A systematic review and meta-analysis of homocysteine concentrations in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) often suffer from other conditions, such as cardiovascular disease, that further increase the risk of adverse outcomes in this group. Serum homocysteine concentrations are positively associated with cardiovascular risk and have also been reported to be increased in COPD. This meta-analysis investigated the association between homocysteine concentrations and COPD. A systematic search of publications in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to September 2021, was conducted using the following terms: "Homocysteine" or "Hcy" and "Chronic Obstructive Pulmonary Disease" or "COPD". Weighted mean differences (WMDs) were calculated to evaluate differences in homocysteine concentrations between COPD patients and non-COPD subjects. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Nine studies in 432 COPD patients (mean age 65 years, 65% males) and 311 controls (mean age 65 years, 56% males) were identified. Pooled results showed that serum homocysteine concentrations were significantly higher in patients with COPD (WMD = 2.91 µmol/L, 95% CI 2.00-3.82 µmol/L; p < 0.001; high certainty of evidence). No publication bias was observed. Our results support the hypothesis that increased homocysteine concentrations are significantly associated with COPD and may account, at least in part, for the increased cardiovascular risk in these patients.

Role of EBUS-TBNA in Non-Neoplastic Mediastinal Lymphadenopathy: Review of Literature.

Mediastinal lymphadenopathy is a condition in which one or more mediastinal lymph nodes are enlarged for malignant or benign causes, generally more than 10 mm. For a long time, the only way to approach the mediastinum was surgery, while in last decades endoscopic techniques gained their role in neoplastic diseases. At the present time, EBUS is the technique of choice for studying the mediastinum in the suspicion of cancer, while there are not strong indications in guidelines for the study of benign mediastinal lymphadenopathy. We reviewed the literature, looking for evidence of the role of EBUS in the diagnostics of non-neoplastic mediastinal lymphadenopathy, with special regard for granulomatous disease, both infectious and non-infectious. EBUS is a reliable alternative to surgery in non-neoplastic mediastinal lymphadenopathy, even if more evidence is needed for granulomatous diseases other than tuberculosis and sarcoidosis.

A prospective pilot study on the effects of endoscopic sinus surgery on upper and lower airway performance.

OBJECTIVE: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease. METHODS: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated. RESULTS: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1st second (FEV1) significantly improved after surgery from 3.23 to 3.45 L/s. CONCLUSIONS: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.

Association between Glucose-6-Phosphate Dehydrogenase Deficiency and Asthma.

BACKGROUND: Among the determinants contributing to the pathogenesis of asthma, antioxidant genetic factors play a leading role. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that is competent to detoxify free radicals. Although a relationship between G6PD deficiency and asthma has been previously reported, the literature is still scanty. In this study, we test this hypothesis in a large cohort of patients from Sardinia, Italy. METHODS: A retrospective case-control study was performed using data from 11,829 clinical records of outpatients referred to a teaching hospital for a medical visit. In total, 455 cases (asthma-positive) and 11,374 controls (asthma-negative) were compared for G6PD status using multivariable analysis, adjusting for all covariates. RESULTS: Overall, G6PD deficiency was detected in 11.2% of study participants and was associated with an increased risk of asthma (odds ratio (OR) 1.63; 95% confidence interval (CI) 1.27-2.10). Additional variables significantly associated with asthma were female sex (OR 1.66; 95% CI 1.34-2.06), overweight/obesity (OR 1.56; 95% CI 1.27-1.92), smoking (OR 1.44; 95% CI 1.449-3.963), and high socioeconomic status (OR 1.40; 95% CI 1.16-1.70), whereas age was inversely related with asthma (OR 0.49; 95% CI 0.39-0.61). CONCLUSIONS: Our study shows that G6PD deficiency is an independent risk for asthma. These findings suggest that G6PD should be assessed in asthmatic patients for better risk stratification.

Oxidative Stress Biomarkers in Chronic Obstructive Pulmonary Disease Exacerbations: A Systematic Review.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease characterized by a not fully reversible airflow limitation associated with an abnormal inflammatory response. Exacerbations of COPD are of major importance in the acceleration of disease progression, in healthcare costs, and negatively affect the patient's quality of life. Exacerbations are characterized by a further increase in the airway inflammation likely driven by oxidative stress. In order to deepen the knowledge about this topic, several studies have focused on oxidative stress biomarkers levels. This review summarizes the literature findings about oxidative stress biomarkers in exacerbated COPD patients compared to ones in the stable state. METHODS: a systematic search in electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to January 2021, was conducted using the terms: "oxidative stress", "chronic obstructive pulmonary disease" or "COPD", "exacerbation". RESULTS: 23 studies were selected for the systematic review. They showed the presence of an imbalance between oxidant and antioxidant molecules in favor of the former in exacerbation of COPD. CONCLUSIONS: future studies using standardized methods in better characterized population are needed. However, this review suggests that targeting oxidative stress could be useful in monitoring the disease progression in COPD patients and especially in those more susceptible to exacerbations.

The PaO2/FiO2 ratio on admission is independently associated with prolonged hospitalization in COVID-19 patients.

INTRODUCTION: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management. METHODOLOGY: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge. RESULTS: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. In univariate logistic regression, Chest CT severity score (OR = 1.1891, p = 0.007), intensity of care (OR = 2.1350, p = 0.022), PaO2/FiO2 ratio (OR = 0.9802, p = 0.007), CRP (OR = 1.0952, p = 0.042) and platelet to lymphocyte ratio (OR = 1.0039, p = 0.036) were significantly associated with PHS. However, in multivariate logistic regression, only the PaO2/FiO2 ratio remained significantly correlated with PHS (OR = 0.9164; 95% CI 0.8479-0.9904, p = 0.0275). In ROC curve analysis, using a threshold of 248, the PaO2/FiO2 ratio predicted PHS with sensitivity and specificity of 60% and 91%, respectively (AUC = 0.780, 95% CI 0.637-0.886 p = 0.002). CONCLUSIONS: The PaO2/FiO2 ratio on admission is independently associated with PHS in COVID-19 patients. Larger prospective studies are needed to confirm this finding.

The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID-19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in-hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID-19) admitted to three COVID-19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91-1.64 vs 1.67; IQR: 1.38-1.97, P = .002) whilst there were no significant between-group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603-0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan-Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05-5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in-hospital mortality in COVID-19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.

The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. METHODS: The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. RESULTS: Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan-Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000-1.0001, p = 0.029) in multivariate Cox regression analysis. CONCLUSIONS: The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report.

INTRODUCTION: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. METHODS: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2-related factor 2 (Nrf2), thiobarbituric acid- reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein -SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age- and sex-matched healthy controls. RESULTS: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 µmol/L vs 723 ± 194 µmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 µmol/L, p = 0.024). CONCLUSION: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.

Laboratory test alterations in patients with COVID-19 and non COVID-19 interstitial pneumonia: a preliminary report.

INTRODUCTION: Coronavirus disease 19 (COVID-19) is the greatest pandemic in modern history. Laboratory test alterations have been described in COVID-19 patients, but differences with other pneumonias have been poorly investigated to date, especially in Caucasian populations. The aim of this study was to investigate differences and prognostic potential of routine blood tests in a series of Italian patients with COVID-19 and non-COVID-19 interstitial pneumonia. METHODOLOGY: Clinical data and routine laboratory tests of a consecutive series of 30 COVID-19 patients and 30 age and sex matched patients with non COVID-19 interstitial pneumonia have been retrospectively collected. Differences in laboratory tests between patients with COVID-19 and non COVID-19 pneumonias have been investigated, as well as differences between COVID-19 survivors and non survivors. RESULTS: COVID-19 patients had lower white blood cells, monocytes, neutrophils, and higher platelet counts. In addition, COVID-19 patients showed higher mean platelet volume, lower C reactive protein concentrations, and higher De Ritis ratio. Combined blood cell indexes of systemic inflammation were significantly lower in COVID-19 patients. In further analysis of the COVID-19 group, the neutrophil count, neutrophil to lymphocyte ratio (NLR), derived NLR, systemic inflammation response index and De Ritis ratio, were significantly higher in non survivors than in survivors, while the number of platelets was significantly lower in non survivors. CONCLUSIONS: Our study showed several alterations in blood cell populations and indexes in patients with COVID-19 pneumonia in comparison with patients with non COVID-19 pneumonia. Some of these indexes showed promising prognostic abilities. Further studies are necessary to confirm these results.

Systemic transsulfuration pathway thiol concentrations in chronic obstructive pulmonary disease patients.

BACKGROUND: It is amply reported that patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular disease (CVD). Recent evidence suggests that COPD patients have elevated concentrations of plasma homocysteine (Hcy), a transsulfuration pathway analyte that is commonly regarded as a CVD risk factor. DESIGN: We comprehensively investigated the plasma concentrations of transsulfuration pathway analytes, and their relationship with markers of oxidative stress and inflammation, to identify which low molecular thiols might play a pathophysiological role both in CVD and in COPD. Hcy, cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), glutamylcysteine (GluCys), taurine (Tau), oxidative stress markers (TBARS and protein-SH, PSH) and the inflammation marker kynurenine/tryptophan (Kyn/Trp) ratio were measured in 54 COPD patients and 54 control subjects. RESULTS: We found increased concentrations of total Hcy (P < .01) and total CysGly (P < .05) in COPD patients when compared to controls. Total Hcy and CysGly were also significantly associated with abnormal lung function parameters and COPD severity. In COPD patients, total Hcy was significantly associated with the Kyn/Trp ratio (P = .0017) whereas total CysGly was significantly associated with both PSH (P = .0298) and the Kyn/Trp ratio (P = <.0001). CONCLUSION: Both total Hcy and CysGly concentrations were significantly associated with the presence and severity of COPD and with markers of oxidative stress (total CysGly) and inflammation (total Hcy and CysGly). This suggests that specific low molecular mass thiols might play a role in the inflammatory and oxidative stress pathways involved in both CVD and COPD.