High apolipoprotein M serum levels correlate with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is common in patients with aortic aneurysms. Severe COPD is associated with an increased risk of aneurysm rupture and perioperative complications. This study assesses the outcomes of COPD and non-COPD patients after fenestrated-branched endovascular aortic aneurysm repair (FBEVAR). A single institution, retrospective study of FBEVAR patients between 2011 and 2020 compared outcomes between COPD and non-COPD patients. COPD patients were stratified by Global Initiative for Chronic Obstructive Lung Disease criteria and oxygen dependence. Outcome measures included 30-day mortality, pulmonary complications, major adverse events (MAE), and mid-term survival. 387 patients (71% male, age 72 years, interquartile range [68-79]) underwent FBEVAR. 181 patients (47%) had COPD. Smoking history was more frequent in COPD patients (P = .022). Among COPD patients, 20.4% were oxygen-dependent. Technical success, defined as successful delivery of the main aortic endograft and all intended side branches, was 98.4%. 30-day mortality (P = .83) and MAE rates (P = .87) were similar between groups. While not statistically significant, COPD patients had more frequent pulmonary complications (6.1% vs. 2.4%, P = .13) and were more frequently discharged on oxygen (P = .002). There were no differences in intensive care unit or hospital length of stay between groups (P = .29; P = .85, respectively). 5-year survival was similar between groups (P = .10). Oxygen-dependent COPD and severe-very severe COPD were associated with decreased mid-term survival (Hazard Ratio 2.39, P = .048). FBEVAR is safe and effective for treating complex aortic pathology in COPD patients, including oxygen-dependent patients. Patients with more severe COPD were more frequently discharged on oxygen. Mid-term survival was slightly reduced in patients with oxygen-dependent and severe-very severe COPD. Level 3, non-randomized controlled cohort/follow-up study.

Bronchodilatory effects of NVA237, a once daily long-acting muscarinic antagonist, in COPD patients

Targeted Deletion of Jun/AP-1 in Alveolar Epithelial Cells Causes Progressive Emphysema and Worsens Cigarette Smoke–Induced Lung Inflammation

RATIONALE: In patients with chronic obstructive lung disease (COPD), expiratory time constant of the respiratory system varies significantly among lung regions causing the Pendelluft (P) phenomenon, defined as asynchronous alveolar ventilation at the beginning of inspiration. This undetected airflow is configured as an “intrinsic” rebreathing, not measurable at the airway opening, that may contribute to worsening hypercapnia. We previously provided evidence that in COPD patients with acute hypercapnic respiratory failure Pendelluft accounts for more than 50% extra tidal volume measured at the airways opening. Aim of the present study was to assess and, if present, quantitate Pendelluft also in stable patients with severe COPD. We also aimed to investigate P effects on CO2 retention and ventilatory response of these patients. METHODS: in 13 patients (age 76±6 yrs, 12 males, 1 female) with stable severe COPD (FEV1/FVC 53,4%±6,8%, FEV1 44,5±7,3 %predicted) we assessed Tidal volume (VT, L), respiratory rate (RR, breaths/min), minute ventilation (VE, L/min), dynamic intrinsic PEEP (PEEPidyn, cm H2O), static intrinsic PEEP (PEEPistat, cm H2O), lung compliance (Clung, L/cm H2O), and arterial blood gases during a15 minutes spontaneous breathing trial. Pendelluft was calculated as follows: P=(PEEPistat – PEEPidyn)[asterisk]Clung, L, and VEP=P[asterisk]RR, L/min. Statistics: results are expressed as mean±SD; agreement between variables was assessed by simple linear regression; the statistical significance of the regressions was considered for a p value<0.05. RESULTS: According to previous literature, patients had moderate levels of PEEPi, dyn (2,4±1,3 cmH2O), being on average 54% of PEEPi, stat (4,3±1,9 cmH2O). Compliance was 0,13±0,09 L/cmH2O. Pendelluft was quite relevant (0,232±0,223 L), representing a substantantial portion (30% on average) of VT measured at the airway opening. A significant linear relationship was found between P and both (PEEPistat – PEEPidyn) and compliance (p<0,0096 and p=0,0260, respectively) suggesting that both variables contributed to its presence. PaCO2 was still within normal limits (38,7±2,6 mmHg), being significantly and positively correlated with Pendelluft (PaCO2=37,154+6,622[asterisk]P; p=0,0425), but not with VT, RR, or VE. Finally, total ventilatory output (VETOT=VE+VEP) exceeded by about 32% the expected VE in absence of P, fact that allowed a normal PaCO2 notwithstanding the significant “intrinsic” rebreathing (figure 1). CONCLUSIONS: in severe stable COPD patients: 1) significant pendelluft is present because of both expiratory time constant inhomogeneities within lungs and increased compliance; 2) resting PaCO2 depends mainly on the “intrinsic” rebreathing caused by Pendelluft; and 3) some hyperventilation is operated by respiratory system to keep PaCO2normal, causing a significant ventilatory (and inspiratory effort) overload.

Background: Chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH) are common and underdiagnosed medical conditions in India. Prevalence of these chronic diseases is high both in rural and urban areas. However, the exact prevalence of PAH in Indian COPD patients is unclear. Comorbid conditions like PAH have a great impact on the outcome of COPD in the form of severity, exacerbations, morbidity, and mortality. Right heart catheterization remains the gold standard test for diagnosis of PAH, but it is invasive and practically not feasible. Aims and objectives: The present study objective was to screen COPD patients for PAH using two-dimensional transthoracic Doppler echocardiography (ECHO) in Tertiary Care Hospital. Results: A total of 2040 patients with a confirmed diagnosis of COPD were enrolled in the study. Among these patients, 1509 were males (73.9%), 531 were females (23.06%), and 1428 were known or ex-smokers (70%). None of the females were smokers, but there was a history of biomass fuel exposure for >10 years. As per global initiative for chronic obstructive lung disease criteria, mild, moderate, severe, and very severe COPD was noted in 525,629,511, and 375 patients, respectively. When they were screened using ECHO, prevalence of PAH was 41.96% as 856 subjects had PAH. Prevalence of PAH among mild, moderate, severe, and very severe COPD was 23.8%, 34.81%, 48.53%, and 70.4%, respectively. There was a linear relationship between PAH and severity of COPD. Conclusion: PAH is very common in COPD patients in India. As the severity of COPD increased, the frequency and degree of PAH also increased. ECHO is an excellent tool for detection of PAH in COPD patients. All patients with severe to very severe COPD should be routinely screened by ECHO for PAH and with mild to moderate COPD, who have dyspnea out of proportion to their clinical condition should also be screened for PAH.

Background and aim of the work: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Many studies reported a high prevalence of Helicobacter pylori (H. pylori) infection in COPD patients and this may have a role on severity of COPD. To estimate impact of H. pylori infection on exacerbation and severity of COPD. Patients and Methods: A prospective observative study was conducted for one year and included 142 well controlled COPD patients. Participants were classified into two groups; group 1 which included 72 COPD patients with +ve H. pylori infection and group 2 which included 70 COPD patients with -ve H. pylori infection. All participants were submitted to full clinical examination, routine laboratory investigations, CXR, arterial blood gases analysis, spirometry, H. pylori serology and stool antigen and COPD assessment test (CAT). Patients were followed monthly for at least three months. Results: High significant statistical differences were found between both groups regarding; FEV1, FVC, PH, PaO2, which were lower in group 1 when compared to group 2. While CRP, CAT score, PCO2, HCO3 were significantly higher in group 1. COPD severity was higher in group 1 when compared to group 2 where the sever and very sever COPD cases were more abundant in group1. Conclusion: H. pylori infection adds an inflammatory burden in the COPD patients by increasing their CAT and number of COPD exacerbations per year.

Non-T2 severe asthma and chronic obstructive pulmonary disease (COPD) are airway chronic inflammatory disorders with a poor response to corticosteroids. LAS194046, a novel pan-Janus kinase (JAK) inhibitor, shows inhibitory effects on T2 allergic lung inflammation in rats. In this work we analyze the effects of LAS194046, fluticasone propionate and their combination in neutrophils from non-T2 severe asthma and COPD patients in vitro. Neutrophils from 23 healthy subjects, 23 COPD and 21 non-T2 severe asthma patients were incubated with LAS194046 (0.01 nM–1 µM), fluticasone propionate (0.1 nM–1 µM) or their combination and stimulated with lipopolysaccharide (LPS 1 µM). LAS194046 shows similar maximal % inhibition and potency inhibiting IL-8, MMP-9 and superoxide anion release in neutrophils from healthy, COPD and asthma. Fluticasone propionate suppresses mediator release only in neutrophils from healthy patients. The combination of LAS194046 with fluticasone propionate shows synergistic anti-inflammatory and anti-oxidant effects. The mechanisms involved in the synergistic effects of this combination include the increase of MKP1 expression, decrease of PI3Kδ, the induction of glucocorticoid response element and the decrease of ERK1/2, P38 and JAK2/STAT3 phosphorylation compared with monotherapies. In summary, LAS194046 shows anti-inflammatory effects in neutrophils from COPD and severe non-T2 asthma patients and induces synergistic anti-inflammatory effects when combined with fluticasone propionate.

Exhaled breath condensate levels of 8-isoprostane, growth related oncogene α and monocyte chemoattractant protein-1 in patients with chronic obstructive pulmonary disease

Objective To explore the relationship between fat-free mass (FFM) and peak exercise performance in chronic obstructive pulmonary disease(COPD) patients. Methods 26 healthy subjects and 62 stable COPD patients performed incremental cardiopulmonary exercise testing with cycle ergometer. 62stable COPD patients were divided three groups(mild COPD,moderate COPD,severe COPD) according to FEV1%pred, peakVO2, peakLoad, peakO2 pulse, AT were measured during exercise. FFM and routine subjects, peakVO2 ,peakVO2 %pred,peakLoad,peakLoad%pred,peakO2 pulse,peakO2 pulse% pred and AT peakLoad%pred,AT and peakO2 pulse% pred ( r =0. 671,0. 478,0. 423,0. 618, P＜0. 05) in COPD patients.Conclusions FFM is significantly associated with muscle aerobic capacity and exercise tolerance in COPD patients. Key words: Fat-free mass; Chronic obstructive pulmonary disease; Cardiopulmonary exercise testing

We systematically reviewed the current research literature to 1) investigate whether there was a difference in bone mineral density (BMD) between chronic obstructive pulmonary disease (COPD) patients and non-COPD controls, 2) determine the influence of severity and subtype of COPD on BMD, and 3) determine the risk factors for lower BMD in COPD patients. The Web of Science and PubMed databases were searched on September 25, 2023. Studies where BMD was evaluated with computed tomography (CT) or quantitative CT in patients with COPD were included in the review. We collected data on the number of COPD patients, the average age, average body mass index, average predicted forced expiratory volume in one second (%) or Global Initiative for Chronic Obstructive Lung Disease stage, the average of low attenuation areas, the use of corticosteroid therapy, the use of osteoporosis therapy, the average BMD, and the location of BMD measurement. Twelve studies met our review criteria. Although in several studies COPD was associated with a decreased BMD, most of the studies suggested that COPD, especially in its milder forms, was not strongly associated with osteopenia or osteoporosis of the thoracic and lumbar spine.

Background: Cardiovascular diseases associated with chronic obstructive pulmonary disease (COPD) account for 50% of COPD deaths. Autonomic dysfunction and poor pulmonary function increase the cardiovascular risk in COPD patients. Severity of COPD can be assessed by forced expiratory volume in 1 s. Autonomic balance can be assessed by heart rate variability (HRV). There are variations in the reports of COPD patients regarding the level or onset of dysfunction is a sympathetic or parasympathetic system in them. Aims and Objectives: In our study, we intended to assess HRV parameters such as, total power (TP), high frequency normalized units (HFnu), low frequency normalized units (LFnu), LF/HF ratio, mean HR, root mean square of the successive differences (RMSSD), NN50, and pNN50 among different stages of COPD and also to identify the association of these HRV parameters with disease severity. Materials and Methods: It is a cross-sectional study done on (n = 130) male stable COPD patients. Anthropometric parameters, HRV parameters, and pulmonary function test were assessed. Later, based on the Global Initiative for Chronic Obstructive Lung Disease stage criteria (mild, moderate, severe, and very severe), they were divided into four subgroups. Data were analyzed by SPSS 19.0 version software. Kruskal–Wallis test was used to find a statistical difference between the groups. Correlations between the variables were done using Spearman correlation test. Results: LF/HF ratio (2 ± 0.5) was increased when compared to reference value reported by the previous studies. TP, HFnu, and RMSSD levels were significantly decreased in very severe, severe, and moderate COPD patients when compared to mild COPD patients. The mean HR, LFnu, and LF/HF ratio levels were significantly increased in very severe, severe, and moderate COPD patients when compared to mild COPD patients. TP, HFnu, and RMSSD levels negatively correlated with disease severity and mean HR, LFnu, and LF/HF ratio positively correlated with disease severity. Conclusion: We have noted that cardiac autonomic dysfunction in the form of increased sympathetic and reduced parasympathetic activity occurs in COPD patients and the association was more prominent when the disease severity increased.

BackgroundTo explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-β1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD).MethodsSmall airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-β1, and FAM13A were measured in lung tissue samples from COPD and non-COPD patients. The correlations of FAM13A expression with COPD severity and EMT marker expression were evaluated. Gain- and loss-of-function assays were performed to explore the functions of FAM13A in cell proliferation, motility, and TGF-β1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B.ResultsIndependent of smoking status, lung tissue samples from COPD patients exhibited significantly increased small airway thickness and collagen fiber deposition, along with enhanced protein levels of remodeling markers (collagen I, fibronectin, and MMP-9), mesenchymal markers (α-SMA, vimentin, and N-cadherin), TGF-β1, and FAM13A, compared with those from non-COPD patients. FAM13A expression negatively correlated with FEV1% and PO2 in COPD patients. In small airway epithelium, FAM13A expression negatively correlated with E-cadherin protein levels and positively correlated with vimentin protein levels. In BEAS-2B cells, TGF-β1 dose-dependently upregulated FAM13A protein levels. FAM13A overexpression significantly promoted cell proliferation and motility in BEAS-2B cells, whereas FAM13A silencing showed contrasting results. Furthermore, FAM13A knockdown partially reversed TGF-β1-induced EMT marker protein alterations in BEAS-2B cells.ConclusionsFAM13A upregulation is associated with TGF-β1-induced EMT in the small airway epithelium of COPD patients independent of smoking status, serving as a potential therapeutic target for anti-EMT therapy in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the lungs in which inflammatory markers are involved with significant extrapulmonary effects that may contribute to its severity and complications. Moreover, some of the inflammatory markers such as C-reactive protein (CRP) are associated with COPD. Pentraxin 3 (PTX3) is the member of long pentraxins. The aim of the present study was to investigate the level of PTX3 in patients with COPD. Fifty-four COPD patients and 31 controls were enrolled in this study. Demographical data such as age, sex, cigarette smoking status, comorbidities, drugs, habits, and modified Medical Research Council (MMRC) dyspnea scores were recorded. All patients were asked for COPD Assessment Test™ (CAT). The mean age was 65.7 ± 9.8years, 92% male. Plasma levels of PTX3 were found to be markedly higher in COPD patients [1.65 (0.32-12.72) ng/ml] than in controls [1.05 (0.43-3.26) ng/ml; p = 0.005]. On the other hand, PTX3 values did not differ between COPD stages [A, 1.73 (0.69-11.03); B, 1.49 (0.84-12.52); C, 0.79 (0.52-1.06); and D, 2.09 (0.32-12.72); p = 0.27]. The plasma PTX3 levels were positively correlated with MMRC scores. We conclude that circulating PTX3 levels are elevated in COPD patients. Plasma levels of PTX3 were correlated with dyspnea (MMRC scores). But PTX3 levels were not correlated with the severity of COPD.

PurposeTo investigate area under diaphragm (AUD) obtained by dynamic digital radiography (DDR) for the differentiation between normal subjects and chronic obstructive pulmonary disease (COPD) patients.MethodsThis retrospective study included healthy volunteers and COPD patients recruited from 2009 to 2014 at Fukujuji Hospital, who received DDR and pulmonary functional test. AUD was defined as an area under a hemidiaphragm and above the line connecting the ipsilateral costophrenic angle to the top of the hemidiaphragm on DDR image. AUD in full inspiration minus AUD in full expiration (ΔAUD) was also calculated. The diaphragmatic surface was demarcated manually on DDR image to calculate AUD. Three-group comparison of AUD and ΔAUD among normal, mild COPD, and severe COPD subjects was tested with one-way analysis of variance, followed by multiple comparison with Tukey-Kramer method. The diagnostic accuracy of COPD by ΔAUD was assessed using receiver-operating-characteristics (ROC) curve.ResultsSixty-eight participants (36 men, 29 COPD patients) were enrolled. AUD in full inspiration was larger in healthy volunteers than in COPD patients (right, p < 0.001; left, p = 0.02). ΔAUD were different in the three-group comparison (right, normal, 208.7 ± 184.6 mm2, mild COPD, −18.1 ± 117.5 mm2, severe COPD −97.5 ± 150.0 mm2, p < 0.001; left, normal, 254.9 ± 131.5 mm2, mild COPD, −12.5 ± 136.5 mm2, severe COPD, −100.7 ± 134.1 mm2, p < 0.001). ROC curve showed high diagnostic performance of COPD by unilateral ΔAUD (right, area-under curve 0.942; left, area-under-curve 0.965).ConclusionThe value of ΔAUD was smaller according to the severity of COPD. ΔAUD can be helpful in distinguishing healthy subjects from COPD patients.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of coronary artery disease (CAD). Proline-glycine-proline (PGP) is an extracellular matrix-derived chemokine ( matrikine ) that is increased in COPD and known to promote neutrophil chemotaxis, endothelial dysfunction, and vascular inflammation through activation of the CXC Chemokine Receptor 2 (CXCR2). Despite these observations, no study has examined PGP as a marker of CAD within COPD patients. Hypothesis: We hypothesized that circulating PGP is associated with comorbid CAD amongst COPD patients. Methods: Current and former smokers with COPD enrolled in the UAB P rospective R epository for coupling EVE nts to N ovel pa T hways in COPD (PREVENT COPD) cohort underwent phlebotomy and spirometry. Cardiovascular diagnoses were adjudicated by two physician reviewers with access to medical records. CAD was defined as a composite of prior myocardial infarction, coronary revascularization, or by physician diagnosis of CAD. Plasma PGP was measured using a solid-phase extraction method coupled with tandem mass spectrometry. Other known CXCR2 ligands (e.g. GRO alpha, IL-8) were measured by multiplex protein assay. SPSSv27 was used for logistic regression models to measure associations between plasma biomarkers and the presence of CAD. Results: The 104 participants were 60±9 years old, 50% male, and 50% Black race. CAD was prevalent in 21 (21%) of the cohort. Plasma PGP was detectable for all participants (0.05 - 15.1 ng/mL). Participants with CAD had higher PGP concentrations compared to participants without CAD (1.26 vs. 0.52 ng/mL, p=0.042). Similarly, PGP was increased among participants with prior coronary revascularization (p&lt;0.01). Associations between plasma PGP and CAD remained significant after adjustment for FEV1 % predicted and smoking status (OR 1.62, 95%CI 1.02-2.56). Concentrations of other CXCR2 ligands were low and not associated with CAD. Conclusions: Our results highlight PGP as a potentially novel biomarker of CAD among individuals with COPD. Future studies are needed to assess whether plasma PGP is predictive of CAD outcomes in COPD, as well as determine the significance of endothelial CXCR2 activation on the development of atherosclerosis.