Comparison of the Clinical Outcomes Between Nebulized and Systemic Corticosteroids in the Treatment of Acute Exacerbation of COPD in China (CONTAIN Study): A Post Hoc Analysis

Figures & data

Figure 1 Flow diagram of the patient selection process for post hoc analysis.

Abbreviations: ICS, inhaled corticosteroids; NCS, nebulized corticosteroids (budesonide); SCS, systemic corticosteroids; NCS+SCS, combination of NCS and SCS therapies; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; RF, respiratory failure.

Table 1 Baseline Characteristics of Hospitalized AECOPD Patients Treated with NCS, SCS, or NCS+SCS Before Propensity Score Matching

Variables	NCS	SCS	NCS+SCS	P
	(N=1091)	(N=709)	(N=1846)
Age (years)	72.9±9.79	72.9±9.59	73.2±9.27	<0.001^a
Sex				0.220^b
Male	790 (72.4%)	564 (79.5%)	1403 (76.0%)
Female	301 (27.6%)	145 (20.5%)	443 (24.0%)
BMI (kg/m^2)	22.2±3.75	21.8±3.38	22.2±3.32	<0.001^a
Duration of COPD (years)	9.2±9.06	10.7±9.19	10.1±9.70	<0.001^a
Duration of AECOPD (days)	19.0±48.09	17.9±34.01	17.0±35.71	<0.001^a
Pneumonia at enrollment	264 (24.2%)	172 (24.3%)	473 (25.6%)	0.919^b
First monitor index
First PaO2 (mmHg)	74.4±26.50	79.8±30.89	79.9±30.93	<0.001^a
First PaCO2 (mmHg)	48.7±15.36	50.9±16.98	51.5±16.90	<0.001^a
First SaO2 (%)	91.3±9.20	92.1±8.72	92.6±7.44	<0.001^a
First pH	7.4±0.06	7.4±0.07	7.4±0.06	<0.001^a
Smoking
Smoking status				0.305^b
Never smoked	350 (32.1%)	229 (32.3%)	547 (29.6%)
Current smokers	276 (25.3%)	163 (23.0%)	462 (25.0%)
Former smokers	456 (41.8%)	305 (43.0%)	814 (44.1%)
Missing data	9 (0.8%)	12 (1.7%)	23 (1.2%)
Smoking duration (years)	35.3±13.19	34.3±12.17	35.0±12.82	<0.001^a
Smoking amount (packets/year)	58.3±93.45	66.8±115.20	63.0±96.59	<0.001^a
Living environment
Long-term passive smoking	91 (8.3%)	53 (7.5%)	143 (7.7%)	0.650^b
Long-term exposure to occupational dust and gas fumes	74 (6.8%)	41 (5.8%)	105 (5.7%)	0.359^b
Air pollution	411 (37.7%)	255 (36.0%)	655 (35.5%)	0.139^b
Damp, cold or foggy	106 (9.7%)	166 (23.4%)	207 (11.2%)	0.081^b
None of the above	518 (47.5%)	311 (43.9%)	925 (50.1%)	0.090^b
Comorbidities	177 (16.2%)	137 (19.3%)	366 (19.8%)	-
Mean total dose (mg)	33.0±25.16	367.9±364.72*	36.9±70.50/442.2±482.75*	-
Mean daily dose (mg)	3.8±1.77	49.9±38.34*	3.1±3.07/61.1±61.36*	-
Mean treatment duration (days)	8.7±5.11	7.9±5.10	12.3±8.29/7.8±5.44	-

Notes: Data were summarized as mean±standard deviation for continuous variables and n (percentage) for categorical data. ^aOne-way analysis of variance. ^bChi-square test. *Equivalent prednisone dose.

Abbreviations: NCS, nebulized corticosteroids; SCS, systemic corticosteroids; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index.

Table 2 Clinical Outcomes of Hospitalized AECOPD Patients Treated with NCS, SCS, or NCS+SCS Before Propensity Score Matching

Variables	NCS	SCS	NCS+SCS	P
	(N=1091)	(N=709)	(N=1846)
Primary outcomes
Length of hospital stay (days)	11.8±6.84	12.0±5.10	13.3±6.46	<0.001^a
Mortality	11 (1.0%)	15 (2.1%)	31 (1.7%)	<0.001^b
Improvement monitor index
Improvement of PaO2 (mmHg)	5.9±31.46	6.4±44.01	5.5±37.07	0.001^a
Improvement of PaCO2 (mmHg)	−5.3±14.42	−4.9±16.78	−4.3±15.30	0.001^a
Improvement of SaO2 (%)	4.8±11.82	3.9±12.92	2.9±8.45	<0.001^a
Improvement of pH	0.0±0.07	0.0±0.08	0.0±0.07	<0.001^a
Secondary outcomes
Intubation rate	32 (2.9%)	15 (2.1%)	53 (2.9%)	0.147^b
New onset pneumonia in hospital	21 (1.9%)	20 (2.8%)	49 (2.7%)	0.966^b
Rate of pneumonia improvement at discharge^#	241 (22.1%)	162 (22.8%)	456 (24.7%)	0.108^b
Hospitalization expense (CNY)	14,668.6±15,563.76	14,614.4±10,242.93	17,905.4±15,503.07	<0.001^a

Notes: Data were summarized as mean±standard deviation for continuous variables and n (percentage) for categorical data. ^#Rate of pneumonia improvement at discharge was defined as the reduction in the incidence of pneumonia from baseline to discharge. ^aOne-way analysis of variance. ^bChi-square test.

Abbreviations: NCS, nebulized corticosteroids; SCS, systemic corticosteroids; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; CNY, China Yuan.

Figure 2 Frequency and logistic regression results for categorical data of clinical outcomes. NCS was used as the reference; adjusted odds ratio was adjusted by age, sex, height, weight, duration of COPD, duration of initial AECOPD, PaO₂ at the first time, PaCO₂ at the first time, SaO₂ at the first time and pH at the first time. OR values of some clinical outcomes were very large or small, and the exact value could not be obtained, *was used instead.

Abbreviations: NCS, nebulized corticosteroids (budesonide); SCS, systemic corticosteroids; NCS+SCS, combination of NCS and SCS therapies;RF, respiratory failure; OR, odds ratio; n/a, not assessed.

Figure 3 The final general linear model results for continuous data of clinical outcomes. NCS was used as the reference; the adjusted regression coefficient was adjusted by age, sex, height, weight, duration of COPD, duration of initial AECOPD, PaO₂ at the first time, PaCO₂ at the first time, SaO₂ at the first time and PH at the first time. The value greater than 8 or less than −8 was not shown in the graph on the right.

Abbreviations: NCS, nebulized corticosteroids (budesonide); SCS, systemic corticosteroids; NCS+SCS, combination of NCS and SCS therapies; RF, respiratory failure; b, regression coefficient; SEM, standard error of the mean.

Table 3 Clinical Outcomes of Hospitalized AECOPD Patients without RF After Propensity Score Matching

Clinical Outcomes	Without RF
	NCS	SCS	NCS+SCS	P
	(N=468)	(N=317)	(N=826)
Primary outcomes
Length of hospital stay (days)	11.6±7.86	11.4±4.61	13.3±6.69	<0.001^a
Mortality	5 (1.1%)	6 (1.9%)	10 (1.2%)	0.565^c
Improvement of PaO2 (mmHg)	−6.3±32.77	−5.5±44.02	−4.8±37.11	0.913^a
Improvement of PaCO2 (mmHg)	−5.4±15.62	−4.0±17.13	−5.0±14.00	0.781^a
Improvement of SaO2 (%)	−0.7±4.32	−1.5±6.55	0.0±5.77	0.050^a
Improvement of pH	0.0±0.08	0.0±0.09	0.0±0.07	0.850^a
Secondary outcomes
Intubation rate	10 (2.1%)	9 (2.8%)	12 (1.5%)	0.291^b
New onset pneumonia in hospital	9 (1.9%)	13 (4.1%)	25 (3.0%)	0.201^b
Rate of pneumoniaimprovement at discharge^#	110 (23.5%)	69 (21.8%)	219 (26.5%)	0.618^c
Hospitalization expense (CNY)	13,268.9±15,582.72	13,752.9±8877.18	17,669.9±14,380.95	<0.001^a

Notes: Data were summarized as mean±standard deviation for continuous variables and n (percentage) for categorical data. ^#Rate of pneumonia improvement at discharge was defined as the reduction in the incidence of pneumonia from baseline to discharge. ^aOne-way analysis of variance. ^bChi-square test. ^cFisher’s exact test.

Abbreviations: RF, respiratory failure; NCS, nebulized corticosteroids; SCS, systemic corticosteroids; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; CNY, China Yuan.

Table 4 Clinical Outcomes of Hospitalized AECOPD Cases with RF After Propensity Score Matching

Clinical Outcomes	Type I RF				Type II RF
	NCS	SCS	NCS+SCS	P	NCS	SCS	NCS+SCS	P
	(N=50)	(N=33)	(N=73)		(N=80)	(N=67)	(N=145)
Primary outcomes
Length of hospital stay (days)	11.3±4.95	12.0±4.86	13.8±5.60	0.022^a	11.8±5.62	12.6±4.67	13.3±6.81	0.208^a
Mortality	3 (6.0%)	1 (3.0%)	2 (2.7%)	0.763^b	0 (0%)	0 (0%)	4 (2.8%)	0.186^b
Improvement of PaO2 (mmHg)	16.8±23.74	24.1±18.86	21.1±27.07	0.640^a	21.3±20.91	29.0±25.89	24.5±23.44	0.241^a
Improvement of PaCO2 (mmHg)	3.5±9.54	2.2±6.13	3.4±8.69	0.875^a	−8.6±14.22	−8.3±15.66	−5.1±14.81	0.243^a
Improvement of SaO2 (%)	6.3±11.85	8.0±10.53	6.5±7.04	0.842^a	14.7±12.69	13.8±13.54	9.9±12.26	0.053^a
Improvement of pH	0.0±0.07	0.0±0.04	0.0±0.05	0.928^a	0.0±0.06	0.0±0.08	0.0±0.07	0.483^a
Secondary outcomes
Intubation rate	2 (4.0%)	0 (0%)	2 (2.7%)	0.819^b	6 (7.5%)	1 (1.5%)	8 (5.5%)	0.253^b
New onset pneumonia in hospital	0 (0%)	1 (3.0%)	1 (1.4%)	0.488^b	2 (2.5%)	1 (1.5%)	3 (2.1%)	1.000^b
Rate of pneumoniaimprovement at discharge^#	8 (16.0%)	10 (30.3%)	12 (16.4%)	–	9 (11.3%)	16 (23.9%)	24 (16.6%)	0.451^b
Hospitalization expense (CNY)	14,992.1±12,627.63	14,436.0±7168.92	18,250.8±13,433.27	0.205^a	17,793.8±16,916.03	17,312.2±10,060.92	18,956.9±13,814.30	0.687^a

Notes: Data were summarized as mean±standard deviation for continuous variables and n (percentage) for categorical data. Type I RF was defined as PaO₂<60 mmHg, with a normal or low PaCO₂. Type II RF was defined as PaO₂<60 mmHg and PaCO₂>50 mmHg. ^#Rate of pneumonia improvement at discharge was defined as the reduction in the incidence of pneumonia from baseline to discharge. ^aOne-way analysis of variance. ^bFisher’s exact test.

Abbreviations: RF, respiratory failure; NCS, nebulized corticosteroids; SCS, systemic corticosteroids; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; CNY, China Yuan.