Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification. AIM OF THE STUDY: To elucidate the alleviative effect and molecular mechanism of SBE on lipopolysaccharides (LPS)/porcine pancreatic elastase (PPE)-induced COPD by blocking ferroptosis. METHODS: The anti-ferroptotic effects of SBE were evaluated in human BEAS-2B bronchial epithelial cells using CCK8, RT-qPCR, western blotting, and transmission electron microscopy. Transwell was employed to detect chemotaxis of neutrophils. COPD model was induced by intranasally administration of LPS/PPE in mice and measured by alterations of histopathology, inflammation, and ferroptosis. RNA-sequencing, western blotting, antioxidant examination, flow cytometry, DARTS, CETSA, and molecular docking were then used to investigate its anti-ferroptotic mechanisms. RESULTS: In vitro, SBE not only suppressed erastin- or RSL3-induced ferroptosis by suppressing lipid peroxides (LPOs) production and glutathione (GSH) depletion, but also suppressed ferroptosis-induced chemotactic migration of neutrophils via reducing mRNA expression of chemokines. In vivo, SBE ameliorated LPS/PPE-induced COPD phenotypes, and inhibited the generation of LPOs, cytokines, and chemokines. RNA-sequencing showed that p53 pathway and mitogen-activated protein kinases (MAPK) pathway were implicated in SBE-mediated anti-ferroptotic action. SBE repressed erastin- or LPS/PPE-induced overactivation of p53 and MAPK pathway, thereby decreasing expression of diamine acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15), and increasing expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Mechanistically, erastin-induced elevation of reactive oxygen species (ROS) was reduced by SBE through directly scavenging free radicals, thereby contributing to its inhibition of p53 and MAPK pathways. CETSA, DARTS, and molecular docking further showed that ROS-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) may be the target of SBE. Overexpression of NOX4 partially impaired the anti-ferroptotic activity of SBE. CONCLUSION: Our results demonstrated that SBE mitigated COPD by suppressing p53 and MAPK pro-ferroptosis pathways via directly scavenging ROS and blocking NOX4. These findings also supported the clinical application of Sea buckthorn in COPD therapy.

A Comparative Observational Study of the Diagnostic Utility of Impulse Oscillometry Versus Spirometry in Obstructive Airway Diseases.

Background Obstructive airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), significantly impact respiratory function, making accurate diagnosis and differentiation essential for proper management. While spirometry is the gold standard for assessing lung function, impulse oscillometry (IOS) has emerged as a complementary tool, especially when spirometry results are inconclusive. This study aimed to compare the diagnostic utility of IOS with spirometry in patients with obstructive airway diseases and evaluate the correlation between these two methods. Methods A comparative observational study was conducted over 18 months at a tertiary care hospital in central India, including 130 patients (65 with asthma and 65 with COPD). Diagnostic evaluations using spirometry and IOS were performed before and after bronchodilator administration. Spirometry parameters assessed were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio, while IOS parameters evaluated included resistance at 5 Hz (R5), resistance at 20 Hz (R20), resonant frequency (Fres), reactance at 5 Hz (X5), and the area under the reactance curve (AX). Statistical analysis was conducted using IBM SPSS version 27.0 (IBM Corp., Armonk, USA) and GraphPad Prism version 7.0 (Dotmatics, Boston, USA). Results Significant differences were observed in spirometry parameters between asthma and COPD groups, with asthma patients showing better lung function (FEV1, FVC, and FEV1/FVC; p<0.05). No significant differences were found in IOS parameters between the groups except for a correlation between FEV1 (%) and IOS measurements in the asthma group. Spirometry demonstrated superior sensitivity in identifying airway obstruction compared to IOS. However, IOS was more effective in detecting peripheral airway obstruction in asthma patients, with 22 out of 65 (33.85%) asthma patients showing peripheral airway obstruction compared to six out of 65 (9.23%) COPD patients (p=0.001). Conclusion While spirometry remains the primary diagnostic tool for assessing obstructive airway diseases, IOS is a valuable adjunct, particularly for detecting peripheral airway involvement in asthma patients. Combining spirometry and IOS enhances diagnostic accuracy and provides a more comprehensive assessment of lung function in patients with asthma and COPD.

Exploring the potential role of microbiota and metabolites in acute exacerbation of chronic obstructive pulmonary disease.

The acute exacerbation of chronic obstructive pulmonary disease seriously affects the respiratory system function and quality of life of patients. This study employed 16S rRNA sequencing and metabolomics techniques to analyze the respiratory microbiota and serum metabolites of COPD and AECOPD patients. The results showed that the microbial diversity in the respiratory tract of AECOPD patients was significantly lower than that of COPD patients, and the relative abundance of Bacteroidetes, Prevotella and Neisseria in the respiratory tract of AECOPD patients was significantly lower than that of COPD patients. However, the relative abundance of Haemophilus_D, Veillonella_A and Pseudomonas_E, in AECOPD patients was significantly higher than that of COPD patients, and the ability of respiratory microbiota in AECOPD patients to participate in alanine metabolism was significantly lower than that of COPD patients. Metabolome results further revealed that the serum alanine levels in AECOPD patients were significantly lower than those in COPD patients, and these differential metabolites were mainly involved in linoleic acid metabolism, protein digestion and absorption and regulation of lipolysis in adipocytes. In summary, the structural characteristics of respiratory microbiota in COPD and AECOPD patients are different from those in healthy populations, and their microbiota diversity decreases and microbial community structure and function will also undergo changes when acute exacerbations occur. In addition, the predicted microbial community function and metabolomics results indicate that the onset of AECOPD is mainly related to energy and amino acid metabolism disorders, especially alanine metabolism.

Significance of serum lncRNA XIST in chronic obstructive pulmonary disease and its progression to pulmonary heart disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become one of the major death-related causes. Chronic pulmonary heart disease (CPHD) is an adverse complication of COPD causing poor prognosis of patients. This study evaluated the role of lncRNA XIST in COPD and CPHD aiming to identify a potential biomarker for the screening and prediction of COPD. METHODS: The study enrolled 127 COPD patients, including 73 patients occurred CPHD with 76 healthy individuals as the control group. The expression of XIST was evaluated by PCR and compared between COPD patients with different severity, grades, and complications. The diagnostic and prognostic values of XIST in COPD and CPHD were assessed by ROC and Kaplan-Meier analyses. RESULTS: Significant upregulation of XIST was observed in the serum of COPD patients relative to healthy individuals, which distinguished COPD patients and showed a correlation with the respiratory and pulmonary function of COPD patients. COPD patients with acute exacerbations and CPHD showed a higher expression level. Increasing serum XIST discriminated COPD patients combined CPHD and positively correlated with right ventricular hypertrophy and pulmonary hypertension. Higher serum XIST levels could indicate the adverse 3-year prognosis of COPD patients, especially for COPD patients combined with CPHD. CONCLUSION: Upregulated XIST served as a biomarker for screening COPD and predicting adverse prognosis of COPD and COPD patients with CPHD.

Nuts and bolts of lung ultrasound: utility, scanning techniques, protocols, and findings in common pathologies.

Point of Care ultrasound (POCUS) of the lungs, also known as lung ultrasound (LUS), has emerged as a technique that allows for the diagnosis of many respiratory pathologies with greater accuracy and speed compared to conventional techniques such as chest x-ray and auscultation. The goal of this narrative review is to provide a simple and practical approach to LUS for critical care, pulmonary, and anesthesia providers, as well as respiratory therapists and other health care providers to be able to implement this technique into their clinical practice. In this review, we will discuss the basic physics of LUS, provide a hands-on scanning technique, describe LUS findings seen in normal and pathological conditions (such as mainstem intubation, pneumothorax, atelectasis, pneumonia, aspiration, COPD exacerbation, cardiogenic pulmonary edema, ARDS, and pleural effusion) and also review the training necessary to achieve competence in LUS.

The critical roles of caveolin-1 in lung diseases.

Caveolin-1 (Cav-1), a structural and functional component in the caveolae, plays a critical role in transcytosis, endocytosis, and signal transduction. Cav-1 has been implicated in the mediation of cellular processes by interacting with a variety of signaling molecules. Cav-1 is widely expressed in the endothelial cells, smooth muscle cells, and fibroblasts in the various organs, including the lungs. The Cav-1-mediated internalization and regulation of signaling molecules participate in the physiological and pathological processes. Particularly, the MAPK, NF-κB, TGFß/Smad, and eNOS/NO signaling pathways have been involved in the regulatory effects of Cav-1 in lung diseases. The important effects of Cav-1 on the lungs indicate that Cav-1 can be a potential target for the treatment of lung diseases. A Cav-1 scaffolding domain peptide CSP7 targeting Cav-1 has been developed. In this article, we mainly discuss the structure of Cav-1 and its critical roles in lung diseases, such as pneumonia, acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, pulmonary fibrosis, and lung cancer.

Socioeconomic status and emergency department visits in adults with a history of severe childhood asthma: a register-based study.

Background and Objective: Our knowledge of socioeconomic status (SES) and emergency department (ED) visits in adults with a history of severe childhood asthma is limited. Our aim was, therefore, to investigate these variables in individuals with a history of severe childhood asthma compared to a control population. Methods: The Kongsberg cohort comprises Danish individuals with a history of severe childhood asthma and a previous 4-month stay at an asthma care facility in Kongsberg, Norway, between 1950 and 1979. The cohort was compared 1:1 to sex and age matched controls with no previous diagnosis of or treatment for obstructive airway disease (OAD). Data from the national Danish health registries were used for comparing cases and controls. Results: A total of 1394 adults from the Kongsberg cohort were alive and residing in Denmark (mean age 63 years, 43% females) at the index date (June 2022). A Charlson comorbidity index score of ≥1 was higher in the study cohort compared to controls (7% versus 3%) (p < 0.01). Cases had a 1.5-fold increased likelihood of having a high educational level (p < 0.001) compared to controls. Compared to the controls, cases had a higher risk of all-cause ED visits, with individuals having lower educational levels showing the highest proportion of ED visits. Furthermore, 31.2% and 22.9%, respectively, of cases and controls with high educational levels had had ED visits. Compared to controls, logistic regression analysis revealed a 1.7-fold higher risk of all-cause ED visits in cases (p < 0.001). Conclusions: In adults with a history of severe childhood asthma, educational level, comorbidity burden, and risk of ED visit were higher compared to matched controls with no history of obstructive airway disease.

Peak Inspiratory Flow and Inhaler Prescription Strategies in a Specialized COPD Clinical Program: A Real-World Observational Study.

BACKGROUND: COPD inhaler regimens should be appropriate for the patient's peak inspiratory flow (PIF) and should ideally consist of single or similar device(s). RESEARCH QUESTIONS: In a subspecialized COPD clinic: 1: What is the prevalence of patients with suboptimal PIF and with inappropriate device(s) for measured PIF? 2: Are there patient-related risk factors associated with suboptimal PIF? 3: What is the prevalence of patients with non-single inhaler therapy (SIT)/non-similar devices? 4: Does point-of-care PIF affect clinical decision-making? STUDY DESIGN AND METHODS: In this single-center real-world observational study, PIF was measured systematically at every outpatient visit in a subspecialized COPD clinic and point-of-care results were provided to the clinician. Co-primary outcomes were the prevalence of outpatients with suboptimal PIF and with inappropriate devices for measured PIF. Secondary outcomes were patient-related risk factors associated with suboptimal PIF, the prevalence of non-SIT/non-similar devices, the prevalence of regimens consisting of either inappropriate device(s) for measured PIF and/or non-SIT/non-similar devices, and the effect of point-of-care PIF on clinical decision-making. RESULTS: Suboptimal PIF was identified in 45 of 161 participants (28%) and inappropriate device(s) for measured PIF were identified in 18 (11.2%) participants. Significant associations were observed between suboptimal PIF and age (1.09 [1.04,1.15]), female sex (10.30 [4.45,27.10]), height (0.92 [0.88,0.96]), BMI (0.90 [0.84,0.96]) and FEV1 (0.09 [0.03,0.26]). Following adjustment for age and sex, the association between suboptimal PIF and BMI, but not height, remained significant. Non-SIT and/or non-similar devices were identified in 50 (31.1%) participants. Regimens consisting of either inappropriate device(s) for measured PIF and/or non-SIT/non-similar devices were observed in fifty-nine (36.6%) participants. Inhaler prescription changes were observed in this latter group (3.39 [1.76,6.64]), as well as in patients with suboptimal PIF already on SIT/similar regimens (2.93 [1.07,7.92]). INTERPRETATION: Suboptimal PIF and inappropriate devices for measured PIF are highly prevalent in outpatients from a subspecialized COPD clinic. Female sex, reduced FEV1 and low BMI are important, readily identifiable risk factors for suboptimal PIF and point-of-care PIF can inform clinical decision-making.

Predictive Value of CCQ and its Subdomains for Hospitalized Exacerbations in Chronic Obstructive Pulmonary Disease: A 3-Year Observational Prospective Study.

BACKGROUND: The prediction capacity of the Clinical COPD Questionnaire (CCQ) and its functional, symptom, and mental subdomain for COPD hospitalized exacerbation were rarely studied. OBJECTIVE: To examine the prognostic capacity of the total CCQ and its three subdomains for 3-year COPD hospitalized exacerbations. METHODS: We analyzed the predictive ability of total CCQ score and its subdomains for hospitalized exacerbations in an observational cohort of 987 subjects with stable COPD from the RealDTC, an ongoing multicenter prospective study. Hospitalized exacerbations were prospectively collected every 6 month for a maximum of 3 years. RESULTS: The total CCQ and its functional and symptom domain, but not the mental domain, were significantly associated with 3-year hospitalized exacerbations by multivariate Cox regression analysis. The predictive capacity of functional domain was similar to that of the total CCQ, but significantly stronger than the symptom and mental domain by ROC analysis (P < 0.05). ROC curves also showed that the AUC of exacerbation history combined with CCQ functional domain was larger than that of exacerbation history alone (P < 0.0001). Additionally, the predictive value of multivariable models that contains CCQ functional domain was significantly better than the corresponding model without CCQ functional domain (P < 0.05). CONCLUSIONS: The total CCQ and its functional and symptom domain were independent risk factors of 3-year hospitalized exacerbations. The prognostic capacity of the functional domain was similar to that of total CCQ, and was significantly stronger than the symptom and mental domain. The CCQ functional domain was able to increase the predictive power of exacerbation history and other multivariable prediction models, indicating it may have an important role in the multivariable prediction tool for hospitalized exacerbation, and its combination with other clinical variables might be used as a low-cost approach for assessments of the disease severity and severe exacerbation in COPD patients in the future.

Relationships between life-space mobility, physical function, and empowerment in patients with chronic obstructive pulmonary disease.

[Purpose] This study aimed to elucidate the relationship between the Life-Space Assessment measure, which conceptualizes physical activity in terms of life-space, and indicators of empowerment, and physical function, in stable patients with chronic obstructive pulmonary disease. [Participants and Methods] This was a cross-sectional study. The participants were 25 stable outpatients with chronic obstructive pulmonary disease (22 males, mean age 75.6 ± 6.1 years). Measurements included the Life-Space Assessment; the Empowerment Scale for the Elderly; respiratory function; grip strength; weight-adjusted knee extension strength; and a six-minute walk test. Pearson's correlation coefficient and a multivariate analysis were used to examine the relationship between the Life-Space Assessment and each indicator, with the significance level set at 5%. [Results] The Life-Space Assessment score (83.4 ± 23.7 points) correlated with the percentage forced vital capacity and the six-minute walk distance. However, the Life-Space Assessment demonstrated no association with the Empowerment Scale for the Elderly (38.3 ± 7.0 points). [Conclusion]The results of this study suggest that physical function correlates with scores on the Life-Space Assessment in patients with stable chronic obstructive pulmonary disease.

RESP-FIT: A Technology-Enhanced Combined Inspiratory and Expiratory Muscle Strength Training Intervention for Adults With COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease associated with respiratory muscle weakness and activity-limiting symptoms such as dyspnea. Respiratory muscle strength training (RMST) is an empirically validated therapy to increase respiratory muscle strength. The theoretically-informed, technology-enhanced RESP-FIT intervention for COPD is a 6-week combined inspiratory and expiratory muscle strength training program with symptom measurement in real time via ecological momentary assessment (EMA). Objectives: In addition to hypothesis generating purposes, the purpose of this randomized control pilot study was to explore whether observed effects (on symptoms, patient-reported outcomes, and respiratory muscle strength) support carrying out a future large-scale trial of RESP-FIT. Methods: Thirty adults with COPD were randomized to intervention (n=15) or control, with intervention group undergoing 6 weeks of mHealth-enhanced RMST. Daily symptom data were collected in real time over the 6-week intervention period using EMA. Results: Compared to the control group, participants in the intervention group reported decreased dyspnea and anxiety, increased happiness, and improved respiratory muscle strength (PIMax). However, reports of fatigue and sleep disturbance increased in the intervention group compared to the control group. Conclusion: Results support the hypothesis that the 6-week RESP-FIT program will improve respiratory muscle strength, emotional state (anxiety and happiness), and breathlessness in COPD but may contribute to fatigue, at least in the short-term. Future work is needed to determine efficacy of RESP-FIT, determine mechanisms of action on dyspnea and fatigue, and conduct within-subject comparisons of EMA data to explore individual or environmental fluctuations in COPD symptoms.

Participant-selected music listening during pulmonary rehabilitation in people with chronic obstructive pulmonary disease: A randomised controlled trial.

To evaluate the impact of participant-selected music listening as an adjunct to pulmonary rehabilitation (PR) in people with COPD. Adults with COPD referred to PR were randomly assigned to participant-selected music listening (intervention group, [IG]) or usual care (control group [CG]) during an 8-weeks PR program. Prior to training, the IG completed an interview with a registered music therapist to identify music preferences. IG participants listened to an individualised playlist; CG participants had usual care. Primary outcomes included end-6-min walk test symptoms (dyspnoea and exertion) and dyspnoea (Multidimensional Dyspnoea Profile [MDP]), measured pre and post PR and 6-months follow-up. 58 participants, FEV1 52.4 (25.9)% pd) were recruited. There were no between-group differences following the intervention (p > .05 for all outcomes at all time points). Within-group differences following PR were significant for MDP sensory quality: IG mean difference [95% CI] -2.2 [-3.3 to -1.2]; CG -1.5 [-2.5 to -0.5] points; MDP emotional response: IG -3.2 [-4.2 to -2.3]; CG -2.2 [-3.2 to -1.3] points). Participant-selected music listening during PR offered no greater benefit to symptoms of dyspnoea or exertion compared to usual care. With the study limited by COVID-19 restrictions, the role of this adjunct remains to be clarified.

Etiology and epidemiology of acute exacerbations of chronic obstructive pulmonary disease in Eastern Nepal: a narrative review.

This narrative review aims to examine the etiology and epidemiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in Eastern Nepal. A systematic search was conducted to identify relevant studies published in English, focusing on combinations of keywords such as "acute exacerbation of chronic obstructive pulmonary disease," "AECOPD," "Nepal," "etiology," "epidemiology," "environmental exposure," "comorbidities," and "socioeconomic factors." Synthesizing findings from recent studies, it highlights the multifactorial nature of AECOPD, including the roles of respiratory infections, environmental exposures, and comorbidities. Key findings indicate that respiratory infections (both viral and bacterial) and non-infectious factors such as air pollution and biomass fuel combustion significantly contribute to AECOPD. Socio-economic factors, particularly among women using traditional biomass fuels and engaged in smoking, also play a critical role. The review emphasizes the need for targeted interventions and preventive strategies to manage AECOPD effectively in this region. Conclusions suggest that understanding local patterns of AECOPD etiology is crucial for developing region-specific interventions to reduce exposure to risk factors and manage comorbidities, thereby improving clinical outcomes and reducing healthcare utilization.

HMGB1 promotes M1 polarization of macrophages and induces COPD inflammation.

Chronic obstructive pulmonary disease (COPD) is a pervasive and incapacitating respiratory condition, distinguished by airway inflammation and the remodeling of the lower respiratory tract. Central to its pathogenesis is an intricate inflammatory process, wherein macrophages exert significant regulatory functions, and High mobility group box 1 (HMGB1) emerges as a pivotal inflammatory mediator potentially driving COPD progression. This study explores the hypothesis that HMGB1, within macrophages, modulates COPD through inflammatory mechanisms, focusing on its influence on macrophage polarization. Our investigation uncovered that HMGB1 is upregulated in the context of COPD, associated with an enhanced proinflammatory M1 macrophage polarization induced by cigarette smoke. This polarization is linked to suppressed cell proliferation and induced apoptosis, indicative of HMGB1's role in the disease's inflammatory trajectory. The study further implicates HMGB1 in the activation of the Nuclear factor kappa-B (NF-κB) signaling pathway and chemokine signaling within macrophages, which are likely to amplify the inflammatory response characteristic of COPD. The findings underscore HMGB1's critical involvement in COPD pathogenesis, presenting it as a significant target for therapeutic intervention aimed at modulating macrophage polarization and inflammation.

Biofilm infections of endobronchial valves in COPD patients after endoscopic lung volume reduction: a pilot study with FISHseq.

Endoscopic lung volume reduction (ELVR) using endobronchial valves (EBV) is a treatment option for a subset of patients with severe chronic obstructive pulmonary disease (COPD), suffering from emphysema and hyperinflation. In this pilot study, we aimed to determine the presence of bacterial biofilm infections on EBV and investigate their involvement in lack of clinical benefits, worsening symptomatology, and increased exacerbations that lead to the decision to remove EBVs. We analyzed ten COPD patients with ELVR who underwent EBV removal. Clinical data were compared to the microbiological findings from conventional EBV culture. In addition, EBV were analyzed by FISHseq, a combination of Fluorescence in situ hybridization (FISH) with PCR and sequencing, for visualization and identification of microorganisms and biofilms. All ten patients presented with clinical symptoms, including pneumonia and recurrent exacerbations. Microbiological cultures from EBV detected several microorganisms in all ten patients. FISHseq showed either mixed or monospecies colonization on the EBV, including oropharyngeal bacterial flora, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., and Fusobacterium sp. On 5/10 EBV, FISHseq visualized biofilms, on 1/10 microbial microcolonies, on 3/10 single microorganisms, and on 1/10 no microorganisms. The results of the study demonstrate the presence of biofilms on EBV for the first time and its potential involvement in increased exacerbations and clinical worsening in patients with ELVR. However, further prospective studies are needed to evaluate the clinical relevance of biofilm formation on EBV and appropriate treatment options to avoid infections in patients with ELVR.

Clinical Effectiveness and Safety of Dupilumab in Chronic Obstructive Pulmonary Disease Patients: A 7-Year Population-based Cohort Study.

BACKGROUND: Previous randomized controlled trials had established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up. OBJECTIVE: This population-based cohort study aimed to explore the long-term clinical effectiveness of dupilumab in COPD patients. METHODS: This population-based cohort study included U.S. patients with COPD between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting ß2-agonists (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes after the initiation of dupilumab versus LABA-containing therapies was measured. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. RESULTS: A total of 1,521 dupilumab initiators and 1,521 propensity score-matched patients receiving LABA-based therapies were included. Dupilumab recipients were associated with lower all-cause mortality (HR:0.53, 95% CI:0.43-0.65), emergency visits (HR:0.78, 95% CI:0.69-0.89), and acute exacerbation (AE) rates (HR:0.59, 95% CI:0.53-0.65). Dupilumab was also associated with reductions in the requirement of short-acting ß2-agonists (HR:0.48, 95% CI:0.43-0.52), short-acting muscarinic antagonists (HR:0.43, 95% CI:0.37-0.49) for symptoms control. Additionally, dupilumab decreased subsequent pneumonia (HR:0.65, 95% CI:0.50-0.86), and COPD-relevant comorbidities including new-onset heart failure (HR:0.69, 95% CI:0.53-0.90) and new-onset anxiety (HR:0.70, 95% CI:0.53-0.93). CONCLUSIONS: Dupilumab was associated with a lower rate of mortality, emergency visits, reduced risk of AEs, respiratory symptoms, and respiratory infections in COPD patients. More studies are required to validate the effectiveness of dupilumab among patients with COPD across various severities.

Impact of Loneliness and Social Support on Acute Health Service Use and Symptom Exacerbation Among Adults with Asthma and COPD.

Loneliness and low social support are associated with negative health outcomes among adults with asthma or COPD. Although social support is correlated with loneliness, low social support is neither necessary nor sufficient for the experience of loneliness. This study compares the relative association of loneliness and social support on symptom exacerbation (i.e., acute deteriorations in respiratory health) and acute health service utilization (i.e., hospitalizations, emergency department visits) among 206 adults with asthma and 308 adults with COPD. Separate logistic regression models were used to simultaneously examine the association of loneliness and social support with each outcome. Among adults with asthma, loneliness was associated with greater odds of hospitalization (AOR = 2.81, 95%CI [1.13, 7.02]), while low social support was not (AOR = 1.44, 95%CI [0.78, 2.65]). However, neither loneliness nor social support were associated with any other acute health service use or symptom exacerbation among adults with asthma. Among adults with COPD, loneliness, and greater social support were associated with increased odds of symptom exacerbation (AOR = 1.67, 95%CI [1.03, 2.69]; AOR = 1.36, 95%CI 1.02, 1.83]) and hospitalization (AOR = 3.46, 95%CI [1.65, 7.24]; AOR = 1.92, 95%CI [1.15, 3.22]), but only social support was significantly associated with ED visits (AOR = 1.72, 95%CI 1.12, 2.66]). These findings support prior research demonstrating that loneliness and social support are related but separate determinants of patients' physical symptoms and service utilization.

Association of the gut microbiome and different phenotypes of COPD and asthma: a bidirectional Mendelian randomization study.

Mounting evidence has revealed the association between gut microbiota and both chronic obstructive pulmonary disease (COPD) and asthma; however, the causal association between gut microbiota and specific disease phenotypes remains to be determined. This study employed bidirectional two-sample Mendelian randomization (MR) analyses to investigate the potential causal relationship between gut microbiota and these conditions. The research utilized genome-wide association study (GWAS) data from the MiBioGen consortium for gut microbiota and the integrative epidemiology unit (IEU) Open GWAS for these conditions. Four MR analysis methods were employed: the inverse variance weighted (IVW) test, MR-Egger, weighted median, and weighted mode methods. The IVW method results are considered the primary findings. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy analysis, and leave-one-out analysis, were used to enhance robustness. Our MR study identified eight gut microbiota taxa potentially associated with the risk of different types of COPD and asthma. These include two taxa for early-onset COPD: Streptococcaceae [odds ratio (OR) = 1.315, 95% confidence interval (CI) = 1.071-1.616, P = 0.009] and Holdemanella (OR = 1.199, 95% CI = 1.063-1.352, P = 0.003); three for later-onset COPD: Acidaminococcaceae (OR = 1.312, 95% CI = 1.098-1.567, P = 0.003), Holdemania (OR = 1.165, 95% CI = 1.039-1.305, P = 0.009), and Marvinbryantia (OR = 0.814, 95% CI = 0.697-0.951, P = 0.009); one for allergic asthma: Butyricimonas (OR = 0.794, 95% CI = 0.693-0.908, P = 0.001); and two for non-allergic asthma: Clostridia (OR = 1.255, 95% CI = 1.043-1.511, P = 0.016) and Clostridiales (OR = 1.256, 95% CI = 1.048-1.506, P = 0.014).IMPORTANCEIndividuals with diverse phenotypes of chronic obstructive pulmonary disease (COPD) and asthma exhibit different responses to the conventional "one treatment fits all" approach. Recent research has revealed the significant role of the gut-lung axis in both COPD and asthma. However, the specific impact of gut microbiota on different subtypes of these conditions remains poorly understood. Our study has identified eight gut microbiota that may be associated with the risk of different types of COPD and asthma. These findings provide evidence suggesting a potential causal relationship between gut microbiota and various phenotypes of COPD and asthma. This offers a new perspective on the origins of different disease phenotypes and points toward future exploration of phenotype-specific and personalized therapies.