A Novel Metabolic Score for Predicting the Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease

Figures & data

Figure 1 Metabolomics-based serum metabolite screening workflow.

Table 1 Clinical Characteristics of Patients with COPD and Control Population in the Study

		COPD	AECOPD	P value	Health Control	P value
Age (ys)		72 (54–88)	70 (58–86)	0.95	69 (49–89)	0.87
Male, n (%)		30 (100%)	30 (100%)		30 (100%)
BMI		21.5 (14.5–28.2)	20.9 (13.2–28.8)	0.18	21.4 (18.5–22.6)	0.25
Smoking		80% (24/30)	87% (26/30)	0.38	17% (5/30)	<0.05*
FVC(L)		1.79 (0.88–3.40)	1.39 (0.48–3.31)	0.008*	3.16 (0.88–3.40)	<0.05*
FVC% pred		49.4 (27.2–103.7)	33.2 (20.2–83.7)	<0.05*	92 (88.2–107.9)	<0.05*
FEV1(L)		1.33 (0.56–2.36)	1.10 (0.36–2.06)	<0.05*	2.42 (2.06–3.16)	<0.05*
FEV1% pred		51.8 (19.8–92.1)	39.8 (16.8–72.1)	<0.05*	90.8 (82.9–99.1)	<0.05*
FEV1/FVC%		50.29 (41.07–69.49)	50.36 (40.14–66.98)	0.65	83.29 (80.23–90.43)	<0.05*
CRP (mg/L)		7.8 (2.8–12.2)	9.1 (5.5–13.7)	<0.05*	3.2 (1.3–6.3)	<0.05*
WBC count (×10^9/L)		8.1 (7.6–8.7)	9.3 (8.6–9.9)	<0.05*	5.1 (3.5–9.5)	<0.05*
PNC (×10^9/L)		5.2 (5.0–5.7)	6.3 (6.1–6.7)	<0.05*	2.2 (1.8–5.9)	<0.05*
PEC (×10^9/L)		0.02 (0.01–0.08)	0.02 (0.01–0.09)	0.84	0.00 (0.00–0.10)	0.50
Comorbidity		43% (13/30)	46% (14/30)	0.39	——	——
Therapy history	ICS	2	1	0.93	——	——
	LAMA	7	10	0.48	——	——
	LAMA combination	12	21	0.32	——	——
	Others	4	3	0.67	——	——

Note: *Indicates statistical significance with P<0.05.

Abbreviations: BMI, body mass index; FEV, forced expiratory volume in first second; FEVl%pred, percentage of FEVl in predicted value LL; FEVl/FVC%, forced expiratory volume in first second occupied forced vital capacity ratio; WBC, white blood cell; PEC, Peripheral eosinophil count; PNC, peripheral neutrophil count; ICS, inhaled corticosteroids; LAMA, long-acting muscarine anticholinergic.

Table 2 A Multivariable Logistic Regression Analysis on the Acute Exacerbation of COPD

Variants	P value	OR	95% CI
CRP	0.028*	2.081	1.243~3.891
WBC	0.004*	1.720	1.260~2.872
PNC	0.026*	1.982	1.093~3.702

Note: *Indicates statistical significance with P<0.05.

Abbreviations: CRP, C reactive protein; WBC, white blood cell count; PNC, peripheral neutrophil count.

Figure 2 (A) Heatmap of metabolite levels in COPD patients including AECOPD and COPD compared to control population. (B) Different metabolites among AECOPD, COPD and controls. (C) Compared with healthy controls, 12 metabolic pathways were significantly altered in COPD patients. (D) Compared with the stable COPD, 8 metabolic pathways were significantly altered in AECOPD patients. (E and F) Enrichment analysis on these differential metabolites showed they can also be expectedly enriched in energy metabolism and nucleotide metabolism. (G) The metabolite-pathway network was constructed using Gephi software.

Table 3 Analysis for the Association Between M-Score and Characteristics of Patients with COPD

Characteristics	M-Score				P value
	1 (n=11)	2 (n=18)	3 (n=23)	4 (n=8)
Age (ys)	68 (55–82)	70 (61–86)	69 (49–89)	68 (53–81)	0.92
BMI	21.2±2.39	22.0±2.66	20.8±2.13	22.1±3.12	0.66
Smoking	83%	75%	89%	66%	0.37
FVC(L)	1.69	2.42	2.83	2.98	0.063
FVC% pred	52.6	61.2	82.1	90.8	<0.05*
FEV1(L)	1.32	1.61	1.42	2.51	<0.05*
FEV1% pred	52.6	63.2	88.6	93.6	<0.05*
FEV1/FVC%	50.3	53.4	57.3	56.8	0.62
CRP (mg/L)	5.2	5.8	5.4	6.2	0.25
WBC count (×10^9/L)	8.0	8.3	8.9	9.6	0.087
PNC (×10^9/L)	5.1	5.6	6.8	5.8	0.092
PEC (×10^9/L)	0.02	0.02	0.02	0.01	0.88
Comorbidity (CVD)	56%	48%	68%	73%	<0.05*

Note: *Indicates statistical significance with P<0.05.

Abbreviations: BMI, body mass index; FEV, forced expiratory volume in first second; FEVl%pred, percentage of FEVl in predicted value LL; FEVl/FVC%, forced expiratory volume in first second occupied forced vital capacity ratio; WBC, white blood cell; PEC, Peripheral eosinophil count; PNC, peripheral neutrophil count.

Figure 3 (A–D) The levels of pyruvate, isoleucine, 1-methylhistidine and glutamine between AECOPD and COPD were quantitatively compared. (E) The related level index among the four metabolites were calculated and a metabolite score based on the related level index was constructed through applying a weighted sum of concentrations of 4 metabolites. (F) The correlation between stable COPD and AECOPD patients with pulmonary ventilation function and symptoms was analyzed by using a Pearson correlation coefficient.