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.

Recent Advances in Inflammation and Treatment of Small Airways in Asthma.

Small airways were historically considered to be almost irrelevant in the development and control of pulmonary chronic diseases but, as a matter of fact, in the past few years we have learned that they are not so "silent". Asthma is still a worldwide health issue due to the great share of patients being far from optimal management. Several studies have shown that the deeper lung inflammation plays a critical role in asthma pathogenesis, mostly in these not well-controlled subjects. Therefore, assessing the degree of small airways inflammation and impairment appears to be a pivotal step in the asthmatic patient's management. It is now possible to evaluate them through direct and indirect measurements, even if some obstacles still affect their clinical application. The success of any treatment obviously depends on several factors but reaching the deeper lung has become a priority and, for inhaled drugs, this is strictly connected to the molecule's size. The aim of the present review is to summarize the recent evidence concerning the small airway involvement in asthma, its physiopathological characteristics and how it can be evaluated in order to undertake a personalized pharmacological treatment and achieve a better disease control.

Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency.

With the aim of providing better clinical characterisation of patients with α1-antitrypsin deficiency (AATD), we analysed the data of adult patients with severe AATD enrolled in the Spanish and Italian national registries. We assessed 745 subjects, 416 of whom were enrolled in the Spanish registry and 329 in the Italian registry. 57.2% were male and 64.9% were smokers or former smokers with a mean±sd age of 49.9±13.8 years. Most (81.2%) were index cases, mainly having the PI*ZZ genotype (73.4%), and the mean±sd diagnostic delay was 9.0±12.1 years. Patients with chronic bronchitis were younger, had better preserved lung function and lower tobacco consumption. Overlap patients (chronic obstructive pulmonary disease with asthma) were mainly females, more frequently never-smokers and received respiratory medications more often. 48% of emphysema, 27.5% of chronic bronchitis and 44.8% of overlap subjects were receiving augmentation therapy. Compared with PI*ZZ patients (n=547), the PI*SZ (n=124) subjects were older at diagnosis and had more preserved lung function, despite a higher mean smoking consumption. Early diagnosis of AATD is still an unmet need. Augmentation therapy is administered to similar proportions of patients with different clinical phenotypes. PI*ZZ patients in both registries had more severe respiratory disease than those with PI*SZ, despite lower smoking levels.

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.

Glutathione Peroxidase in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by a state of persistent inflammation and oxidative stress. The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of this review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. A systematic search for relevant studies was conducted in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to June 2021. Standardized mean differences (SMDs) were used to express the differences in GPx concentrations between COPD patients and non-COPD subjects. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = -1.91, 95% CI -2.55 to -1.28, p < 0.001; moderate certainty of evidence). By contrast, in 10 studies assessing serum/plasma (GPx isoform 3), the pooled results showed that GPx concentrations were not significantly different between the two groups (very low certainty of evidence). The concentration of GPx-1, but not GPx-3, is significantly lower in COPD patients, suggesting an impairment of antioxidant defense mechanisms in this group.

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.

Circulating Malondialdehyde Concentrations in Obstructive Sleep Apnea (OSA): A Systematic Review and Meta-Analysis with Meta-Regression.

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: "malondialdehyde" or "MDA"; and "Obstructive Sleep Apnea Syndrome", "OSAS" or "OSA". We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 µmol/L, 95% confidence interval (CI) 1.03 to 1.83 µmol/L, p < 0.001). There was extreme heterogeneity between the studies (I2 = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use.

Reliability and Usefulness of Different Biomarkers of Oxidative Stress in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation that is not fully reversible after inhaled bronchodilator use associated with an abnormal inflammatory condition. The biggest risk factor for COPD is cigarette smoking. The exposure to noxious chemicals contained within tobacco smoke is known to cause airway epithelial injury through oxidative stress, which in turn has the ability to elicit an inflammatory response. In fact, the disruption of the delicate balance between oxidant and antioxidant defenses leads to an oxidative burden that has long been held responsible to play a pivotal role in the pathogenesis of COPD. There are currently several biomarkers of oxidative stress in COPD that have been evaluated in a variety of biological samples. The aim of this review is to identify the best studied molecules by summarizing the key literature findings, thus shedding some light on the subject. METHODS: We searched for relevant case-control studies examining oxidative stress biomarkers in stable COPD, taking into account the analytical method of detection as an influence factor. RESULTS: Many oxidative stress biomarkers have been evaluated in several biological matrices, mostly in the blood. Some of them consistently differ between the cases and controls even when allowing different analytical methods of detection. CONCLUSIONS: The present review provides an overview of the oxidative stress biomarkers that have been evaluated in patients with COPD, bringing focus on those molecules whose reliability has been confirmed by the use of different analytical methods.

Treatment of COPD and COPD-heart failure comorbidity in primary care in different stages of the disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may have a negative impact on both patients' quality of life and survival. Patients with COPD frequently suffer from heart failure (HF), likely owing to several shared risk factors. AIM: To evaluate the differences in treatment of COPD with and without HF comorbidity according to COPD severity in the general practitioner setting. METHODS: We conducted an observational, retrospective study using data obtained from the Italian Health Search Database, which collects information generated by the routine activity of general practitioners. The study sample included 225 patients with COPD, alone or combined with HF. FINDINGS: It has been found that the prevalence of some comorbidities such as diabetes and HF significantly increases with the severity of COPD. Regarding pharmacological treatment, a reduction in the prescription of individually administered long-acting ß 2-agonists (LABAs) and long-acting anticholinergics (LAMAs) has been observed with increasing severity of the disease. Moreover, an increase in the prescription of both the combination of the two bronchodilators (LABA + LAMA) and their association with inhaled corticosteroids has been observed with increasing severity of COPD. The prescription of ß-blockers in patients with COPD suffering from HF comorbidity decreases from 100% in stage I to less than 50% in the other stages of COPD. This study shows that general practitioners do not follow the guidelines recommendations for the management of patients with COPD in the different stages of the disease, with and without HF comorbidity, as well as in the management of HF. Further efforts must be made to ensure adequate treatment for these patients.

Airflow reversibility and long-term outcomes in patients with COPD without comorbidities.

BACKGROUND: The forced expiratory volume at first second (FEV(1)) during spirometry reflects the severity of chronic obstructive pulmonary disease (COPD) and is known to be an important prognostic factor. It is uncertain whether the response to short-acting bronchodilators may predict long-term outcomes such as hospitalizations and mortality. METHODS: We retrospectively studied a total of 1203 consecutive COPD patients without significant comorbidities during a mean (±SD) of 69 ± 39 months of follow-up. At baseline the subjects were classified as those with positive or negative bronchodilator test (BDT) and also in quartiles of absolute bronchodilator response to 400 µg of salbutamol. Hospital visits and mortality were the end points. RESULTS: A positive bronchodilator test was observed in 332 (27.6%) of the patients. There were 73 (21.9%) deaths in patients with a positive BDT versus 253 (28.7%) in those with a negative BDT (p = 0.04). In adjusted Cox regression analysis a positive BDT was significantly associated with a prolonged time to first hospitalization. After stratifying the population by quartiles of response to BDT, a dose-response relationship was observed with the best outcomes in the quartile with highest level of airflow reversibility, even after controlling for age, sex, BMI, smoking status and baseline postbronchodilator FEV(1). CONCLUSIONS: In a large population of well characterized COPD patients without significant comorbidities, those demonstrating higher levels of reversibility at baseline presented better long-term outcomes even after controlling for other known prognostic factors.