Increased risk of community-acquired pneumonia in COPD patients with comorbid cardiovascular disease

Figures & data

Figure 1 Flowchart of study profile.

Abbreviations: CAP, community-acquired pneumonia; PFT, pulmonary function test.

Table 1 Demographic and clinical characteristics of the patients who did and did not develop CAP during follow-up after stratification based on the presence of comorbid CVD

	All patients (N=2,440)			No CVD (n=1,918)			CVD (n=522)
	No CAP (n=1,965)	CAP (n=475)	P-value	No CAP (n=1,574)	CAP (n=344)	P-value	No CAP (n=391)	CAP (n=131)	P-value
Male, n (%)	1,537 (78.3)	394 (82.9)	0.012	1,218 (77.4)	287 (83.4)	0.014	319 (81.6)	107 (81.7)	1.000
Age (years), median (IQR)	69.1 (57.9–77.2)	77.4 (69.0–82.5)	<0.001	67.6 (56.1–76.3)	77.0 (67.6–82.2)	<0.001	73.0 (64.5–79.5)	78.3 (72.0–83.1)	<0.001
Body weight (kg)a, median (IQR)	62.0 (54.0–71.0)	60.0 (52.0–69.0)	0.001	62.0 (54.0–70.0)	60.0 (52.0–68.0)	0.002	63 (55.5–73.0)	63.0 (53.0–71.0)	0.163
BMI (kg/m^2)b, median (IQR)	23.7 (21.0–26.4)	23.0 (20.3–26.0)	0.001	23.6 (21.0–26.2)	22.5 (20.2–25.1)	0.001	24.0 (21.8–27.0)	24.1 (20.8–26.3)	0.423
Pulmonary function
FEV1 (L), median (IQR)	1.7 (1.2–2.3)	1.36 (0.9–1.9)	<0.001	1.7 (1.2–2.4)	1.4 (0.9–1.9)	<0.001	1.64 (1.2–2.2)	1.3 (1.0–1.8)	<0.001
FEV1% predicted, median (IQR)	72.1 (54.0–88.5)	61.4 (45.3–79.7)	<0.001	72.6 (54.2–88.8)	61.6 (44.5–79.2)	<0.001	70.7 (52.6–87.4)	60.9 (48.6–80.8)	0.002
FEV1% predicted stage, n (%)
Stage I: mild (≥80%)	773 (39.3)	117 (24.6)	<0.001	627 (39.8)	83 (24.1)	<0.001	146 (37.3)	34 (26.0)	0.023
Stage II: moderate (50%–79%)	796 (40.5)	201 (42.3)	0.505	632 (40.2)	143 (41.6)	0.671	164 (41.9)	58 (44.3)	0.715
Stage III: severe (30%–49%)	310 (15.8)	127 (26.7)	<0.001	243 (15.4)	95 (27.6)	<0.001	67 (17.1)	32 (24.4)	0.087
Stage IV: very severe (<30%)	86 (4.4)	30 (6.3)	0.097	72 (4.6)	23 (6.7)	0.134	14 (3.6)	7 (5.3)	0.528
Cardiovascular disease	391 (19.9%)	131 (27.6)	<0.001
DM	226 (11.5%)	88 (18.53%)	<0.001	144 (9.15%)	51 (14.83%)	0.002	82 (20.97%)	37 (28.24%)	0.110
Comorbid pulmonary disease	210 (10.69%)	115 (24.21%)	<0.001	184 (11.69%)	94 (27.33%)	<0.001	26 (6.65%)	21 (16.03%)	0.002
CVA	141 (7.18%)	30 (6.32%)	0.510	111 (7.05%)	19 (5.52%)	0.307	30 (7.67%)	11 (8.4%)	0.790
Respiratory therapy, n (%)
None regularly used	1,140 (58.0)	178 (37.5)	<0.001	933 (59.3)	131 (38.1)	<0.001	207 (52.9)	47 (35.9)	0.001
ICS + LABA	497 (25.3)	169 (35.6)	<0.001	389 (24.7)	120 (34.9)	<0.001	108 (27.6)	49 (37.4)	0.045
LAMA	170 (8.7)	49 (10.3)	0.294	136 (8.6)	34 (9.9)	0.529	34 (8.7)	15 (11.5)	0.446
ICS + LABA + LAMA	158 (8.0)	79 (16.6)	<0.001	116 (7.4)	59 (17.2)	<0.001	42 (10.7)	20 (15.3)	0.219
Death, n (%)	153 (7.8)	111 (23.4)	<0.001	127 (8.1)	89 (25.9)	<0.001	26 (6.6)	22 (16.8)	0.001
Exacerbation frequency (per year)
0	1,924 (97.91%)	402 (84.63%)	<0.001	1,538 (97.71%)	294 (85.47%)	<0.001	386 (98.72%)	108 (82.44%)	<0.001
1	24 (1.22%)	37 (7.79%)		21 (1.33%)	25 (7.27%)		3 (0.77%)	12 (9.16%)
>1	17 (0.87%)	36 (7.58%)		15 (0.95%)	25 (7.27%)		2 (0.51%)	11 (8.4%)
Mean ± SD	0.09±1.12	0.67±3.51	<0.001	0.1±1.2	0.59±3.07	<0.001	0.05±0.66	0.88±4.46	0.003

Notes: Comorbid pulmonary disease (inclusive of bronchiectasis, history of tuberculosis, and lung cancer).

a One subject with missing information;

b 18 subjects with missing information.

Abbreviations: BMI, body mass index; CAP, community-acquired pneumonia; CVA, cerebral vascular accident; CVD, cardiovascular disease; DM, diabetes mellitus; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; IQR, interquartile range; LABA, long-acting β agonist; LAMA, long-acting muscarinic antagonist; SD, standard deviation.

Table 2 Factors associated with CAP occurrence during follow-up after stratification based on the presence of comorbid CVD

	All patients				No CVD				CVD
	Univariate		Multivariatea		Univariate		Multivariateb		Univariate		Multivariatec
	cHR (95% CI)	P-value	aHR (95% CI)	P-value	cHR (95% CI)	P-value	aHR (95% CI)	P-value	cHR (95% CI)	P-value	aHR (95% CI)	P-value
Male versus female	1.32 (1.04, 1.67)	0.023	1.158 (0.915, 1.465)	0.220	0.989 (0.636, 1.54)	0.960	1.197 (0.906, 1.58)	0.210	1.43 (1.08, 1.9)	0.012	1.136 (0.721, 1.79)	0.580
Age (per 1 year)	1.04 (1.03, 1.05)	<0.001	1.032 (1.023, 1.042)	<0.001	1.04 (1.02, 1.06)	<0.001	1.032 (1.021, 1.043)	<0.001	1.04 (1.03, 1.05)	<0.001	1.035 (1.013, 1.06)	0.002
BMI (per 1 kg/m^2)	0.964 (0.942, 0.986)	0.002	0.975 (0.952, 0.998)	0.030	0.975 (0.935, 1.02)	0.250	0.969 (0.942, 0.997)	0.031	0.955 (0.929, 0.982)	0.001	0.995 (0.955, 1.04)	0.810
Body weight (per 1 kg)	0.988 (0.981, 0.995)	0.001			0.989 (0.977, 1)	0.100			0.987 (0.978, 0.995)	0.002
FEV1 (per 1 L)	0.617 (0.534, 0.713)	<0.001			0.557 (0.427, 0.727)	<0.001			0.639 (0.539, 0.758)	<0.001
FEV1% predicted (per 1%)	0.987 (0.983, 0.991)	<0.001	0.994 (0.990, 0.999)	0.013	0.989 (0.981, 0.997)	0.006	0.995 (0.990, 1.000)	0.057	0.986 (0.982, 0.991)	<0.001	0.992 (0.983, 1)	0.056
Exacerbation frequency (per one time)	1.10 (1.06, 1.14)	<0.001	1.081 (1.046, 1.118)	<0.001	1.09 (1.04, 1.14)	<0.001	1.069 (1.019, 1.12)	0.006	1.13 (1.09, 1.17)	0.004	1.115 (1.078, 1.15)	<0.001
Cardiovascular disease	1.42 (1.16, 1.73)	0.001	1.278 (1.039, 1.571)	0.020
DM	1.62 (1.29, 2.04)	<0.001	1.535 (1.211, 1.946)	<0.001	1.60 (1.19, 2.16)	0.002	1.556 (1.154, 2.097)	0.004	1.43 (0.983, 2.08)	0.061	1.441 (0.964, 2.15)	0.075
Comorbid pulmonary disease	2.37 (1.92, 2.93)	<0.001	1.907 (1.518, 2.395)	<0.001	2.5 (1.97, 3.18)	<0.001	1.935 (1.496, 2.503)	<0.001	2.35 (1.46, 3.78)	<0.001	1.969 (1.203, 3.22)	0.007
CVA	1.81 (1.37, 2.39)	<0.001	1.252 (0.926, 1.692)	0.140	1.56 (1.1, 2.23)	0.013	1.078 (0.738, 1.576)	0.700	2.33 (1.47, 3.67)	<0.001	1.79 (1.089, 2.94)	0.022
Respiratory therapy
ICS versus non–ICS	1.84 (1.53, 2.2)	<0.001	1.304 (1.066, 1.594)	0.010	1.55 (1.1, 2.18)	0.013	1.323 (1.041, 1.681)	0.022	1.92 (1.55, 2.37)	<0.001	1.192 (0.816, 1.74)	0.360

Notes: Comorbid pulmonary disease (inclusive of bronchiectasis, history of tuberculosis, and lung cancer).

a N=2,440 in the final multivariate model;

b n=1,918 in the final multivariate model;

c n=522 in the final multivariate model.

Abbreviations: aHR, adjusted hazard ratio; BMI, body mass index; CAP, community-acquired pneumonia; cHR, crude hazard ratio; CI, confidence interval; CVA, cerebral vascular disease; CVD, cardiovascular disease; DM, diabetes mellitus; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid.

Figure 2 Kaplan–Meier curve for pneumonia-free survival of COPD patients stratified by comorbid CVD and ICS-containing therapy (N=2,440).

Notes: These groups include patients without CVD with ICS-containing therapy, patients without CVD with non–ICS-containing therapy, patients with CVD with ICS-containing therapy, patients with CVD with non–ICS-containing therapy.
Abbreviations: CVD, cardiovascular disease; HR, hazard ratio; ICS, inhaled corticosteroid.