Lymphocyte-HDL Ratio Outperforms Other Biomarkers for Predicting Pulmonary Function in COPD

Investigators found that the ratio of lymphocytes to high-density lipoprotein (HDL) performed better in predicting pulmonary function than the neutrophil-lymphocyte ratio and the platelet-lymphocyte ratio.

Lymphocyte to high-density lipoprotein ratio (LHR) was a better predictor of pulmonary function and more severe airway obstruction in chronic obstructive pulmonary disease (COPD) than other inflammatory biomarkers, according to a recent study published in the International Journal of Chronic Obstructive Pulmonary Disease. Additionally, lower LHR levels were independently associated with poorer lung function.

“Our preliminary study could provide reference for clinicians to judge rapidly the pulmonary function of COPD patients,” wrote the authors.

Lymphocytes and neutrophils interact to cause inflammation associated with COPD. This can affect the lung parenchyma and peripheral airways, leading to irreversible and progressive airflow limitations for patients with COPD.

Previous research has investigated the neutrophil-lymphocyte ratio (NLR) as a promising marker for systemic inflammation, acute exacerbations, and mortality in patients with COPD. The platelet-lymphocyte ratio (PLR) may also be a potential marker for chronic inflammation and COPD disease severity.

However, NLR and PLR have not been shown to have credible relationships with pulmonary function, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), suggesting that a better biomarker of pulmonary function is needed.

Investigators aimed to establish whether LHR, the ratio of lymphocyte counts to serum high-density lipoprotein (HDL) levels, is correlated with pulmonary function in patients with COPD and compare its predictive ability with that of NLR and PLR.

Between February 2018 and February 2019, investigators conducted a cross-sectional study among 134 patients with COPD who were enrolled from the respiratory ward of the Third Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. After applying inclusion and exclusion criteria, the investigators included 77 patients in the study.

All patients were 40 years or older and had a diagnosis of COPD with a GOLD stage of 2 or higher, as defined in the GOLD guidelines, with symptoms of dyspnea, chronic cough, sputum production, or wheezing. Patients were age- and sex-matched with 77 healthy controls.

Investigators found that patients with COPD had a higher neutrophil count (P < .001), NLR (P < .001), and PLR (P < .001), but they had lower levels of lymphocytes (P < .001) and HDL (P < .001).

Further, patients were categorized into 3 groups according to their percentage of forced expiratory volume in 1 second (FEV1%), a measurement of airflow limitation. Groups with more severe airflow limitations were often younger and had lower lymphocyte counts and a lower LHR than the group with more severe limitations (P = .003, P = .009, and P < .001, respectively). Additionally, HDL levels were higher among patients with more severe limitations (P = .028).

Investigators said the lower lymphocyte counts could be due to aging, which can lead to increases in cortisol production and a decrease in lymphocyte count; impaired immunity, which can increase the risk of respiratory tract infections that can cause exacerbations; or malnutrition, which is positively correlated with COPD severity and is associated with low lymphocyte counts.

Although patients with a FEV1% of at least 50 had a significantly higher LHR than those with lower FEV1% (FEV1% 30-<50: P = .002; FEV1% <30: P < .001), no differences in NLR or PLR were observed across the pulmonary function severity groups. Investigators concluded that LHR was positively correlated with FEV1% (r = .0333; P = .003), whereas NLR and PLR were not.

Patients with a low LHR (LHR < 1.42; n = 39) had worse health-related quality of life as measured by the St George’s Respiratory Questionnaire and more severe air flow limitation. Of the patients with a low LHR, 87.2% had poor pulmonary function (FEV1% < 50). In contrast, 65.8% of patients in the high-LHR group (LHR ≥ 1.42; n = 38) had poor lung function (P = .006).

Investigators said that because their study was a single-center cross-sectional survey limited to a small retrospective cohort and lacked exploration of the cellular and molecular mechanisms that influence the effect of LHR on COPD, more research needs to be conducted in this area.


Huang Y, Jiang B, Maio X, et al. The relationship of lymphocyte to high-density lipoprotein ratio with pulmonary function in COPD. Int J Chron Obstruct Pulmon Dis. 2020;15:3159-3169. doi:10.2147/COPD.S276372