Inhaled corticosteroids might not increase the risk of pneumonia in patients with chronic obstructive pulmonary disease in Japan

Figures & data

Table 1 Demographic and clinical characteristics of patients with COPD

Parameters	ICS group (n=252)	Non-ICS (n=387)	P-value
Median (range) age (years)	75 (47–94)	73 (31–95)	0.074
Gender (male/female)	211/41	337/50	0.248
Median (range) number of days of follow-up	160 (12–1,688)	118 (1–1,684)	0.631
Duration of ICS treatment (days)
0–365	142
366–730	27
731–1,095	20
Over 1,096	60
Type of ICS, n (%)
FP/SM	193 (76.6)
BUD/FM	30 (11.9)
FP	12 (4.8)
BUD	2 (0.8)
Others	15 (6.0)
Doses of ICS treatment
Low dose	45
Intermediate	122
High	30
Others (changed doses)	55
Combination of bronchodilators, n
LABA	228	188	<0.001
LAMA	149	170	<0.001
Comorbidities, n
Malignant tumor	72	104	0.651
Diabetes mellitus	23	51	0.130
Ischemic heart disease	11	18	1.000
Heart failure	10	27	0.122
GOLD score
A	32	217	<0.001
B	90	88	0.233
C	14	18	0.711
D	113	64	<0.001

Note: P-values in bold <0.05 were regarded as statistically significant.

Abbreviations: BUD, budesonide; BUD/FM, budesonide/formoterol; COPD, chronic obstructive pulmonary disease; FP, fluticasone; FP/SM, fluticasone/salmeterol; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting beta 2 agonist; LAMA, long-acting muscarinic antagonist.

Table 2 Demographic and clinical characteristics of pneumonia in patients with COPD

Parameters	Pneumonia group in ICS (n=13)	Nonpneumonia in ICS (n=239)	P-value	Pneumonia group in ICS untreated (n=38)	Nonpneumonia in ICS untreated (n=349)	P-value
Median (range) age (years)	80 (69–94)	75 (47–94)	0.052	78 (51–91)	72 (31–95)	0.009
Gender (male/female)	12/1	199/40	0.700	34/4	303/46	0.802
Median (range) number of days of follow-up	972 (29–1,677)	139 (12–1,688)	0.010	441 (1–1,680)	100 (1–1,684)	0.025
Duration of ICS treatment (days)
0–365	3	139	0.250
366–730	2	25	0.637
731–1,095	2	18	0.276
Over 1,096	6	54	0.087
Type of ICS, n (%)
FP/SM	11 (84.6)	182 (76.2)	0.738
BUD/FM	0 (0)	30 (12.6)	0.375
FP	1 (7.7)	11 (4.6)	0.478
BUD	0 (0)	2 (0.8)	1.000
Others	1 (7.7)	14 (5.9)	0.559
Combination of bronchodilators, n (%)
LABA	11 (84.6)	217 (90.8)	1.000	28 (73.6)	160 (45.8)	0.001
LAMA	8 (61.5)	141 (59.0)	1.000	25 (65.7)	145 (41.5)	0.006
Comorbidities, n
Malignant tumor	6	66	0.204	9	95	0.705
Diabetes mellitus	2	21	0.337	7	44	0.314
Ischemic heart disease	0	11	1.000	1	17	1.000
Heart failure	2	8	0.088	3	24	0.739
GOLD score
A	2	30	0.673	15	202	0.038
B	4	86	0.776	10	78	0.547
C	1	13	0.533	1	17	1.000
D	6	107	1.000	12	52	0.019

Note: P-values in bold <0.05 were regarded as statistically significant.

Abbreviations: BUD, budesonide; BUD/FM, budesonide/formoterol; COPD, chronic obstructive pulmonary disease; FP, fluticasone; FP/SM, fluticasone/salmeterol; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting beta 2 agonist; LAMA, long-acting muscarinic antagonist.

Table 3 Incidence of pneumonia in patients with COPD with or without ICS number of pneumonia cases and observation days in this study

Parameters	ICS-treated group	ICS-untreated group	P-value
Pneumonia
Number of cases	13	38	0.037
Total observation (days)	12,324	11,249	0.004
Without pneumonia
Number of cases	239	349
Total observation (days)	120,679	115,461

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid.

Figure 1 Incidence rate of pneumonia and the observation period.

Notes: The relationship of the incidence rate of pneumonia and the observation period is shown. The dashed line indicates pneumonia cases in ICS-untreated patients with COPD. The solid line indicates pneumonia cases in ICS-treated patients. In the early phase of the observation period, the rate of pneumonia was high in ICS-untreated patients. In the late phase, the incidence of pneumonia was similar between ICS-treated and ICS-untreated patients.
Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid.

Table 4 Non-ICSrisk factors for pneumonia

Parameters	Pneumonia (n=6)	Nonpneumonia (n=12)	P-value	Multivariate analysis, P-value
Duration of hospitalization (days)	1,022.2	945.7	0.72
History of smoking	6	12	1
Using oral corticosteroids	5	10	1
Oxygen therapy	2	3	0.71
Pneumococcal vaccine	3	2	0.14
Albumin (g/dL)	3.8	3.86	0.76
BMI	18.3	21.9	0.02	0.055

Abbreviations: BMI, body mass index; ICS, inhaled corticosteroid.