Chronic Obstructive Pulmonary Disease Comorbidities Research Articles

Assessment of Serum Electrolytes, Biochemical, and Inflammatory Markers in Predicting COVID-19 Severity in COPD Patients

Background: Chronic obstructive pulmonary disease (COPD) is the most prevalent long-term respiratory condition. Patients with COPD experience detrimental effects of COVID-19 infection. Objective: To figure out whether COPD is a risk factor influencing the progression of COVID-19 and to explore the clinical value of laboratory biomarkers to assess the severity of COVID-19 in patients with COPD comorbidity. Methods: In total, 1572 participants aged 35 to 70 years were enrolled to a tertiary hospital in Bangladesh between March 2022 and October 2022. Participants were categorized into four groups: (1) control, (2) COPD, (3) COVID-19, and (4) COVID-19 with COPD, and blood levels of clinical laboratory markers were assessed to analyze how these markers differ among the study groups. Results: COVID-19 patients with COPD had a significantly lower level of sodium (131.81 ± 2.8 mmol/L) and calcium (1.91 ± 0.28 mmol/L), and a significantly higher level of NT-proBNP (568.45 ± 207.40 pg/mL), bilirubin (1.34 ± 0.54 mg/dL), fibrinogen (577.27 ± 145.24 mg/dL), D-dimer (2.97 ± 2.25 μg/mL), C-reactive protein (71.08 ± 62.42 mg/L), interleukin-6 (166.47 ± 174.39 pg/mL), and procalcitonin (0.25 ± 0.30 ng/mL) compared to other study groups patients (p < 0.0001). In addition, the GOLD 4 group demonstrated significantly altered clinical parameters among COVID-19 patients with COPD. Furthermore, NT-proBNP, interleukin 6, D-dimer, C-reactive protein, and fibrinogen demonstrated excellent diagnostic performance in predicting disease severity among the COVID-19 patients with COPD, with a cut-off value of 511.2 pg/mL, 51.375 pg/mL, 1.645 μg/mL, 40.2 mg/L, and 510 mg/dL, respectively. Our results also indicate that inflammatory markers had significant positive correlations with the biochemical and coagulation markers in the COVID-19 patients suffering with COPD (p < 0.0001). Conclusions: NT-proBNP, interleukin 6, D-dimer, C-reactive protein, and fibrinogen are the most potential parameters for differentiating severe cases of COVID-19.

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6months later, and to identify factors associated with these outcomes. We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. ClinicalTrials.gov identifier: NCT02986425. December 8, 2016.

Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis.

Tobacco smoking is a major cause of chronic obstructive pulmonary disease (COPD) and atherosclerotic cardiovascular disease (ASCVD). These diseases share common pathogenesis and significantly influence each other's clinical presentation and prognosis. There is increasing evidence that the mechanisms underlying the comorbidity of COPD and ASCVD are complex and multifactorial. Smoking-induced systemic inflammation, impaired endothelial function and oxidative stress may contribute to the development and progression of both diseases. The components present in tobacco smoke can have adverse effects on various cellular functions, including macrophages and endothelial cells. Smoking may also affect the innate immune system, impair apoptosis, and promote oxidative stress in the respiratory and vascular systems. The purpose of this review is to discuss the importance of smoking in the mechanisms underlying the comorbid course of COPD and ASCVD.

Comparison of cognitive functions and quality of life in chronic obstructive pulmonary disease patients depending on the presence of obstructive sleep apnea syndrome

There are more and more studies that focus on cognitive decline in patients with chronic obstructive pulmonary disease (COPD). Obstructive sleep apnea syndrome (OSAS) is characterized by a repetitive cessation or decrease in airflow due to upper airway obstruction. Chronic sleep disturbance and intermittent hypoxemia lead to neurocognitive changes. Patients with comorbidity of COPD and OSAS may develop more severe nocturnal hypoxia than those with OSAS or COPD alone. At the same time, cognitive dysfunction in elderly patients with comorbidity of OSA and COPD has not been previously studied. Objective. The study the effects of OSAS on cognitive impairment and quality of life in elderly patients with COPD. Materials and methods. We examined 84 patients with COPD of moderate severity, controlled course at the age of 60–74 years (mean age – 66.3±4.1 years), of which the first group consisted of 43 patients with COPD, the second group – 41 patients with COPD and OSA of moderate severity. Results. Patients with COPD and moderate OSA had worse MMSE and EQ-5D-3L scores compared to patients with COPD alone, and were more likely to have dementia on the MMSE scale (MMSE≤24 scores), which may require an individual approach to the treatment of such patients.

Dose-dependent cardiovascular disorders in a rat model with exacerbated emphysema: Implication of inflammation

Chronic obstructive pulmonary disease (COPD) is currently the third cause of death worldwide. Emphysema is an abnormal enlargement of air spaces in the lungs, with destruction of alveolar parishes. Cardiovascular disorders are the most frequent and serious comorbidities of COPD. Their interconnection is poorly understood but several hypotheses have been proposed, including hyperinflation, oxidative stress, and inflammation. In a rat model with exacerbated elastase (ELA)-induced emphysema that develops heart failure with preserved ejection fraction, our goal is to (1) describe the relationship between exacerbated emphysema and cardiovascular hemodynamic disorders, (2) characterize the inflammation status 24 h and 5 weeks after an exacerbation. The model includes a weekly intra-tracheal instillation of ELA, during four weeks with doses of 4, 6 or 10UI. At week 4, lipopolysaccharide (LPS) was instillated with ELA to mimic an exacerbation and approximate clinical conditions. Experiments were performed 24 hours after the last intra-tracheal instillation (ELA + LPS) and at week 9 just before sacrifice. In vivo, we did a cardiac stress test on metabolic treadmill, whole body plethysmography, echocardiography, arterial pressure, and collected blood samples. Ex vivo, we explanted the heart/lung block to assess pulmonary compliance and histology analyses. We identified a respiratory functional impairment proportional to the dose of elastase instilled. An exercise intolerance appeared after the exacerbation and persisted 5 weeks later. We observed a diastolic dysfunction after the exacerbation and at week 9, with a significantly dose dependent increased E/E’ ratio, correlated with the extent of emphysema. A systolic and diastolic arterial hypertension appeared at week 9, especially in the 10UI elastase group. There was an increased lung compliance and decreased elastance. The characterization of inflammation is under investigation. This ELA-LPS animal model presents a chronic profile of heart failure with preserved ejection fraction linked in a dose-dependent manner to the intensity of the emphysema. Cardiopulmonary changes are accompanied by a reduction in exercise tolerance as well as arterial hypertension. This model seems useful to better understand the mechanisms of cardiac changes induced by emphysema. At length, we aim to develop an inhibition of T1 or T2 inflammation pathway, to determine the part played by this inflammation.

Hemodynamic characteristics in patients with pulmonary hypertension and chronic obstructive pulmonary disease: A retrospective monocentric cohort study

BackgroundPulmonary hypertension (PH) is a hemodynamic condition characterized by an abnormal elevation in pulmonary arterial pressures. Several pathophysiological pre-capillary and post-capillary mechanisms have been described. PH is a common complication of chronic obstructive pulmonary disease (COPD), however, the prevalence of each mechanism in the development of PH in patients with COPD has been hardly studied. MethodsWe reported the clinical, functional, hemodynamic characteristics and outcomes of patients diagnosed with COPD and PH among the expert PH center of Nancy between January 1st, 2015 and March 31st, 2021. Results123 patients with COPD and PH were included. Most patients (n=122, 99%) had a pre-capillary mechanism, 9% (n=11) a post-capillary mechanism, and 1% (n=1) an unclassified mechanism. 111 (90%) patients had pure pre-capillary PH and 11 (9%) patients had combined pre- and post-capillary PH. Combined pre- and post-capillary PH group was characterized by higher prevalence of cardiovascular comorbidities and of sleep apnea-hypopnea syndrome, a higher body mass index, lower lung volumes, higher mean pulmonary arterial pressure, pulmonary arterial wedge pressure and right atrial pressure. At follow-up (median 30 months), 52 patients had died, and 11 had undergone lung transplantation. One-year, three-year and five-year transplant-free survival rates were 71%, 29% and 11% respectively. There was no difference on outcomes between groups. ConclusionPH in COPD patients is mostly due to pre-capillary mechanism. However, the existence of various and numerous comorbidities in COPD, especially cardiovascular, can lead to the participation of post-capillary mechanisms in the development of PH. Further studies are needed to confirm these findings and to assess the impact on outcomes and management strategies in these different patients.

The study on association of elevated cardiac biomarker in patients of acute exacerbation of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and also resulting in economic and social burden which is substantial and is significantly increasing with time. Chronic obstructive pulmonary disease is frequently associated with right ventricular loading and pulmonary hypertension. Study aimed to evaluate a possible association between cardiac biomarker levels and adverse events in hospitalized patients with Acute exacerbations of chronic obstructive pulmonary disease comorbidities are important determinants of outcome and quality of life of patients with chronic obstructive pulmonary disease. An observational, cross-sectional study was conducted on 89 patients with AECOPD admitted in the medicine emergency ward of Baba Raghav Das medical college and Nehru Hospital Gorakhpur India. Acute exacerbations of chronic obstructive pulmonary disease were diagnosed according to Global Initiative for chronic obstructive lung disease guidelines. cTnI levels were estimated at the time of admission by method based on chemiluminescence with other investigations. Levels ≥ 0.01ng/ml was taken as positive. Tabulation and statistical analysis were performed using Microsoft Excel and SPSS v.17.0 software. p –value< 0.05 at 95% confidence intervals taken as statistically significant. 89 patients with AECOPD were enrolled, among them mean age was 59.59±8.72. We found that cardiac biomarker elevation (cTnI≥0.01ng/ml) is significantly associated with increased mortality, duration of hospitalization, need of ventilation (both invasive or non-invasive) & cardiovascular morbidity. cTnI positivity predicted increased need of ICU admission and significantly increased duration of hospital stay (P=0.0001). cTnI positivity can prognosticate need of NIV or ventilator support. It was found in our study that ventilator support necessity & mortality was more in cTnI positive patients which shows statical significance (P=0.006).cTnI in AECOPD has close relation with exacerbation od disease, right ventricular dysfunction, so it can be used as prognostic marker for mechanical ventilation requirement in future.

Investigating the comorbidity of COPD and tuberculosis, a computational study

Recent research has shown that people who suffer from chronic obstructive pulmonary disease (COPD) have a greater propensity to contract and develop tuberculosis (TB) than the general population. Not only is the hazard ratio for contracting active tuberculosis triple that of the general population for those with COPD, but that the probability of death from any cause during the first year was double that of the tuberculosis population as a whole. This observation suggests that patients with COPD are less likely to progress to latent tuberculosis infection (LTBI) and are more likely to develop active tuberculosis than the general population. While similar susceptibility rates to TB are known to occur in populations with other ailments of the lung, particularly HIV, emphysema or asthma, patients with COPD (both emphysema and chronic bronchitis) are statistically more at risk for the disease. To examine the comorbidity effects of COPD on tuberculosis disease and granuloma formation, the process by which Mycobacterium tuberculosis (Mtb) is either contained or disseminates, we used a multi-scale model that integrates pathophysiological and immunopathological aspects of COPD and TB. Depicting chronic obstructive pulmonary disease smoker and non-smoker populations, we integrate agent-based models (ABM) of cellular immune response, physiological models of pulmonary capacity for COPD smoker/non-smoker, systems biology models of macrophage immune response to Mtb, and metabolic models to capture intracellular and extracellular Mtb metabolism and proliferation. We use our model to investigate key drivers of disease outcomes of clearance, granuloma-based containment, and disseminated disease in individuals with COPD and TB for smoking and non-smoking populations.

Influence of chronic obstructive pulmonary disease on long-term hospitalization and mortality in patients with heart failure with reduced ejection fraction

BackgroundHeart failure with reduced ejection fraction (HFrEF) can coexist with chronic obstructive pulmonary disease (COPD), which complicates the clinical situation and worsens quality of life. The study used standard diagnostic criteria for detecting COPD in hospitalized HFrEF patients and to survey the influence of other comorbidities and medications on the long-term outcomes of HFrEF + COPD patients.MethodsWe retrospectively recruited patients hospitalized due to HFrEF in a tertiary medical center and examined and followed up clinical outcomes, including length of hospital stay, mortality, and readmission episodes, for a 5-year period. Risk factors for mortality were analyzed using multivariate analysis.ResultsOf the 118 hospitalized HFrEF study participants, 68 had concurrent COPD whereas 50 did not. There was a significant increase in the male predominance, smoking history, higher hemoglobin level and increased length of hospital stay in the HF + COPD group than in the HF-only group. Lower left ventricular ejection fraction was found in the HF and COPD comorbidity group. In multivariate analysis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use independently associated with a beneficial effect on survival in HF patients with COPD. Oral corticosteroid uses and stroke as a comorbidity were independently associated with a shorter time to the first readmission episode.ConclusionIn HFrEF patients, COPD was associated with a prolonged length of hospital stay. ACEI/ARB use might relate to a beneficial effect on survival in HF patients with COPD. The use of maintenance oral corticosteroid in patients with both HF and COPD should be crucially evaluated to determine the clinical benefit and disadvantages.

Multidimensional individualized nutritional therapy for individuals with severe chronic obstructive pulmonary disease: study protocol for a registry-based randomized controlled trial

BackgroundIndividuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD.MethodsAn open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline.DiscussionCurrently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD.Trial registrationClinicalTrials.gov NCT04873856. Registered on May 3, 2021.

Features of Atrial Fibrillation Pathogenesis and Prognosis in Chronic Obstructive Pulmonary Patients during the COVID-19 Pandemic.

Atrial fibrillation (AF) is observed in arterial hypertension, heart failure, ischemic heart disease, and pulmonary pathology, particularly, chronic obstructive pulmonary disease (COPD). COPD in turn is a risk factor for developing these cardiovascular diseases and various arrhythmias. In the coronavirus disease (COVID) situation, such comorbid patients are the most vulnerable group with a high risk of adverse outcomes. The relevance of the relationship between COPD and coronavirus infection is explained by the similarity of clinical and pathophysiological manifestations, creating more difficulties in diagnosing and determining rational treatment. The aim of the current study is to explore the role COPD plays in the onset and progression of AF, especially in the situation of COVID-19. We searched PubMed databases and included studies with information on comorbid patients suffering from COPD and AF, as well as similar patients in the context of COVID-19. A modern view on the problem of comorbidity of COPD and AF is presented. In the presence of cardiorespiratory comorbidity, symptoms of mutual worsening of the clinical course are observed, due to the commonality of some links of pathogenesis, including hypoxia, hemodynamic disturbances, activation of the sympathoadrenal system, systemic inflammation, and development of fibrosis, leading to myocardial remodeling, a decrease in the effectiveness of the therapy, and a worsening prognosis, especially in the context of COVID-19. The results of a study of the features of the pathogenesis and course of AF in COPD are presented, as well as the formation and progression of this comorbid pathology in the context of the COVID-19 pandemic.

Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

Mechanisms Contributing to the Comorbidity of COPD and Lung Cancer.

Lung cancer and chronic obstructive pulmonary disease (COPD) often co-occur, and individuals with COPD are at a higher risk of developing lung cancer. While the underlying mechanism for this risk is not well understood, its major contributing factors have been proposed to include genomic, immune, and microenvironment dysregulation. Here, we review the evidence and significant studies that explore the mechanisms underlying the heightened lung cancer risk in people with COPD. Genetic and epigenetic changes, as well as the aberrant expression of non-coding RNAs, predispose the lung epithelium to carcinogenesis by altering the expression of cancer- and immune-related genes. Oxidative stress generated by tobacco smoking plays a role in reducing genomic integrity, promoting epithelial-mesenchymal-transition, and generating a chronic inflammatory environment. This leads to abnormal immune responses that promote cancer development, though not all smokers develop lung cancer. Sex differences in the metabolism of tobacco smoke predispose females to developing COPD and accumulating damage from oxidative stress that poses a risk for the development of lung cancer. Dysregulation of the lung microenvironment and microbiome contributes to chronic inflammation, which is observed in COPD and known to facilitate cancer initiation in various tumor types. Further, there is a need to better characterize and identify the proportion of individuals with COPD who are at a high risk for developing lung cancer. We evaluate possible novel and individualized screening strategies, including biomarkers identified in genetic studies and exhaled breath condensate analysis. We also discuss the use of corticosteroids and statins as chemopreventive agents to prevent lung cancer. It is crucial that we optimize the current methods for the early detection and management of lung cancer and COPD in order to improve the health outcomes for a large affected population.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is one of the common diseases of the respiratory system. As the disease recurs, damage to the airways and lung tissue gradually worsens, leading to a progressive decline in lung function, affecting the patient's workforce and quality of life, and causing a huge social and economic burden. Diabetes is a common comorbidity of COPD and patients with COPD are at increased risk of developing diabetes, while hyperglycemia can also reduce lung function and contribute to the progression and poor prognosis of COPD. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is a new type of hypoglycemic agent that has been shown to regulate blood glucose levels, reduce inflammatory responses and oxidative stress, and regulate lipid metabolism, among other effects. GLP-1RAs may benefit COPD patients by acting directly on the lung from mechanisms such as reducing the inflammatory response, improving oxidative stress, regulating protease/anti-protease imbalance, improving airway mucus homeostasis, and reducing airway remodeling. This study provides a review of the potential role of GLP-1RAs in COPD and offers new ideas for the prevention and treatment of COPD.

P292 Complications in elderly-onset Inflammatory Bowel Diseases – A population-based study from the epidemiological database of the Israeli IBD Research Nucleus (Epi-IIRN)

Abstract Background The population of elderly-onset (diagnosis &amp;gt;=65 years old) inflammatory bowel disease (IBD) is growing worldwide. Management of this population poses challenges, given the overall increased morbidity at the elderly age. Data related to complications in this population are limited. We performed a population-based study of elderly IBD patients to characterize complications compared with non -IBD matched individuals. Methods As part of the validated epidemiological cohort of the Israeli IBD Research Nucleus (epi-IIRN), we included all elderly-onset IBD patients (age at diagnosis &amp;gt;65 years) from the four Israeli health funds diagnosed from 1.1.2005 until 30.06.2020, covering 98% of the Israeli population. Each IBD case was matched at diagnosis to 3 non-IBD individuals by year of birth, sex, geographic district, and health fund. Comparison of incidence of pneumonia, osteoporotic fractures, bacteremia/septicemia and venous thromboembolism events were made. Time to complication was compared using the Kaplan-Meier survival analysis, stratified by IBD subtype, sex and any exposure of &amp;gt;3 months to immunosuppressive IBD medications. Cox proportional hazard models were sought to explore complications risk adjusted by comorbidities (chronic obstructive pulmonary disease, ischemic heart disease and other diseases). Results A total of 2,163 elderly-onset IBD patients were identified (46% males; 48% with Crohn’s disease, median (IQR) age at inclusion 71 [68, 76] years, exposure to &amp;gt;3 months of systemic CS 25%, thiopurines 10%, methotrexate 3.3%, anti-TNF 10.2%, Vedolizumab 5.7%, Ustekinumab 1.7%) and compared to 6,489 matched non-IBD controls. Median (IQR) follow-up time was 74 (40, 118) months. Incidence rates of pneumonia, fractures, bacteremia and venous thromboembolism are shown in table 1. On univariate analysis event-free survival analyses were similar in IBD and controls in pneumonia (p=0.72), osteoporotic fractures (p=0.79), bacteremia (p=0.085) and venous thromboembolism (p=0.14) Figure 1. Survival analysis remained similar when stratified by sex, IBD subtype and drug exposure. Using the comorbidity adjusted Cox model, the overall HR of pneumonia was 1.04 (95% CI 0.835-1.294), for osteoporotic fractures was 1.026 (95% CI 0.815-1.293); of bacteremia 2.161 (95% CI 0.865-5.397) and of venous thromboembolism 0.579 (95% CI 0.272-1.23). Conclusion In this population-based nation-wide study elderly onset IBD was not associated with increased risk of pneumonia, bacteremia, venous thromboembolism, and osteoporotic fractures compared with matched non-IBD elderly individuals. Studies in other populations are still needed to assess complications risk in diverse populations.

Systemic and Airway Epigenetic Disruptions Are Associated with Health Status in COPD.

Epigenetic modifications are common in chronic obstructive pulmonary disease (COPD); however, their clinical relevance is largely unknown. We hypothesized that epigenetic disruptions are associated with symptoms and health status in COPD. We profiled the blood (n = 57) and airways (n = 62) of COPD patients for DNA methylation (n = 55 paired). The patients' health status was assessed using the St. George's Respiratory Questionnaire (SGRQ). We conducted differential methylation analyses and identified pathways characterized by epigenetic disruptions associated with SGRQ scores and its individual domains. 29,211 and 5044 differentially methylated positions (DMPs) were associated with total SGRQ scores in blood and airway samples, respectively. The activity, impact, and symptom domains were associated with 9161, 25,689 and 17,293 DMPs in blood, respectively; and 4674, 3730 and 5063 DMPs in airways, respectively. There was a substantial overlap of DMPs between airway and blood. DMPs were enriched for pathways related to common co-morbidities of COPD (e.g., ageing, cancer and neurological) in both tissues. Health status in COPD is associated with airway and systemic epigenetic changes especially in pathways related to co-morbidities of COPD. There are more blood DMPs than in the airways suggesting that blood epigenome is a promising source to discover biomarkers for clinical outcomes in COPD.

Assessing Lung Inflammation and Pathology in Preclinical Models ofChronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an incurable disease that is a major cause of mortality and morbidity worldwide. Cigarette smoking is a major cause of COPD and triggers progressive airflow limitation, chronic lung inflammation, and irreversible lung damage and decline in lung function. COPD patients often experience various extrapulmonary comorbid diseases, including cardiovascular disease, skeletal muscle wasting, lung cancer, and cognitive decline which markedly impact on disease morbidity, progression, and mortality. People with COPD are also susceptible to respiratory infections which cause exacerbations of the underlying disease (AECOPD). The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. We and others have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD, and comorbidities of COPD with the goal of identifying novel therapeutic targets. Here we provide a preclinical model and protocols to assess the cellular, molecular, and pathological consequences of cigarette smoke exposure and the development of comorbidities of COPD.

Comorbidities of COPD: Mechanisms and Treatment. Update 2023

Chronic obstructive pulmonary disease (COPD) is chronic disease that affects mostly the lungs but there is growing evidence that it is also a systemic condition associated with a number of accompanying diseases known as comorbidities. Chronic inflammation and oxidative stress are the highlight pathogenic processes that interrelate COPD and comorbidities with additional disease specific risk factors and mechanisms. Through complex interactions COPD increases the risk for certain comorbidities and they in turn have negative impact on health status and contribute to mortality in COPD patients. Treatment of comorbidities in terms of coexistence with COPD may require more specific personalized therapeutic approach. Here we review the pathogenic mechanisms which define COPD as a systemic disease; the most common comorbidities of COPD: cardiovascular disease, diabetes and metabolic syndrome, cachexia, osteoporosis, depression/anxiety and obstructive sleep apnea; the pathways which connect these diseases with COPD and the latest treatment approaches.

Efficacy of Combination Therapy in Patients with Stable Coronary Heart Disease with Comorbid Chronic Obstructive Pulmonary Disease

The objective: to analyze the quality of life (QoL) and functional status after combination therapy in patients with stable coronary heart disease (CHD) and comorbid chronic obstructive pulmonary disease (COPD). Materials and methods. The study included 60 men with stable CHD in combination with COPD. The patients were divided into two groups of 30 people, comparable according to the main indicators. Study group (1) received basic treatment with nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin for CHD and basic COPD treatment with combination of umeclidinium bromide (a long-acting cholinolytic) and vilanterol (a long-acting beta2-agonist). Patients from Group 2 in addition tj the basic treatment received L-arginine in the form of an infusion of 4.2% 100 ml solution for 10 days, followed by oral administration at a dose of 3 g per day. The duration of treatment was 6 months. Quality of life was evaluated by validated standardized non-specific questionnaire «The 36-Item Short Form Health Survey» (SF-36), a validated specific respiratory questionnaire of St. George’s Hospital – St. George’s Respiratory Questionnaire (SGRQ). The functional state of patients before and after treatment was evaluated by cardiorespiratory test, which included the distance 6-minutes walk test (6MWT) according to the standard method in combination with pulse oximetry (SpO2), calculation of desaturation level (ΔSpO2), recording of electrocardiogram and blood pressure before and after exercise. Results. After the treatment, patients in both groups noted a significant improvement in quality of life across all domains of the SF-36 questionnaire, which includes 36 questions with physical and mental components. Patients from group 2 demonstrated better results of treatment in all indicators of physical functioning, general health and vital activity than patients from group 1. The results of the quality of life evaluation according to the specific respiratory questionnaire SGRQ also showed a significant improvement in patients of both groups. In both groups, the distance of 6MWT significantly increased, the heart rate at rest and after exercise decreased, and the level of desaturation decreased. In group 2, the increase in the distance of 6MWT, the decrease of desaturation level was significantly better than in group 1. Conclusions. Rational combination treatment of patients with stable coronary heart disease (CHD) with comorbid chronic obstructive pulmonary disease (COPD) includes nebivolol, valsartan, eplerenone, acetylsalicylic acid, rosuvastatin and a combination of vilanterol and umeclidinium bromide, contributes to improving the quality of life of patients and their functional status. Addition of L-arginine to the basic combination treatment of patients with CHD and COPD increases the efficacy of therapy and improves cardiohemodynamics. Addition of L-arginine to the treatment complex contributed to the additional improvement of the physical and mental patterns of quality of life and indicators of cardiorespiratory test.