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Pulmonary hemodynamics and lung function in patients with COPD and DPLD

Enhanced monocyte migration to CXCR3 and CCR5 chemokines in COPD.

Introduction: Little is known about protease, anti-protease markers in chronic obstructive pulmonary disease (COPD) patients. Objectives: The objective of present study was to identify and try to correlate serum markers of protease and anti-protease with pulmonary functions in different stages of patients with COPD and to determine the ratio of neutrophil elastase/alpha-1-antitrypsin in different stages of COPD patients. Methods: This prospective observational study was carried out in patients with stable COPD. Activities of serum alpha-1-antitrypsin and neutrophil elastase were measured in 220 stable COPD patients and in 60 healthy controls by ELISA method. 220 COPD patients were divided into 4 stages according to severity: stage I, II, III and IV. Results: An increase in serum neutrophil elastase and neutrophil elastase/alpha-1-antitrypsin ratio was observed in COPD patients with the advancement of the stage. In contrast to that, decreased activity of alpha-1-antitrypsin in serum was observed in different stages of COPD and is correlated positively with lung function parameters. Conclusion: From these findings we conclude that as the severity increases there is decrease in alpha-1-antitrypsin resulting in concomitant increase in neutrophil elastase activity causing imbalance between protease-antiprotease in COPD patients and this imbalance is associated with impairment of lung function. The neutrophil elastase/ α-1-antitrypsin ratio can tell us the severity of the chronic obstructive pulmonary disease it may be in terms of increased fibrosis of the lung. Though the magnitude of neutrophil elatase/alpha-1-antitrypsin ratio is minute, still it can be a good marker of pulmonary function in term of severity of the COPD.

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.

To investigate the correlations between lipid ratio/oxidative stress status in chronic obstructive pulmonary disease (COPD) patients and pulmonary hypertension as well as the prognosis. Methods: A total of 120 patients with COPD were randomly selected and served as the COPD group and 30 healthy persons were selected as the control group. The ratios of low density lipoprotein (LDL)/high-density lipoprotein (HDL), triglyceride (TG)/HDL and total cholesterol (TC)/HDL were measured. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) level in the control group and COPD patients were detected. Pulmonary hypertension incidence and 3-year survival rate for COPD patients were statistically analyzed. Spearman rank correlation method was used to analyze relationship between lipid ratio /oxidative stress status and pulmonary hypertension. Results: Compared with control group, the ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA level in the COPD group were increased, while the serum SOD and T-AOC level in the COPD group were decreased; compared with stable period, lipid ratios and MDA levels in the acute period were elevated, while serum SOD and T-AOC levels were reduced (P<0.05). Pulmonary hypertension incidence and 3-year survival rates in the COPD group were 56.67% and 81.67% respectively; the lipid ratios and serum MDA levels in COPD patients with pulmonary hypertension were elevated compared with that in COPD patients without pulmonary hypertension; the serum SOD and T-AOC levels in COPD patients with pulmonary hypertension were reduced compared with that in patients without pulmonary hypertension (P<0.05). Spearman rank correlation analysis showed that ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA levels in COPD patients were positively correlated with 3-years pulmonary hypertension incidence (r=0.752, 0.748, 0.752, 0.748; P<0.05), and negatively correlated with 3-years survival rate (r=-0.722, -0.751, -0.736, -0.748; P<0.05); serum SOD and T-AOC levels in COPD patients were negatively correlated with 3-years pulmonary hypertension (r=-0.711, -0.734; P<0.05), and positively correlated with 3-year survival rate (r=0.726, 0.733; P<0.05). Conclusion: Blood lipid ratio and oxidative stress levels in COPD patients are elevated while antioxidant abilities were attenuated. The lipid ratio and oxidative stress status in COPD patients is closely related to the prognosis of pulmonary hypertension. Therefore, blood lipid ratio and oxidative stress status may be used in evaluation of pulmonary hypertension and prognosis for COPD patients.

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

Background and aimsRecently a multidimensional grading system based on the body mass index (B), degree of airflow obstruction (O), dyspnea (D) and exercise capacity (E) - the BODE index - has begun to be used increasingly for the evaluation of chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to investigate the relationship between the BODE index and disease duration, annual exacerbation and hospitalization rates, health related quality of life and systemic inflammatory markers like C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-8.Materials and methodsIn 88 stable COPD patients we evaluated the body-mass index, pulmonary function tests, Modified Medical Research Council dyspnea scale and six-minute walk test (6 MWT). BODE scores were determined. Disease duration, number of exacerbations and hospitalization in the previous year were recorded. We also performed arterial blood gases analysis, administered the St. George's Respiratory Questionnaire (SGRQ) and measured serum levels of CRP, TNF-α, IL-8.ResultsAccording to BODE score 52% of patients were BODE 1, 21% BODE 2, 15% BODE 3 and 12% were BODE 4. There was a significant relationship between BODE index and COPD stage as classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (p < 0.001). Correlations between BODE score and disease duration (p = 0.011), number of exacerbations (p < 0.001) and hospitalizations (p < 0.001) in the last year were also observed. SGRQ symptom, activity, emotion scores and total scores were found to be significantly correlated to BODE (p < 0.001). Serum CRP levels and BODE were also correlated (p = 0.014); however, no correlation was found between serum levels of TNF-α and IL-8 and BODE.ConclusionsAs the BODE index shows a strong correlation with various prognostic and follow up parameters of COPD and systemic inflammation, its use should be considered for the evaluation of COPD patients.

Background: Identifying comorbidities in chronic obstructive pulmonary disease (COPD) may lead to improved disease management, survival and costs. Objective: To compare comorbidities and associated healthcare use between COPD and non-COPD patients. Methods: COPD patients9 medical records data from primary care in Sweden were linked to primary and secondary care national registries information. Data included prescriptions, mortality, income/social characteristics, and pre- and post-COPD diagnosis comorbidities. Comorbidity prevalence was compared between COPD patients and an age-, gender- and calendar year-matched reference population. Healthcare costs were categorized as COPD- and non-COPD related, and comprised drug costs and primary and secondary care visits. Results: There were 17,545 COPD and 84,514 reference group patients. A higher pre-COPD diagnosis comorbidity of asthma (10.1% vs 5.6%), depression (5.0% vs 2.8%), type II diabetes (5.6% vs 3.8%), osteoporosis (1.3% vs 0.7%), fractures (7.5% vs 5.7%), cardiovascular disease (30.2% vs 21.6%), rheumatoid arthritis (1.5% vs 0.9%), and lung cancer (0.4% vs 0.1%) was observed in COPD patients compared with reference patients. Two years post-diagnosis, the comorbidity rate increased for both the COPD and the reference patients, but the proportion of COPD patients with each comorbidity was considerably higher than for the reference patients. Costs of treating COPD comorbidities were higher than COPD-related costs at all time points (e.g. €8,295 vs €620 for non-COPD vs COPD-related hospital nights, respectively, in 2013). Conclusion: Comorbidities are more prevalent in COPD than non-COPD patients and are the major contributor to healthcare costs.

Chronic obstructive pulmonary disease (COPD) is an incomplete, reversible disease with progressive inflammation obstruction in airways. This study aims to explore the regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in inflammatory response and progression of COPD. 71 bronchoalveolar lavage fluid (BALF) samples were collected, including 59 samples from COPD patients (COPD group) and 12 from patients with normal pulmonary function (control group). The mRNA and protein levels of HIF-1α and epidermal growth factor receptor (EGFR) in BALF were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Serum levels of interleukin-13 (IL-13), IL-9, IL-1, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Hypoxia cell model was constructed by COCl2 induction in human embryonic lung cells. Expression levels of HIF-1α, EGFR and p-AKT in NCI-H1563 cells treated with 740Y-P, the phosphoinositide 3-kinase (PI3K) agonist were detected. Finally, we detected proliferation and apoptosis in NCI-H1563 cells with HIF-1α overexpression by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The mRNA and protein levels of HIF-1α and EGFR were higher in COPD groups compared with those of control group. Serum levels of IL-13, IL-9, IL-1, and TNF-α in COPD patients were elevated. CoCl2 induction in NCI-H1563 cells led to upregulated levels of IL-13, IL-9, IL-1, and TNF-α. 740Y-P treatment remarkably activated EGFR/PI3K/AKT pathway. Overexpressed HIF-1α inhibited proliferation but induced apoptosis of NCI-H1563 cells. HIF-1α was overexpressed in COPD, which upregulated expressions of inflammatory factors via activating the EGFR/PI3K/AKT pathway. The activated EGFR/PI3K/AKT pathway induced by pulmonary inflammation further upregulated HIF-1α expression in a feedback loop, thus aggravating COPD pathological changes.

The IL-33/sST2 axis is associated with inflammation and cardiac stress. This study examined the roles of serum IL-33/sST2 and other inflammatory cytokines in chronic obstructive pulmonary disease (COPD) patients, with or without chronic cor pulmonale (CCP). The levels of serum IL-33 and sST2 in 36 COPD patients without CCP, 42 cases with CCP, and 37 healthy controls (HCs) were analyzed by enzyme-linked immunosorbent assay. The concentrations of serum TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were analyzed by cytometric bead array. The pulmonary function was also determined. The levels of IL-33 in COPD patients were lower than in patients with CCP during the acute episode stage and HCs, and increased as patients transitioned into the stable phase, especially in patients whose modified medical research council scale values decreased. IL-33 levels were correlated positively with FEV1%pre, FVC%pre, FEF50%pre, and MMEF75/25%pre, while they correlated negatively with center airway resistance. There were no differences in the levels of sST2 among these groups. The concentrations of IL-6 and IL-10 in COPD patients during acute episodes were significantly higher, and decreased during stable phases. IL-33 may be considered an important factor in the pathogenesis of COPD, and decreased IL-33 levels may be an indicator of the pulmonary function decline of COPD patients.

The mechanism responsible for the reversibility of airflow limitation in stable chronic obstructive pulmonary disease (COPD) patients is unknown. The aim of this study is to assess the relationship between the reversibility of airflow limitation, the redox balance and the inflammatory cells in the sputum of patients with stable COPD. For this purpose we examined 15 normal healthy control subjects and 20 nonatopic COPD patients. The COPD patients were divided into two groups: reversible COPD (increase in FEV1> 200 ml and/or > or =12> or = after 200 microg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL-4 and IL-6 and TNF-alpha in plasma and sputum. GSH oxidation and protein oxidation were lower in reversible COPD patients than in those with no reversibility. The sputum eosinophil count was significantly higher in the reversible group than in the non-reversible group, and IL-4 concentration was higher in the same patients both in sputum and in plasma. In contrast, IL-6 and TNF-alpha were increased in non-reversible COPD patients in both biological samples. We conclude that airflow reversibility in COPD patients is associated with airway oxidative stress and activation of eosinophil inflammatory pattern in sputum and blood, suggesting that these patients could respond to specific pharmacological treatment.

Bacground: Chronic obstructive pulmonary disease (COPD) is a prevalent chronic inflammatory disorder of the airways. A fundamental aspect of airway remodeling in COPD, following prolonged inflammation, involves specific molecular and phenotypic alterations in airway basal cells (BCs). Preliminary large-scale single-cell analyses of COPD patients have revealed an enrichment of CAVIN2+ BCs. We aim to investigate the mechanistic role of CAVIN2+ BCs in COPD. By doing so, it seeks to offer novel theoretical foundations and potential therapeutic targets for COPD intervention. Methods: This research integrates single-cell data from multiple studies involving lung tissues from COPD patients. After data integration, cell clustering and subgroup identification were performed. Lung tissues and BCs from COPD patients and healthy controls were then collected for further analysis. Using in situ multicolor immunofluorescence, the CAVIN2+ BCs subgroup was identified. Additionally, cell culture and animal experiments were conducted to explore the influence of CAVIN2 on BC proliferation and differentiation. In vitro, CAVIN2 was either overexpressed or knocked out, and its impact on BC proliferation and differentiation was assessed using CCK-8 assays, migration assays, and air-liquid interface differentiation experiments. In vivo, BC differentiation was evaluated through subcutaneous tumor formation in nude mice, with genetic modifications either overexpressing or knocking out CAVIN2. Results: Analysis of large-scale single-cell data revealed a significant enrichment of CAVIN2+ BCs in the airways of COPD patients. Both gene and protein expression levels of CAVIN2 were markedly elevated in COPD patients compared to healthy controls. Further investigations suggested that the AREG/EGFR signaling pathway plays a pivotal role in the interaction between macrophages and CAVIN2+ BCs, influencing the process of airway remodeling in COPD. In situ multicolor immunohistochemistry of lung tissues from COPD and control groups confirmed a higher proportion of CAVIN2+ BCs in COPD airways. In vitro experiments, including CCK-8 and Transwell assays, demonstrated that knocking out CAVIN2 promoted the proliferation and migration of airway basal stem cells, while its overexpression inhibited these processes. Similarly, air-liquid interface differentiation and in vivo differentiation experiments revealed that overexpression of CAVIN2 significantly suppressed BC differentiation. Conclusion: CAVIN2+ BCs play a crucial role in airway remodeling during COPD progression. This study provides new insights into the pathological mechanisms of COPD and lays a theoretical foundation for future COPD therapies targeting stem cell regulation.

The goal of this study was to estimate the prevalence of spirometry testing among patients with asthma and chronic obstructive pulmonary disease (COPD) in general practices (GPs) in Germany. This retrospective cross-sectional study was based on data from the Disease Analyzer database (IQVIA), This retrospective cross-sectional study included all patients with at least one confirmed asthma or COPD diagnosis in one of those 50 general practices in Germany between January 2020, and January 2021, as well as at least one visit to these general practices between January 2021, and January 2022. The main outcomes of the study aimed to ascertain the proportion of spirometry testing among asthma and COPD patients between January 2021, and January 2022, overall, and separately, in men, women, six age groups (≤30, 31-40, 41-50, 51-60, 61, 70, &gt;70), and patients who received at least one prescription of anti-asthma or anti-COPD drugs. This study included 8835 patients with asthma only, 5597 with COPD only, and 1897 with both asthma and COPD diagnoses. Of these, 27.2% of COPD patients, 7% of asthma patients, and 54.7% of asthma + COPD patients, received spirometry testing during the study period. Among COPD and asthma + COPD patients, the prevalence of spirometry testing was much higher in women than in men (COPD: 31.6% vs. 23.2%; asthma + COPD: 59.6% vs. 46.3%) and much higher in treated than in non-treated patients (COPD: 31.7% vs. 15.0%; asthma + COPD: 57.5% vs. 27.8%). The prevalence of spirometry testing was relatively low among COPD and asthma patients followed in GP practices, but usually higher in female patients, treated patients, and patients suffering from both asthma and COPD.

The FGL2/fibroleukin prothrombinase is involved in alveolar macrophage activation in COPD through the MAPK pathway

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterised by a modified inflammatory response to chronic irritants which is often associated with some degree of systemic inflammation. Exacerbations in COPD are characterized by exaggeration of the ongoing inflammation. A number of inflammatory mediators are found to be raised in COPD exacerbations but most of them are expensive and not readily available. The Neutrophil-lymphocyte Ratio (NLR) is a rapid, easy and cheap biomarker that has been shown to be raised in patients of COPD. Aim: To evaluate the role of NLR in patients of stable and acute exacerbation of COPD. Materials and Methods: This cross-sectional observational study was conducted in Department of Pulmonary Medicine at Government Medical College, Patiala, Punjab, India. Study included 150 patients of stable COPD, 150 patients of Acute Exacerbation COPD (AECOPD) and 100 subjects as controls. NLR was calculated from a peripheral blood sample of the study participants. Continuous variables were summarised as mean with standard deviation and compared between groups using Unpaired t-test. A p-value &lt;0.05 was considered statistically significant. Results: The mean age in AECOPD group was 61.7±10.4 years, in stable COPD group was 63.1±8.9 years and 63.2±7.8 years in controls. Mean NLR was found to be highest in AECOPD group (4.0±1.7) followed by stable COPD (2.9±0.8) and then control (1.8±0.4).NLR showed good predictive value for predicting exacerbations in stable COPD patients with sensitivity and specificity of 75.3% and 70.7% respectively (cut-off 3.4 and AUC=0.806). Conclusion: NLR is an easily available biomarker of inflammation and can be used as a predictor of exacerbation in patients of COPD.