Chronic Obstructive Pulmonary Disease Function Research Articles

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions

Background and objectiveEndothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients.MethodsA total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro.ResultsEndothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05).ConclusionNP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Revisiting airway epithelial dysfunction and mechanisms in chronic obstructive pulmonary disease: Role of mitochondrial damage.

Chronic exposure to environmental hazards causes airway epithelial dysfunction, primarily impaired physical barriers, immune dysfunction, and repair or regeneration. Impairment of airway epithelial function subsequently leads to exaggerated airway inflammation and remodeling, the main features of chronic obstructive pulmonary disease (COPD). Mitochondrial damage has been identified as one of the mechanisms of airway abnormalities in COPD, which is closely related to airway inflammation and airflow limitation. In this review, we evaluate updated evidence for airway epithelial mitochondrial damage in COPD and focus on the role of mitochondrial damage in airway epithelial dysfunction. In addition, the possible mechanism of airway epithelial dysfunction mediated by mitochondrial damage is discussed in detail, and recent strategies related to airway epithelial-targeted mitochondrial therapy are summarized. Results have shown that dysregulation of mitochondrial quality and oxidative stress may lead to airway epithelial dysfunction in COPD. This may result from mitochondrial damage as a central organelle mediating abnormalities in cellular metabolism. Mitochondrial damage mediates pro-cellular senescence effects due to mitochondrial reactive oxygen species, which effectively exacerbate different types of programmed cell death, participate in lipid metabolism abnormalities, and ultimately promote airway epithelial dysfunction and trigger COPD airway abnormalities. These can be prevented by targeting mitochondrial damage factors and mitochondrial transfer. Thus, because mitochondrial damage is involved in COPD progression as a central factor of homeostatic imbalance in airway epithelial cells, it may be a novel target for therapeutic intervention to restore airway epithelial integrity and function in COPD.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Chronic aryl hydrocarbon receptor activity impairs muscle mitochondrial function with tobacco smoking.

Accumulating evidence has demonstrated that chronic tobacco smoking directly contributes to skeletal muscle dysfunction independent of its pathological impact to the cardiorespiratory systems. The mechanisms underlying tobacco smoke toxicity in skeletal muscle are not fully resolved. In this study, the role of the aryl hydrocarbon receptor (AHR), a transcription factor known to be activated with tobacco smoke, was investigated. AHR related gene (mRNA) expression was quantified in skeletal muscle from adult controls and patients with chronic obstructive pulmonary disease (COPD), as well as mice with and without cigarette smoke exposure. Utilizing both skeletal muscle-specific AHR knockout mice exposed to chronic repeated (5days per week for 16weeks) cigarette smoke and skeletal muscle-specific expression of a constitutively active mutant AHR in healthy mice, a battery of assessments interrogating muscle size, contractile function, mitochondrial energetics, and RNA sequencing were employed. Skeletal muscle from COPD patients (N=79, age=67.0±8.4years) had higher levels of AHR (P=0.0451) and CYP1B1 (P<0.0001) compared to healthy adult controls (N=16, age=66.5±6.5years). Mice exposed to cigarette smoke displayed higher expression of Ahr (P=0.008), Cyp1b1 (P<0.0001), and Cyp1a1 (P<0.0001) in skeletal muscle compared to air controls. Cigarette smoke exposure was found to impair skeletal muscle mitochondrial oxidative phosphorylation by ~50% in littermate controls (Treatment effect, P<0.001), which was attenuated by deletion of the AHR in muscle in male (P=0.001), but not female, mice (P=0.37), indicating there are sex-dependent pathological effects of smoking-induced AHR activation in skeletal muscle. Viral mediated expression of a constitutively active mutant AHR in the muscle of healthy mice recapitulated the effects of cigarette smoking by decreasing muscle mitochondrial oxidative phosphorylation by ~40% (P=0.003). These findings provide evidence linking chronic AHR activation secondary to cigarette smoke exposure to skeletal muscle bioenergetic deficits in male, but not female, mice. AHR activation is a likely contributor to the decline in muscle oxidative capacity observed in smokers and AHR antagonism may provide a therapeutic avenue aimed to improve muscle function in COPD.

Lixisenatide ameliorated lipopolysaccharide (LPS)-induced expression of mucin and inflammation in bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) induces serious social and economic burdens due to its high disability and mortality, the pathogenesis of which is highly involved with inflammation, oxidative stress (OS), and mechanism of mucin 5AC (MUC5AC) secretion. Lixisenatide is a selective glucagon-like peptide 1 receptor agonist recently reported to have anti-inflammatory properties. Our study will focus on the potential impact of lixisenatide on lipopolysaccharide (LPS)-induced mucin secretion and inflammation in 16 human bronchial epithelial (16HBE) cells to check its potential function in COPD. 16HBE cells were treated with LPS, with or without lixisenatide (10 and 20 nM) for 1 day. Remarkably declined cell viability, enhanced lactate dehydrogenase release, activated OS, and elevated release of inflammatory cytokines were observed in LPS-treated 16HBE cells, accompanied by the activation of nuclear factor-κB signaling, all of which were signally reversed by lixisenatide. Moreover, elevated expression and release of MUC5AC were observed in LPS-treated 16HBE cells but were markedly repressed by lixisenatide. Furthermore, the repressed nuclear factor erythroid 2-related factor 2 (Nrf2) level in LPS-treated 16HBE cells was notably rescued by lixisenatide. Lastly, following the knockdown of Nrf2, the protective function of lixisenatide on LPS-triggered MUC5AC release in 16HBE cells was significantly abrogated. Collectively, lixisenatide ameliorated LPS-induced expression of mucin and inflammation in bronchial epithelial cells by regulating Nrf2.

Exercise training influence on cognitive capacity and mental health within chronic obstructive pulmonary disease - A pilot study.

Although pulmonary rehabilitation and regular exercise have improved negative emotions and cognitive capacity within cases of chronic obstructive pulmonary disease (COPD), influence by exercise training upon different cognitive and memory functions in COPD is still controversial. This investigation aimed to assess whether cognitive performance and mental health are affected by the benefits of exercise training within cases of COPD. This pilot investigation included thirty-three patients with Global Initiative for Chronic Obstructive Lung Disease stage ≥B. Based on the subjects' rights, all included patients could choose to join either the exercise group or the control group, according to their free will. Twelve patients were assigned to receive exercise treatment over a 2-month period, while the remaining 16 patients were assigned to the control group. Cognitive capacity outcomes were measured using the Wechsler Memory Scale-III Word List Test, Stroop task, and psychomotor vigilance task (PVT). Mood states were assessed through the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Most cases demonstrated major improvement for BDI and BAI scorings post-60-day therapy. During PVT, the omission rate decreased, while the hit rate increased, indicating an improvement in attention performance. Furthermore, this investigation found a significant increase in immediate verbal and recognition memory for word-list test. However, no major performance shifts were found on Stroop analysis. This investigation demonstrated that a 2-month exercise training program resulted in significant improvement in negative emotions, immediate memory, recognition memory, and attention.

The future landscape of immunology in COPD: A bibliometric analysis

BackgroundThis study was conducted to provide a comparative and comprehensive analysis of the last 50 years of research in the immunology of chronic obstructive pulmonary disease (COPD) and to identify future research priorities and directions. MethodsWe obtained publication information from the Web of Science Core Collection (WoSCC) database. Scimago Graphica, CiteSpace, VOSviewer, GraphPad Prism, Microsoft Excel 365, and the R package “bibliometrix” were used for bibliometric analysis. The methodologies used were burst citation, clustering and co-citation, keyword co-occurrence, and cooperative network graph clustering algorithms. ResultsA total of 2239 articles and reviews were included in the analysis. The number of annual publications showed an upward trend amidst fluctuations. The countries, institutions, journals, and authors with the highest number of publications were the USA, Imperial College London (ICL), Journal of Allergy and Clinical Immunology, and Murphy TF. There are 58 references and 13 keywords with a burst citation nature in the last 3 years, related to the study of inflammatory mechanisms. ConclusionWe used bibliometric analysis to understand the research progress regarding immune function in COPD. Meanwhile, we found that the hotspots of COPD immunology in basic research focus on the analysis of etiology and risk factors, and the exploration of the immune system; and the hotspots of COPD in clinical research focus on epidemiology, and the prevention and management of different subtypes of COPD.

Laboratory and instrumental characteristics of patients with chronic obstructive pulmonary disease and hypertension

The article defines the clinical-laboratory and clinical-instrumental features of the comorbid course of chronic obstructive pulmonary disease (COPD) and hypertension (HTN). The aim of the study was to determine the clinical, laboratory and instrumental features of the comorbid course of COPD and HTN. The study was carried out in accordance with the existing recommendations of bioethical norms and rules. All patients took part in the study of their own free will with the signing of informed consent. 125 patients aged 18–50 years were examined, who were divided into 3 groups: group I – 48 patients with COPD and HTN, group II – 47 patients with an isolated course of COPD, group III (control) – 30 practically healthy people. Medical and statistical calculation was performed using the IBM SPSS 25.0 software package. Calculated median (Me) levels and their 25.0% (LQ) and 75.0% (UQ) quartiles. The probability of differences was determined using the Man-Whitney U-test with a statistical significance threshold of 0.05 (p=0.05). According to the results of the study, an excess of systolic and diastolic blood pressure levels was significantly stated in comorbidity of COPD and HTN and in patients with isolated COPD. The presence of lymphocytopenia and monocytosis in such patients has been reliably established and significant protein loss in COPD has been determined. Significant predominances of biochemical values of the blood of patients with comorbidity of COPD and HNT and with isolated COPD compared to the control were significantly recorded. Significant decreases in the levels of external respiratory function in COPD (especially in its comorbidity with HNT) were noted and a significant predominance of Caspase-8 levels was determined in the following patients: in comorbidity of COPD and HTN – 3.79 [3.57; 3.84] U/l and in isolated COPD – 3.48 [2.99; 3.72] U/l. Keywords: patients with chronic obstructive pulmonary disease, comorbidity of arterial hypertension, clinical and laboratory characteristics, clinical and instrumental characteristics, caspase-8.

Factors Related to Fatigue and Physical Function in COPD: A Secondary Analysis Using National Survey Data.

Fatigue in chronic obstructive pulmonary disease (COPD) is debilitating and associated with considerable morbidity. The aim of this study is to present a model based on the Theory of Unpleasant Symptoms of physiologic, psychologic, and situational factors with COPD-related fatigue and the relationship with physical functioning. This study used data collected from Wave 2 (2010-2011) of the National Social, Health, and Aging Project (NSHAP). A total of 518 adults with self-reported COPD were included in this study. Path analysis was used for hypothesis testing. Depression was the only psychologic factor found to have a direct relation to both fatigue (β = 0.158, p < .001) and physical function (β = -0.131, p = .001). Factors related to physical function included fatigue, depression, sleep, loneliness, and pain. Additionally, fatigue was indirectly associated with physical function via depression (β = -0.064, p = .012). These findings suggest avenues for future research on predictors of COPD-related fatigue in relation to physical functioning.

Circulating liver function markers and the risk of COPD in the UK Biobank.

To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD). We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05). We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.

Isokinetic testing of quadriceps function in COPD: feasibility, responsiveness, and minimal important differences in patients undergoing pulmonary rehabilitation

BackgroundIsokinetic testing of peripheral muscle function is valid and reliable in patients with chronic obstructive pulmonary disease (COPD). ObjectiveTo evaluate whether and to what extent isokinetic testing of quadriceps function meets pre-defined test criteria in patients with COPD; to determine the response to pulmonary rehabilitation (PR), and to calculate minimal important differences (MIDs) of isokinetic quadriceps function. MethodsRetrospective analysis of 2033 patients with COPD (age: 65±9 years, body mass index: 26±6 kg/m2, FEV1: 49±22% predicted) who followed a comprehensive PR program. Pre and post PR isokinetic quadriceps function was assessed with 30 maximal extension-flexion contractions at an angular speed of 90°/s on a computerized dynamometer. The chosen anchors were 6-min walk test and COPD assessment test. ResultsPre PR, 27% of the patients performed the isokinetic test incorrectly. In male and female patients with a correct pre and post PR isokinetic test, peak torque (Δ=10±13 Nm or 9% and Δ=7±9 Nm or 10%, respectively) and total work (Δ=263±270 J or 14% and Δ=198±190 J or 15%, respectively) improved significantly. There was no change in work fatigue index following PR. Using distribution-based calculations, MID estimates for peak torque and total work ranged between 6–7 Nm and 97–135 J in males and between 4–5 Nm and 62–99 J in females. ConclusionsBased on the current test criteria, three in four patients with COPD performed the isokinetic quadriceps test correctly during baseline PR assessment. Furthermore, peak torque and total work, but not work fatigue index, were responsive to PR and sex-specific MIDs were established.

Pulmonary rehabilitation ameliorates regional lung function in chronic obstructive pulmonary disease: a prospective single-arm clinical trial.

BackgroundPulmonary rehabilitation (PR) is a widely recognized nonpharmacologic therapy for chronic obstructive pulmonary disease (COPD), but most of the current studies on whether PR can benefit COPD patients are based on the evaluation of symptoms and pulmonary function, which is limited to a certain extent. Because COPD is characterized by potential regional lung changes in morphology and pathophysiology, this study was designed to evaluate the effects of individualized PR on regional lung function in patients with stable COPD.MethodsIn this study, patients with stable COPD who met the criteria were included, and they were treated with PR for 2 weeks using the respiratory rehabilitation training instrument. The symptoms, and global and regional lung function before and after 2 weeks of PR treatment were evaluated using surveys, spirometry, and electrical impedance tomography (EIT), respectively. The spatial coefficient of variation (CV) of regional spirometry parameters were calculated to quantify spatial heterogeneity of lung function. Temporal inhomogeneity was determined by the regional expiration time.ResultsA total of 34 participants were recruited in this study, of whom 24 completed the PR. After 2 weeks of intervention, the modified Medical Research Council (mMRC) dyspnea scale and the COPD assessment test (CAT) score was significantly lower compared to those measured before the treatment (2.3±1.17 vs. 2.1±0.93, P=0.034; and 15.0±7.18 vs. 10.9±6.06, P<0.001, respectively). Global spirometry forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 predicted percentage (%pred), and peak expiratory flow (PEF) were significantly better than they were pre-rehabilitation (2.1±0.86 vs. 2.3±0.90 L, P=0.018; 1.2±0.65 vs. 1.4±0.66 L, P=0.001; 46.8%±23.16% vs. 51.4%±24.41%, P<0.001; and 3.1±1.80 vs. 3.8±2.23 L/s, P=0.005, respectively). In addition, the CV for regional FEV1/FVC was significantly decreased after the PR treatment (0.26±0.161 vs. 0.17±0.077, P=0.002). Regional lung ventilation was more homogeneous and regional expiration time was shorter after 2 weeks of the PR treatment.ConclusionsTwo weeks of PR treatment can improve both spatial and temporal regional ventilation in COPD. In addition, EIT may be useful in developing individualized PR treatment program to improve regional lung function in COPD.

PREFUL MRI Depicts Dual Bronchodilator Changes in COPD: A Retrospective Analysis of a Randomized Controlled Trial.

PurposeTo assess whether dynamic ventilation and perfusion (Q) biomarkers derived by phase-resolved functional lung (PREFUL) MRI can measure treatment response to 14-day therapy with indacaterol-glycopyrronium (IND-GLY) and correlate to clinical outcomes including lung function, symptoms, and cardiac function in patients with chronic obstructive pulmonary disease (COPD), as determined by spirometry, body plethysmography, cardiac MRI, and dyspnea score measurements.Materials and MethodsThe cardiac left ventricular function in COPD (CLAIM) study enrolled patients aged 40 years or older with COPD, stable cardiovascular function, and hyperinflation (residual volume > 135% predicted). Dynamic MRI data of these patients were retrospectively analyzed using the PREFUL technique to assess the effect of 14-day IND-GLY treatment versus placebo on regional measurements of ventilation dynamics. After manual segmentation of the lung parenchyma, flow-volume loops of each voxel were correlated to an individualized reference flow-volume loop, creating a two-dimensional flow-volume loop correlation map (FVL-CM) as a measure of ventilation dynamics. Ventilation-perfusion match (VQM) was evaluated in combination with perfusion and regional ventilation (VQMRVent) and with perfusion and the FVL-CM measurement (VQMCM). For image and statistical analysis, the lung parenchyma was segmented as a region of interest by manually delineating the lung boundary and excluding the large (central) vessels for each section. Differences in ventilation, perfusion, and VQM between IND-GLY and placebo were compared using analysis of variance, with study treatment, patient, and period included as factors.ResultsFifty patients (mean age, 64.3 years ± 7.65 [SD]; 35 men) were included in this analysis. IND-GLY significantly increased mean correlation as measured with FVL-CM versus that of placebo (least squares [LS] means treatment difference: 0.05 [95% CI: 0.03, 0.07]; P < .0001). Compared with placebo, IND-GLY increased mean Q (LS means treatment difference: 9.27 mL/min/100 mL [95% CI: 0.05, 18.49]; P = .049) and improved both VQMCM and VQMRVent (LS means treatment difference: 0.06 [95% CI: 0.03, 0.08]; P < .0001 and 0.05 [95% CI: 0.02, 0.08]; P = .001, respectively).ConclusionRegional ventilation dynamics and VQM measured by PREFUL MRI show treatment response in COPD. Supplemental material is available for this article. Clinical trial registration no. NTR6831Keywords: MRI, COPD, Perfusion, Ventilation, Lung, PulmonaryPublished under a CC BY 4.0 license

Myostatin is involved in skeletal muscle dysfunction in chronic obstructive pulmonary disease via Drp-1 mediated abnormal mitochondrial division.

BackgroundSkeletal muscle dysfunction (SMD) is one of the most prominent extrapulmonary effects of chronic obstructive pulmonary disease (COPD). Myostatin negatively regulates the growth of skeletal muscle. We confirmed that myostatin expression is significantly increased in the quadriceps femoris muscle tissue of rats with COPD and is involved in the development of SMD in COPD, but the mechanism by which this occurs has yet to be uncovered. Dynamin-related protein 1 (Drp-1) has been shown to promote apoptosis and affect cellular energy metabolism by mediating enhanced mitochondrial division. Preliminary findings from our group illustrated that mitochondrial division and Drp-1 expression were increased in COPD quadriceps femoris cells. However, it is not yet clear whether mitochondrial dynamics are affected by myostatin in COPD quadriceps myocytes.MethodsThe study sought to explore the effects and potential mechanisms of myostatin on skeletal muscle atrophy, mitochondrial dynamics, apoptosis, and the links between related processes in COPD.ResultsOur findings showed that cigarette smoke exposure stimulated an increase in myostatin, increased superoxide production, decreased mitochondrial membrane potential, significantly promoted Drp-1-mediated mitochondrial fission, and promoted apoptosis.ConclusionsIn summary, our study demonstrated that cigarette smoke led to increased Drp-1 expression and enhanced mitochondrial division by upregulating myostatin, which in turn promoted apoptosis and affected cellular energy metabolism, leading to the development of SMD in COPD. This study extends understandings of skeletal muscle function in COPD and provides a basis for the use of myostatin and Drp-1 as novel therapeutic targets for SMD in COPD.

Attention, memory, and executive functioning in hypoxemic chronic obstructive pulmonary disease patients

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow obstruction and is one of the leading causes of death globally. The changes in pulmonary functions in COPD are irreversible with devastating consequences. Cognitive functioning in COPD patients is often found impaired and postulated to happen due to hypoxemia, i.e., oxygen deprivation to the brain. An impaired cognitive functioning can have direct impact on functional abilities as well as quality of life of patients and could be a vital treatment goal. The study aimed to explore the attention, memory, and executive functioning in hypoxemic COPD patients in backdrop of dearth of studies from India. Materials and Methods: Using purposive sampling, 30 patients with COPD, having mild-to-moderate level of illness severity, and having minimum illness for duration of 5 years were compared with 30 healthy controls. Participants were assessed for cognitive functioning in the domains of sustained attention, processing and psychomotor speed, working memory, verbal learning, and memory and executive functions using neuropsychological tests, namely, Digit Symbol Substitution Test, Trial Making Test, Verbal N Back Test, Rey's Audio Visual Learning Test, Controlled Oral Word Association Test, Animal Naming Test, Stroop Neuropsychological Test, and Modified Wisconsin Card Sorting Test. Results: Findings suggest significant differences between COPD patients and healthy controls over processing and psychomotor speed, working memory, memory, learning, and executive functioning. Conclusion: In addition to pulmonary distress, COPD patients also have compromised cognitive functions affecting overall daily functioning and quality of life. Understanding the nature of decline in cognitive functions could be vital in improving daily psychosocial functioning of the patients with COPD, and the exploration could help professionals in intervention of specific cognitive functioning.

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis.

Osteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), of patients with COPD. A PubMed/Medline search was conducted using the search terms "chronic obstructive pulmonary disease", "osteoporosis" and "vertebral compression fracture". Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335. Of the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I2=89%, P<0.01), decreased FEV1/FVC with a mean difference of -4.80% (95% CI: -6.69; -2.90, I2=83%, P<0.01) and decreased FEV1, with a mean difference of -4.91% (95% CI: -6.51; -3.31, I2=95%, P<0.01) and -0.41 L (95% CI: -0.59; -0.24, I2=97%, P<0.01), compared to control subjects. Apart from FEV1 (liters) in subgroup 1 (P=0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies. Osteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.

Efficacy of Pippali Rasayana as an Adjuvant Therapy on Pulmonary Function in Patients of Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic, recurrent condition, prevalent in the general population. In modern medicine, treatment modalities are aimed to diminish the incidence and extreme aggravation of clinical features. Nowadays, pippali rasayana being considered as a promising treatment approach for COPD. However, due to methodological limitations, there is no strong evidence to support pippali rasayana. &#x0D; Aim: The goal of the study is to evaluate the efficacy of Pippali Rasayana on pulmonary function in COPD patients&#x0D; Materials and Methods: It is double arm randomized placebo controlled single blind clinical trial. Total 60 patients of COPD will be randomly divided into two groups (each group contain 30). In both groups, standard treatment of modern medicine will be continued. With this, in Group A (Intervention), pippali rasayana 5 gm (25 gm twice a day after meal ) with honey will be given for 45 days and Group B (placebo group) will be given placebo (250 mg twice a day after meal ) with water for 45 days. Assessment will be done on 15th, 30th and 45st day.&#x0D; Results: Result will be declared on the basis of effect of pippali rasayana with pulmonary function test as well as frequency of Dyspnea, Chronic cough, Excessive sputum production.&#x0D; Conclusion: This trial may provide evidence on the efficacy of pippali rasayanaon pulmonary function in COPD.

The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.

Serum cadmium positively correlates with inflammatory cytokines in patients with chronic obstructive pulmonary disease.

Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 μg/L, L), medium (0.77-1.01 μg/L, M), and high (1.01 μg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.

Leukocyte Function in COPD: Clinical Relevance and Potential for Drug Therapy.

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition affecting 10% of the global population over 45 years. Currently, there are no disease-modifying treatments, with current therapies treating only the symptoms of the disease. COPD is an inflammatory disease, with a high infiltration of leukocytes being found within the lung of COPD patients. These leukocytes, if not kept in check, damage the lung, leading to the pathophysiology associated with the disease. In this review, we focus on the main leukocytes found within the COPD lung, describing how the release of chemokines from the damaged epithelial lining recruits these cells into the lung. Once present, these cells become active and may be driven towards a more pro-inflammatory phenotype. These cells release their own subtypes of inflammatory mediators, growth factors and proteases which can all lead to airway remodeling, mucus hypersecretion and emphysema. Finally, we describe some of the current therapies and potential new targets that could be utilized to target aberrant leukocyte function in the COPD lung. Here, we focus on old therapies such as statins and corticosteroids, but also look at the emerging field of biologics describing those which have been tested in COPD already and potential new monoclonal antibodies which are under review.