C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity

Figures & data

Table 1 Baseline and clinical characteristics of 118 patients with severe COPD and acute infectious exacerbations

Subjects	N=118
Follow-up (days)	1,003±306
Age (years)	69.5±8.2
Current smoking	13 (11)
Pack-years	63.3±31.9
Alcohol abuse >80 g/L	3 (2.5)
Influenza vaccination	105 (89)
Pneumococcus vaccination	57 (48.3)
Body mass index (kg/m^2)	27.5±4.6
FEV1 post-BD (L)	0.97±0.3
FEV1 post-BD (% predicted)	34±11
GOLD stage IV	71 (60)
BODE score	5.1±1.6
Basal hypercapnia	49 (41.5)
LTOT	50 (42.4)
Charlson Comorbidity Index	4.13±1.5
Bronchiectasis	56 (47.5)

Notes: Data are presented as mean ± SD or n (%), unless otherwise stated. Hypercapnia defined as PaCO₂ >5.9 Kpa.

Abbreviations: BODE, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LTOT, long-term oxygen therapy; m, mean; post-BD, post bronchodilator; SD, standard deviation.

Figure 1 Flowchart for sputum samples included in the study.

Abbreviation: RT-PCR, retrotranscriptase-nested polymerase chain reaction.

Figure 2 Seasonal pattern of virus detection in episodes of acute exacerbation (AE) of COPD (265 episodes analyzed).

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 2 Clinical characteristics and inflammatory biomarkers by microorganism (N=265)*

	HI, n=66	SP, n=28	MC, n=28	PS, n=28	Other, n=17	Negative, n=53	Only virus, n=45	P-value$
Fever (%)+	40	56	36	11.5	33.3	41.7	34.9	0.061
UAS (%)#	26.2	17.9	28.6	5.6	6.0	18.4	25.6	0.315
WBC count, median (IQR)	10,480 (8,560–12,970)	11,500 (9,670–14,740)	9,420 (7,862–9,420)	8,985 (7,927–10,365)	9,250 (6,740–13,250)	10,435 (8,487–11,427)	9,585 (7,230–11,355)	0.039
CRP (mg/L), median (IQR)	74.50 (23.90–167.90)	74.10 (42.0–220.7)	38.10 (20.60–95.40)	45.20 (11.10–70.10)	51.90 (23.60–166.0)	36.40 (10.80–93.70)	37.30 (18.60–79.10)	0.026
Hospital admission (%)	47	60.7	21.4	57	41.1	22.6	37.8	0.002

Notes:

* Primary pathogen included; when more than two bacteria were isolated, the higher bacterial load was analyzed.

+ Missing values: 1 in HI group, 1 in SP, 3 in MC, 2 in PS, 2 in Other, 5 in Negative, and 2 in Only virus.

# Missing values: 1 in HI, 4 in Negative, and 2 in Only virus.

$ Chi-squared across all groups (median test in case of continuous variables).

Abbreviations: CRP, C-reactive protein; HI, Haemophilus influenzae; IQR, interquartile range; MC, Moraxella catarrhalis; PS, Pseudomonas aeruginosa; SP, Streptococcus pneumoniae; UAS, upper airway symptoms; WBC, white blood cell.

Figure 3 Relationship between bacterial load and CRP (Spearman’s correlation coefficient rho =0.92; P=0.006 in exacerbations due to S. pneumoniae).

Abbreviations: cfu, colony forming units; CRP, C-reactive protein; H. influenzae, Haemophilus influenzae; M. catarrhalis, Moraxella catarrhalis; P. aeruginosa, Pseudomonas aeruginosa; S. pneumoniae, Streptococcus pneumoniae.

Table 3 Markers of exacerbation severity (N=380)

	Reference values	Community-managed, n=227	Hospital admitted, n=153	P-value*
CRP	<5 mg/L	37.3 (12.8–82.7)	67.4 (27.0–189.0)	<0.0001
WBC count	4,000–11,000	9,900 (7,860–11,460)	10,030 (8,500–14,002)	0.001
RR	12–16 breath/min	24 (20–28)	26 (24–30)	0.002
SaO2	96%–100%	94 (92–95)	89 (85–92)	<0.0001
PaO2+	10.6–13.3 KPa	7.9 (7.3–8.6)	7.0 (6.2–7.6)	0.002
PaCO2+	4.6–5.9 KPa	5.7 (5.2–6.6)	6.2 (5.4–7.5)	0.001
pH+	7.35–7.45	7.42 (7.40–7.44)	7.41 (7.39–7.44)	0.443

Notes:

* Univariate generalized estimating equation.

+ Only obtained in 197 episodes. Data presented as median (interquartile range).

Abbreviations: CRP, C-reactive protein; IQR, interquartile range; min, minutes; RR, respiratory rate; WBC, white blood cell.

Table 4 Analysis of factors associated with hospital admission. Results of univariate and multivariate GEE

	OR (95% CI)	P-value	OR (95% CI)	P-value
GOLD stage IV	1.28 (0.75–2.18)	0.36	–	–
Charlson Comorbidity Index	1.15 (0.95–1.40)	0.14	1.12 (0.95–1.32)	0.15
Bronchiectasis	1.39 (0.78–2.47)	0.26	–	–
BODE	1.13 (0.93–1.37)	0.21	–	–
LTOT	1.89 (1.08–3.32)	0.02	1.14 (0.61–2.13)	0.67
Baseline hypercapnia	2.69 (1.56–4.64)	<0.0001	2.70 (1.46–4.9)	0.01
CRP (mg/L)
<18.6	1		1
18.7–47.7	1.74 (0.91–3.33)	0.09	1.64 (0.85–3.15)	0.13
47.8–100	2.56 (1.25–5.24)	0.01	2.21 (1.05–4.68)	0.03
>100	4.44 (2.25–8.78)	<0.0001	4.23 (2.12–8.44)	<0.0001

Note: CRP data is presented as quartiles.

Abbreviations: BODE, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index; CI, confidence interval; CRP, C-reactive protein; GEE, generalized estimating equation; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LTOT, long-term oxygen therapy; OR, odds ratio.