Biological treatment of obstructive lung diseases.

In the last 30 years, the treatment of obstructive lung diseases, such as asthma and COPD, has seen significant advancements. Introduction of inhaled corticosteroids (ICS) and, more recently, biological treatments has revolutionized care. Biological treatments are very successful in severe asthma and are expected to be approved for COPD soon. Systematic assessment and multidimensional treatment approaches are crucial in both conditions. Future care may involve specialized centres for severe obstructive lung diseases, focusing on personalized approaches and monitoring, as argued in this review.

Individualised treatment of COPD exacerbations using biomarkers.

This review highlights key aspects of treating chronic obstructive pulmonary disease (COPD) exacerbation, focusing on the optimisation of systemic corticosteroid and antibiotic use through personalised treatment using biomarkers. Eosinophil-guided therapy reduces corticosteroid usage which might reduce side effects, while procalcitonin-guided therapy contributes to reduced antibiotic consumption. These approaches, documented through well-conducted randomized controlled trials, suggest the possibility of enhancing COPD exacerbation management, reducing potential side effects, and addressing concerns related to antibiotic resistance.

Inefficient antiviral response in reconstituted small-airway epithelium from chronic obstructive pulmonary disease patients following human parainfluenza virus type 3 infection.

Chronic obstructive pulmonary disease (COPD) affects over 250 million individuals globally and stands as the third leading cause of mortality. Respiratory viral infections serve as the primary drivers of acute exacerbations, hastening the decline in lung function and worsening the prognosis. Notably, Human Parainfluenza Virus type 3 (HPIV-3) is responsible for COPD exacerbations with a frequency comparable to that of Respiratory Syncytial Virus and Influenza viruses. However, the impact of HPIV-3 on respiratory epithelium within the context of COPD remains uncharacterized.In this study, we employed in vitro reconstitution of lower airway epithelia from lung tissues sourced from healthy donors (n = 4) and COPD patients (n = 5), maintained under air-liquid interface conditions. Through a next-generation sequencing-based transcriptome analysis, we compared the cellular response to HPIV-3 infection.Prior to infection, COPD respiratory epithelia exhibited a pro-inflammatory profile, notably enriched in canonical pathways linked to antiviral response, B cell signaling, IL-17 signaling, and epithelial-mesenchymal transition, in contrast to non-COPD epithelia. Intriguingly, post HPIV-3 infection, only non-COPD epithelia exhibited significant enrichment in interferon signaling, pattern recognition receptors of viruses and bacteria, and other pathways involved in antiviral responses. This deficiency could potentially hinder immune cell recruitment essential for controlling viral infections, thus fostering prolonged viral presence and persistent inflammation.

Comparative Efficacy of Budesonide/Formoterol Versus Fluticasone/Salmeterol in Patients With Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies comparing BF versus FS in the treatment of COPD from inception to July 17, 2023. Outcomes, including exacerbations, hospitalizations, pneumonia, emergency department (ED) visits for COPD, length of hospitalization, and number of exacerbations, were compared using risk ratio (RR) with corresponding 95% confidence interval (CI) or weighted mean difference (WMD) with 95% CI. All statistical analyses were performed using Stata version 12.0. RESULTS: Ten studies comprising a total of 136,369 participants were included. Compared with those treated with FS, patients with COPD treated with BF experienced a reduced number of exacerbations (RR 0.91 [95% CI 0.83-1.00]; p = 0.040), hospitalizations (RR 0.77 [95% CI 0.67-0.88]; p < 0.001), and frequency of pneumonia (RR 0.77 [95% CI 0.64-0.92]; p = 0.05). However, no significant difference was observed between BF and FS in terms of ED visits for COPD (RR 0.87 [95% CI 0.69-1.10]; p = 0.243), length of hospitalization (WMD -0.18 [95% CI -0.62-0.27]; p = 0.437), and number of exacerbations (WMD -0.06 [95% CI -0.28-0.16]; p = 0.602). Notably, no significant heterogeneity was noted in length of hospitalization between the two groups, whereas clear heterogeneity was observed in other outcomes (I2 > 50%, p < 0.05). CONCLUSION: Compared with FS, BF therapy appears to be a more promising treatment strategy for patients with moderate-to-severe COPD; however, this should be verified in further high-quality studies.

Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations.

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

Treatment with systemic corticosteroid versus placebo for exacerbations of COPD: A systematic review and meta-analysis.

BACKGROUND: For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations. METHODS: We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO2 and PaCO2, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest. RESULTS: We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to -0.78) and improved FEV1 (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14). CONCLUSIONS: In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV1 and dyspnea.

Safety and tolerability of ß-blockers: importance of cardioselectivity.

Cardioselective ß-blockade is generally well tolerated in practice and contraindications to this therapy are uncommon. ß-blockers are a diverse therapeutic class, and their individual tolerability profiles are influenced strongly by their pharmacodynamic effects across different adrenergic receptors. Bisoprolol, probably the ß-blocker with the highest selectivity for blockade of ß1- vs. ß2-adrenoceptors, does not block ß2-adrenoceptors to an appreciable extent at doses in therapeutic use. Side-effects often attributed to ß-blockers, such as erectile dysfunction and adverse metabolic effects are uncommon with bisoprolol and other ß-blockers used at doses which only block ß1-adrenoceptors. Cautious use of a cardioselective ß-blocker is not contraindicated in people with chronic obstructive pulmonary disease or asthma and the outcomes benefits of ß-blockers in patients with coronary heart disease or heart failure are also apparent in patients with concurrent COPD. Starting with a low dose and titrating upwards carefully is important for optimising the tolerability of a ß-blocker. Most people with hypertension will receive combination antihypertensive therapy in practice, and the low-dose combination therapy approach provides a useful strategy for optimising the efficacy and tolerability of a regimen that includes a ß-blocker, compared with up-titrating an existing monotherapy.

Rate of severe exacerbations, healthcare resource utilisation and clinical outcomes in patients with COPD in low-income and middle-income countries: results from the EXACOS International Study.

INTRODUCTION: The EXAcerbations of Chronic obstructive lung disease (COPD) and their OutcomeS (EXACOS) International Study aimed to quantify the rate of severe exacerbations and examine healthcare resource utilisation (HCRU) and clinical outcomes in patients with COPD from low-income and middle-income countries. METHODS: EXACOS International was an observational, cross-sectional study with retrospective data collection from medical records for a period of up to 5 years. Data were collected from 12 countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Hong Kong, Mexico, Panama, Russia and Taiwan. The study population comprised patients ≥40 years of age with COPD. Outcomes/variables included the prevalence of severe exacerbations, the annual rate of severe exacerbations and time between severe exacerbations; change in lung function over time (measured by the forced expiratory volume in 1 s (FEV1)); peripheral blood eosinophil counts (BECs) and the prevalence of comorbidities; treatment patterns; and HCRU. RESULTS: In total, 1702 patients were included in the study. The study population had a mean age of 69.7 years, with 69.4% males, and a mean body mass index of 26.4 kg/m2. The mean annual prevalence of severe exacerbations was 20.1%, and 48.4% of patients experienced ≥1 severe exacerbation during the 5-year study period. As the number of severe exacerbations increased, the interval between successive exacerbations decreased. A statistically significant decrease in mean (SD) FEV1 from baseline to post-baseline was observed in patients with ≥1 severe exacerbation (1.23 (0.51) to 1.13 (0.52) L; p=0.0000). Mean BEC was 0.198 x109 cells/L, with 64.7% of patients having a BEC ≥0.1 x109 cells/L and 21.3% having a BEC ≥0.3 x109 cells/L. The most common comorbidity was hypertension (58.3%). An increasing number of severe exacerbations per year was associated with greater HCRU. DISCUSSION: The findings presented here indicate that effective treatment strategies to prevent severe exacerbations in patients with COPD remain a significant unmet need in low-income and middle-income countries.

Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

Systematic review of the effects of patient errors using inhaled delivery systems on clinical outcomes in COPD.

BACKGROUND: Errors using inhaled delivery systems for COPD are common and it is assumed that these lead to worse clinical outcomes. Previous systematic reviews have included patients with both asthma and COPD and much of the evidence related to asthma. More studies in COPD have now been published. Through systematic review, the relationship between errors using inhalers and clinical outcomes in COPD, including the importance of specific errors, was assessed.MethodsElectronic databases were searched on 27 October 2023 to identify cohort, case-control or randomised controlled studies, which included patients with COPD, an objective assessment of inhaler errors and data on at least one outcome of interest (forced expiratory volume in 1 s, (FEV1), dyspnoea, health status and exacerbations). Study quality was assessed using the Newcastle and Ottawa scales. A narrative synthesis of the results was performed as there was insufficient detail in the publications to allow quantitative synthesis. There was no funding for the review. RESULTS: 19 publications were included (7 cohort and 12 case-control) reporting outcomes on 6487 patients. 15 were considered low quality, and most were confounded by the absence of adherence data. There was weak evidence that lower error rates are associated with better FEV1, symptoms and health status and fewer exacerbations. Only one considered the effects of individual errors and found that only some were related to worse outcomes. CONCLUSION: Evidence about the importance of specific errors using inhalers and outcomes would optimise the education and training of patients with COPD. Prospective studies, including objective monitoring of inhalation technique and adherence, are needed. PROSPERO REGISTRATION NUMBER: CRD42023393120.

Comparison of the Application of Vibrating Mesh Nebulizer and Jet Nebulizer in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Objective: To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD). Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC). Results: Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV1 showed MD (0.05 [95% CI, -0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, -0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them. Conclusion: VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.

Impact of omitting annual reviews for COPD on patient reported care quality- outcomes from the Asthma+Lung COPD patient passport.

BACKGROUND: Regular clinical reviews of people with COPD provide an opportunity to optimise management and are recommended in national and international guidelines. However, there are limited data about the relationship between having an annual review and other aspects of care quality, which might influence decision-making by healthcare professionals and commissioners. METHOD: Using data from 74 827 people with COPD completing the Asthma+Lung UK COPD Patient Passport, between 2014 and 2022, we conducted adjusted logistic regression (adjusting for year) and compared receipt of key items of care between those reporting that they had had an annual review (65.3%) and those who did not (34.7%). To further capture patient experience, we also analysed 4228 free-text responses to the 2021 Asthma+Lung UK annual COPD survey to the question 'What is the one thing that could improve your COPD care?' RESULTS: We found that the absence of an annual review was associated with significantly worse COPD care across all domains studied; in particular, inhaler training (yes: 80.8% vs no: 38.4%, adjusted OR (AOR): 8.18, 95% CI (7.89 to 8.47), having a written care plan (89.6% vs 56.9%, AOR 6.68 (95% CI 6.35 to 7.05) and medication knowledge (72.6% vs 33.6%, AOR 5.73 (95% CI 5.51 to 5.96). Thematic analysis of the 2021 COPD survey responses identified three areas to improve care: (1) access and support from healthcare services, (2) improved treatment effectiveness and (3) interaction between COPD and the social environment. DISCUSSION: Failure to deliver annual COPD reviews is associated with worse patient-reported experience of care quality. In parallel, people with COPD express a desire for greater support and access to healthcare services.

Alleviatory Role of Panax Notoginseng Saponins in Modulating Inflammation and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease: mechanisms and Implications.

COPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1ß. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.

A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS).

BACKGROUND: Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed. METHOD/DESIGN: A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test. ETHICS/DISSEMINATION: This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations. TRIAL REGISTRATION: Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022-07-12, 1401/04/21.

An in-hospital intervention to reduce the proportion of misused inhalers at hospital discharge among patients with COPD: a non-randomised intervention study.

AIMS OF THE STUDY: Misuse of inhalers during chronic obstructive pulmonary disease (COPD) treatment is common and may result from errors in inhalation technique or insufficient peak inspiratory flow (PIF). We aimed to evaluate the impact of an in-hospital intervention to reduce inhaler misuse at hospital discharge among patients with COPD. METHODS: We conducted a monocentric, non-randomised intervention study to compare the proportion of misused inhalers at hospital discharge by patients with COPD between a group with standard care and a group receiving an in-hospital intervention. The control group successively included all patients hospitalised between March and June 2022, and the intervention group included patients hospitalised between August and December 2022. The intervention consisted of (a) an evaluation of inhalation technique and PIF at admission, (b) the provision of a written guide to assist in the selection of an inhaler, and (c) therapeutic education. The primary outcome was the proportion of misused inhalers, defined as an inhaler used with a critical error and/or insufficient PIF, at hospital discharge. The primary outcome was assessed by observing inhalation technique and measuring PIF using the In-Check DIAL G16® . RESULTS: The study included 93 patients: 46 in the control group and 47 in the intervention group. Mean age was 70.5 years (SD 10.9 years), 56 patients (60.2%) were men, and 57 patients (62%) were hospitalised for a COPD exacerbation. Patients used an average of 1.9 inhalers at hospital discharge; 98 inhalers were assessed in the control group and 81 in the intervention group. The proportion of misused inhalers at discharge was 61.2% in the control group and 21.0% in the intervention group (absolute risk reduction 40.2% [95% CI 25.5-55.0]; p <0.01). In the intervention group, the proportion of inhalers used with at least one critical error was reduced by 38.6% (95% CI 24.3-52.3%) and that of inhalers used with insufficient PIF by 13.9% (95% CI 4.2-23.6%). CONCLUSIONS: An in-hospital intervention was associated with a reduction in the proportion of misused inhalers at hospital discharge. This intervention should be considered for hospitalised patients with COPD. The trial was registered with ClinicalTrials.gov (NCT05207631).

Cost-related medication nonadherence in adults with COPD in the United States 2013-2020.

BACKGROUND: Cost-related medication nonadherence (CRN) is associated with poor prognosis among patients with chronic obstructive pulmonary disease (COPD), a population that requires long-term treatment for secondary prevention. In this study, we aimed to estimate the prevalence and sociodemographic characteristics of CRN in individuals with COPD in the US. METHODS: In a nationally representative survey of US adults in the National Health Interview Survey (2013-2020), we identified individuals aged ≥18 years with a self-reported history of COPD. Cross-sectional study. RESULTS: Of the 15,928 surveyed individuals, a weighted 18.56% (2.39 million) reported experiencing CRN, including 12.50% (1.61 million) missing doses, 13.30% (1.72 million) taking lower than prescribed doses, and 15.74% (2.03 million) delaying filling prescriptions to save costs. Factors including age < 65 years, female sex, low family income, lack of health insurance, and multimorbidity were associated with CRN. CONCLUSIONS: In the US, one in six adults with COPD reported CRN. The influencing factors of CRN are multifaceted and necessitating more rigorous research. Targeted interventions based on the identified influencing factors in this study are recommended to enhance medication adherence among COPD patients.

Acute Exacerbation of Chronic Obstructive Pulmonary Disease Due to Carbapenem-Resistant Klebsiella pneumoniae-Induced Pneumonia: Clinical Features and Prognostic Factors.

Purpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is closely related to respiratory tract infection. The aim of this study was to investigate the clinical features and prognostic factors of CRKP-induced pneumonia in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Methods: A single-centre, retrospective case-control study on COPD patients hospitalized for acute exacerbation and CRKP-induced pneumonia was conducted from January 1, 2016, to December 31, 2022. The mortality rate of acute exacerbation due to CRKP-induced pneumonia was investigated. The patients were divided into the CRKP-induced pneumonic acute exacerbation (CRKPpAE) group and the non-CRKP-induced pneumonic acute exacerbation (non-CRKPpAE) group, and the clinical characteristics and prognostic factors were compared using univariate analysis and multivariate analysis. Results: A total of 65 AECOPD patients were included, composed of 26 patients with CRKPpAE and 39 patients with non-CRKPpAE. The mortality rate of CRKPpAE was 57.69%, while non-CRKPpAE was 7.69%. Compared with non-CRKPpAE, a history of acute exacerbation in the last year (OR=8.860, 95% CI: 1.360-57.722, p=0.023), ICU admission (OR=11.736, 95% CI: 2.112-65.207, p=0.005), higher NLR levels (OR=1.187, 95% CI: 1.037-1.359, p=0.013) and higher D-dimer levels (OR=1.385, 95% CI: 1.006-1.905, p=0.046) were independently related with CRKPpAE. CRKP isolates were all MDR strains (26/26, 100%), and MDR strains were also observed in non-CRKP isolates (5/39, 12.82%). Conclusion: Compared with non-CRKPpAE, CRKPpAE affects the COPD patient's condition more seriously and significantly increases the risk of death.

Probiotics combined with Budesonide and Ipratropium bromide for chronic obstructive pulmonary disease: A retrospective analysis.

To explore the effect of probiotics combined with budesonide and ipratropium bromide in the treatment of chronic obstructive pulmonary disease (COPD) on lung function and gut microbiota. This was a retrospective study of prospectively collected clinical data of 118 patients with COPD admitted to our hospital between January 2020 and December 2022. According to the treatment records, 59 patients received budesonide and irpratropium bromide (control group), and 59 patients received probiotics combined with budesonide and irpratropium bromide (observation group). The lung function, inflammatory factor levels, airway remodeling, and gut microbiota before and after treatment were compared between the 2 groups. After treatment, FVC, MMEF, PEF, and FEV1 in the 2 groups were higher than before treatment, and the values in the observation group were higher than those in the control group (P < .05). After treatment, the serum levels of TNF-α, IL-6, and PCT in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of serum MMP-9, VEGF, basic fibroblast growth factor, and NGF in the 2 groups were lower than before treatment, and the levels in the observation group were lower than those in the control group (P < .05). After treatment, the levels of lactobacilli and bifidobacteria in the 2 groups increased compared to those before treatment, and the observation group had a higher level, while the levels of Enterobacteriaceae and Enterococcus were lower in the observation group than those before treatment (P < .05). Based on budesonide and irpratropium bromide, probiotic treatment of COPD is more conducive to reducing the degree of inflammatory reactions, inhibiting airway remodeling, regulating the level of gut microbiota, and promoting the recovery of lung function.

Polyphyllin B inhibited STAT3/NCOA4 pathway and restored gut microbiota to ameliorate lung tissue injury in cigarette smoke-induced mice.

OBJECTIVE: Smoking was a major risk factor for chronic obstructive pulmonary disease (COPD). This study plan to explore the mechanism of Polyphyllin B in lung injury induced by cigarette smoke (CSE) in COPD. METHODS: Network pharmacology and molecular docking were applied to analyze the potential binding targets for Polyphyllin B and COPD. Commercial unfiltered CSE and LPS were used to construct BEAS-2B cell injury in vitro and COPD mouse models in vivo, respectively, which were treated with Polyphyllin B or fecal microbiota transplantation (FMT). CCK8, LDH and calcein-AM were used to detect the cell proliferation, LDH level and labile iron pool. Lung histopathology, Fe3+ deposition and mitochondrial morphology were observed by hematoxylin-eosin, Prussian blue staining and transmission electron microscope, respectively. ELISA was used to measure inflammation and oxidative stress levels in cells and lung tissues. Immunohistochemistry and immunofluorescence were applied to analyze the 4-HNE, LC3 and Ferritin expression. RT-qPCR was used to detect the expression of FcRn, pIgR, STAT3 and NCOA4. Western blot was used to detect the expression of Ferritin, p-STAT3/STAT3, NCOA4, GPX4, TLR2, TLR4 and P65 proteins. 16S rRNA gene sequencing was applied to detect the gut microbiota. RESULTS: Polyphyllin B had a good binding affinity with STAT3 protein, which as a target gene in COPD. Polyphyllin B inhibited CS-induced oxidative stress, inflammation, mitochondrial damage, and ferritinophagy in COPD mice. 16S rRNA sequencing and FMT confirmed that Akkermansia and Escherichia_Shigella might be the potential microbiota for Polyphyllin B and FMT to improve CSE and LPS-induced COPD, which were exhausted by the antibiotics in C + L and C + L + P mice. CSE and LPS induced the decrease of cell viability and the ferritin and LC3 expression, and the increase of NCOA4 and p-STAT3 expression in BEAS-2B cells, which were inhibited by Polyphyllin B. Polyphyllin B promoted ferritin and LC3II/I expression, and inhibited p-STAT3 and NCOA4 expression in CSE + LPS-induced BEAS-2B cells. CONCLUSION: Polyphyllin B improved gut microbiota disorder and inhibited STAT3/NCOA4 pathway to ameliorate lung tissue injury in CSE and LPS-induced mice.