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

Abstract

Background: The aim of this study was to disclose the correlation between the serum levels of hypoxia-inducible factor 1 alpha (HIF-1α) and IL-19 and stable COPD.

Methods: The serum levels of HIF-1α and IL-19 were tested by ELISA. The relationships between their levels and clinical parameters of stable COPD patients were analyzed by linear regression methods.

Results: Patients with stable COPD showed higher serum levels of HIF-1α and IL-19 compared with healthy control group (P<0.001), and serum levels of HIF-1α and IL-19 had a positive linear correlation (P<0.05). In stable COPD patients, increased serum levels of HIF-1α and IL-19 were positively correlated with the GOLD grading (P<0.005), modified British Medical Research Council (mMRC) score (P<0.05), and medical history (P<0.05) but negatively related to the pulmonary function (P<0.05). The serum level of HIF-1α (P<0.05) was affected by the patient's FEV₁/FVC value and COPD grading, and the serum level of IL-19 was associated with the mMRC scores and the serum level of HIF-1α (P<0.05).

Conclusion: Increased serum levels of HIF-1α and IL-19 correlated with the disease progression of COPD, suggesting that they can be used as indicators to help us understand the COPD.

Keywords: COPD; chronic obstructive pulmonary disease; hypoxia-inducible factor 1 alpha; interleukin-19; pulmonary function; serum.

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.

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.

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.

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.

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.