Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.

Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications. Because lung stem cells are crucial for the regeneration of lung tissue following injury, we hypothesized that airway stem cells from patients with COPD with lung cancer might contribute to increased radiation sensitivity. We used the air-liquid interface model, a three-dimensional (3D) culture system, to compare the radiation response of primary human airway stem cells from healthy and patients with COPD. We found that COPD-derived airway stem cells, compared to healthy airway stem cell cultures, exhibited disproportionate pathological mucociliary differentiation, aberrant cell cycle checkpoints, residual DNA damage, reduced survival of stem cells and self-renewal, and terminally differentiated cells post-irradiation, which could be reversed by blocking the Notch pathway using small-molecule γ-secretase inhibitors. Our findings shed light on the mechanisms underlying the increased radiation sensitivity of COPD and suggest that airway stem cells reflect part of the pathological remodeling seen in lung tissue from patients with lung cancer receiving thoracic RT.

Development and Validation of an Evidence-Based Home Pursed Lip Breathing Protocol for Improving Health Outcomes in Patients With Chronic Obstructive Pulmonary Disease.

AIM: To develop and validate an evidence-based home pursed lip breathing (PLB) intervention protocol for improving related health outcomes (e.g., dyspnea and exercise capability) in patients with chronic obstructive pulmonary disease (COPD) and to present a detailed intervention development process. METHODS: This home PLB intervention protocol employed phase one of the Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions to guide the development process of the PLB intervention. We searched for research evidence on 5 July 2023 from several databases, including PubMed, Embase (via Ovid), Cochrane Library, Google Scholar and China Biology Medicine Disk (CBM). Using the content validity index, a panel of experts assessed the appropriateness of the PLB protocol. RESULTS: We developed the preliminary home PLB intervention protocol on the basis of several underlying rationales, which encompass the extension of expiration time, enhancement of respiratory muscle strength, augmentation of tidal volume and integration of the most reliable research evidence obtained from four systematic reviews, five RCTs, five clinical trials, and 10 recommendations. We structured the PLB intervention with a designated time ratio of inspiration to expiration, set at 1:2. Additionally, this study recommends that the training parameters of the PLB intervention were as follows: three sessions per day, each lasting for 10 min, over 8 weeks. Individualised PLB training intensity adjusted the inhalation component according to each participant's tolerance level while emphasising the exhalation phase to ensure the complete expulsion of air from the lungs. The home PLB intervention protocol established strong content validity through consensus, which was reached among all panel experts. The item-level and scale-level content validity indices (CVIs) reached a maximum score of 1.0, indicating a high level of agreement and credibility in the protocol's content as evaluated by the expert panel. CONCLUSION: An optimal evidence-based home PLB protocol has been adapted and developed to manage health-related outcomes of patients with COPD. The protocol is transparent and fully supported by relevant mechanisms, concrete evidence, recommendations and experts' consensus. IMPLICATIONS FOR PRACTICE: In this study, we consulted patients with COPD about the 'Prepared Conditions Before PLB Practice', to ensure appropriate measures to prevent patients with COPD from potential risks. In addition, patients with COPD also contributed to the PLB exercise frequency distribution.

Role of exosomes in exacerbations of asthma and COPD: a systematic review.

Asthma and chronic obstructive pulmonary disease are chronic respiratory disorders characterized by airways obstruction and chronic inflammation. Exacerbations lead to worsening of symptoms and increased airflow obstruction in both airways diseases, and they are associated with increase in local and systemic inflammation. Exosomes are cell-derived membrane vesicles containing proteins, lipids, and nucleic acids that reflect their cellular origin. Through the transfer of these molecules, exosomes act as mediators of intercellular communication. Via selective delivery of their contents to target cells, exosomes have been proved to be involved in regulation of immunity and inflammation. Although, exosomes have been extensively investigated in different diseases, little is currently known about their role in asthma and COPD pathogenesis, and particularly in exacerbations. This review aims to systemically assess the potential role of exosomes in asthma and COPD exacerbations.

Roles of pigment epithelium-derived factor in exercise-induced suppression of senescence and its impact on lung pathology in mice.

Senescent cells contribute to tissue aging and underlie the pathology of chronic diseases. The benefits of eliminating senescent cells have been demonstrated in several disease models, and the efficacy of senolytic drugs is currently being tested in humans. Exercise training has been shown to reduce cellular senescence in several tissues; however, the mechanisms responsible remain unclear. We found that myocyte-derived factors significantly extended the replicative lifespan of fibroblasts, suggesting that myokines mediate the anti-senescence effects of exercise. A number of proteins within myocyte-derived factors were identified by mass spectrometry. Among these, pigment epithelium-derived factor (PEDF) exerted inhibitory effects on cellular senescence. Eight weeks of voluntary running increased Pedf levels in skeletal muscles and suppressed senescence markers in the lungs. The administration of PEDF reduced senescence markers in multiple tissues and attenuated the decline in respiratory function in the pulmonary emphysema mouse model. We also showed that blood levels of PEDF inversely correlated with the severity of COPD in patients. Collectively, these results strongly suggest that PEDF contributes to the beneficial effects of exercise, potentially suppressing cellular senescence and its associated pathologies.

Advances in inhaler therapy for asthma and chronic obstructive pulmonary disease: a comprehensive review of Fostair™ and Trimbow™.

The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions. Fostair™ and Trimbow™, two pressurized metered dose inhalers, have emerged as noteworthy therapeutic options for treating both asthma and COPD. Fostair combines an inhaled corticosteroid, specifically beclometasone dipropionate, with a long-acting beta2-agonist, formoterol fumarate dihydrate, offering a dual-action approach to mitigate airway inflammation and bronchoconstriction. Conversely, Trimbow integrates a tri-particulate formulation consisting of beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide, providing a comprehensive strategy to target the pathophysiology of COPD and asthma. Recent clinical trials have underscored Trimbow's superior efficacy compared with Fostair, particularly in terms of reducing exacerbation rates and enhancing lung function. However, despite their therapeutic promise, both inhalers encounter challenges, including limited generalizability of study findings and a disparity between in vitro and human trial results. This literature review offers an in-depth analysis of Fostair and Trimbow, delving into their mechanisms of action, clinical applications, and outcomes in human studies for asthma and COPD. Additionally, the review discusses the role of combination therapy in managing respiratory diseases and underscores the necessity for further research to address existing knowledge gaps and optimize therapeutic outcomes.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

What is pre-COPD and do we know how to treat it?

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The lung damage in COPD is associated with an enhanced chronic inflammatory response in the airways and lung tissue to harmful particles or gases. Early detection and treatment of COPD can help manage symptoms and slow the progression of the disease. AREAS COVERED: Status of knowledge regarding early diagnosis, definition of pre-COPD, possible new tools for early diagnosis, possibilities of early treatment, and the results of studies in this population are discussed. Literature search (2014-2024) was done in PubMed, EMBASE, and WoS databases using the keywords COPD, early diagnosis, treatment, smoking, prevention; with additional search of literature in found articles. EXPERT OPINION: No early case-finding programs have been proposed or validated, so we still have many patients diagnosed in the late stage of the disease. Clinically manifest COPD is characterized as typically progressive and irreversible with current therapeutic options. If we aim to reduce the mortality and morbidity from COPD we should target these steps: Prevention; Early diagnosis; Form registries of persons at risk for COPD development; Diagnose preclinical COPD; and discover new preventive therapeutic interventions.

Changes in primary care visits for respiratory illness during the COVID-19 pandemic: a multinational study by the International Consortium of Primary Care Big Data Researchers (INTRePID).

Objectives: The majority of patients with respiratory illness are seen in primary care settings. Given COVID-19 is predominantly a respiratory illness, the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), assessed the pandemic impact on primary care visits for respiratory illnesses. Design: Definitions for respiratory illness types were agreed on collectively. Monthly visit counts with diagnosis were shared centrally for analysis. Setting: Primary care settings in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden and the United States. Participants: Over 38 million patients seen in primary care settings in INTRePID countries before and during the pandemic, from January 1st, 2018, to December 31st, 2021. Main outcome measures: Relative change in the monthly mean number of visits before and after the onset of the pandemic for acute infectious respiratory disease visits including influenza, upper and lower respiratory tract infections and chronic respiratory disease visits including asthma, chronic obstructive pulmonary disease, respiratory allergies, and other respiratory diseases. Results: INTRePID countries reported a marked decrease in the average monthly visits for respiratory illness. Changes in visits varied from -10.9% [95% confidence interval (CI): -33.1 to +11.3%] in Norway to -79.9% (95% CI: -86.4% to -73.4%) in China for acute infectious respiratory disease visits and - 2.1% (95% CI: -12.1 to +7.8%) in Peru to -59.9% (95% CI: -68.6% to -51.3%) in China for chronic respiratory illness visits. While seasonal variation in allergic respiratory illness continued during the pandemic, there was essentially no spike in influenza illness during the first 2 years of the pandemic. Conclusion: The COVID-19 pandemic had a major impact on primary care visits for respiratory presentations. Primary care continued to provide services for respiratory illness, although there was a decrease in infectious illness during the COVID pandemic. Understanding the role of primary care may provide valuable information for COVID-19 recovery efforts and planning for future global emergencies.

Aspergillus fumigatus binding IgA and IgG1 are increased in bronchoalveolar lavage fluid of horses with neutrophilic asthma.

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.

Examining the Impact of Social Support on Psychological Well-Being Among Canadian Individuals With COPD: Implications for Government Policies.

Chronic obstructive pulmonary disease (COPD) is a significant respiratory disease and is globally ranked as the third leading cause of death. In Canada, the direct healthcare costs associated with COPD are estimated to be $1.5 billion annually. This study utilized quantitative analyses to examine the impact of specific dimensions of social support, namely, guidance, reliable alliance, reassurance of worth, attachment, and social integration within a clinically identified population of individuals with COPD who exhibit symptoms of depression and anxiety. The study was based on the Social Provisions Theory and stress-buffering hypothesis, utilizing large-scale population data from Statistics Canada's 2012 Canadian Community Health Survey (CCHS) Mental Health component. On a national scale, individuals were more likely to report a decreased sense of belonging to a group of friends (social integration) and struggle to depend on others in stressful times (reliable alliance) while experiencing symptoms of anxiety and depression. These findings underscore the potential benefits of integrating peer support, socialization initiatives, and caregiver training into clinical programs designed for individuals with COPD.

A Case Report of an Elderly Patient With Cushing's Disease and Multiple Chronic Conditions.

Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.

Inhalation of nicotine-containing electronic cigarette vapor exacerbates the features of COPD by inducing ferroptosis in ßENaC-overexpressing mice.

Introduction: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood. Methods: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics. Results: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells. Discussion: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.

COPD Exacerbations Before and During COVID-19 in France, Germany, Italy, the UK and the US.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation rates before and during this pandemic. Methods: Exacerbation patterns were analysed using electronic medical records or claims data of patients with COPD before (2017-2019) and during the COVID-19 pandemic (2020 through early 2022) in France, Germany, Italy, the United Kingdom and the United States. Data from each country were analysed separately. The proportions of patients with COPD receiving maintenance treatment were also estimated. Results: The proportion of patients with exacerbations fell 45-78% across five countries in 2020 versus 2019. Exacerbation rates in most countries were reduced by >50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53-22.13% in 2019 to 9.94-34.17% in 2021. Conclusion: Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.

Association of Severe Vitamin D Deficiency with Hospitalization in the Previous Year in Hospitalized Exacerbated COPD Patients.

Purpose: Vitamin D deficiency (VDD, 25-hydroxyvitamin D < 20 ng/mL) has been reported associated with exacerbation of chronic obstructive pulmonary disease (COPD) but sometimes controversial. Research on severe vitamin D deficiency (SVDD, 25-hydroxyvitamin D < 10 ng/mL) in exacerbation of COPD is limited. Patients and Methods: We performed a retrospective observational study in 134 hospitalized exacerbated COPD patients. 25-hydroxyvitamin D was modeled as a continuous or dichotomized (cutoff value: 10 or 20 ng/mL) variable to evaluate the association of SVDD with hospitalization in the previous year. Receiver operator characteristic (ROC) analysis was performed to find the optimal cut-off value of 25-hydroxyvitamin D. Results: In total 23% of the patients had SVDD. SVDD was more prevalent in women, and SVDD group tended to have lower blood eosinophils counts. 25-hydroxyvitamin D level was significantly lower in patients who were hospitalized in the previous year (13.6 vs 16.7 ng/mL, P = 0.044), and the prevalence of SVDD was higher (38.0% vs 14.3%, P = 0.002). SVDD was independently associated with hospitalization in the previous year [odds ratio (OR) 4.34, 95% CI 1.61-11.72, P = 0.004] in hospitalized exacerbated COPD patients, whereas continuous 25-hydroxyvitamin D and VDD were not (P = 0.1, P = 0.9, separately). The ROC curve yielded an area under the curve of 0.60 (95% CI 0.50-0.71) with an optimal 25-hydroxyvitamin D cutoff of 10.4 ng/mL. Conclusion: SVDD probably showed a more stable association with hospitalization in the previous year in hospitalized exacerbated COPD patients. Reasons for lower eosinophil counts in SVDD group needed further exploration.

Exercise-Induced Oxygen Desaturation Increases Arterial Stiffness in Patients with COPD During the 6WMT.

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was -0.53 (-0.95 to -0.31) in non-EID group, -0.20 (-1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Real-life evaluation of NIV to CPAP switch in patients with chronic respiratory failure. A case control study.

BACKGROUND: Non-invasive ventilation (NIV) is a standard of care for hypercapnic chronic respiratory failure (CRF). Obstructive sleep apnea syndrome (OSA) frequently contributes to hypoventilation in CRF patients. CPAP improves hypercapnia in selected COPD and obese patients, like NIV. We aimed to describe the profile of patients switching from NIV to CPAP in a cohort of patients on long-term ventilation and to identify the factors associated with a successful switch. METHODS: In this case-control study, 88 consecutive patients who were candidates for a NIV-CPAP switch were compared with 266 controls among 394 ventilated patients treated at the Dijon University Hospital between 2015 and 2020. They followed a standardized protocol including a poly(somno)graphy recorded after NIV withdrawal for three nights. CPAP trial was performed if severe OSA was confirmed. Patients were checked for recurrent hypoventilation after 1 and 23[14-46] nights under CPAP. RESULTS: Patients were 53% males, median age 65 [56-74] years, and median BMI 34 [25-38.5] kg/m2. Sixty four percent of patients were safely switched and remained on long-term CPAP. In multivariate analysis, the probability of a NIV-CPAP switch was correlated to older age (OR: 1.3 [1.01-1.06]), BMI (OR: 1.7 [1.03-1.12]), CRF etiology (OR for COPD: 20.37 [4.2-98,72], OR for obesity: 7.31 [1.58-33.74]), circumstances of NIV initiation (OR for acute exacerbation: 11.64 [2.03-66.62]), lower pressure support (OR: 0.90 [0.73-0.92]), lower baseline PaCO2 (OR: 0.85 [0.80-0.91]) and lower compliance (OR: 0.76 [0.64-0.90]). Among 72 patients who went home under CPAP, pressure support level was the only factor associated with the outcome of the NIV-CPAP switch, even after adjustment for BMI and age (p=0.01) with a non-linear correlation. Etiology of chronic respiratory failure, age, BMI, baseline PaCO2, circumstances of NIV initiation, time under home NIV or NIV compliance were not predictive of the outcome of the NIV-CPAP switch. CONCLUSIONS: A NIV-CPAP switch is possible in real life conditions in stable obese and COPD patients with underlying OSA.

Successful Management of Pasteurella multocida Pneumonia in a Chronic Obstructive Pulmonary Disease Patient: A Case Report Highlighting the Importance of Tailored Antibiotic Therapy.

This report describes a patient with Pasteurella multocida pneumonia. The patient was a man in his 70s with significant comorbid conditions, including chronic obstructive pulmonary disease (COPD), and is an example of the diverse presentations of P. multocida infections increasingly found in the literature. The novelty of this case lies in the manifestation of P. multocida pneumonia in a patient with underlying respiratory conditions and its successful management, outlining a unique clinical scenario and a tailored therapeutic approach. A 71-year-old male with a medical history of COPD, asthma, tremors, hypertension, and arthritis presented to the emergency department with progressive shortness of breath, productive cough, and chest tightness. The initial diagnosis was COPD exacerbation and left lower lobe pneumonia, for which a regimen of ceftriaxone and azithromycin was initiated. The patient's condition was further complicated by the persistence of symptoms. Following sputum culture analysis, P. multocida infection was identified. Consequently, the antibiotic regimen was tailored, transitioning the patient to doxycycline, which led to substantial clinical improvement, enabling discharge with a 10-day course of oral doxycycline. This case elucidates the importance of precise microbiological diagnosis in patients with complex respiratory conditions, as it guides more targeted antibiotic therapy. It highlights the need for clinical vigilance for atypical pathogens like P. multocida in patients with COPD exacerbations, especially when conventional treatment strategies yield suboptimal responses. The successful resolution of the pneumonia underscores the effectiveness of antibiotic stewardship guided by sputum culture findings.

Dissecting causal relationships between immune cells, plasma metabolites, and COPD: a mediating Mendelian randomization study.

Objective: This study employed Mendelian Randomization (MR) to investigate the causal relationships among immune cells, COPD, and potential metabolic mediators. Methods: Utilizing summary data from genome-wide association studies, we analyzed 731 immune cell phenotypes, 1,400 plasma metabolites, and COPD. Bidirectional MR analysis was conducted to explore the causal links between immune cells and COPD, complemented by two-step mediation analysis and multivariable MR to identify potential mediating metabolites. Results: Causal relationships were identified between 41 immune cell phenotypes and COPD, with 6 exhibiting reverse causality. Additionally, 21 metabolites were causally related to COPD. Through two-step MR and multivariable MR analyses, 8 cell phenotypes were found to have causal relationships with COPD mediated by 8 plasma metabolites (including one unidentified), with 1-methylnicotinamide levels showing the highest mediation proportion at 26.4%. Conclusion: We have identified causal relationships between 8 immune cell phenotypes and COPD, mediated by 8 metabolites. These findings contribute to the screening of individuals at high risk for COPD and offer insights into early prevention and the precocious diagnosis of Pre-COPD.

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PURPOSE: This study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. STUDY DESIGN AND METHODS: The present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. RESULTS: ULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. CONCLUSION: The combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.