Influence of Cell Quality on Inflammatory Biomarkers in COPD Sputum Supernatant

Figures & data

Table 1 Influence of Cell Quality Level on Sputum Soluble Biomarker Concentrations, Variability and Cellular Characteristics

Soluble Biomarker		Cell Quality Level			Cell Quality Level			Correlations			Multiple Regr.
		Low	Med.	High	Low	Med.	High
		Geometric Mean			Geometric SD			log SC %	log TCC/mL	log NG/mL	R^2
	n	28	25	101	28	25	101
Alpha-1-Antitrypsin (AAT)	µg/mL	1.20	1.01	1.56	4.3	3.0	2.6	***	***	***	0.21
Alpha-2-Macroglobulin (A2M)	µg/mL	5.26	4.03	4.36	2.3	2.1	1.9				0.09
Beta-2-Microglobulin (B2M)	ug/mL	0.68	0.68	0.83	2.4	2.0	1.9	*		*	0.09
Complement C3 (C3)	µg/mL	0.61	0.55	0.87	9.9	8.5	4.7	**	***	***	0.18
Fibrinogen (FIB)	µg/mL	0.15	0.15	0.13	5.0	4.3	3.7	**	***	***	0.25
Ferritin (FRTN)	ng/mL	3.35	3.56	5.08	4.1	3.1	3.0	***	***	***	0.3
Haptoglobin (Hglob)	µg/mL	0.35	0.32	0.26	8.9	5.4	4.3	**	***	***	0.25
Interleukin-1 alpha (IL1a)	pg/mL	6.76	4.28	3.35	3.0	2.7	2.9			**	0.19
Interleukin-1 beta (IL1b)	pg/mL	39.1	60.0	43.4	3.3	4.8	4.6	***	***	***	0.3
Interleukin-1 receptor antagonist (IL1RA)	ng/mL	4.80	3.51	2.56	2.9	2.0	1.9	***			0.25
Interleukin-6 (IL6)	pg/mL	20.4	37.6	67.9	3.8	3.1	3.4	***			0.13
Interleukin-8 (IL8)	ng/mL	2.84	4.90	5.43	3.8	4.2	3.2	***	***	***	0.24
Macrophage Inflammatory Protein-1 beta (MIP1b)	ng/mL	0.22	0.26	0.30	3.8	3.4	3.8	***	***	***	0.23
Matrix Metalloproteinase-9 (MMP9)	ng/mL	87.2	103.3	155.0	3.5	3.2	3.3	***	***	***	0.41
Monocyte Chemotactic Protein-1 (MCP1)	pg/mL	156.8	221.1	211.7	2.0	2.6	2.6				0.02
T-cell specific protein (Rantes)	pg/mL	15.8	18.8	19.6	2.0	1.8	1.7	***	***	***	0.32
Tissue Inhibitor of Metalloproteinases-1 (TIMP1)	ng/mL	72.7	90.0	126.6	4.5	3.0	1.9	***	***	***	0.26
Tumor Necrosis Factor Receptor-2 (TNFR2)	ng/mL	0.29	0.44	0.57	2.9	3.0	2.7	***	***	***	0.42
Vascular Cell Adhesion Molecule-1 (VCAM1)	ng/mL	1.88	1.73	1.94	2.5	2.3	2.2		***	***	0.19
Vascular Endothelial Growth Factor (VEGF)	ng/mL	0.34	0.34	0.33	2.9	2.5	2.3				0.06
Vitamin D-Binding Protein (VDBP)	ug/mL	0.20	0.14	0.22	3.0	2.7	2.2	**	***	**	0.15
Sputum Cells	n	15	25	101	15	25	101
Macrophages	%NSC	12.5	13.2	13.6	3.9	2.5	2.3			r
Neutrophil granulocytes	%NSC	56.0	70.8	71.7	1.7	1.7	1.4			> 0.5
Eosinophil granulocytes	%NSC	1.3	0.3	0.7	14.3	8.9	8.7			> 0.4
Lymphocytes	%NSC	0.3	0.1	0.4	6.9	7.8	6.1			> 0.3
Non-squamous epithelial cells	%NSC	1.6	0.8	0.4	6.3	9.1	7.3			> 0.2
Monocytes	%NSC	0.02	0.02	0.03	3.1	3.7	5.0			> 0.1
Squamous cells	%	14.4	4.4	1.1	2.8	6.6	5.7			< −0.2
Total cell count/mL sputum	10^6/mL	1.56	2.70	3.88	2.5	3.0	3.0			< −0.3
Viability	%	62.0	81.2	88.8	1.5	1.2	1.1			< −0.4

Notes: ***p<0.001; **p<0.01; *p<0.05. Colored shades indicate Pearsons r correlations coeffients in the respective columns.

Abbreviations: Med, medium; NSC, non-squamous cells; SC%, squamous cells percentage; TCC, total cell count; NG, neutrophil numbers.

Figure 1 Multiple Regression model (Biomarker ~ NG% + SC + TCC/mL + via + Score). The model includes total cell count/mL (TCC/mL), squamous cell contamination (SC), the cell quality score (Score), the percentage of neutrophils in sputum (NG%) and the viability (via). The arrows illustrate the model. The effect of squamous cell contamination (SC) is likely to be indirect, via TCC/mL and/or the cell quality score, indicated by dotted arrow. The biomarkers which were significant with respect to the included factors are listed and the respective format indicates the level of significance (p<0.001; p<0.01; p<0.05). Abbreviations of biomarkers, please see Table 1.