Chronic obstructive pulmonary disease (COPD) is a disabling condition that is characterised by poorly reversible airflow limitation and inflammation Acute exacerbations of COPD are a common cause of hospitalisation and death among COPD patients Several biochemical markers have been studied as outcome predictors in COPD; however, their measurement often requires significant time and resources Relatively simple biomarkers of inflammation calculated from routine complete blood count tests, such as the neutrophil to lymphocyte ratio (NLR), might also predict COPD progression and outcomes This review discusses the available evidence from studies investigating the associations between the NLR, COPD exacerbations and death in this patient group

https://err.ersjournals.com/content/errev/27/147/170113.full.pdf

Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives.

BACKGROUND AND OBJECTIVES Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the leading causes of hospitalization and is associated with considerable mortality, for which clinicians are seeking useful and easily obtained biomarkers for prognostic evaluation. This study aimed to determine the potential role of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as prognostic makers for hospital mortality in patients with AECOPD. METHODS We included 303 patients with AECOPD in this retrospective study. Clinical characteristics, NLR, PLR, and serum levels of C-reactive protein (CRP) and other data were collected. Relationships between NLR/PLR and CRP were evaluated by Pearson's correlation test. Receiver operating characteristics curve and the area under the curve (AUC) were used to assess the ability of NLR and PLR to predict hospital mortality in patients with AECOPD. RESULTS Mean levels of NLR and PLR of all patients with AECOPD were 7.92±8.79 and 207.21±148.47, respectively. NLR levels correlated with serum CRP levels (r=0.281, P<0.05). The overall hospital mortality rate was 12.21% (37/303). Levels of NLR and PLR were signifi-cantly higher among non-survivors compared to survivors of AECOPD (both P<0.05). At a cut-off value of 6.24, the sensitivity and specificity of the NLR in predicting hospital mortality were 81.08% and 69.17%, respectively, with an AUC of 0.803. At a cut-off of 182.68, the corresponding sensitivity, specificity and AUC of PLR were 64.86%, 58.27%, and 0.639. The combination of NLR, PLR, and CRP increased the prognostic sensitivity. CONCLUSION NLR and PLR levels were increased in non-survivor patients with AECOPD, and the NLR may be simple and useful prognostic marker for hospital mortality in patients with AECOPD. More studies should be carried out to confirm our findings.

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Prognostic role of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio for hospital mortality in patients with AECOPD.

Chronic obstructive pulmonary disease (COPD) is a disease characterised by persistent airflow limitation that is not fully reversible and is currently the fourth leading cause of death globally. It is now well established that cardiovascular-related comorbidities contribute to morbidity and mortality in COPD, with approximately 50% of deaths in COPD patients attributed to a cardiovascular event (e.g. myocardial infarction). Cardiovascular disease (CVD) and COPD share various risk factors including hypertension, sedentarism, smoking and poor diet but the underlying mechanisms have not been fully established. However, there is emerging and compelling experimental and clinical evidence to show that increased oxidative stress causes pulmonary inflammation and that the spill over of pro-inflammatory mediators from the lungs into the systemic circulation drives a persistent systemic inflammatory response that alters blood vessel structure, through vascular remodelling and arterial stiffness resulting in atherosclerosis. In addition, regulation of endothelial-derived vasoactive substances (e.g. nitric oxide (NO)), which control blood vessel tone are altered by oxidative damage of vascular endothelial cells, thus promoting vascular dysfunction, a key driver of CVD. In this review, the detrimental role of oxidative stress in COPD and comorbid CVD are discussed and we propose that targeting oxidant-dependent mechanisms represents a novel strategy in the treatment of COPD-associated CVD.

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New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease.

https://hub.hku.hk/bitstream/10722/279900/1/content.pdf

Environmental correlates of chronic obstructive pulmonary disease in 96 779 participants from the UK Biobank: a cross-sectional, observational study

BACKGROUND Blood biomarkers are easily accessible and might reflect chronic obstructive pulmonary disease (COPD) activity. AIM The aim of this study was to determine whether a panel of blood biomarkers [C-reactive protein (CRP), neutrophils, eosinophils, albumin and vitamin D] could predict mortality in COPD. METHODS We analyzed data from 431 COPD participants to the 2007-2010 National Health and Nutrition Examination Surveys who were followed for a median time of 36 months. COPD was defined as post-bronchodilator forced expiratory volume in 1 second (FEV1) and forced vital capacity ratio <0.70. Weibull survival analysis adjusted for covariates was performed to calculate the risk of mortality associated with the biomarkers, and C-statistics was used to assess their added predictive value. RESULTS During follow-up, 38 of the 431 participants died. Participants with high CRP, eosinophil count <2%, hypoalbuminemia and hypovitaminosis D had worse baseline FEV1 and subsequently higher mortality compared to controls. In adjusted analysis, increasing CRP [hazard ratio (HR): 4.45, 95% CI: 1.91-10.37] and neutrophil count (HR: 1.07, 95% CI: 1.03-1.11) as well as decreasing eosinophil count (HR: 7.03, 95% CI: 2.05-24.01) were associated with an increased risk of mortality. The addition of CRP with eosinophil and/or neutrophil count significantly improved a base model for the prediction of mortality which included age, gender, race/ethnicity, body mass index, smoking, poverty income ratio, asthma, diabetes, hypertension and history of stroke or myocardial infarction. CONCLUSION High CRP and neutrophils as well as low eosinophils are predictive of poor COPD prognosis. They also add significant value to prediction models of mortality in COPD.

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Blood biomarkers as predictors of long-term mortality in COPD.

Background The major characteristic of COPD is systemic inflammation. The parameters such as neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-basophil ratio (EBR) in routine blood test (RBT) are considered to be the underlying biomarkers of inflammation. We hypothesized that the prognosis of patients with COPD can be predicted with RBT. Methods Patients with COPD in stable stage were enrolled. The RBT, pulmonary function testing (PFT), BODE index, C-reactive protein (CRP), procalcitonin, and erythrocyte sedimentation rate (ESR) were performed at enrollment and every follow-up once in every 3 months during the 24-month follow-up period. Meanwhile, exacerbation count and mortality incidence were recorded. The correlation between the prognostic biomarkers and the prognosis of patients was analyzed. Results The NLR and EBR in RBT have a significant correlation with the severity of patients with COPD. The NLR is an independent predictor for mortality and the EBR is an independent predictor for exacerbation. Conclusion As an inexpensive, accessible, and convenient assay, RBT may be used as a practical means in the prediction of prognosis of patients with COPD in future clinical settings.

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Can we predict the prognosis of COPD with a routine blood test

// Wei Xiong 1, * , Yunfeng Zhao 2, * , Mei Xu 3 , Jian Guo 4, * , Bigyan Pudasaini 1 , Xueling Wu 5 and Jinming Liu 1 1 Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 2 Department of Respiratory Medicine, Punan Hospital, Pudong New District, Shanghai, China 3 Department of Respiratory Medicine, Gongli Hospital, Pudong New District, Second Military Medical University, Shanghai, China 4 Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 5 Department of Respiratory Medicine, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China * Joint first authors Correspondence to: Jinming Liu, email: jinmingliu2013@126.com Keywords: tumor markers, pulmonary embolism, lung cancer, panel of combined tumor markers, CEA Received: March 06, 2017      Accepted: May 01, 2017      Published: May 17, 2017 ABSTRACT Background: Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. Results: The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend < 0.001), CEA (R2 0.735, P0.003) and CYFRA21-1 (R2 0.718, P0.005) were positively correlated with D-Dimer in patients with pulmonary embolism. The multivariate logistic regression analysis showed that, for tumor markers, TMs panel (OR5.98, P < 0.001) had the strongest correlation with pulmonary embolism. The AUC (area under curve) of TMs panel and CEA were 0.82 [95%CI (0.71–0.95), P < 0.001] and 0.71 [95%CI (0.62–0.84), P 0.002] by ROC (receiver operating characteristic) curve analysis, respectively. Materials and Methods: Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. Conclusions: There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

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The relationship between tumor markers and pulmonary embolism in lung cancer.

Immunotherapy is a major breakthrough in the treatment of cancer in recent years. Immune checkpoint inhibitors (ICIs) including programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have been used for different histologic types of cancer including primary lung cancer that represents the most common and fatal cancer globally. Among ICI immunotherapy agents, atezolizumab, durvalumab, ipilimumab, nivolumab, and pembrolizumab are currently used as standard-of-care (SOC) treatment for metastatic or earlier stages of lung cancer. Major issues of ICI immunotherapy in lung cancer comprise the use of immune biomarkers prior to ICI therapy, selection of ICI agents, combination of ICIs/chemotherapy, combination of ICIs/radiotherapy, sequence of tyrosine kinase inhibitor (TKI) targeted therapy and ICI immunotherapy, sequence of chemotherapy and ICI immunotherapy, treatment duration of ICI regimen and ICI therapy for different histopathology, stage, PD-L1, and performance status. Based on the contemporary major clinical trials and authoritative guidelines, the objective of this review is to present an overview of the current status of ICI immunotherapy in lung cancer.

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Current Status of Immune Checkpoint Inhibitor Immunotherapy for Lung Cancer.

Risk assessment of pulmonary arterial hypertension (PAH) contributes to its management. Unfortunately, the existing risk assessment approaches are defective for clinicians to practice in daily clinical settings to some extent. We designed a modified Risk Assessment Score of PAH (mRASP) comprising four non-invasive variables which were World Health Organization functional class(WHO FC), 6-min walk distance (6MWD), N-terminal of the pro-hormone brain natriuretic peptide(NT-pro BNP), and right atrial area(RAA), then validated it in the prediction of one-year survival rate for patients with PAH by contrast with the REVEAL risk score. For the validation cohort(n = 216), the predicted one-year survival rate were 95–100%, 90–95%, and < 90% in the mRASP risk score strata of 0–2, 3–5, and 6–8, respectively; meanwhile, the observed one-year survival rates were 97.1, 92.6, and 52.2%, in each corresponding stratum, respectively. The mRASP (c-index = 0.727) demonstrated similar predictive power in contrast with the REVEAL risk assessment score (c-index = 0.715) in the prediction of one-year survival rate. The mRASP is an eligible risk assessment tool for the prognostic assessment of PAH. In contrast with the REVEAL score, it demonstrated similar predictive power and accuracy, with extra simplicity and convenience.

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A modified risk score in one-year survival rate assessment of group 1 pulmonary arterial hypertension.

Background: The Chinese government has promoted the ‘tiered medical services’ policy in which diseases are classified by severity, mode of onset and difficulty of treatment since 2015 to optimize medical resources. We evaluated the diagnosis and treatment of acute exacerbation (AE) of chronic obstructive pulmonary disease (AECOPD) under the tiered system. Methods: We conducted a cross-sectional study. COPD characteristics and treatments were compared among hospitals in different tiers. Associations were examined by univariate and multivariable logistic regression analysis. In addition, multivariate logistic regression was performed to identify the possible influencing factors of antibiotics, glucocorticoids and anticoagulant usages. Results: Eligible COPD patients (n = 432) were consecutively recruited from eight hospitals in different tiers in China. Patients in the countryside preferred the community hospitals, whereas patients in cities preferred second-tier and teaching hospitals when they suffer from AECOPD. It indicates most COPD patients are likely to treat their disease locally. The severity of COPD AE increased with tiers of hospitals (p < 0.001). However, our results clearly show that most community hospitals can only deal with mild exacerbation of COPD. Approximately 90% of AE patients received antibiotics. We speculated that antibiotics abuse might exist in the three tiers of hospitals. Multivariate analysis demonstrated that long-term antibiotics usage (⩾14 days) was associated with moderate exacerbation [odds ratio (OR): 5.295, 95% confidence intervals (CI) 2.248–12.473, p < 0.001], radiographic progression (OR: 2.176, 95% CI: 1.047–4.522, p = 0.037), positive sputum etiology (OR: 3.073, 95% CI: 1.477–6.394, p = 0.003) and increased white blood cells (OR: 2.470, 95% CI: 1.190–5.126, p = 0.015). The proportion of glucocorticoids increased with the hospital hierarchy (18.6% versus 45.6% versus 69.2%, p < 0.001). The proportions of severe cases in the second-tier hospitals were 26.9%; however, non-invasive positive pressure ventilation (NPPV) rate was only 14.7%. Anticoagulant is not commonly used in AECOPD, and the community hospitals had the lowest proportion of anticoagulation regimen (1.7% versus 14.3% versus 20.5%, p = 0.002). Conclusions: The ‘tiered medical services’ policy in AECOPD management has been unsatisfactory in the past years. Irrational treatment strategies in different hospitals were still found when comparing with international guideline. Further reform of the policy is still needed to optimize the management of AECOPD in China.

https://journals.sagepub.com/doi/pdf/10.1177/17534666221075499

Yunfeng Zhao

Papers

Can we predict the prognosis of COPD with a routine blood test

The relationship between tumor markers and pulmonary embolism in lung cancer.

Current Status of Immune Checkpoint Inhibitor Immunotherapy for Lung Cancer.

A modified risk score in one-year survival rate assessment of group 1 pulmonary arterial hypertension.

Management of acute exacerbation of chronic obstructive pulmonary disease under a tiered medical system in China