Chronic Obstructive Pulmonary Disease Function Research Articles

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.

Sputum Gene Expression Reveals Dysregulation of Mast Cells and Basophils in Eosinophilic COPD

PurposeThe clinical and inflammatory associations of mast cells (MCs) and basophils in chronic obstructive pulmonary disease (COPD) are poorly understood. We previously developed and validated a qPCR-based MC/basophil gene signature in asthma to measure these cells in sputum samples. Here, we measured this gene signature in a COPD and control population to explore the relationship of sputum MCs/basophils to inflammatory and COPD clinical characteristics.Patients and MethodsMC/basophil signature genes (TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2) were measured by qPCR in sputum from a COPD (n=96) and a non-respiratory control (n=17) population. Comparative analyses of gene expression between the COPD and the control population, and between eosinophilic COPD and non-eosinophilic COPD were tested. Logistic regression analysis and Spearman correlation were used to determine relationships of sputum MC/basophil genes to inflammatory (sputum eosinophil proportions, blood eosinophils) and clinical (age, body mass index, quality of life, lung function, past year exacerbations) characteristics of COPD.ResultsMC/basophil genes were increased in COPD versus control participants (CPA3, KIT, GATA2, HDC) and between eosinophilic-COPD and non-eosinophilic COPD (TPSB2, CPA3, HDC, SOCS2). We found all MC/basophil genes were positively intercorrelated. In COPD, MC/basophil genes were associated with eosinophilic airway inflammation (GATA2, TPSB2, CPA3, GPR56, HDC, SOCS2), blood eosinophilia (all genes) and decreased lung function (KIT, GATA2, GPR56, HDC).ConclusionWe demonstrate associations of MCs and basophils with eosinophilic inflammation and lower lung function in COPD. These findings are consistent with prior results in asthma and may represent a new tool for endotyping eosinophilic-COPD.

Effect of Oxidative Stress on Diaphragm Dysfunction and Exercise Intervention in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) can cause extrapulmonary injury such as diaphragm dysfunction. Oxidative stress is one of the main factors causing diaphragm dysfunction in COPD. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. Therefore, on the basis of the review of oxidative stress and the changes in diaphragm structure and function in COPD, this article analyzed the effects of exercise on oxidative stress and diaphragm dysfunction in COPD and explored the possible mechanism by which exercise improves oxidative stress. Studies have found that diaphragm dysfunction in COPD includes the decline of muscle strength, endurance, and activity. Oxidative stress mainly affects the structure and function of the diaphragm in COPD through protein oxidation, protease activation and calcium sensitivity reduction. The effects of exercise on oxidative stress level and diaphragm dysfunction may differ depending on the intensity, duration, and style of exercise. The mechanism of exercise on oxidative stress in the diaphragm of COPD may include improving antioxidant capacity, reducing oxidase activity and improving mitochondrial function.

Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial.

Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD.Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio.Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49–1.77] vs. 1.85 [0.95–2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = −0.007, p = 0.001).Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.

The Relationship of Lymphocyte to High-Density Lipoprotein Ratio with Pulmonary Function in COPD.

PurposeThis study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR).Patients and MethodsIn total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited. LHR, NLR, PLR, lung function and other data were collected and compared. Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR. Besides, univariate and multivariate logistic regression analyses were conducted.ResultsCOPD patients with poorer lung function had a lower LHR level (P < 0.001). In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006). LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = 0.333, P = 0.003). At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV1% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR. Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV1 <50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048–0.811, P = 0.024).ConclusionIn contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function.

Moderate-to-Severe Obstructive Sleep Apnea and Cognitive Function Impairment in Patients with COPD.

PurposePrior studies have indicated that patients with chronic obstructive pulmonary disease (COPD) exhibit significant cognitive defects on neuropsychological testing. Obstructive sleep apnea (OSA) is common in patients with COPD and is associated with reduced cognitive function; however, the combined impact of these two conditions on cognitive function is unknown. The aim of the study was to investigate the impact of OSA on cognitive impairment in patients with COPD.MethodsSixty-five stable COPD patients aged over 60 years underwent overnight polysomnography (PSG). Global cognitive functions were evaluated using the Mini-Mental State Examination (MMSE).ResultsCompared to patients with COPD alone, patients with both COPD and OSA performed worse on the MMSE (25.5±2.9 vs 23.5±3.2; p=0.01) and were more likely to be at risk for developing dementia based on the MMSE score (MMSE≤24) (31% vs 66%; p<0.01), independent of key demographic, educational and medical variables known to affect cognitive function in COPD. COPD patients with an apnea hypopnea index (AHI) of ≥30 events/h had lower MMSE scores than those with an AHI of <15 events/h. In addition to age and education level, the severity of nocturnal intermittent hypoxia is an independent predictor of the risk of dementia in patients with COPD (OR=1.24, 95% CI 1.04–1.48, p = 0.02).ConclusionThe current findings indicate that patients with COPD with comorbid OSA may be at greater risk for global cognitive impairment relative to patients with COPD alone. The mechanisms underlying the exaggerated cognitive dysfunction seem to be related to intermittent hypoxia. Further work is needed to understand the impact of OSA on the specific domains of cognitive impairment and the therapeutic implications of OSA in COPD.

Epithelial-mesenchymal crosstalk in COPD: An update from in vitro model studies.

Chronic Obstructive Pulmonary disease (COPD) involves airway inflammation and remodeling leading to small airways disease and emphysema, which results in irreversible airflow obstruction. During lung development, reciprocal interactions between the endoderm and mesoderm (epithelial-mesenchymal trophic unit (EMTU)) are essential for morphogenetic cues that direct cell proliferation, differentiation, and extracellular (ECM) production. In COPD, a significant number of the inflammation and remodeling mediators resemble those released during lung development, which has led to the hypothesis that aberrant activation of the EMTU may occur in the disease. Studies assessing lung epithelial and fibroblast function in COPD, have been primarily focused on monoculture studies. To capture the in vivo environment of the human lung and aid in the understanding of mechanisms and mediators involved in abnormal epithelial-fibroblast communication in COPD, complex co-culture models are required. In this review, we describe the studies that have used co-culture models to assess epithelial-fibroblast interactions and their role in the pathogenesis of COPD.

Management of cardiovascular comorbidities in chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) is а highly prevalent, complex and heterogeneous clinical condition which is associated with significant concomitant diseases. COPD and cardiovascular diseases (CVDs) often coexist due to the high prevalence of each of these pathological conditions separately as well as the common risk factors (particularly smoking), mechanisms of interaction and influence of systemic inflammation. In addition, decreased pulmonary function in COPD is closely associated with an increased risk of congestive CVDs. One of the most important pathophysiological markers of COPD—lung hyperinflation—plays a significant role in the appearance of functional limitations of the pumping function of the heart, creating unfavorable conditions by exerting a compression effect on the heart muscle. The latter was confirmed by significant correlation between the COPD severity according to GOLD classification and the basic dimensions of the heart chambers. Several decades ago, the term “microcardia” was commonly used and indicated a radiological sign of emphysema. Some studies demonstrated a close relationship between the chance of occurrence of CVD and the severity of pulmonary dysfunction. Such an association has been demonstrated for the whole spectrum of CVD—including cerebrovascular disease, congestive heart failure (CHF) and rhythm disturbances—and was detected in the early stages of the disease. A large proportion of patients with mild and moderate COPD die due to CVD, which is much more likely than deaths in the same group due to respiratory insufficiency. COPD patients have a higher rate of hospitalization and death, the cause of which are coronary heart disease (CHD), stroke and CHF. Treatment of COPD today is mainly determined by national and international clinical guidelines, which should pay more attention to the problems of the treatment of COPD patients with comorbid conditions.

Measuring Airway Resistance and Characterizing the Flow‐Volume Envelope with External Expiratory Loading in Healthy Adults

Expiratory flow limitation is a key characteristic in chronic obstructive pulmonary disease (COPD). Increased airway resistance occurs due to bronchoconstriction, destruction of elastic tissue in the airways, and mucus hypersecretion from goblet cells caused by irritation of the epithelium. Obstruction can lead to dynamic hyperinflation, dyspnea, and exercise intolerance. However, increased airway resistance is just one of many abnormalities in COPD and asthma ‐ COPD in particular is an exceedingly heterogeneous disease. Therefore, isolating the effects of expiratory airflow limitation is challenging.PURPOSEIn order to study abnormal lung mechanics in isolation, we measured pulmonary function with and without expiratory loading in healthy adults.METHODSForty‐eight volunteers (26±5 yr, 171.8±10.2 cm, 72.2±13.3 kg) completed spirometry and body plethysmography according to the ATS/ERS standards under three randomized conditions: control, expiratory loading of 7 and 11 cmH2O. The expiratory load was added by installing a threshold inspiratory muscle trainer in reverse. We analyzed the shape of the flow‐volume (F‐V) loops with rectangular area ratio (RAR) using custom MATLab software.RESULTSAirway resistance was increased (F[1.5, 27.5]= 446.0, p&lt;0.05) with 7 and 11 cmH2O vs control (9.20±1.02 and 11.76±1.68 cmH2O vs. 2.53± 0.80 cmH2O). RAR (F[1.9, 77.9]= 3.71, p&gt;0.05) was reduced with 7 and 11 cmH2O vs control (0.45±0.07 and 0.47±0.09L vs. 0.48±0.08L). FEV1 was reduced (F[1.6, 60.38.6]= 67.54, p&lt;0.05) with 7 and 11 cmH2O vs control (3.26±0.82 and 3.23±0.79L vs. 4.03±1.04L). FVC was also reduced (F[1.5, 55.31] = 77.71, p&lt;0.05) with 7 and 11 cmH2O vs control (4.15±1.01 and 4.17±1.02L L vs. 5.05±1.33L L). PEF was reduced (F[1.5, 55.99] = 72.69, p&lt;0.05) with 7 and 11 cmH2O vs control (6.02±1.65 and 5.95±1.85L vs. 8.39±2.85L L). FEV1/FVC (F[1.9, 69.17] = 5.5, p&gt; 0.05) and FRC (F[1.863, 33.53]= 0.93, p&lt;0.05) were not different between resistance conditions or compared to the control.CONCLUSIONSExpiratory loading reduced FEV1, FVC, PEF and provided a doseresponse in airway resistance and RAR. There were no differences in FEV1/FVC. While RAR was reduced with expiratory loading, the magnitude was of little clinical importance. Therefore, a concave expiratory F‐V relationship was consistently absent – a key limitation for model comparison with pulmonary function in COPD. This is most likely due to the imposed resistance being applied outside of the airways, leading to higher airway pressures. The higher airway pressures are likely to resist dynamic airway compression and either maintain the equal pressure point position or possibly move it proximally.

Imposed Expiratory Resistance and Pulmonary Function in Young Healthy Volunteers

Expiratory flow limitation is a primary characteristic in chronic obstructive pulmonary disease (COPD) and asthma. High airway resistance results from bronchoconstriction, destruction of elastic tissue, and mucus hypersecretion caused by irritation of the epithelium. As a result, the airways become narrowed. Obstruction can lead to dynamic hyperinflation, dyspnea, and exercise intolerance. However, increased airway resistance is just one of many abnormalities in COPD and asthma – COPD in particular is an exceedingly heterogeneous disease. Isolating the effects of expiratory airflow limitation, alone, is therefore challenging. In order to study abnormal lung mechanics in isolation, we aimed to test whether adjustable imposed external expiratory resistance in young healthy volunteers produced deficits in the flow‐volume relationship similar to that of patients with COPD or asthma.PURPOSEMeasure pulmonary function in young healthy volunteers with and without imposed external expiratory resistance.METHODSThirty‐nine healthy adults (25.6 ± 4.7 years, 171.6 ± 10.5 cm, 72 ± 13.7 kg, 23 men, 16 women) completed standard pulmonary function testing according to the ATS/ERS standards. The testing included four conditions in random order: control, imposed expiratory loading of 7 cmH2O, 11 cmH2O, and 20 cmH2O. Resistance was imposed with a threshold inspiratory muscle trainer (Vacumed, Ventura, CA) installed in reverse in the spirometer (Parvo Medics, Sandy, UT). Volunteers with FEV1/FVC&lt;0.70 were excluded from analysis (n=6).RESULTSParticipants had reduced FEV1 (F[1.6, 51.8] = 68.2, p &lt; 0.05) at 7 and 11 cmH2O vs. control (3.28 ± 0.84 and 3.26 ± 0.83 L, respectively, vs. 4.10 ± 1.08 L). FVC was reduced (F[1.4, 45.6] = 71.6, p &lt; 0.05) at 7 and 11 cmH2O vs control (4.15 ± 1.05 and 4.16 ± 1.05 L, respectively, vs. 5.10 ± 1.36 L). FEV1/FVC was reduced (F[1.5, 46.5] = 5.4, p &lt; 0.05) at 7 and 11 cmH2O vs control (77.6 ± 8.48 and 78.7 ± 6.18 %, respectively, vs. 80.7 ± 5.30 %). PEF was reduced (F[1.6, 51.5] = 74.7, p &lt; 0.05) with 7 and 11 cmH2O vs control (6.12 ± 1.73 and 6.07 ± 1.91 L/s, respectively, vs. 8.70 ± 2.87 L/s).Volunteers with additional imposed expiratory loading of 20 cmH2O (n=7) had reduced FEV1 (F[3, 18] = 10.6, p &lt; 0.05) at 11 and 20 cmH2O vs. control (3.07 ± 0.52, and 3.15 ± 0.63 L, respectively, vs. 4.09 ± 0.91 L). FVC was reduced (F[1.2, 6.9] = 16.7, p &lt; 0.05) at 7, 11, and 20 cmH2O vs control (4.01 ± 0.76, 3.93 ± 0.74, and 4.04 ± 0.85 L, respectively, vs. 5.02 ± 1.14 L). FEV1/FVC was reduced (F[3, 18] = 2.7, p = 0.08) at 20 cmH2O vs control (78.5 ± 5.99 % vs. 81.9 ± 5.48 %, p &lt; 0.05). PEF was reduced (F[1.3, 7.6] = 12.9, p &lt; 0.05) with 7 and 20 cmH2O vs control (5.76 ± 1.22 and 5.50 ± 1.78 L/s, respectively, vs. 8.05 ± 2.47 L/s).CONCLUSIONSImposed expiratory resistance reduced key spirometric variables. A concave expiratory flow‐volume relationship was consistently absent – a key limitation for model comparison with pulmonary function in COPD. This is most likely due to the external imposed loading leading to higher airway pressures. This likely resists dynamic airway compression and either maintains the equal pressure point position or possibly moves it proximally.

Muscle metabolomics analysis reveals potential biomarkers of exercise‑dependent improvement of the diaphragm function in chronic obstructive pulmonary disease.

Decreased diaphragm function is a crucial factor leading to reduced ventilatory efficiency and worsening of quality of life in chronic obstructive pulmonary disease (COPD). Exercise training has been demonstrated to effectively improve the function of the diaphragm. However, the mechanism of this process has not been identified. The emergence of metabolomics has allowed the exploration of new ideas. The present study aimed to analyze the potential biomarkers of exercise-dependent enhancement of diaphragm function in COPD using metabolomics. Sprague Dawley rats were divided into three groups: COPD + exercise group (CEG); COPD model group (CMG); and control group (CG). The first two groups were exposed to cigarette smoke for 16 weeks to establish a COPD model. Then, the rats in the CEG underwent aerobic exercise training for 9 weeks. Following confirmation that exercise effectively improved the diaphragm function, a gas chromatography tandem time-of-flight mass spectrometry analysis system was used to detect the differential metabolites and associated pathways in the diaphragm muscles of the different groups. Following exercise intervention, the pulmonary function and diaphragm contractility of the CEG rats were significantly improved compared with those of the CMG rats. A total of 36 different metabolites were identified in the comparison between the CMG and the CG. Pathway enrichment analysis indicated that these different metabolites were involved in 17 pathways. A total of 29 different metabolites were identified in the comparison between the CMG and the CEG, which are involved in 14 pathways. Candidate biomarkers were selected, and the pathways analysis of these metabolites demonstrated that 2 types of metabolic pathways, the nicotinic acid and nicotinamide metabolism and arginine and proline metabolism pathways, were associated with exercise-induced pulmonary rehabilitation.

Association of plasma roundabout 4 concentration with pulmonary ventilation function decline in COPD patients

Objective: To investigate the association of plasma roundabout 4 concentration with pulmonary ventilation function decline in chronic obstructive pulmonary disease (COPD) patients. Methods: To get the effective data, the study was conducted in the outpatient department of West China Hospital from September 2017 to September 2018. The subjects meeting the inclusion and exclusion criteria were continuously included. Among them, the COPD group (75 cases) was from the respiratory outpatient department, and the healthy control group (57 cases) was from the health examination center at the same time. Data of basic demographic characteristics, clinical characteristics, pulmonary ventilation function parameters and blood samples were collected. The concentrations of roundabout 4, C reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1b and tumor necrosis factor (TNF)-α in plasma were detected, and the differences among groups were compared, the correlation between plasma roundabout 4 and pulmonary ventilation function parameters and inflammatory factors was analyzed. The diagnostic efficiency of roundabout 4 to COPD was analyzed according to receiver operating characteristic (ROC) curve. Results: The plasma concentration of roundabout 4 in COPD group was significantly higher than that in healthy control group [(41.3±14.2) vs (27.7±13.3) ng/L; P<0.001], the sensitivity and specificity of roundabout 4 in the diagnosis of COPD were 0.827 and 0.702 respectively. Correlation analysis showed that the plasma concentration of roundabout 4 was negatively correlated with lung function parameters forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), the first second forced expiratory volume as a percentage of the estimated value (FEV(1)%pred), forced exhalation of 50% and 25% lung capacity (MEF50, MEF25) and maximal mid-expiratory flow (MMEF) (r=-0.399, -0.321, -0.439, -0.363, -0.458; all P<0.001), positively correlated with CRP (adjusted r=0.311, P<0.001). Conclusion: The increased concentration of roundabout 4 in plasma leads to the decline of pulmonary ventilation function in COPD patients.

Plasma Cathelicidin is Independently Associated with Reduced Lung Function in COPD: Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.

The antimicrobial peptide cathelicidin, also known in humans as LL-37, is a defensin secreted by immune and airway epithelial cells. Deficiencies in this peptide may contribute to adverse pulmonary outcomes in chronic obstructive pulmonary disease (COPD). Using clinical and biological samples from the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we assessed the associations of plasma cathelicidin levels with cross-sectional and longitudinal COPD outcomes. A total of 1609 SPIROMICS participants with COPD and available plasma samples were analyzed. Cathelicidin was modeled dichotomously (lowest quartile [< 50 ng/ml] versus highest 75% [≥ 50 ng/ml]) and continuously per 10 ng/ml. Fixed-effect multilevel regression analyses were used to assess associations between cathelicidin and cross-sectional as well as longitudinal lung function. The associations between cathelicidin and participant-reported retrospective and prospective COPD exacerbations were assessed via logistic regression. Cathelicidin < 50 ng/ml (N=383) was associated with female sex, black race, and lower body mass index (BMI).At baseline,cathelicidin < 50 ng/ml was independently associated with 3.55% lower % predicted forced expiratory volume in 1 second (FEV1)(95% confidence interval [CI] -6.22% to -0.88% predicted; p=0.01), while every 10 ng/ml lower cathelicidin was independently associated with 0.65% lower % predicted FEV1 (95% CI -1.01% to -0.28% predicted; p< 0.001). No independent associations with longitudinal lung function decline or participant-reported COPD exacerbations were observed. Reduced cathelicidin is associated with lower lung function at baseline. Plasma cathelicidin may potentially identify COPD patients at increased risk for more severe lung disease.

Bu-Shen-Fang-Chuan formula attenuates T-lymphocytes recruitment in the lung of rats with COPD through suppressing CXCL9/CXCL10/CXCL11-CXCR3 axis

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible airflow limitation. The current medications show limited effects on the decline of pulmonary function in COPD. Our multicenter clinical trial found that Bu-Shen-Fang-Chuan fomula (BSFCF), a Chinese herbal formula, markedly reduced the frequencies of acute exacerbation of COPD and delayed lung function decline. However, the underlying mechanisms are still unclear. In this study, we established a COPD rat model through a 6-month exposure to cigarette smoke (CS) and found that BSFCF (7.2 g/kg) effectively improved CS-induced reduction in pulmonary function and remarkably decreased the numbers of inflammatory cells in bronchoalveolar lavage fluid (BALF). Importantly, BSFCF treatment notably prevented the accumulation of T-lymphocytes (especially CD8+ T-cells) in the lung of COPD rats. RNA sequencing analysis of lung tissue demonstrated that CXCL9/CXCL10/CXCL11-CXCR3 chemokine axis in the lung of CS-exposed rats was significantly suppressed by BSFCF. Moreover, our Real-time PCR data verified that BSFCF evidently inhibited the mRNA expressions of CXCL9, CXCL10, CXCL11 and CXCR3. Conclusively, BSFCF markedly improved pulmonary function and attenuated CD8+ T-cells recruitment in the lung of CS-exposed rats, which were partially through inhibition of CXCL9/CXCL10/CXCL11-CXCR3 axis.

Mitochondria: at the crossroads of regulating lung epithelial cell function in chronic obstructive pulmonary disease.

Disturbances in mitochondrial structure and function in lung epithelial cells have been implicated in the pathogenesis of various lung diseases, including chronic obstructive pulmonary disease (COPD). Such disturbances affect not only cellular energy metabolism but also alter a range of indispensable cellular homeostatic functions in which mitochondria are known to be involved. These range from cellular differentiation, cell death pathways, and cellular remodeling to physical barrier function and innate immunity, all of which are known to be impacted by exposure to cigarette smoke and have been linked to COPD pathogenesis. Next to their well-established role as the first physical frontline against external insults, lung epithelial cells are immunologically active. Malfunctioning epithelial cells with defective mitochondria are unable to maintain homeostasis and respond adequately to further stress or injury, which may ultimately shape the phenotype of lung diseases. In this review, we provide a comprehensive overview of the impact of cigarette smoke on the development of mitochondrial dysfunction in the lung epithelium and highlight the consequences for cell function, innate immune responses, epithelial remodeling, and epithelial barrier function in COPD. We also discuss the applicability and potential therapeutic value of recently proposed strategies for the restoration of mitochondrial function in the treatment of COPD.

Measuring and monitoring skeletal muscle function in COPD: current perspectives.

Skeletal muscle dysfunction is an important systemic consequence of chronic obstructive pulmonary disease (COPD) that worsens the natural cause of the disease. Up to a third of all people with COPD express some form of impairment which encompasses reductions in strength and endurance, as well as an increased fatigability. Considering this complexity, no single test could be used to measure and monitor all aspects of the impaired skeletal muscle function within the COPD population, resulting in a wide range of available tests and measurement techniques. The aim of the current review is to highlight current and new perspectives relevant to skeletal muscle function measurements within the COPD population in order to provide guidance for researchers as well as for clinicians. First of all, standardized and clinically feasible measurement protocols, as well as normative values and predictive equations across the spectrum of impaired function in COPD, are needed before assessment of skeletal muscle function can become a reality in clinical praxis. This should minimally target the quadriceps muscle; however, depending on the objective of measurements, eg, to determine upper limb muscle function or walking capacity, other muscles could also be tested. Furthermore, even though muscle strength measurements are important, current evidence suggests that other aspects, such as the endurance and power capacity of the muscle, should also be considered. Moreover, although static (isometric) measurements have been favored, dynamic measurements of skeletal muscle function should not be neglected as they, in a larger extent than static measurements, are related to tasks of daily living. Lastly, the often modest relationships between functional tests and skeletal muscle function measurements indicate that they evaluate different constructs and thus cannot replace one another. Therefore, for accurate measurements of skeletal muscle function in people with COPD, specific and formal measurements should still be prioritized.

Statins versus placebo for people with chronic obstructive pulmonary disease

Statins versus placebo for people with chronic obstructive pulmonary disease

The effect of pulmonary rehabilitation on carotid chemoreceptor activity and sensitivity in chronic obstructive pulmonary disease.

Recent work demonstrates that carotid chemoreceptor (CC) activity/sensitivity is elevated in patients with chronic obstructive pulmonary disease (COPD) compared with healthy controls, and this elevated chemoreception appears to contribute to increased cardiovascular risk. Exercise training has been shown to normalize CC activity/sensitivity in other populations, and therefore, the purpose of this study was to determine whether pulmonary rehabilitation (PR) can reduce CC activity/sensitivity in COPD. Forty-five COPD patients [mean FEV1 (forced expiratory volume in 1 s) = 56.6% predicted] completed PR, while 15 COPD patients (mean FEV1 = 74.6% predicted) served as non-PR controls. CC activity was determined by the reduction in ventilation while breathing transient hyperoxia ([Formula: see text] = 1.0); CC sensitivity was evaluated by the increase in ventilation relative to the drop in arterial saturation while breathing hypoxia. Dyspnea, six-minute walk and autonomic function data were also obtained. PR improved 6-minute walk distance (P < 0.001) and dyspnea (P = 0.04); however, there was no effect on CC activity (P = 0.60), sensitivity (P = 0.69), or autonomic function (P > 0.05 for all). Subgroup analyses indicated that PR reduced CC activity in those with elevated baseline CC activity, independent of changes in autonomic function. No change in dyspnea (P = 0.24), CC activity (P = 0.19), sensitivity (P = 0.80), or autonomic function (P > 0.05 for all) was observed in the control group. Despite improvements in exercise tolerance and dyspnea, PR appears to be generally ineffective at reducing CC sensitivity in stable COPD patients; while PR reduced CC activity in those with elevated basal CC activity, the physiological significance of this is unclear. Further investigations aimed at improving CC function in COPD are needed.NEW & NOTEWORTHY While work in other chronic diseases has shown that exercise training may help normalize carotid chemoreceptor (CC) activity/sensitivity, the current study found that exercise training through pulmonary rehabilitation did not consistently reduce CC activity/sensitivity in patients with chronic obstructive pulmonary disease (COPD). These results suggest that other interventions are needed to normalize CC activity/sensitivity in COPD.

Advances in research on the role of alveolar macrophage burial function in chronic obstructive pulmonary disease

As one of the top three causes of death in the world, chronic obstructive pulmonary disease (COPD)is a serious hazard to human health. Macrophages play an important role in COPD, and their efferocytosis function is essential for ending chronic inflammation of COPD. Efferocytosis damage of alveolar macrophages (AM) in patients with COPD causes the rising of bacterial infection and airway bacterial colonization risk in lungs, which is the main reason for the acute exacerbation and the rising of incidence rate and mortality rate in COPD. In recent years, the regulation of macrophage efferocytosis function in COPD has becoming a research hotspot. Progress on the role of macrophage efferocytosis function on COPD, and the breakthrough points of improving AM efferocytosis dysfunction by traditional Chinese medicine is reviewed, so as to provide new ideas for the prevention and treatment of COPD.