Pathogens in COPD exacerbations identified by comprehensive real-time PCR plus older methods

Figures & data

Table 1 Baseline characteristics of patients (n=46)

	n (%)
Male, n (%)	43 (93.5)
Mean age, years ± SD (range)	76±8.6 (57–92)
Mean FEV1 (L), ± SD (range)	1.41±0.28 (0.5–2.370)
Mean %FEV1 (%), ± SD (range)	54.7±18.1 (26–92.9)
Frequencies of COPD exacerbations n/year (range)	1.5 (1–3)
GOLD Stage, n (%)*
I	2 (4.3)
II	13 (28.3)
III	7 (15.2)
IV	21 (45.7)
Home oxygen therapy, n (%)	21 (45.7)
Current smoker, n (%)	4 (8)
Immunization status
Streptocoocus pneumoniae	23 (50)
Influenza virus	36 (78.3)
Prior antibiotics use	11 (23.9)
Macrolides	6 (13)
Fluoroquinolones	2 (4.3)
Cephalosporins	3 (6.5)
Underline disease,** n (%)
Interstitial pneumonia	2 (4.3)
Diabetes mellitus	4 (8.7)
Ischemic heart disease	4 (8.7)
Arrhythmia	3 (6.5)
Cerebrovascular disease	2 (5.5)
Malignant disease	4 (9)
Psychiatric disease	2 (4.3)

Notes:

* GOLD Stage used, GOLD 2011.¹⁴

** Some overlap exists.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; SD, standard deviation.

Figure 1 Monthly distribution of frequencies of COPD exacerbations for time of year and for pathogens.

Abbreviations: COPD, chronic obstructive pulmonary disease; S. pn, Streptococcus pneumoniae; H. inf, Haemophilus influenzae; FLU, influenza virus; RSV, respiratory syncytial virus; PIV, parainfluenza virus.

Table 2 Identity of pathogens in patients with COPD exacerbation

Pathogen	Comprehensive real-time PCR			Conventional method	Total
	NPS	Sputum	Total
Pathogens detected from samples	25 (50)	24 (48)	32 (64)	26 (52)	44 (88)
Single pathogen	21 (42)	19 (38)	24 (48)	21 (42)	28 (56)
Mixed pathogen	4 (8)	5 (10)	8 (16)	5 (10)	16 (32)
Viral pathogen*	15 (30)	9 (18)	16 (32)	4 (8)	17 (34)
Influenza virus	7 (14)	4 (8)	7 (14)	5 (10)	8 (16)
Influenza virus A	6 (12)	3 (6)	6 (14)	4 (8)	7 (14)
Influenza virus B	1 (2)	1 (2)	1 (2)	1 (2)	1 (2)
Rhinovirus	2 (4)	0 (2)	2 (4)	ND	2 (4)
Respiratory syncytial virus	4 (8)	2 (4)	4 (8)	ND	4 (8)
Respiratory syncytial virus subgroup A	2 (4)	1 (2)	2 (4)	ND	2 (4)
Respiratory syncytial virus subgroup B	2 (4)	1 (2)	2 (4)	ND	2 (4)
Parainfluenza virus	3 (6)	3 (6)	4 (8)	ND	4 (8)
Parainfluenza virus type 1	1 (2)	1 (2)	1 (2)	ND	1 (2)
Parainfluenza virus type 3	2 (4)	2 (4)	3 (6)	ND	3 (6)
Bacterial pathogen*	13 (26)	17 (34)	21 (42)	23 (46)	22 (44)
Streptococcus pneumoniae	7 (14)	11 (22)	11 (22)	10 (20)	13 (26)
Haemophilus influenzae	3 (6)	8 (16)	9 (18)	2 (4)	9 (18)
Mycoplasma pneumoniae	3 (6)	1 (2)	4 (8)	0 (0)	4 (8)
Chlamydophila pneumoniae	1 (2)	0 (0)	1 (2)	0 (0)	1 (2)
Staphylococcus aureus	ND	ND	ND	5 (10)	5 (10)
Enteric/nonfermenting Gram-negative bacilli**	ND	ND	ND	11 (22)	11 (22)
No pathogen detected	25 (50)	26 (52)	18 (36)	24 (48)	6 (12)

Notes: Data are presented as the number (percentage) of patients.

* Some overlap exists.

** Enteric or nonfermenting Gram-negative bacilli, Pseudomonas aeruginosa (4), Enterobacter cloacae (3), Klebsiella pneumoniae (1), Serratia marcescens (1), Proteus mirabilis (1), Acinetobactor baumanii (1), Stenotrophomonas maltophilia (1).

Abbreviations: COPD, chronic obstructive pulmonary disease; ND, not determined; NPS, nasopharyngeal swab; PCR, polymerase chain reaction.

Figure 2 Percentages of pathogens underlying COPD exacerbations.

Notes: *Viruses were as follows: Parainfluenza virus, four cases (8%); influenza virus, three cases (6%); RSV, three cases (6%). **Combined virus and bacterial infections were as follows: influenza virus + Streptococcus pneumoniae, two cases (4%); influenza virus + Mycoplasma pneumoniae, one case (1%); influenza virus + Haemophilus influenzae + M. pneumoniae, one case (1%); RSV + S. pneumoniae, one case (2%); rhinovirus + S. pneumoniae + H. influenzae, one case (2%). ***Mixed bacterial infections were as follows: S. pneumoniae + H. influenzae, one case (2%); Pseudomonas aeruginosa + Citrobactor freundii, one case (2%); P. aeruginosa + Staphylococcus aureus, one case (2%); Enterobacter cloacae + S. aureus, one case (2%); Stenotrophomonas maltophilia + Acinetobacter baumannii, one case (2%); E. cloacae + H. influenzae, one case (2%); S. aureus + H. influenzae, one case (2%); Klebsiella pneumoniae + H. influenzae, one case (2%); E. cloacae + C. pneumoniae, one case (2%). ****Other bacteria were as follows: Proteus mirabilis, one case (2%); Serratia marcesens, one case (2%).
Abbreviations: COPD, chronic obstructive pulmonary disease; RSV, respiratory syncytial virus.

Figure 3 Box-and-whisker plots showing (A) white blood cell (WBC) count and (B) C-reactive protein (CRP) comparing the Streptococcus pneumoniae (S. pn) group, including isolated only S. pneumoniae infection (n=8) with Gram-negative bacilli (GNB) group, including enteric and nonfermenting GNB (n=11); the other bacteria (OthrBac) group, including Haemophilus influenzae, Mycoplasma pneumoniae, and Staphylococcus aureus (n=8); the V-B Mix group, including mixed viral and bacterial infection (n=6); the viral group (n=11); and the not determined (ND) group, in which no pathogen was detected (n=6). Data are presented as median (interquartile range).

Notes: *P<0.005; **P<0.0005.

Table 3 Risk factors for prolonged hospitalization associated with COPD exacerbation

Variable	Hospitalization		P-value
	≤14 days* (n=30)	>14 days** (n=20)
Age >75 years old	18 (60)	10 (50)	0.9621***
Male sex	30 (100)	17 (85)	0.9999****
Albumin <3.5 mg/dL	13 (43.3)	8 (40)	0.8642***
WBC >10,000/µL	14 (46.7)	9 (45)	0.7435***
Home oxygen therapy	9 (30)	12 (60)	0.008***
Streptococcus pneumoniae	9 (30)	4 (20)	0.746****
Haemophilus influenzae	7 (23.3)	2 (10)	0.4589****
Enteric or nonfermentig Gram-negative bacilli	4 (13.3)	7 (35)	0.0406****
Influenza virus	6 (20)	2 (10)	0.6939****

Notes: Data are presented as the number (percentage) of patients.

* Hospitalization ≤14 days, including outpatients;

** hospitalization >14 days, including patients who died;

*** chi-squared test;

**** Fisher’s exact test.

Abbreviations: COPD, chronic obstructive pulmonary disease; WBC, white blood cell.

Table 4 Multivariate analysis of risk factors for prolonged hospitalization associated with COPD exacerbation

Variable	Logistic multivariate analysis*	P-value
	Odds ratio (95% confidence interval)
Age >75 years old	1.055 (0.260–4.275)	0.9404
Male sex	1.301 (0.029–57.586)	0.8919
Albumin <3.5 mg/dL	0.898 (0.216–3.731)	0.8827
WBC >10,000/µL	1.548 (0.391–6.132)	0.5341
Home oxygen therapy	6.232 (1.506–25.784)	0.0115
Enteric or nonfermenting Gram-negative bacilli	5.249 (1.059–26.027)	0.0424

Note:

* Logistic multivariate analysis performed using age, male sex, albumin, home oxygen therapy, WBC, and enteric or nonfermenting Gram-negative bacilli.

Abbreviations: COPD, chronic obstructive pulmonary disease; WBC, white blood cell.

Global Initiative for Chronic Obstructive Lung DiseaseGlobal Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung DiseaseNHLBI/WHO Workshop ReportClaude Lenfant, MDNational Heart, Lung, and Blood Institute2011

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