Incidence and Prognostic Factors of Respiratory Viral Infections in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Characteristics of Enrolled Patients

Variables	Number of Patients (N=192)
Age (years)	76.5±7.9
Sex, n (%)
Male	155 (80.7)
Female	37 (19.3)
Body mass index (kg/m^2)	21.5±4.5
Smoking, n (%)
Current smoker	56 (29.2)
Ex-smoker	122 (63.5)
Never smoker	13 (7.3)
Comorbidities, n(%)
Coronary artery disease	18 (9.4)
Heart failure	17 (8.9)
Chronic kidney disease	10 (5.2)
Cerebrovascular disease	18 (9.4)
Diabetes mellitus	31 (16.1)
Hypertension	67 (34.9)
Spirometry after bronchodilator
FVC	69.1±16.2
FEV1	49.3±18.8
Ratio of FEV1 to FVC	47.5±13.3
Maintenance inhaler medication
LAMA	24 (12.5)
LAMA+LABA	53 (27.6)
LAMA+LABA+ICS	58 (30.2)
ICS+LABA	26 (13.5)
No use	31 (16.1)
History of acute exacerbation in the last year	56 (29.7)

Note: Data are presented as means ± standard deviations or numbers (percentages).

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV, forced expiratory volume in one second; FVC, forced vital capacity; LAMA, long-acting muscarinic antagonist; LABA, long-acting β₂ agonist; ICS, inhaled corticosteroid.

Figure 1 Flowchart of participant enrollment. A total of 420 patients were hospitalized with acute exacerbation of chronic obstructive pulmonary disease. After excluding patients who were hospitalized for other causes of dyspnea and those with no multiplex polymerase chain reaction (PCR) results available, 262 final exacerbation cases from 192 patients were enrolled in the study.

Table 2 Respiratory Viruses Identified in Severe Chronic Obstructive Pulmonary Disease Exacerbation Events

Pathogen	No. of Virus Positive Events (N=108)
Rhino/enterovirus	33 (30.1)
Influenza	27 (25.0)
Influenza A	18 (16.7)
Flu A/H1	0 (0)
Flu A/H1-2009	7 (6.5)
Flu A/H3	12 (11.1)
Influenza B	10 (9.3)
Parainfluenza	15 (13.9)
Parainfluenza 1	6 (5.6)
Parainfluenza 2	0 (0)
Parainfluenza 3	5 (4.6)
Parainfluenza 4	4 (3.7)
Coronavirus	15 (13.9)
Coronavirus 229E	3 (2.8)
Coronavirus HKU1	1 (0.9)
Coronavirus OC43	7 (6.5)
Coronavirus NL63	4 (3.7)
Metapneumovirus	9 (8.3)
Respiratory syncytial virus	16 (14.8)
Adenovirus	5 (4.6)
Multiple virus infection	11 (10.2)

Note: Data are presented as numbers (percentages).

Table 3 Comparison of Clinical Data Between Virus-Positive Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) and Virus-Negative AECOPD Groups

Variables	All Events (N=262)	Respiratory Virus – Positive Events (108)	Respiratory Virus – Negative Events (154)	P-value
Age	75.4±7.5	76.3±7.9	76.5±7.2	0.804
Male, n (%)	220 (84.0)	89 (82.4)	131 (85.1)	0.564
Current smoker, n (%)	73 (27.9)	26 (24.1)	47 (30.5)	0.252
Body mass index (Kg/m^2)	21.3±4.2	21.1±3.4	21.4±4.6	0.619
Symptoms at admission				0.483
Duration of symptom prior to admission	4.2±3.4	4.4±3.3	4.1±3.5
Nasopharyngeal symptoms	52 (19.8)	29 (26.9)	23 (14.9)	0.017
Increased cough	69 (26.9)	29 (28.4)	40 (26.0)	0.874
Increased sputum production	67 (25.6)	34 (27.6)	33 (21.4)	0.066
Dyspnea	237 (90.5)	100 (97.7)	137 (89.0)	0.21
ICS use	118 (45)	57 (52.8)	61 (39.6)	0.035
Frequent exacerbation	45 (17.2)	14 (13.0)	31 (20.1)	0.130
Vital sign on admission
Systolic blood pressure	127.1±24.3	127.3±26.7	127.0±22.5	0.921
Diastolic blood pressure	78.2±15.6	77.6±16.7	78.6±14.9	0.596
Mean blood pressure	110.8±20.7	110.7±22.8	110.9±19.1	0.955
Heart rate	95.2±21.5	95.5±23.1	94.9±20.4	0.829
Respiration rate	21.8±4.0	22.0±5.3	21.7±2.8	0.543
Body temperature	37.4±0.8	37.5±0.8	37.3±0.8	0.104
Spirometry after bronchodilator
FVC (% of predicted value)	69.1±16.2	68.0±17.1	68.2±15.5	0.890
FEV1 (% of predicted value)	49.3±18.8	48.0±19.5	47.3±18.0	0.761
Ratio of FEV1 to FVC (%)	47.5±13.3	47.1±14.0	46.2±13.7	0.617
Severity of COPD, n (%)				0.499
GOLD 1	16(6.2)	8(7.5)	8(5.2)
GOLD 2	91(35)	38(35.8)	53(44.2)
GOLD 3	106(40.8)	38(35.8)	68(44.2)
GOLD 4	47(18.1)	22(20.8)	25(16.2)
Bacterial infection	56 (21.4)	22 (23.1)	34 (22.1)	0.740
Outcomes
Hospital stay, day	11.4±8.2	11.7±9.4	11.2±7.3	0.610
ICU admission	20	6 (5.6)	14 (9.1)	0.289
In hospital death	13 (5.0)	6 (5.6)	7 (4.5)	0.711
Readmission in 3 months	68 (25.5)	22 (28.0)	46 (29.9)	0.084

Note: Data are presented as means ± standard deviations or numbers (percentages).

Abbreviations: ICS, inhaled corticosteroid; FEV, forced expiratory volume in one second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICU, intensive care unit.

Table 4 Comparison of Laboratory Findings Between Virus-Positive and Virus-Negative Events

Variables	All Events (N=262)	Respiratory Virus – Positive Events (108)	Respiratory Virus – Negative Events (154)	P-value
Complete blood count (normal range)  White blood cells, ×10^9/L)	11.5±5.1	12.3±6.2	11.0±4.2	0.063
>10	152 (58.3)	63 (58.3)	89 (58.6)	0.930
Neutrophil count, ×10^9/L (1.8–6.3)	8.9±4.4	9.6±4.8	8.4±4.2	0.036
>4.8, n (%)	207 (79.3)	92 (85.2)	115 (75.2)	0.049
Eosinophil count,/uL (50–500)	163.2±212.2	124.80±171.6	190.1±233.4	0.010
>100, n (%)	120 (45.8)	40 (37)	80 (51.8)	0.017
Eosinophil percent	1.7±2.4	1.3±2.0	2.0±2.5	0.032
>2%, n (%)	71 (37.2)	22 (20.6)	49 (31.8)	0.044
Blood chemistry (normal range)
Albumin, g/dL (3.5–5)	3.5±0.8	3.5±0.5	3.5±0.9	0.763
Creatinine	1.1±0.7	1.1±0.8	1.0±0.7	0.157
Infection markers (normal range)
C-reactive protein, mg/dL (0–0.5)	7.5±10.2	9.2±13.1	6.4±7.5	0.043
>0.5, n (%)	220 (84.3)	98 (91.6)	122 (79.2)	0.007
Procalcitonin, ng/mL (0–0.5)	0.6±1.6	0.6±1.5	0.6±1.6	0.88

Note: Data are presented as means ± standard deviations or numbers (percentages).

Table 5 Factors Associated with Viral Detection in Severe Chronic Obstructive Pulmonary Disease Exacerbation Based on Multivariable Logistic Regression Analysis

	Univariable		Multivariable Model^a
	OR (95% CI)	P value	OR (95% CI)	P value
Age >70	0.89 (0.47–1.7)	0.732	0.878 (0.43–1.80)	0.723
Female, sex	1.22 (0.63–2.36)	0.564	1.40 (0.68–2.87)	0.357
Nasopharyngeal symptoms	2.09 (1.13–3.87)	0.019	1.98 (1.03–3.78)	0.040
Use of ICS	1.70 (1.04–2.80)	0.036	1.69 (1.01–2.84)	0.047
Eosinophil<100/uL	1.84 (1.12–3.04)	0.018	1.74 (1.03–2.92)	0.038
CRP>0.5 mg/dL	2.86 (1.302–6.27)	0.009	2.76 (1.24–6.15)	0.013
ANC>4.8, ×10^9/L	1.90 (0.997–3.622)	0.051	1.41 (0.71–2.80)	0.332

Note: ^aAdjusted for age, sex, rhinopharyngitis symptom, ICS use, eosinophil count, CRP level, ANC.

Abbreviations: ANC, absolute neutrophil count; CI, confidence interval; CRP, C-reactive protein; ICS, inhaled corticosteroid; OR, odds ratio.