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Table 1 Clinical characteristics of cases and matched controls

From: Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: a disease risk score-matched nested case–control study

Characteristics

At Baseline, No. (%)a

During Follow-up, No. (%)c

Cases (n = 2700)

Controls (n = 9272)

SDb

Cases (n = 2700)

Controls (n = 9272)

SDb

Age, mean ± s.d

73.2 ± 10.3

71.3 ± 10.1

0.193

72.8 ± 10.1

71.9 ± 9.9

0.193

Sex, male No. (%)

1800 (66.7)

6210 (67.0)

0.007

1912 (69.3)

7364 (70.1)

0.007

Periods from the first COPD visit to the initial use of antidiabetic agents, days (mean ± s.d.)

519 ± 922

435 ± 826

0.052

NA

NA

NA

DM severity indicators, No. (%)

 aDCSI

  0

742 (27.5)

2930 (31.6)

0.090

764 (28.3)

3074 (33.2)

0.105

  1–2

1061 (39.3)

3778 (40.8)

0.030

1024 (37.9)

3622 (39.1)

0.023

  3–4

626 (23.2)

1846 (19.9)

0.080

633 (23.4)

1845 (19.9)

0.086

  ≥ 5

271 (10.0)

718 (7.7)

0.090

279 (10.3)

731 (7.9)

0.085

 Insulin

  Nonusers

1786 (66.2)

6634 (71.6)

0.117

1801 (66.7)

6864 (74.0)

0.161

  Short acting only

831 (30.8)

2366 (25.5)

0.117

754 (27.9)

1899 (20.5)

0.174

  Long acting

83 (3.1)

272 (2.9)

0.008

145 (5.4)

509 (5.5)

0.005

 Regimens of oral hypoglycemic agentsd

  Nonusers

0

0

 

333 (12.3)

919 (9.9)

0.077

  Monotherapy

1376 (51.0)

4958 (53.5)

0.050

940 (34.8)

2939 (31.7)

0.066

  Dual therapy

944 (35.0)

3286 (35.4)

0.010

900 (33.3)

3508 (37.8)

0.094

   Triple therapy or more

380 (14.1)

028 (11.1)

0.090

527 (19.5)

1906 (20.6)

0.026

 Metabolic acidosis

9 (0.3)

21 (0.2)

0.020

21 (0.8)

22 0.2)

0.076

 New users of oral hypoglycemic agents

1589 (58.9)

5744 (62.0)

0.063

NA

NA

NA

COPD severity indicators, No. (%)

 No. of inpatient visit for COPD exacerbationse

  0

2589 (95.9)

9032 (97.4)

0.085

NA

NA

NA

  1

85 (3.2)

201 (2.2)

0.061

NA

NA

NA

  ≥ 2

26 (1.0)

39 (0.4)

0.065

NA

NA

NA

 No. of ER visit for COPD exacerbations

  0

2590 (95.9)

9017 (97.3)

0.073

2488 (92.2)

8940 (96.4)

0.185

  1

85 (3.2)

221 (2.4)

0.047

149 (5.5)

304 (3.3)

0.109

  ≥ 2

25 (0.9)

34 (0.4)

0.070

63 (2.3)

28 (0.3)

0.179

 No. of OPD visit for COPD exacerbationsf

  0

2284 (84.6)

7876 (84.6)

0.010

2252 (83.4)

8129 (87.7)

0.121

  1

296 (11.0)

1013 (11.0)

0.001

289 (10.7)

768 (8.3)

0.083

 ≥ 2

120 (4.4)

383 (4.4)

0.015

159 (5.9)

375 (4.0)

0.085

 Types of COPD regimens

  Nonusers

894 (33.1)

3,040 (32.8)

0.007

360 (13.3)

1,306 (14.0)

0.022

  Triple therapy

15 (0.6)

33 (0.4)

0.030

15 (0.6)

15 (0.2)

0.066

  Dual therapy

224 (8.3)

722 (7.8)

0.019

305 (11.3)

719 (7.8)

0.121

  Others

1567 (58.0)

5477 (59.1)

0.021

2020 (74.8)

7,232 (78.0)

0.075

Comorbidities, No. (%)

 CV diseases

  Hypertension

1951 (72.4)

6572 (70.9)

0.033

1906 (70.6)

6720 (72.5)

0.042

  Coronary artery disease

895 (33.2)

3009 (32.5)

0.015

853 (31.6)

2873 (31.0)

0.013

  Stroke

826 (30.6)

2122 (22.9)

0.175

911 (33.7)

2416 (26.1)

0.168

  Hyperlipidemia

636 (23.6)

2390 (25.8)

0.052

581 (21.5)

2695 (29.1)

0.174

  Heart failure

488 (18.1)

1387 (15.0)

0.084

625 (23.2)

1518 (16.4)

0.171

  Arrhythmia

387 (14.3)

1193 (12.9)

0.043

427 (15.8)

1166 (12.6)

0.093

  Peripheral vascular disease

171 (6.3)

551 (5.9)

0.016

168 (6.2)

540 (5.8)

0.017

  Rheumatic heart disease

46 (1.7)

122 (1.3)

0.032

51 (1.9)

151 (1.6)

0.020

  Pulmonary embolism

7 (0.3)

15 (0.2)

0.021

10 (0.4)

21 (0.2)

0.026

 Pulmonary disease

  Acute bronchitis

1090 (40.4)

4107 (44.3)

0.079

905 (33.5)

3188 (34.4)

0.018

  Asthma

819 (30.3)

3092 (33.4)

0.065

897 (33.2)

2729 (29.4)

0.082

  Pneumonia

804 (29.8)

2386 (25.7)

0.090

972 (36.0)

2598 (28.0)

0.172

  Influenza

193 (7.2)

780 (8.4)

0.047

109 (4.0)

500 (5.4)

0.064

 Mental disease

  Dementia

264 (9.8)

523 (5.6)

0.156

342 (12.7)

709 (7.7)

0.167

  Depression

153 (5.7)

476 (5.1)

0.024

148 (5.5)

433 (4.7)

0.037

  Schizophrenia

15 (0.6)

49 (0.5)

0.004

15 (0.6)

43 (0.5)

0.013

  Chronic liver disease

322 (11.9)

1214 (13.1)

0.035

257 (9.5)

1004 (10.8)

0.043

  Cancer

311 (11.5)

1011 (10.9)

0.019

345 (12.8)

1279 (13.8)

0.030

  Sepsis

227 (8.4)

424 (4.6)

0.156

390 (14.4)

769 (8.3)

0.195

  Chronic renal disease

216 (8.0)

538 (5.8)

0.087

347 (12.9)

917 (9.9)

0.093

  GERD

144 (5.3)

397 (4.3)

0.049

212 (7.9)

617 (6.7)

0.046

  Parkinsonism

132 (4.9)

303 (3.3)

0.082

148 (5.5)

365 (3.9)

0.073

Co-medication, No. (%)

 CV medication

  Diuretics

1771 (65.6)

5709 (61.6)

0.084

1755 (65.0)

5425 (58.5)

0.134

  Calcium channel blockers

1724 (63.9)

5766 (62.2)

0.034

1616 (59.9)

5275 (56.9)

0.060

  Antiplatelets

1688 (61.8)

5508 (59.4)

0.049

1465 (54.3)

4722 (50.9)

0.067

  Angiotensin-converting enzyme inhibitors

874 (32.4)

3113 (33.6)

0.026

579 (21.4)

2014 (21.7)

0.007

  Angiotensin receptor blockers

849 (31.4)

2754 (29.7)

0.038

938 (34.7)

3479 (37.5)

0.058

  Nitrates

665 (24.6)

2011 (21.6)

0.072

617 (22.9)

1773 (19.1)

0.092

 β-blockers

  Non-CV selective

641 (23.7)

2088 (22.5)

0.029

418 (15.5)

1402 (15.1)

0.010

  CV selective

567 (21.0)

1983 (21.4)

0.009

348 (12.9)

1404 (15.1)

0.065

  Digoxin

334 (12.4)

979 (10.6)

0.057

334 (12.4)

979 (10.6)

0.057

  Anticoagulants

221 (8.2)

555 (6.0)

0.086

174 (6.4)

519 (5.6)

0.036

  Antiarrhythmic agents

132 (4.9)

310 (3.3)

0.078

193 (7.2)

390 (4.2)

0.127

 Lipid-lowering agents

  Statins

469 (17.4)

1567 (16.9)

0.012

458 (17.0)

2,135 (23.0)

0.152

  Others

218 (8.1)

853 (9.2)

0.040

133 (4.9)

635 (6.9)

0.082

 COPD medications

  Inhaled corticosteroids

392 (14.5)

1411 (15.2)

0.020

432 (16.0)

1230 (13.3)

0.077

  LABA

250 (9.3)

801 (8.6)

0.022

341 (126)

1002 (10.8)

0.057

  LAMA

58 (2.2)

202 (2.2)

0.002

103 (3.8)

206 (2.2)

0.093

 Short-acting β2 agonists

  Nebulized

810 (30.0)

2174 (23.5)

0.148

1067 (39.5)

2583 (27.9)

0.249

 Inhaled

  0 canister

2254 (83.5)

7768 (83.8)

0.008

2174 (80.5)

8051 (86.8)

0.171

  ≤ 6 canisters

381 (14.1)

1291 (13.9)

0.005

493 (18.3)

1158 (12.5)

0.160

  > 6 canisters

65 (2.4)

213 (2.3)

0.007

33 (1.2)

63 (0.7)

0.056

 Short-acting muscarinic antagonists

  Nebulized

674 (25.0)

1717 (18.5)

0.157

970 (35.9)

2365 (25.5)

0.227

 Inhaled

  0 canister

2465 (91.3)

8567 (92.4)

0.040

2442 (90.4)

8814 (95.1)

0.179

  ≤ 6 canisters

205 (7.6)

610 (6.6)

0.040

246 (9.1)

433 (4.7)

0.176

  > 6 canisters

30 (1.1)

95 (1.0)

0.008

12 (0.4)

25 (0.3)

0.029

  Oral β2 agonists

1511 (56.0)

5586 (60.3)

0.087

1329 (49.2)

4279 (46.2)

0.062

  Methylxanthines

1223 (45.3)

4600 (49.6)

0.086

1208 (44.7)

3783 (40.8)

0.080

 Gastric acid suppressants

  H-blockers

1054 (39.0)

3338 (36.0)

0.063

851 (31.5)

2599 (28.0)

0.076

  PPI

414 (15.3)

1006 (10.9)

0.133

454 (16.8)

976 (10.5)

0.184

 Anti-inflammatory agents

  NSAID

1953 (72.3)

6998 (75.5)

0.072

1309 (48.5)

5117 (55.2)

0.135

  Systemic corticosteroid

1593 (59.0)

5449 (58.8)

0.005

1570 (58.2)

4213 (45.4)

0.256

  Aspirin (≥ 325 mg)

521 (19.3)

1722 (18.6)

0.018

387 (14.3)

1103 (11.9)

0.072

 Psychotropic drugs

  Benzodiazepines and Z-drugs

1785 (66.1)

6134 (66.2)

0.001

1478 (54.7)

4807 (51.8)

0.058

  Antipsychotics

611 (22.6)

1771 (19.1)

0.087

518 (19.2)

1529 (16.5)

0.070

  Opioids

1443 (53.4)

5132 (55.4)

0.038

1092 (40.4)

3535 (38.1)

0.047

  Vaccines (influenza and pneumonia)

1061 (39.3)

3682 (39.7)

0.008

798 (29.6)

3195 (34.5)

0.105

  1. SD, standardized difference; s.d., standard deviation; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; aDCSI, adapted diabetes complications severity index; NA, not applicable; No., number; ER, emergency room; OPD, outpatient department; CV, cardiovascular; GERD, gastroesophageal reflux disease; LABA, inhaled long-acting β2 agonists; LAMA, inhaled long-acting antimuscarinic antagonists; PPI, proton pump inhibitor; NSAID, nonsteroidal anti-inflammatory drug
  2. a All comorbidities, DM severity indicators, COPD severity indicators, and co-medications were measured in the year before the cohort entry date
  3. b SD with > 0.1 represents meaningful differences between two groups
  4. c All comorbidities, COPD severity indicators, aDSCI metabolic acidosis, and pneumonia and influenza vaccinations were measured in the year preceding the index date; co-medications and other DM severity indicators were measured in the 6 months before the index date
  5. d Regimens of oral hypoglycemic agents were measured at the cohort entry date, and the measurements during follow-up were similar to those of co-medications
  6. e Number of inpatient visit for COPD exacerbations was measured during 31–365 days before the cohort entry date
  7. f OPD visits for COPD exacerbations were defined as patients with a primary diagnosis of COPD refilling oral corticosteroids or antibiotics for use 3–14 days after an outpatient visit