Table 1. Characteristics of total subjects and stratified by airflow limitation.
Characteristics
|
Total (n=1859)
|
Without airflow limitation (n=1027)
|
Airflow limitation (n=832)
|
P value
|
Age, y
|
61.3 ± 8.2
|
58.5 ± 7.9
|
64.7 ± 7.1
|
<0.001
|
Male sex, %
|
1375 (74.0)
|
613 (59.7)
|
762 (91.6)
|
<0.001
|
BMI, kg/m2
|
22.7 ± 3.2
|
23.3 ± 3.2
|
22.1 ± 3.2
|
<0.001
|
Educational level, %
|
|
|
|
<0.001
|
Primary school or less
|
882 (47.4)
|
501 (48.8)
|
381 (45.7)
|
|
Middle or high school
|
927 (49.9)
|
487 (47.4)
|
440 (52.9)
|
|
College or higher
|
50 (2.7)
|
39 (3.8)
|
11 (1.3)
|
|
Annual household income, %
|
|
|
|
<0.001
|
low
|
370 (19.9)
|
174 (16.9)
|
196 (23.6)
|
|
medium
|
1286 (69.2)
|
747 (72.7)
|
539 (64.9)
|
|
high
|
130 (7.0)
|
87 (8.5)
|
43 (5.2)
|
|
unknown
|
73 (3.9)
|
19 (1.9)
|
54 (6.5)
|
|
Smoking status, %
|
|
|
|
<0.001
|
Never smoker
|
649 (34.9)
|
538 (52.4)
|
111 (13.4)
|
|
Former smoker
|
385 (20.7)
|
133 (13.0)
|
252 (30.2)
|
|
Current smoker
|
825 (44.4)
|
356 (34.7)
|
469 (56.4)
|
|
Smoking index, pack-yrs
|
27.3 ± 31.5
|
19.6 ± 29.0
|
36.9 ± 31.8
|
<0.001
|
Smokers living at home, %
|
732 (39.4)
|
430 (41.9)
|
302 (36.3)
|
0.324
|
Parental history of respiratory diseases, %
|
245 (13.2)
|
91 (8.9)
|
154 (18.5)
|
<0.001
|
Occupation exposure > 6 months, %
|
382 (20.6)
|
168 (16.4)
|
214 (25.8)
|
<0.001
|
Indoor exposure to biomass for cooking or heating, %
|
662 (35.6)
|
351 (34.2)
|
311 (37.4)
|
0.348
|
History of comorbidities, %
|
|
|
|
|
asthma
|
27 (1.5)
|
5 (0.5)
|
22 (2.6)
|
0.007
|
Tuberculosis
|
47 (2.5)
|
18 (1.8)
|
29 (3.5)
|
0.034
|
Chronic bronchitis
|
93 (5.0)
|
31 (3.0)
|
62 (7.5)
|
0.007
|
History of prior year exacerbation, %
|
184 (9.9)
|
63 (6.1)
|
121 (14.6)
|
<0.001
|
Respiratory symptoms without colds, %
|
|
|
|
|
Cough
|
520 (27.9)
|
179 (17.4)
|
341 (41.0)
|
<0.001
|
Sputum
|
657 (35.3)
|
248 (24.1)
|
409 (49.2)
|
<0.001
|
Wheeze
|
209 (11.2)
|
58 (5.6)
|
151 (18.1)
|
<0.001
|
mMRC
|
0.37 ± 0.62
|
0.25 ± 0.51
|
0.52 ± 0.70
|
<0.001
|
CAT
|
4.28 ± 6.80
|
3.64 ± 7.76
|
5.06 ± 5.28
|
<0.001
|
Spirometry parameters after bronchodilator use
|
|
|
|
|
FEV1/FVC,
|
69.8 ± 12.9
|
79.0 ± 5.6
|
58.3 ± 9.8
|
<0.001
|
FEV1, %predicted
|
87.2 ± 20.2
|
97.0 ± 14.5
|
75.1 ± 19.8
|
<0.001
|
MMEF, %predicted
|
50.4 ± 27.7
|
68.6 ± 23.1
|
28.0 ± 11.9
|
<0.001
|
FEF50, %predicted
|
56.4 ± 30.5
|
76.7 ±24.2
|
31.2 ± 14.7
|
<0.001
|
FEF75, %predicted
|
40.7 ± 26.6
|
55.1 ± 27.1
|
22.9 ± 9.9
|
<0.001
|
CT parameters
|
|
|
|
|
LAA−950, %
|
2.63 ± 5.36
|
0.74 ± 1.59
|
4.96 ± 7.16
|
<0.001
|
LAA−856, %
|
17.0 ±19.5
|
7.0 ± 9.9
|
29.3 ± 21.3
|
<0.001
|
RV, L
|
2.77 ± 1.03
|
2.23 ± 0.65
|
3.43 ± 1.03
|
<0.001
|
TLC, L
|
5.04 ± 1.17
|
4.65 ± 1.06
|
5.52 ± 1.12
|
<0.001
|
IOS parameters
|
|
|
|
|
R5, Ka/L/s
|
0.35 ± 0.10
|
0.33 ± 0.09
|
0.37 ± 0.13
|
<0.001
|
R20, Ka/L/s
|
0.28 ± 0.07
|
0.28 ± 0.07
|
0.27 ± 0.07
|
0.160
|
R5-R20, Ka/L/s
|
0.07 ± 0.07
|
0.05 ± 0.04
|
0.09 ± 0.09
|
<0.001
|
X5, Ka/L/s
|
-0.12 ± 0.08
|
-0.10 ± 0.04
|
-0.15 ± 0.10
|
<0.001
|
AX, Ka/L
|
0.68 ± 0.88
|
0.39 ± 0.33
|
1.04 ± 1.17
|
<0.001
|
Fres, Hz
|
15.1 ± 5.64
|
13.1 ± 3.7
|
17.7 ± 6.5
|
<0.001
|
Note: Data are expressed as Mean ± SD or n (%) as appropriate. Differences of characteristics between subjects with and without airflow limitation were compared with the Student’s t test, Mann-Whitney U test, the χ² test ,or Fisher exact test as appropriate.
Abbreviations: BMI = body mass index, yrs = years; mMRC = modified Medical Research Council, CAT = COPD Assessment Test; FEV1/FVC = the ratio of forced expiratory volume in the first second to forced vital capacity; FEV1,%predicted = the ratio of forced expiratory volume in the first second to its predicted value; MMEF, %predicted = maximal mid-expiratory flow of percent predicted; FEF50, %predicted and FEF75, %predicted = forced expiratory flow at 50 and 75 of forced vital capacity of percent predicted; CT = computed tomography; IOS = impulse oscillometry; LAA−950 = low-attenuation area of the lung with attenuation values below -950 Hounsfield units on full-inspiration CT; LAA-856 = low-attenuation area of the lung with attenuation values below -856 Hounsfield units on full-expiration CT; RV = residual volume; TLC = total lung capacity; IOS = impulse oscillometry; R5 = resistance at 5 Hz; R20 = resistance at 20 Hz; R5-R20 = the difference from resistance at 5 Hz to resistance at 20 Hz; X5 = reactance at 5 Hz; AX = reactance area; Fres = resonant frequency; % = percent.
Table 2. Prevalence of SAD defined by CT, IOS, and spirometry in total subjects with age stratification.
Prevalence (%) of SAD in Subgroups stratified by definitional methods
|
age (yrs)
|
P for trend
|
<= 49
|
50-59
|
60-69
|
>=70
|
Prevalence of SAD defined by CT
|
2.5
(4/157)
|
14.0 (83/592)
|
36.3 (302/831)
|
57.3 (160/279)
|
<0.001
|
Prevalence of SAD defined by IOS
|
24.2 (38/157)
|
21.3 (126/592)
|
37.4 (311/831)
|
45.9 (310/830)
|
<0.001
|
Prevalence of SAD defined by spirometry
|
43.3 (68/157)
|
61.1 (362/592)
|
82.1 (682/831)
|
93.2 (260/279)
|
<0.001
|
Note: P for trend was calculated by linear-by-linear association test. SAD defined by CT was LAA-856 > 20%. SAD defined by IOS was R5-R20 > 0.07. SAD defined by spirometry was post bronchodilator MMEF %predicted, FEF50 %predicted or FEF75 %predicted (any two of the three) < 65%. Abbreviations: SAD = small airway dysfunction, CT = computed tomography, IOS = impulse oscillometry, yrs = years.
Table 3. Multivariate binary logistic regression analysis of age and SAD risk in total subjects.
Variables
|
definitional methods for SAD
|
OR (95%CI)
|
P value
|
Age (per 10 yrs increase)
|
SAD defined by CT
|
2.57 (2.13-3.10)
|
<0.001
|
SAD defined by IOS
|
1.79 (1.54-2.08)
|
<0.001
|
SAD defined by spirometry
|
2.38 (2.01-2.80)
|
<0.001
|
Note: CT-defined SAD was defined as LAA-856 > 20%. IOS-defined SAD was defined as R5-R20 > 0.07. Spirometry-defined SAD was defined as post-bronchodilator MMEF %predicted, FEF50 %predicted or FEF75 %predicted (any two of the three) < 65%. All these models were adjusted for sex, BMI, smoking status, smoking index, educational level, asthma, tuberculosis, chronic bronchitis, annual household income, smokers living at home, parental history of respiratory disease, occupation exposure > 6 months, indoor exposure to biomass for cooking or heating. All the variables of age in these models indicate per 10 years increase. Abbreviations: SAD = small airway dysfunction, CT = computed tomography, IOS = impulse oscillometry, % = percent, OR = odds ratio, CI = confidence interval, yrs = years.
Table 4. Multi-adjusted contributions of age to the extent of SAD among CT-defined SAD subjects (n = 549) from total subjects.
Outcomes for SAD markers
|
Unstandardized β
|
Standardized β
|
95%CI
|
P value
|
CT
|
|
|
|
|
LAA−950, %
|
0.95
|
0.08
|
-0.06,1.95
|
0.064
|
LAA−856, %
|
2.09
|
0.08
|
-0.06, 4.25
|
0.057
|
RV, L
|
-0.11
|
-0.07
|
-0.23, 0.02
|
0.106
|
TLC, L
|
-0.26
|
-0.16
|
-0.39, -0.14
|
<0.001
|
IOS
|
|
|
|
|
R5, Ka/L/s
|
0.02
|
0.10
|
0.00, 0.04
|
0.021
|
R20, Ka/L/s
|
0.00
|
0.004
|
-0.00, 0.01
|
0.918
|
R5-R20, Ka/L/s
|
0.02
|
0.13
|
0.01, 0.03
|
0.003
|
X5, Ka/L/s
|
-0.02
|
-0.14
|
-0.04, -0.01
|
0.002
|
AX, Ka/L
|
0.30
|
0.16
|
0.13, 0.47
|
<0.001
|
Fres, Hz
|
1.75
|
0.17
|
0.85, 2.66
|
<0.001
|
postbronchodilator
|
|
|
|
|
MMEF, %predicted
|
-3.95
|
-0.15
|
-6.19, -1.71
|
0.001
|
FEF50, %predicted
|
-5.42
|
-0.19
|
-7.88, -2.95
|
<0.001
|
FEF75, %predicted
|
-0.75
|
-0.03
|
-2.99, 1.49
|
0.512
|
All the models were adjusted for sex, BMI, smoking status, smoking index, educational level, asthma, tuberculosis, chronic bronchitis, annual household income, smokers living at home, parental history of respiratory disease, occupation exposure > 6 months, indoor exposure to biomass for cooking or heating. All the variables of age in these models indicate per 10 years increase. Abbreviations: CI =confidence interval; β = estimate; % = percent; definitions of other abbreviations see Table 1.
Table 5. Multi-adjusted contributions of age to the extent of SAD among IOS-defined SAD subjects (n = 603) from total subjects.
Outcomes for SAD markers
|
Unstandardized β
|
Standardized β
|
95%CI
|
P value
|
CT
|
|
|
|
|
LAA−950, %
|
0.64
|
0.07
|
-0.07,1.34
|
0.078
|
LAA−856, %
|
6.12
|
0.21
|
4.13,8.14
|
<0.001
|
RV, L
|
0.16
|
0.11
|
0.05,0.26
|
0.003
|
TLC, L
|
-0.17
|
-0.11
|
-0.28,-0.07
|
0.001
|
IOS
|
|
|
|
|
R5, Ka/L/s
|
0.01
|
0.04
|
-0.01,0.02
|
0.382
|
R20, Ka/L/s
|
-0.00
|
-0.01
|
-0.01,0.01
|
0.755
|
R5-R20, Ka/L/s
|
0.01
|
0.07
|
-0.00,0.01
|
0.116
|
X5, Ka/L/s
|
-0.02
|
-0.16
|
-0.03,-0.01
|
<0.001
|
AX, Ka/L
|
0.18
|
0.12
|
0.06,0.30
|
0.004
|
Fres, Hz
|
0.80
|
0.14
|
0.32,1.29
|
0.001
|
postbronchodilator
|
|
|
|
|
MMEF, %predicted
|
-6.17
|
-0.22
|
-8.20,-4.13
|
<0.001
|
FEF50, %predicted
|
-7.01
|
-0.22
|
-9.31,-4.72
|
<0.001
|
FEF75, %predicted
|
-4.02
|
-0.15
|
-6.20,-1.84
|
<0.001
|
Note: All the models were adjusted for sex, BMI, smoking status, smoking index, educational level, asthma, tuberculosis, chronic bronchitis, annual household income, smokers living at home, parental history of respiratory disease, occupation exposure > 6 months, indoor exposure to biomass for cooking or heating. All the variables of age in these models indicate per 10 years increase. Definitions of abbreviations see Table 1.
Table 6. Multi-adjusted contributions of age to the extent of SAD among spirometry-defined SAD subjects (n = 1372) from total subjects.
Outcomes for SAD markers
|
Unstandardized β
|
Standardized β
|
95%CI
|
P value
|
CT
|
|
|
|
|
LAA−950, %
|
1.03
|
0.13
|
0.63,1.43
|
<0.001
|
LAA−856, %
|
6.86
|
0.26
|
5.56,8.16
|
<0.001
|
RV, L
|
0.17
|
0.12
|
0.10,0.23
|
<0.001
|
TLC, L
|
-0.17
|
-0.12
|
-0.24,-0.10
|
<0.001
|
IOS
|
|
|
|
|
R5, Ka/L/s
|
0.02
|
0.10
|
0.01,0.02
|
<0.001
|
R20, Ka/L/s
|
0.00
|
-0.001
|
-0.01,0.004
|
0.964
|
R5-R20, Ka/L/s
|
0.02
|
0.15
|
0.01,0.02
|
<0.001
|
X5, Ka/L/s
|
-0.02
|
-0.16
|
-0.02,-0.01
|
<0.001
|
AX, Ka/L
|
0.21
|
0.16
|
0.14,0.28
|
<0.001
|
Fres, Hz
|
1.60
|
0.21
|
1.18, 2.03
|
<0.001
|
postbronchodilator
|
|
|
|
|
MMEF, %predicted
|
-5.32
|
-0.26
|
-6.40,-4.24
|
<0.001
|
FEF50, %predicted
|
-6.77
|
-0.27
|
-8.08,-5.46
|
<0.001
|
FEF75, %predicted
|
-2.40
|
-0.14
|
-3.33,-1.46
|
<0.001
|
Note: All the models were adjusted for sex, BMI, smoking status, smoking index, educational level, asthma, tuberculosis, chronic bronchitis, annual household income, smokers living at home, parental history of respiratory disease, occupation exposure > 6 months, indoor exposure to biomass for cooking or heating. All the variables of age in these models indicate per 10 years increase. Definitions of abbreviations see Table 1.