
Underweight/normal	1,110 (41.7)	729 (38.8)	381 (48.1)	0.0180
Overweight	552 (25.6)	397 (26.5)	155 (23.6)
Obesity	758 (32.7)	553 (34.7)	205 (28.3)
Ethnicity, n (%)
Mexican American	302 (6.6)	202 (6.3)	100 (7.3)	0.1829
Other Hispanic	259 (5.6)	187 (5.8)	72 (5.1)
Non-Hispanic White	957 (66.4)	672 (67.4)	285 (64.2)
Non-Hispanic Black	683 (14.8)	456 (13.8)	227 (17.0)
Other race	219 (6.6)	162 (6.7)	57 (6.4)
Poverty, n (%)
0.0 - 1.0	872 (24.6)	574 (23.1)	298 (28.1)	0.0648
1.1 - 3.0	848 (32.6)	598 (32.5)	250 (32.7)
> 3.0	700 (42.8)	507 (44.4)	193 (39.2)
Education, n (%)
Less than 12th grade	1,223 (36.7)	847 (36.6)	376 (36.8)	0.9376
High school/GED	353 (16.3)	242 (16.2)	111 (16.4)
Some college or AA	533 (26.2)	369 (25.9)	164 (27.1)
College or above	311 (20.8)	221 (21.3)	90 (19.7)
Personal history
Smoking exposure, n (%)
No	1,625 (62.1)	1,110 (61.4)	515 (63.7)	0.4345
Yes	795 (37.9)	569 (38.6)	226 (36.3)
Early-onset asthma, n (%)
No	729 (35.55)	503 (36.0)	226 (34.5)	0.5379
Yes	1,691 (64.45)	1,176 (64.0)	515 (65.5)
Family history of asthma, n (%)
No	1,310 (58.4)	482 (62.5)	828 (55.9)	0.1997
Yes	1,110 (41.6)	313 (37.5)	797 (44.1)
Accessory examination
BEC ≥ 150/µL, n (%)	1,440 (59.0)	1,440 (85.5)	-	-
FeNO ≥ 20 ppb, n (%)	862 (38.8)	862 (55.2)	-	-
Clinical outcome
Recurrent wheezing/whistling, n (%)	458 (18.1)	336 (19.4)	122 (15.3)	0.0588
Severe wheezing/whistling, n (%)	306 (15.1)	297 (16.0)	99 (13.2)	0.1577
Dry cough, n (%)	219 (8.0)	154 (8.5)	65 (7.0)	0.3447
Hay fever, n (%)	548 (28.6)	359 (29.0)	189 (28.0)	0.6983

Table 1. Baseline Characteristics of Asthmatics Stratified by T2 Phenotype: NHANES 2007 - 2012

Baseline characteristics

All (N = 2,420)

T2 exposure

P-value^a

Yes (n = 1,679)

No (n = 741)

^aP-value is identified by ANOVA test for continuous variables and Chi-square test for categorical variables and stratified by T2 and non-T2 exposure. ANOVA: analysis of variance; BEC: blood eosinophil count; BMI: body mass index; CI: confidence interval; NHANES: National Health and Nutrition Examination Survey; FeNO: fractional exhaled nitric oxide.

Demographic characteristic

Age, mean (95% CI), years

33.5 (32.4, 34.6)

34.0 (32.9, 35.2)

32.3 (30.3, 34.2)

0.0315

Female sex, n (%)

1,229 (54.3)

782 (49.8)

447 (64.4)

< 0.0001

BMI group, n (%)

Underweight/normal

1,110 (41.7)

729 (38.8)

381 (48.1)

0.0180

Overweight

552 (25.6)

397 (26.5)

155 (23.6)

Obesity

758 (32.7)

553 (34.7)

205 (28.3)

Ethnicity, n (%)

Mexican American

302 (6.6)

202 (6.3)

100 (7.3)

0.1829

Other Hispanic

259 (5.6)

187 (5.8)

72 (5.1)

Non-Hispanic White

957 (66.4)

672 (67.4)

285 (64.2)

Non-Hispanic Black

683 (14.8)

456 (13.8)

227 (17.0)

Other race

219 (6.6)

162 (6.7)

57 (6.4)

Poverty, n (%)

0.0 - 1.0

872 (24.6)

574 (23.1)

298 (28.1)

0.0648

1.1 - 3.0

848 (32.6)

598 (32.5)

250 (32.7)

> 3.0

700 (42.8)

507 (44.4)

193 (39.2)

Education, n (%)

Less than 12th grade

1,223 (36.7)

847 (36.6)

376 (36.8)

0.9376

High school/GED

353 (16.3)

242 (16.2)

111 (16.4)

Some college or AA

533 (26.2)

369 (25.9)

164 (27.1)

College or above

311 (20.8)

221 (21.3)

90 (19.7)

Personal history

Smoking exposure, n (%)

1,625 (62.1)

1,110 (61.4)

515 (63.7)

0.4345

Yes

795 (37.9)

569 (38.6)

226 (36.3)

Early-onset asthma, n (%)

729 (35.55)

503 (36.0)

226 (34.5)

0.5379

Yes

1,691 (64.45)

1,176 (64.0)

515 (65.5)

Family history of asthma, n (%)

1,310 (58.4)

482 (62.5)

828 (55.9)

0.1997

Yes

1,110 (41.6)

313 (37.5)

797 (44.1)

Accessory examination

BEC ≥ 150/µL, n (%)

1,440 (59.0)

1,440 (85.5)

FeNO ≥ 20 ppb, n (%)

862 (38.8)

862 (55.2)

Clinical outcome

Recurrent wheezing/whistling, n (%)

458 (18.1)

336 (19.4)

122 (15.3)

0.0588

Severe wheezing/whistling, n (%)

306 (15.1)

297 (16.0)

99 (13.2)

0.1577

Dry cough, n (%)

219 (8.0)

154 (8.5)

65 (7.0)

0.3447

Hay fever, n (%)

548 (28.6)

359 (29.0)

189 (28.0)

0.6983

**Table 2.** Overview of Main Indices From Participants
Indice^a	All groups (N = 2,420)	T2 exposure (n = 1,679)	Non-T2 exposure (n = 741)	P-value^b
^aData are presented as mean (SD). ^bP-value was identified by ANOVA test for continuous variables and associated with T2 inflammation and non-T2 exposure. ANOVA: analysis of variance; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity; SD: standard deviation.
FEV₁, L	3.06 (0.98)	3.08 (0.98)	3.02 (0.99)	0.1573
FEV₁/FEV₆, %	81.0 (7.09)	80.6 (7.03)	81.9 (7.11)	< 0.0001
FEV₃, L	3.64 (1.15)	3.67 (1.15)	3.56 (1.15)	0.027
FEV₃/FEV₆, %	95.9 (3.32)	95.7 (3.14)	96.3 (3.67)	< 0.0001
FEF_25-75, L/s	2.89 (1.31)	2.86 (1.27)	2.97 (1.38)	0.0572
FEF_25-75/FVC, /s	0.75 (0.28)	0.74 (0.27)	0.80 (0.28)	< 0.0001

Table 2. Overview of Main Indices From Participants

Indice^a

All groups (N = 2,420)

T2 exposure (n = 1,679)

Non-T2 exposure (n = 741)

P-value^b

^aData are presented as mean (SD). ^bP-value was identified by ANOVA test for continuous variables and associated with T2 inflammation and non-T2 exposure. ANOVA: analysis of variance; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity; SD: standard deviation.

FEV₁, L

3.06 (0.98)

3.08 (0.98)

3.02 (0.99)

0.1573

FEV₁/FEV₆, %

81.0 (7.09)

80.6 (7.03)

81.9 (7.11)

< 0.0001

FEV₃, L

3.64 (1.15)

3.67 (1.15)

3.56 (1.15)

0.027

FEV₃/FEV₆, %

95.9 (3.32)

95.7 (3.14)

96.3 (3.67)

< 0.0001

FEF_25-75, L/s

2.89 (1.31)

2.86 (1.27)

2.97 (1.38)

0.0572

FEF_25-75/FVC, /s

0.75 (0.28)

0.74 (0.27)

0.80 (0.28)

< 0.0001

**Table 3.** Overview of CV for Unadjusted and Adjusted Indices
Subjects	CV, %	Adjusted CV^a, %	P-value^b
^aFEV₁ and FEV₃ are adjusted by FEV₆, and FEF_25-75 is adjusted by FVC. ^bP-value is identified by an asymptotic test between conventional and paired indices. CV: coefficient of variation; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity.
All groups
FEV₁	32.0	8.8	< 0.0001
FEV₃	31.7	3.5	< 0.0001
FEF_25-75	45.1	36.6	7.89 × 10^-19
T2 exposure
FEV₁	31.7	8.7	< 0.0001
FEV₃	31.4	3.3	< 0.0001
FEF_25-75	44.5	36.7	8.80 × 10^-12
Non-T2 exposure
FEV₁	32.8	8.7	6.97 × 10^-202
FEV₃	32.3	3.8	< 0.0001
FEF_25-75	46.4	35.8	1.31 × 10^-9

Table 3. Overview of CV for Unadjusted and Adjusted Indices

Subjects

CV, %

Adjusted CV^a, %

P-value^b

^aFEV₁ and FEV₃ are adjusted by FEV₆, and FEF_25-75 is adjusted by FVC. ^bP-value is identified by an asymptotic test between conventional and paired indices. CV: coefficient of variation; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity.

All groups

FEV₁

32.0

8.8

< 0.0001

FEV₃

31.7

3.5

< 0.0001

FEF_25-75

45.1

36.6

7.89 × 10^-19

T2 exposure

FEV₁

31.7

8.7

< 0.0001

FEV₃

31.4

3.3

< 0.0001

FEF_25-75

44.5

36.7

8.80 × 10^-12

Non-T2 exposure

FEV₁

32.8

8.7

6.97 × 10^-202

FEV₃

32.3

3.8

< 0.0001

FEF_25-75

46.4

35.8

1.31 × 10^-9

**Table 4.** Overview of aORs for Outcomes and Target Indices
Target indices	N	SD	Recurrent wheezing	Severe attack	Dry cough	Hay fever
aORs are associated with per 1 SD unit increase in target indices. ^aModel is adjusted for age, gender, BMI group, ethnicity, smoking exposure. ^bModel is adjusted for age, gender, BMI group, education, smoking exposure, early-onset, family history. ^cModel is adjusted for age, gender, poverty, smoking exposure, early-onset. ^dModel is adjusted for age, ethnicity, poverty, education, early-onset. aOR: adjusted odds ratio; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity; SD: standard deviation.
All subjects	2,420
FEV₁/FEV₆, %		7.09	0.76 (0.71, 0.81)	< 0.0001	0.89 (0.81, 0.96)	0.0049	0.90 (0.87, 0.92)	< 0.0001	1.02 (0.87, 1.19)	0.8300
FEV₃/FEV₆, %		3.32	0.73 (0.68, 0.78)	< 0.0001	0.76 (0.62, 0.94)	0.0125	0.80 (0.73, 0.87)	< 0.0001	0.90 (0.80, 1.02)	0.0885
FEF_25-75, L/s		1.31	0.70 (0.65, 0.76)	< 0.0001	0.67 (0.62, 0.73)	0.0086	0.71 (0.60, 0.85)	0.0001	0.93 (0.83, 1.04)	0.1735
FEF_25-75/FVC, /s		0.28	0.80 (0.74, 0.86)	< 0.0001	0.94 (0.84, 1.04)	0.2158	0.94 (0.87, 1.01)	0.0873	0.99 (0.82, 1.19)	0.8875
Subjects with FEV₁/FVC ≥ 0.70	2,114
FEV₁/FEV₆, %		5.42	0.84 (0.75, 0.96)	0.0072	0.85 (0.74, 0.97)	0.0168	0.92 (0.85, 0.99)	0.0326	0.99 (0.94, 1.03)	0.5452
FEV₃/FEV₆, %		2.74	0.81 (0.76, 0.85)	< 0.0001	0.81 (0.76, 0.85)	< 0.0001	0.83 (0.77, 0.88)	< 0.0001	0.86 (0.75, 0.99)	0.0346
FEF_25-75, L/s		1.22	0.76 (0.66, 0.87)	0.0001	0.76 (0.71, 0.82)	< 0.0001	0.66 (0.62, 0.72)	< 0.0001	0.71 (0.59, 0.86)	0.0003
FEF_25-75/FVC, /s		0.24	0.90 (0.79, 1.02)	0.0914	0.90 (0.79, 1.03)	0.1314	0.95 (0.88, 1.02)	0.1589	1.00 (0.89, 1.12)	0.9888
Subjects with FEV₁% predicted > 0.80	2,034
FEV₁/FEV₆, %		6.10	0.78 (0.73, 0.83)	< 0.0001	0.78 (0.74, 0.83)	< 0.0001	0.90 (0.84, 0.97)	0.0049	0.94 (0.84, 1.06)	0.3226
FEV₃/FEV₆, %		2.70	0.78 (0.71, 0.84)	< 0.0001	0.78 (0.71, 0.86)	< 0.0001	0.80 (0.67, 0.95)	0.0125	0.79 (0.66, 0.94)	0.0084
FEF_25-75, L/s		1.24	0.76 (0.70, 0.81)	< 0.0001	0.80 (0.77, 0.83)	< 0.0001	0.69 (0.64, 0.74)	<0.0001	0.73 (0.69, 0.77)	< 0.0001
FEF_25-75/FVC, /s		0.25	0.81 (0.75, 0.87)	< 0.0001	0.81 (0.76, 0.87)	< 0.0001	0.94 (0.85, 1.04)	0.2158	0.95 (0.92, 0.99)	0.0054

Table 4. Overview of aORs for Outcomes and Target Indices

Target indices

Recurrent wheezing

Severe attack

Dry cough

Hay fever

aOR^a

P-value

aOR^b

P-value

aOR^c

P-value

aOR^d

P-value

aORs are associated with per 1 SD unit increase in target indices. ^aModel is adjusted for age, gender, BMI group, ethnicity, smoking exposure. ^bModel is adjusted for age, gender, BMI group, education, smoking exposure, early-onset, family history. ^cModel is adjusted for age, gender, poverty, smoking exposure, early-onset. ^dModel is adjusted for age, ethnicity, poverty, education, early-onset. aOR: adjusted odds ratio; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity; SD: standard deviation.

All subjects

2,420

FEV₁/FEV₆, %

7.09

0.76 (0.71, 0.81)

< 0.0001

0.89 (0.81, 0.96)

0.0049

0.90 (0.87, 0.92)

< 0.0001

1.02 (0.87, 1.19)

0.8300

FEV₃/FEV₆, %

3.32

0.73 (0.68, 0.78)

< 0.0001

0.76 (0.62, 0.94)

0.0125

0.80 (0.73, 0.87)

< 0.0001

0.90 (0.80, 1.02)

0.0885

FEF_25-75, L/s

1.31

0.70 (0.65, 0.76)

< 0.0001

0.67 (0.62, 0.73)

0.0086

0.71 (0.60, 0.85)

0.0001

0.93 (0.83, 1.04)

0.1735

FEF_25-75/FVC, /s

0.28

0.80 (0.74, 0.86)

< 0.0001

0.94 (0.84, 1.04)

0.2158

0.94 (0.87, 1.01)

0.0873

0.99 (0.82, 1.19)

0.8875

Subjects with FEV₁/FVC ≥ 0.70

2,114

FEV₁/FEV₆, %

5.42

0.84 (0.75, 0.96)

0.0072

0.85 (0.74, 0.97)

0.0168

0.92 (0.85, 0.99)

0.0326

0.99 (0.94, 1.03)

0.5452

FEV₃/FEV₆, %

2.74

0.81 (0.76, 0.85)

< 0.0001

0.81 (0.76, 0.85)

< 0.0001

0.83 (0.77, 0.88)

< 0.0001

0.86 (0.75, 0.99)

0.0346

FEF_25-75, L/s

1.22

0.76 (0.66, 0.87)

0.0001

0.76 (0.71, 0.82)

< 0.0001

0.66 (0.62, 0.72)

< 0.0001

0.71 (0.59, 0.86)

0.0003

FEF_25-75/FVC, /s

0.24

0.90 (0.79, 1.02)

0.0914

0.90 (0.79, 1.03)

0.1314

0.95 (0.88, 1.02)

0.1589

1.00 (0.89, 1.12)

0.9888

Subjects with FEV₁% predicted > 0.80

2,034

FEV₁/FEV₆, %

6.10

0.78 (0.73, 0.83)

< 0.0001

0.78 (0.74, 0.83)

< 0.0001

0.90 (0.84, 0.97)

0.0049

0.94 (0.84, 1.06)

0.3226

FEV₃/FEV₆, %

2.70

0.78 (0.71, 0.84)

< 0.0001

0.78 (0.71, 0.86)

< 0.0001

0.80 (0.67, 0.95)

0.0125

0.79 (0.66, 0.94)

0.0084

FEF_25-75, L/s

1.24

0.76 (0.70, 0.81)

< 0.0001

0.80 (0.77, 0.83)

< 0.0001

0.69 (0.64, 0.74)

<0.0001

0.73 (0.69, 0.77)

< 0.0001

FEF_25-75/FVC, /s

0.25

0.81 (0.75, 0.87)

< 0.0001

0.81 (0.76, 0.87)

< 0.0001

0.94 (0.85, 1.04)

0.2158

0.95 (0.92, 0.99)

0.0054

**Table 5.** aORs of Outcomes Stratified by T2 Exposure
Outcome	aORs in subjects for
aORs are associated with per 1 SD unit increase in target indices. ^aModel is adjusted for age, gender, BMI group, ethnicity, smoking exposure. ^bModel is adjusted for age, gender, BMI group, education, smoking exposure, early-onset, family history. ^cModel is adjusted for age, gender, poverty, smoking exposure, early-onset. ^dModel is adjusted for age, ethnicity, poverty, education, early-onset. aOR: adjusted odds ratio; CI: confidence interval; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity.
Recurrent wheezing/whistling^a
FEV₁/FEV₆	0.75 (0.68, 0.84)	< 0.0001	0.76 (0.65, 0.88)	0.0004
FEV₃/FEV₆	0.73 (0.70, 0.77)	< 0.0001	0.72 (0.44, 1.17)	0.1811
FEF_25-75	0.75 (0.68, 0.83)	< 0.0001	0.70 (0.66, 0.74)	< 0.0001
FEF_25-75/FVC	0.81 (0.72, 0.90)	0.0002	0.78 (0.72, 0.84)	< 0.0001
Severe wheezing/whistling^b
FEV₁/FEV₆	0.76 (0.63, 0.90)	0.0021	1.12 (1.04, 1.21)	0.0042
FEV₃/FEV₆	0.70 (0.53, 0.91)	0.0091	0.95 (0.83, 1.10)	0.5142
FEF_25-75	0.57 (0.48, 0.68)	< 0.0001	0.90 (0.80, 1.01)	0.0818
FEF_25-75/FVC	0.77 (0.62, 0.95)	0.0138	1.14 (1.08, 1.22)	< 0.0001
Dry cough^c
FEV₁/FEV₆	0.83 (0.76, 0.91)	< 0.0001	1.08 (0.86, 1.36)	0.4923
FEV₃/FEV₆	0.78 (0.76, 0.80)	< 0.0001	0.83 (0.74, 0.93)	0.0012
FEF_25-75	0.71 (0.59, 0.86)	0.0004	0.75 (0.72, 0.78)	< 0.0001
FEF_25-75/FVC	0.84 (0.76, 0.94)	0.0022	1.22 (0.88, 1.69)	0.2297
Hay fever^d
FEV₁/FEV₆	1.11 (0.89, 1.37)	0.3627	0.85 (0.71, 1.03)	0.0929
FEV₃/FEV₆	1.02 (0.85, 1.23)	0.8350	0.70 (0.55, 0.91)	0.0070
FEF_25-75	0.95 (0.80, 1.12)	0.5207	0.87 (0.73, 1.05)	0.1429
FEF_25-75/FVC	1.04 (0.84, 1.28)	0.7390	0.90 (0.78, 1.05)	0.1821

Table 5. aORs of Outcomes Stratified by T2 Exposure

Outcome

aORs in subjects for

T2 exposure

Non-T2 exposure

aOR (95% CI)

P-value

aOR (95% CI)

P-value

aORs are associated with per 1 SD unit increase in target indices. ^aModel is adjusted for age, gender, BMI group, ethnicity, smoking exposure. ^bModel is adjusted for age, gender, BMI group, education, smoking exposure, early-onset, family history. ^cModel is adjusted for age, gender, poverty, smoking exposure, early-onset. ^dModel is adjusted for age, ethnicity, poverty, education, early-onset. aOR: adjusted odds ratio; CI: confidence interval; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity.

Recurrent wheezing/whistling^a

FEV₁/FEV₆

0.75 (0.68, 0.84)

< 0.0001

0.76 (0.65, 0.88)

0.0004

FEV₃/FEV₆

0.73 (0.70, 0.77)

< 0.0001

0.72 (0.44, 1.17)

0.1811

FEF_25-75

0.75 (0.68, 0.83)

< 0.0001

0.70 (0.66, 0.74)

< 0.0001

FEF_25-75/FVC

0.81 (0.72, 0.90)

0.0002

0.78 (0.72, 0.84)

< 0.0001

Severe wheezing/whistling^b

FEV₁/FEV₆

0.76 (0.63, 0.90)

0.0021

1.12 (1.04, 1.21)

0.0042

FEV₃/FEV₆

0.70 (0.53, 0.91)

0.0091

0.95 (0.83, 1.10)

0.5142

FEF_25-75

0.57 (0.48, 0.68)

< 0.0001

0.90 (0.80, 1.01)

0.0818

FEF_25-75/FVC

0.77 (0.62, 0.95)

0.0138

1.14 (1.08, 1.22)

< 0.0001

Dry cough^c

FEV₁/FEV₆

0.83 (0.76, 0.91)

< 0.0001

1.08 (0.86, 1.36)

0.4923

FEV₃/FEV₆

0.78 (0.76, 0.80)

< 0.0001

0.83 (0.74, 0.93)

0.0012

FEF_25-75

0.71 (0.59, 0.86)

0.0004

0.75 (0.72, 0.78)

< 0.0001

FEF_25-75/FVC

0.84 (0.76, 0.94)

0.0022

1.22 (0.88, 1.69)

0.2297

Hay fever^d

FEV₁/FEV₆

1.11 (0.89, 1.37)

0.3627

0.85 (0.71, 1.03)

0.0929

FEV₃/FEV₆

1.02 (0.85, 1.23)

0.8350

0.70 (0.55, 0.91)

0.0070

FEF_25-75

0.95 (0.80, 1.12)

0.5207

0.87 (0.73, 1.05)

0.1429

FEF_25-75/FVC

1.04 (0.84, 1.28)

0.7390

0.90 (0.78, 1.05)

0.1821

Table 6. Interactions Between Target Indices and T2 Exposure in the Risk of Outcome

Target indices

T2 exposure

Recurrent wheezing/whistling

Severe wheezing/whistling

Dry cough

Hay fever

RERI (95% CI)

P-value

RERI (95% CI)

P-value

RERI (95% CI)

P-value

RERI (95% CI)

P-value

*P < 0.05 for multiplicative scale. CI: confidence interval; FEF_25-75: forced expiratory flow between 25% and 75% of forced vital capacity; FEV₁: forced expiratory volume in 1 second; FEV₃: forced expiratory volume in 3 seconds; FEV₆: forced expiratory volume in 6 seconds; FVC: forced vital capacity; RERI: relative excess risk of interaction.

FEV₁/FEV₆

High (> 33th)

0.34 (0.09, 0.60)

0.2497

0.43 (0.28, 0.57)

7.71 × 10^-9

0.18 (0.14, 0.21)

< 0.0001

-0.45 (-0.88, -0.03)

0.0368

Yes

Low (≤ 33th)

Yes

FEV₃/FEV₆

High (> 33th)

0.41 (0.28, 0.53)

2.10 × 10^-8

0.50 (0.29, 0.71)

2.93 × 10^-6

0.27 (0.10, 0.44)

2.37 × 10^-3

-0.78 (-0.62, -0.07)

0.0002

Yes

Low (≤ 33th)

Yes

FEF_25-75

High (> 33th)

0.34 (0.21, 0.47)

3.77 × 10^-4

0.58 (0.39, 0.78)

3.98 × 10^-9

0.48 (-0.18, 1.14)

< 0.0001*

-0.05 (-0.64, 0.55)

0.8780

Yes

Low (≤ 33th)

Yes

FEF_25-75/FVC

High (> 33th)

0.42 (0.23, 0.62)

6.21 × 10^-3

0.41 (0.27, 0.56)

1.07 × 10^-8

0.30 (0.06, 0.54)

0.0159

-0.16 (-0.27, -0.04)

0.0067

Yes

Low (≤ 33th)

Yes