Chronic Obstructive Pulmonary Disease Therapy Research Articles

A Cost-Effectiveness Analysis of Azithromycin for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Rationale: Daily oral azithromycin therapy can reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (COPD). However, given its adverse events and additional costs, it is not known whether adding long-term azithromycin as an adjunct therapy to inhaled pharmacotherapy is cost effective. Objectives: The objective of this study was to evaluate the cost-effectiveness of add-on azithromycin therapy in COPD as recommended by contemporary COPD management guidelines. Methods: We extended a previously validated Canadian COPD policy model to include azithromycin-related inputs and outcomes. The cost-effectiveness of azithromycin was evaluated over a 20-year time horizon in patients who continue to exacerbate despite receiving maximal inhaled therapies. The benefit of azithromycin was modeled as a reduction in exacerbation rates. Adverse events included cardiovascular death, hearing loss, gastrointestinal symptoms, and antimicrobial resistance. The incremental cost-effectiveness ratio (ICER) was calculated with costs in 2020 Canadian dollars ($) and quality-adjusted life-years (QALYs) discounted at 1.5% per year. The analysis was stratified among patient subgroups based on exacerbation histories. Results: In patients with a positive exacerbation history (one or more events in the previous 12 mo), azithromycin was associated with $49,732 costs, 7.65 QALYs, and 10.95 exacerbations per patient over 20 years. The corresponding values were $48,436, 7.62, and 11.86 for the reference group, resulting in an ICER of $43,200 per QALY gained. In patients defined as frequent exacerbators (two or more moderate or one or more severe events in the past 12 mo), the ICER was reduced to $8,862 per QALY gained. In patients with no history of exacerbation, azithromycin had lower QALYs and higher costs than the reference group. Conclusions: Add-on azithromycin is cost effective in patients with a recent history of exacerbations at commonly accepted willingness-to-pay thresholds of $50,000-$100,000/QALY. Guidelines should consider recommending add-on azithromycin for patients who had at least one moderate or severe exacerbation in the past year, albeit more information about treatment efficacy would strengthen this recommendation.

Astaxanthin attenuated cigarette smoke extract-induced apoptosis via decreasing oxidative DNA damage in airway epithelium

Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease that is associated with environmental allergic component exposure. Cigarette smoke is an environmental toxicant that induces lung malfunction leading to various pulmonary diseases. Astaxanthin (AST) is a carotenoid that shows antioxidant and anti-inflammatory activities which might be a promising candidate for COPD therapy. In this study, we released that AST could attenuate cigarette smoke-induced DNA damage and apoptosis in vivo and in vitro. AST administration ameliorated cigarette smoke extract (CSE)-induced activation of Caspase-3 and apoptosis. Pretreated mice with AST significantly decrease CSE-induced DNA damage which shows lower nuclear γ-H2AX level. AST treatment also dramatically reduces the production of intracellular reactive oxygen species (ROS) by suppressing the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and dual oxidase 1 (DUOX1). Taken together, this study suggested that AST can decrease CSE-induced DNA damage and apoptosis by inhibiting NOX4/DUOX1 expression that promotes ROS generation. AST may be a potential protective agent against CSE-associated lung disease that is worth in-depth investigation.

Harnessing the Therapeutic Potential of Stem Cells in the Management of Chronic Obstructive Pulmonary Disease: A Comprehensive Review.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition with limited treatment options. Stem cell therapy has emerged as a promising approach for COPD management due to its regenerative and immunomodulatory properties. This review article aims to comprehensively explore the therapeutic potential of stem cells in COPD management. The introduction provides background on COPD, highlighting its impact on health and the need for novel therapies. The different types of stem cells relevant to COPD, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, are described along with their properties and characteristics. The pathogenesis of COPD is discussed, emphasizing the key mechanisms involved in disease development and progression. Subsequently, the role of stem cells in tissue repair, regeneration, and immunomodulation is examined, highlighting their ability to address specific pathological processes in COPD. Mechanisms of action, such as paracrine signaling, immunomodulation, anti-inflammatory effects, and tissue regeneration, are explored. The interaction between stem cells and the host environment, which promotes lung repair, is also discussed. Challenges in stem cell therapy for COPD, including optimal cell sources, delivery methods, safety, and efficacy, are identified. Regulatory considerations and the importance of standardization are emphasized. Potential strategies for optimizing the therapeutic potential of stem cells in COPD management, such as combination therapies and preconditioning techniques, are outlined. Emerging trends and future directions are highlighted, including advanced cell engineering and patient-specific induced pluripotent stem cells. In conclusion, stem cell therapy holds significant promise for COPD management, addressing the limitations of current treatments. Continued research and development are necessary to overcome challenges, optimize therapies, and realize stem cells' full potential in improving the lives of patients with COPD.

Sodium pyruvate exerts protective effects against cigarette smoke extract-induced ferroptosis in alveolar and bronchial epithelial cells through the GPX4/Nrf2 axis

BackgroundFerroptosis in alveolar and bronchial epithelial cells is one of the main mechanisms underlying the development of chronic obstructive pulmonary disease (COPD). Sodium pyruvate (NaPyr) is a natural antioxidant in the body, exhibiting anti-inflammatory and antioxidant activities. NaPyr has been used in a Phase II clinical trial as a novel therapy for COPD; however, the mechanism underlying NaPyr-mediated therapeutic benefits in COPD is not well understood.ObjectiveWe aimed to assess the protective effects of NaPyr and elucidate its potential mechanism in cigarette smoke extract (CSE)-induced ferroptosis.To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, we expose a human bronchial epithelial cells to CSE.MethodsTo minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, the A549 (human lung carcinoma epithelial cells) and BEAS-2B (bronchial epithelial cells) cell lines were cultured, followed by treatment with CSE. To measure cellular viability and iron levels, we determined the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), mitochondrial superoxide (MitoSOX), membrane potential (MMP), and inflammatory factors (tumor necrosis factor [TNF] and interleukin [IL]-8), and examined CSE-induced pulmonary inflammation and ferroptosis. To clarify the molecular mechanisms of NaPyr in COPD therapy, we performed western blotting and real-time PCR (qPCR) to determine the expression of glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (Nrf2), and cyclooxygenase 2 (COX2).ResultsWe found that NaPyr effectively mitigated CSE-induced apoptosis and improved apoptosis induced by erastin, a ferroptosis inducer. NaPyr significantly decreased iron and MDA levels and increased GSH levels in CSE-induced cells. Furthermore, NaPyr suppressed ferroptosis characteristics, such as decreased levels of ROS, MitoSOX, and MMP. NaPyr significantly increases the expression levels of GPX4 and Nrf2, indicating that activation of the GPX4/Nrf2 axis could inhibit ferroptosis in alveolar and bronchial epithelial cells. More importantly, NaPyr inhibited the secretion of downstream inflammatory factors, including TNF and IL-8, by decreasing COX2 expression levels to suppress CSE-induced inflammation.ConclusionAccordingly, NaPyr could mitigate CSE-induced ferroptosis in alveolar and bronchial epithelial cells by activating the GPX4/Nrf2 axis and decreasing COX2 expression levels. In addition, NaPyr reduced the secretion of inflammatory factors (TNF and IL-8), affording a novel therapeutic candidate for COPD.Graphical

Nalmefene combined noninvasive positive-pressure ventilation in Chinese patients with chronic obstructive pulmonary disease coupled with type II respiratory failure: A meta-analysis.

Nalmefene is an opioid system modulator with antagonist activity at the μ and δ receptors and partial agonist activity at the κ receptor. Previous studies have suggested that nalmefene could improve respiratory function in patients with chronic obstructive pulmonary disease (COPD). However, there is no comprehensive systematic review published regarding the clinical efficacy of nalmefene. We explored the following electronic bibliographic databases: EMBASE, Web of Science, PubMed, Wanfang, and Chinese national knowledge infrastructure. To collect data from randomized controlled trials on the therapy of COPD coupled with type II respiratory failure and nalmefene + noninvasive ventilator treatment. The retrieved articles were screened to determine the final inclusion criteria and to extract relevant data, such as the clinical efficacy rate, pulmonary function, blood gas analysis, and adverse reactions. In our study, we used relative risk and weighted mean deviation, as well as a 95% confidence interval for describing nalmefene effectiveness and safety while treating COPD with type II respiratory failure. The outcomes of the meta-analysis demonstrated that the clinical efficacy rate of the nalmefene + noninvasive ventilation group was higher than that of the naloxone + noninvasive ventilation and noninvasive ventilation groups. Moreover, the improvement indices of pH value, partial pressure and saturation of blood oxygen, partial pressure of carbon dioxide, and pulmonary function of the nalmefene + noninvasive ventilation group were better than those of the noninvasive ventilation group, and there was no increase in the occurrence of adverse drug reactions. Nalmefene combined with noninvasive ventilation can significantly improve the blood gas index and lung function in patients with COPD combined with type II respiratory failure.

One-Year Outcomes of Patients Requiring Tracheostomy Placement Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

What are the characteristics of patients who develop the need for tracheostomy due to SARS-CoV-2 with acute respiratory distress syndrome (ARDS)? What is their 90-day and 1-year survival and are there any identifiable risk factors for mortality and ventilator dependency? Retrospective, follow-up cohort study of adult patients with COVID-19 infection and ARDS who required tracheostomy placement in a large healthcare system. One hundred sixty-four consecutive patients with SARS-CoV-2 admitted to ICUs for ARDS who required tracheostomy placement between March 2020 and March 2021 were identified. One hundred nine (66.5%) were male. Average age was 63.5 years. The most common comorbidities were obesity, hypertension, diabetes mellitus, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), atrial fibrillation, and asthma. The most common complications during hospitalization were delirium, secondary infections, acute kidney injury, pneumothorax, and venous thromboembolism. Ninety-day and 1-year mortality were 29.9% and 44.5%, respectively. Ninety-six patients (58.5%) were liberated from the ventilator, and 84 (51.2%) had the tracheostomy tube decannulated. Asthma, COPD, atrial fibrillation, and renal replacement therapy requirement in the ICU correlated with increased risk of ventilator dependency. Among survivors at 1 year, 71 patients (43.3%) were residing at home and 20 patients (12.2%) remained in a skilled nursing facility. COVID-19 has resulted in a significant burden of acute critical illness and acute respiratory failure with the need for tracheostomy. A significant percentage of patients with SARS-CoV-2 requiring tracheostomy were alive and at home 1 year after tracheostomy placement. Long-term care support, including tracheostomy, beyond 90 days appears to be beneficial in this patient population and warrants further investigation.

Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.

Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.

Chronic Obstructive Pulmonary Disease Part 3: Inhaler Technique and Counseling Pearls.

Chronic obstructive pulmonary disease therapy management can be complex given the various types of inhaler devices available, even within a therapeutic class. Appropriateness of an inhaler relies on many patient-specific factors. Senior care pharmacists can positively impact patient care by providing appropriate inhaler assessment as well as education on inhaler technique to ensure maximal benefit from therapeutic treatment choices.

New concept and algorithm for the management of patients with chronic obstructive pulmonary disease

Currently, chronic obstructive pulmonary disease (COPD) is a global problem and one of the leading causes of death worldwide. COPD therapy includes pharmacological and non-pharmacological approaches that can significantly reduce clinical symptoms and decrease the frequency of exacerbations of the disease. Methods. The updates of guidelines for the diagnosis and treatment of COPD is expected to have a significant impact on patients with COPD in clinical practice. Simplification of the treatment algorithms and inclusion of triple therapy will help clinicians provide appropriate and timely treatment to patients with COPD with a focus on reducing the risk of future exacerbations. Recognition of mortality reduction as a treatment goal in COPD supports the increased use of triple therapy, the only pharmacologic intervention shown to improve survival in patients with COPD. Conclusion. Although further guidance and clarification are needed in some areas, such as the use of blood eosinophil count in treatment decisions and the implementation of post-hospitalizaton treatment protocols, the recent guideline updates will help clinicians address current gaps in patient care.

Effectiveness of Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease Therapy: Focusing on Traditional Medical Practices.

Chronic obstructive pulmonary disease (COPD) is a complex and serious disease that is characterized by dyspnea, fatigue, decreased exercise tolerance, peripheral muscle dysfunction, and mood disorders. These manifestations are successfully treated with pulmonary rehabilitation, a comprehensive intervention and holistic approach designed to improve the physical and psychological condition of people with COPD. Exercise is a big component of pulmonary rehabilitation programs, but the efficacy of non-traditional forms of exercise as used in alternative medicine is poorly understood. Here, we aim to address this gap in knowledge and summarize the clinical evidence for the use of traditional exercise regimens in the pulmonary rehabilitation of COPD patients.

The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD.

Over the past 22years, annual GOLD Reports have documented important changes in guidance and recommendations for uniformly treating patients with chronic obstructive pulmonary disease (COPD) with the goal of improving outcomes in patients suffering from this condition. The most recent GOLD Report, released in 2023, shows continued refinement in several areas, including more precise definitions of COPD and exacerbations of COPD, a new set of parameters to assess exacerbation severity, an updated COPD assessment tool, updated guidelines for initial and follow-up treatment, new information regarding the association between pharmacological triple therapy and reduction in mortality, and new discussions of inhaler device choice and adherence to COPD medications. Whereas we do not address all of the new or updated material in GOLD's 2023 Report, we summarize key changes in GOLD's recommendations regarding inhalation therapy for stable COPD and frame these changes in the context of previous GOLD recommendations.

Design and methods of a randomized trial testing "Advancing care for COPD in people living with HIV by implementing evidence-based management through proactive E-consults (ACHIEVE)"

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbid diseases among aging people with HIV (PWH) and is often mismanaged. To address this gap, we are conducting the study, “Advancing care for COPD in people living with HIV by Implementing Evidence-based management through proactive E-consults (ACHIEVE).” This intervention optimizes COPD management by promoting effective, evidence-based care and de-implementing inappropriate therapies for COPD in PWH receiving care at Veteran Affairs (VA) medical centers. Study pulmonologists are proactively supporting ID providers managing a population of PWH who have COPD, offering real-time evidence-based recommendations tailored to each patient. We are leveraging VA clinical and informatics infrastructures to communicate recommendations between the study team and clinical providers through the electronic health record (EHR) as an E-consult. If effective, ACHIEVE could serve as a model of effective, efficient COPD management among PWH receiving care in VA. This paper outlines the rationale and methodology of the ACHIEVE trial, one of a series of studies funded by the National Heart, Lung, and Blood Institute (NHLBI) within the ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (PRECluDE) consortium to study chronic disease comorbidities in HIV populations.

Theophylline for the management of respiratory disorders in adults in the 21st century: A scoping review from the American College of Clinical Pharmacy Pulmonary Practice and Research Network.

Theophylline is an oral methylxanthine bronchodilator recommended as alternate therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD). However, it is not generally recommended for the treatment of other respiratory disorders such as obstructive sleep apnea (OSA) or hypoxia. Most clinical practice guidelines rely on evidence published prior to the year 2000 to make these recommendations. This scoping review aimed to gather and characterize evidence describing theophylline for the management of respiratory disorders in adults between January 1, 2000 and December 31, 2020. Databases searched included Ovid MEDLINE, Embase, CINAHL Complete, Scopus, and International Pharmaceutical Abstracts. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Studies were included if they were published in English, theophylline was used for any respiratory disorder, and the study outcomes were disease- or patient-oriented. After removal of duplicates, 841 studies were screened and 55 studies were included. Results aligned with current clinical guideline recommendations relegating theophylline as an alternative therapy for the treatment of respiratory disorders, in favor of inhaled corticosteroids and inhaled bronchodilators. This scoping review identified the need for future research including: theophylline versus other medications deemed alternative therapies for asthma and COPD, meta-analyses of low-dose theophylline, and studies evaluating evidence-based patient-oriented outcomes for OSA, hypoxia, ventilator-induced diaphragmatic dysfunction, and spinal cord injury-related pulmonary function.

Pulmonary rehabilitation assessment in COPD based on the ICF brief core set: a latent profile analysis

Background Chronic obstructive pulmonary disease (COPD) is the most burdened chronic respiratory disease in the world, resulting in a reduced quality of life and limited physical activity for patients. Pulmonary rehabilitation (PR) is an effective therapy for COPD. Effective PR relies on an accurate pulmonary rehabilitation program. An adequate pre-rehabilitation assessment helps healthcare professionals to develop an accurate pulmonary rehabilitation program. However, pre-rehabilitation assessment strategies lack specific selection criteria and an assessment of the patient’s overall functioning. Methods This study explored the functional characteristics of COPD patients before pulmonary rehabilitation and collected COPD patients from October 2019 to March 2022. A cross-sectional survey of 237 patients was conducted using the ICF brief core set as the study tool. Latent profile analysis identified subgroups of patients with different rehabilitation needs based on body function and activity participation. Results Four subgroups of functional dysfunction were identified: 5.42%, 21.03%, 29.44%, and 34.11% in the high dysfunction group, the moderate dysfunction group, the lower-middle dysfunction but high mobility impairment group, and the low dysfunction group, respectively. Patients in the high dysfunction group were older, had a higher proportion of widowed spouses, and experienced more exacerbation. Most patients in the low-dysfunction group did not use inhaled medication and had a lower participation rate in oxygen therapy. Patients with a more severe disease classification and symptom burden mostly belonged to the high dysfunction group. Conclusions COPD patients require an adequate assessment before implementing a pulmonary rehabilitation program to determine their rehabilitation needs. The four subgroups were heterogeneous in terms of the degree of functional impairment in body function and activity participation. Patients in the high dysfunction group can improve basic cardiorespiratory fitness; patients in the moderate dysfunction group should focus on improving cardiorespiratory endurance and muscle fitness, patients in the lower-middle-dysfunction but high mobility impairment group should focus on improving mobility and patients in the low functional disability group should focus more on preventive measures. Healthcare providers can tailor rehabilitation programs to the functional impairments of patients with different characteristics. Trial registration This study has been registered in the Chinese Clinical Trials Registry (ChiCTR2000040723).

Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists.

To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables. In Search A, we identified 165150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19696 prescriptions; C:1145) and SAMA inhalers (A and B:35310; C:564). We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.

MANAGEMENT OF PULMONAL HYPERTENSION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is an obstructive pulmonary disease due to inflammatory processes of the respiratory tract and lung parenchyma. In some cases of COPD, changes in the pulmonary vessels are found which are not uncommon, causing impaired gas exchange and causing pulmonary hypertension which is associated with increased morbidity and mortality. Pulmonary hypertension is an increase in the mean pulmonary artery pressure (Pulmonary Arterial Pressure) greater than or equal to 25 mmHg at rest as assessed by a right heart catheterization procedure. Pulmonary hypertension (HP) can exacerbate the occurrence of COPD where HP patients with COPD must receive optimal COPD management according to GOLD guidelines. Pulmonary hypertension can be caused by a variety of conditions which WHO divides into five major groups. Pulmonary hypertension in patients with COPD belongs to the third group. The pathophysiology of pulmonary hypertension in patients with hypoxia or chronic lung disease is caused by tunica media hypertrophy and tunica intima proliferation leading to distal pulmonary artery obstruction. Clinical and physical symptoms in HP patients in COPD usually overlap. If HP is suspected, echocardiography is the best initial examination. Definitive diagnosis obtained through right heart catheterization. In contrast to idiopathic pulmonary hypertension, examination of the vasoreactivity of blood vessels during right heart catheterization in this group is not recommended. The goal of therapy is improvement of clinical symptoms, hemodynamic status, right ventricular function and ultimately increase in quality of life and life expectancy. Oxygen therapy is the main therapy in HP and COPD after medical therapy. Providing adequate therapy for HP with COPD is expected to provide good outcomes for patients.

Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15-lipoxygenase.

Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, is involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Therefore, ferroptosis inhibition represents an attractive strategy for COPD therapy. Herein, we identified natural flavonoid scutellarein as a potent ferroptosis inhibitor for the first time, and characterized its underlying mechanisms for inhibition of ferroptosis and COPD. In vitro, the anti-ferroptotic activity of scutellarein was investigated through CCK8, real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, flow cytometry, and transmission electron microscope (TEM). In vivo, COPD was induced by lipopolysaccharide (LPS)/cigarette smoke (CS) and assessed by changes in histopathological, inflammatory, and ferroptotic markers. The mechanisms were investigated by RNA-sequencing (RNA-seq), electrospray ionization mass spectra (ESI-MS), local surface plasmon resonance (LSPR), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and molecular dynamics. Our results showed that scutellarein significantly inhibited Ras-selective lethal small molecule (RSL)-3-induced ferroptosis and mitochondria injury in BEAS-2B cells, and ameliorated LPS/CS-induced COPD in mice. Furthermore, scutellarein also repressed RSL-3- or LPS/CS-induced lipid peroxidation, GPX4 down-regulation, and overactivation of Nrf2/HO-1 and JNK/p38 pathways. Mechanistically, scutellarein inhibited RSL-3- or LPS/CS-induced Fe2+ elevation through directly chelating Fe2+ . Moreover, scutellarein bound to the lipid peroxidizing enzyme arachidonate 15-lipoxygenase (ALOX15), which resulted in an unstable state of the catalysis-related Fe2+ chelating cluster. Additionally, ALOX15 overexpression partially abolished scutellarein-mediated anti-ferroptotic activity. Our findings revealed that scutellarein alleviated COPD by inhibiting ferroptosis via directly chelating Fe2+ and interacting with ALOX15, and also highlighted scutellarein as a candidate for the treatment of COPD and other ferroptosis-related diseases.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans

BackgroundTreatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover...

Use and persistence of single and multiple inhaler triple therapy prescribed for patients with COPD in France: a retrospective study on THIN database (OPTI study)

IntroductionFrom 2018 single inhaler triple therapy (SITT) became available in France to treat moderate-to-severe chronic obstructive pulmonary disease (COPD). Given its simplified inhaler use compared with multiple inhaler triple therapy...

Smad3-mediated lncRNA HSALR1 enhances the non-classic signalling pathway of TGF-β1 in human bronchial fibroblasts by binding to HSP90AB1.

Chronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined. lncRNAs highly correlated with transforming growth factor beta 1(TGF-β1) expression were chosen, the lncRNA ENST00000440406 (named HSP90AB1 Assoicated LncRNA 1, HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck-8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno-associated virus (AAV) to express HSALR1 by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed. Herein, lncRNA HSALR1 was identified as highly correlated with the TGF-β1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressed HSALR1 by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice. Our results suggest that lncRNA HSALR1 binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF-β1 smad3-independent pathway. This finding described here suggest that lncRNA can participate in COPD development, and HSLAR1 is a promising molecular target of COPD therapy.