Correlation of serum levels of HIF-1α and IL-19 with the disease progression of COPD: a retrospective study

Figures & data

Table 1 Clinical information and general data of included patients (80 cases)

Items	Classification	COPD group (N, %)	Control group (N, %)
Gender	Male	49 (61.3)	22 (43.1)
	Female	31 (38.7)	29 (56.9)
Age (years)	<70	36 (45)	30 (58.8)
	≥70	44 (55)	21 (41.2)
Pack years of smoking	>40	28 (35)	15 (29.4)
	20.1–40	10 (12.5)	6 (11.8)
	0.1–20	3 (3.8)	1 (1.9)
	0	39 (48.7)	29 (56.9)
GOLD grade	1	5 (6.2)
	2	16 (20)
	3	32 (40)
	4	27 (33.8)
mMRC score	2	11 (13.8)
	3	35 (43.7)
	4	34 (42.5)
Clinical history (years)	<10	27 (33.7)
	≥10 <20	23 (28.8)
	≥20	30 (37.5)

Notes: GOLD grade: 1=FEV₁% predicted is greater than or equal to 80%, 2=FEV₁% predicted is greater than or equal to 50%, but less than 80%, 3=FEV₁% predicted is greater than or equal to 30%, but less than 50%, and 4=FEV₁% predicted is less than 30%; mMRC, dyspnea scale for symptom classification of COPD.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council for dyspnea scale for symptom classification of COPD.

Table 2 Relationship between clinical parameters and the level of HIF-1α in serum of stable COPD patients (n=80)

Parameter	Group	N	Level of HIF-1α in serum of stable COPD patients
			Value (M ± SD pg/mL)	Degrees of freedom	Statistical value	P-value
Resources	Control	51	63.2±16.8	129	6.976	<0.001
	Stable COPD	80	91.9±20.4
Gender	10.332 pt	49	90.9±20.0	78	−0.526	0.600
	Female	31	93.4±21.2
Age (years)	<70	36	90.6±20.0	78	−0.510	0.612
	≥70	44	92.9±20.6
Pack years of smoking	>40	28	94.1±16.1	78	0.631	0.392
	20.1–40	10	90.2±19.3
	0.1–20	3	88.2±21.7
	0	39	89.9±22.6
GOLD grade	1	5	85.8±25.8	3	7.115	<0.001
	2	16	90.7±12.4
	3	32	103.6±22.9⋆
	4	27	114.3±14.9⋆
mMRC score	2	11	85.6±15.5	2	5.373	0.007
	3	35	105.8±21.3⋆⋆
	4	34	106.9±18.7⋆⋆
Medical history (years)	<10	27	94.9±18	2	5.062	0.009
	≥10 to <20	23	103.3±25.2
	≥20	30	111.4±15.6⋆⋆⋆

Notes:

⋆ The level of HIF-1α in stable COPD patients with GOLD grades 3 and 4 was significantly higher than that in patients with GOLD grades 1 and 2.

⋆⋆ The patients with mMRC scores of 3 and 4 showed a higher expression level of serum HIF-1α than those with mMRC score of 2.

⋆⋆⋆ The expression of serum HIF-1α in the patients with a longer history was also upregulated compared to those with relatively short history.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; HIF-1α, hypoxia-inducible factor 1 alpha; mMRC, modified British Medical Research Council.

Figure 1 Relationship between the clinical parameters and serum level of HIF-1α in stable COPD patients.

Notes: (A) ^⋆Patients with stable COPD showed a higher expression of serum HIF-1α compared with control group (P<0.001). (B) Serum HIF-1α expression did correlate with the patient’s age (P=0.612). (C) Serum HIF-1α expression did correlate with the patient’s smoking status (P=0.392). (D) ^⋆⋆Serum HIF-1α level of patients with GOLD 3 and 4 was increased compared with that of GOLD 1 and 2 (P<0.001). (E) ^♦The patients with mMRC scores of 3 and 4 showed a higher serum level of HIF-1α compared with those with mMRC score of 2 (P=0.007). (F) ^♦♦Serum HIF-1α in the patients with longer clinical history was increased compared to those with short history (P=0.009).
Abbreviations: HIF-1α, hypoxia-inducible factor 1 alpha; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council.

Table 3 Relationship between the clinical parameters and the serum level of IL-19 in stable COPD patients (n=80)

Parameter	Group	N	Level of IL-19 in serum of stable COPD patients
			Value (M ± SD pg/mL)	Degrees of freedom	Statistical value	P-value
Resources	Control	51	43.1±12.6	129	−6.223	<0.001
	Stable COPD	80	70.2±16.6
Gender	Male	49	70.5±17.9	78	0.202	0.841
	Female	31	69.8±14.2
Age (years)	<70	36	66.8±17.2	78	−1.671	0.099
	≥70	44	72.9±15.7
Pack years of smoking	>40	28	74.2±16.9	78	0.56	0.110
	20.1–40	10	71.8±16.1
	0.1–20	3	72.4±17.9
	0	39	66.9±15
GOLD grade	1	5	55.3±11.1	3	4.874	0.004
	2	16	62.7±17.7
	3	32	70.1±15.2⋆
	4	27	77.6±14.9⋆
mMRC score	2	11	58.6±14.6	2	9.453	<0.001
	3	35	66.3±15.1
	4	34	78.4±15⋆⋆
Clinical history (years)	<10	27	62.5±16.6	2	6.86	0.002
	≥10 to <20	23	69.6±14.9
	≥20	30	77.6±14.7⋆⋆⋆

Notes:

⋆ The level of IL-19 in stable COPD patients with GOLD grades 3 and 4 was significantly higher than that in patients with GOLD grades 1 and 2;

⋆⋆ Patients with mMRC score of 4 showed a higher expression level of serum IL-19 than those with mMRC scores of 3 and 2;

⋆⋆⋆ The expression of serum IL-19 in patients with long clinical history was also upregulated compared to those with relatively short history.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council.

Figure 2 Relationship between the clinical parameters and serum level of IL-19 in serum of stable COPD patients.

Notes: (A) ^⋆Patients with stable COPD showed a higher expression of serum IL-19 compared with the control group (P<0.001). (B) Serum IL-19 expression did correlate with the patient’s age (P=0.841). (C) Serum IL-19 expression did correlate with the patient’s smoking status (P=0.110). (D) ^⋆⋆Serum IL-19 level of patients with GOLD 3 and 4 of COPD was increased compared with those of GOLD 1 and 2 (P=0.004). (E) ^♦The patients with mMRC scores of 3 and 4 showed a higher serum level of IL-19 compared with those with mMRC score of 2 (P<0.001). (F) ^♦♦Serum IL-19 in patients with longer medical history was increased compared to those with short history (P=0.002).
Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council.

Table 4 Correlation analysis of important observed values (n=80)

Items	Linear correlation analysis of continuous variables
	Correlations		Variance analysis			Coefficients
	Pearson correlation	P-value	R square	F-value	P-value	Regression coefficient	T-value	P-value	95% CI	Equation
HIF-1α and IL-19	0.347	0.001	0.120	10.67	0.002	0.279	3.26	0.002	0.109–0.339	^∧Y=41+0.28X
HIF-1α and FEV1/FVC	−0.595	<0.001	0.355	42.73	<0.001	−88.89	−6.53	<0.001	−115.96 to −61.82	^∧Y=142-88.89X
HIF-1α and FEV1% predicted	−0.555	<0.001	0.308	34.64	<0.001	−63.65	−5.88	<0.001	−85.19 to −42.12	^∧Y=130-63.66X
IL-19 and FEV1/FVC	−0.397	<0.001	0.158	14.59	<0.001	−47.71	−3.82	<0.001	−75.58 to −22.84	^∧Y=90-47.71X
IL-19 and FEV1% predicted	−0.424	<0.001	0.180	17.13	<0.001	−39.18	−4.13	<0.001	−58.03 to −20.33	^∧Y=86-39.18X

Abbreviation: HIF-1α, hypoxia-inducible factor 1 alpha.

Figure 3 Relationship between serum levels of HIF-1α and IL-19 in stable COPD patients.

Notes: (A) The histogram of normal curve showed that the normalized residuals are normal distributions (P>0.05). (B) The cumulative probability plot of the observations suggested that the two variables have a feature of normal distribution (P<0.05). (C) The dependent variable is approximately linear with the standardized predictive value, indicating that HIF-1α and IL-19 have a linear correlation (P>0.05). (D) The vast majority of normalized residuals did not exceed 3, suggesting no specific value was found.
Abbreviations: cum prob, cumulative probability; HIF-1α, hypoxia-inducible factor 1 alpha.

Figure 4 Relationship between serum level of HIF-1α and pulmonary function in patients with stable COPD.

Notes: (A) The scatter point plot for HIF-1α and FEV₁/FVC indicated that the two variables belonged to normal distribution (P>0.05). (B) The dependent variable is approximately linear with the standardized predictive value, indicating that serum HIF-1α and FEV₁/FVC of patients have a linear correlation (P<0.05). (C) The scatter point plot for HIF-1α and FEV₁% predicted indicated that the two variables belonged to normal distribution (P>0.05). (D) The dependent variable is approximately linear with the standardized predictive value, indicating that serum HIF-1α and FEV₁% predicted of patients have a linear correlation (P<0.05).
Abbreviations: cum prob, cumulative probability; HIF-1α, hypoxia-inducible factor 1 alpha.

Figure 5 Relationship between the serum level of IL-19 and pulmonary function in patients with stable COPD.

Notes: (A) The scatter point plot for IL-19 and FEV₁/FVC indicated that the two variables belonged to normal distribution (P>0.05). (B) The dependent variable is approximately linear with the standardized predictive value, indicating that serum IL-19 and FEV₁/FVC of patients had a linear correlation (P<0.05). (C) The scatter point plot for IL-19 and FEV₁% predicted indicated that the two variables belonged to normal distribution (P>0.05). (D) The dependent variable is approximately linear with the standardized predictive value, indicating that serum IL-19 and FEV₁% predicted that patients had a linear correlation (P<0.05).
Abbreviation: cum prob, cumulative probability.

Table 5 Multiple linear regression analysis to determine the factors that affect the serum levels of HIF-1α and IL-19 (n=80)

	Model	Multiple linear regression analysis for HIF-1α and IL-19
		Unstandardized coefficients		Variance analysis		Standardized coefficients	T-value	P-value	95% CI for B
		Partial regression analysis (B)	Std. error	F-value	P-value	Beta value			Lower bound	Upper bound
The factors that affect HIF-1α	FEV1/FVC	−140.21	30.82	42.732	<0.001	−0.938	−4.56	<0.001	−201.58	−78.82
	GOLD grading	8.781	4.75			0.381	1.85	0.046	18.34	67.92
The factors that affect IL-19	mMRC scores	8.988	2.431	13.033	<0.001	0.379	3.697	<0.001	4.146	13.829
	HIF-1α	0.195	0.082			0.243	2.367	0.020	0.031	0.359

Abbreviations: HIF-1α, hypoxia-inducible factor 1 alpha; mMRC, modified British Medical Research Council; Std., standard.

Figure 6 The clinical factors that affect the serum levels of HIF-1α and IL-19 in stable COPD.

Notes: (A) The patient’s FEV₁/FVC and COPD grading correlated with the expression of HIF-1α (P<0.05). (B) Scatterplot suggested that the influence of FEV₁/FVC on the expression of HIF-1α was greater than that of GOLD grading. (C) The patient’s mMRC scores and HIF-1α correlated with the expression of IL-19 (P<0.05). (D) Scatterplot suggested that the influence of HIF-1α on the expression of IL-19 was greater than that of mMRC scores.
Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; HIF-1α, hypoxia-inducible factor 1 alpha; mMRC, modified British Medical Research Council.