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.

Tracking Real-World Physical Activity in Chronic Obstructive Pulmonary Disease Over One Year: Results from a Monocentric, Prospective, Observational Cohort Study.

Introduction: Lung function constraints and comorbidities such as coronary heart disease, sarcopenia, and mood disorders make chronic obstructive pulmonary disease (COPD) patients avoid physical activity (PA). However, PA represents an important pillar of COPD management and is explicitly recommended by professional associations to enhance physical functioning and positively modulate disease progression. Methods: In this monocentric, prospective, observational feasibility study, it was our primary objective to investigate the association between PA and the evolution of the COPD assessment test (CAT) and the occurrence of acute exacerbations of COPD (AECOPD), respectively. To this end, we equipped 42 COPD patients with an activity tracking wearable and telemonitored their daily PA levels over one year using a dedicated web-based interface. Patients additionally provided weekly CAT scores using the same telehealth platform and came in for 3 study visits to assess functional parameters and biochemical markers related to nutrition and inflammation. Results: A principal study finding was that PA was inversely associated with CAT score (drop of 0.21 points associated with an increase of 1000 daily steps, p = 0.004), and that the 50% of patients with higher PA levels showed less CAT score progression over time (0.42 points per year) than the 50% of patients with lower PA levels (3.26 points per year) (p < 0.001). In addition, higher PA levels were significantly associated with a lower likelihood of experiencing a moderate-to-severe AECOPD (31% risk reduction associated with an increase of 1000 daily steps, p = 0.0097). Discussion: Our study demonstrates the relevance of PA for key COPD outcome metrics in a real-world setting and underpins the importance of PA for COPD self-management in everyday life. Our study paves the way for future intervention trials to prospectively identify medically relevant PA thresholds and establish training recommendations for different patient subgroups.

The Real-World Efficacy of Fixed Triple Inhalation Therapy in the Treatment of Moderate COPD Patients (RATIONALE Study).

Purpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy. Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients' consent. The primary objective was the change of adherence to treatment during the study, compared to baseline. Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly - proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p<0.001). The average CAT score improved by 7.02 points (95% CI 5.82-8.21, p<0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51-19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly. Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.

Quality Improvement Project to Develop a Pictorial Chronic Obstructive Pulmonary Disease (COPD) Action Plan.

Introduction Chronic obstructive pulmonary disease (COPD) is a global health concern and a leading cause of morbidity and mortality worldwide. COPD action plans help patients manage exacerbations by recognizing symptoms early and taking necessary steps. We found our COPD written action plan difficult to understand, potentially affecting the patient's ability to self-manage their COPD. Aims We aim to design a new COPD action plan to increase the knowledge scores of our patients during competency checks by 20%. Methods We employed the quality improvement methodology of needs analysis and root cause analysis and used a Pareto chart to identify the top four contributory factors to an ineffective COPD action plan. These include being too wordy, lacking pictorial illustrations, being only available in a single language (English), and too much medical jargon. Using the prioritization matrix to assess possible solutions, the team decided to implement a pictorial COPD action plan. After two cycles of Plan-Do-Study-Act, the final pictorial COPD plan was compared with the original written action plan. Results Ten English-speaking COPD patients from our outpatient respiratory clinics were surveyed with the original action plan while 11 more were surveyed after the introduction of the pictorial action plan. There was an improvement in mean knowledge scores by 92.8% (t(19) = 6.67, p < 0.01, at 95% CI). Patient satisfaction rates also increased from 44% to 100%. Sixty-three percent (63.6%) of patients surveyed said they referred back to the pictorial action plan 3 months after being introduced to it. Conclusion Pictorially enhanced COPD action plans have been shown to improve our patients' knowledge of COPD self-management.

Flavonoid intakes, COPD, adult asthma, and lung function: a cohort study in the UK Biobank.

INTRODUCTION: Given their antioxidative stress, anti-allergic, anti-inflammatory, and immune-modulating effects, flavonoids are hypothesised to play a role in preventing chronic obstructive pulmonary disease (COPD) and asthma. OBJECTIVE: The objective of this cohort study was to examine associations between flavonoid intake and COPD, asthma and lung function. METHODS: Among 119,466 participants of the UK Biobank, median [IQR] age of 60 [53, 65], we estimated intakes of flavonoids, flavonoid-rich foods and a flavodiet score from 24-hour diet assessments. Prospective associations with both incident COPD and asthma and cross-sectional associations with measures of lung function [%predicted forced expiratory volume in 1 second (FEV1); and FEV1/forced vital capacity (FVC)] were examined using multivariable-adjusted Cox proportional hazards and linear regression models, respectively. We investigated mediation by inflammation--represented by the INFLA score--and stratified analyses by smoking status. RESULTS: Compared to low intakes, moderate intakes of total flavonoids, flavonols, theaflavins + thearubigins, and flavanones, and moderate-high intakes of flavanol monomers, proanthocyanidins, anthocyanins, flavones, and the flavodiet score were associated with up to an 18% lower risk of incident COPD [e.g., [HR (95% CI) for total flavonoids: 0.83 (0.75, 0.92)] but not incident asthma. Furthermore, compared to low intakes, higher intakes of all flavonoid subclasses (except theaflavins + thearubigins), and the flavodiet score were associated with better percent predicted FEV1 baseline. Associations were most apparent in ever (current or former) smokers. Flavonoid intakes were inversely associated with the INFLA score, which appeared to mediate 11-14% of the association between intakes of proanthocyanidins and flavones and incident COPD. CONCLUSIONS: Moderate to high flavonoid intakes were associated with a lower risk of COPD and better lung function, particularly among ever smokers. Promoting intakes of healthy flavonoid-rich foods, namely tea, apples and berries, may improve respiratory health and lower COPD risk, particularly in individuals with a history of smoking.

Chest CT Airway and Vascular Measurements in Females with COPD or Long-COVID.

Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID. Our objective was to evaluate CT airway and pulmonary vascular and quality-of-life measurements in females with COPD as compared to ex-smokers and patients with long-COVID. Chest CT was acquired 3-months post-COVID-19 infection in females with long-COVID for comparison with the same inspiratory CT in female ex-smokers and COPD patients. TAC, LA, WT, and pulmonary vascular measurements were quantified. Linear regression models were adjusted for confounders including age, height, body-mass-index, lung volume, pack-years and asthma diagnosis. Twenty-one females (53 ± 14 years) with long-COVID, 17 female ex-smokers (69 ± 9 years) and 13 female COPD (67 ± 6 years) patients were evaluated. In the absence of differences in quality-of-life scores, females with long-COVID reported significantly different LA (p = 0.006) compared to ex-smokers but not COPD (p = 0.7); WT% was also different compared to COPD (p = 0.009) but not ex-smokers (p = 0.5). In addition, there was significantly greater pulmonary small vessel volume (BV5) in long-COVID as compared to female ex-smokers (p = 0.045) and COPD (p = 0.003) patients and different large (BV10) vessel volume as compared to COPD (p = 0.03). In females with long-COVID and highly abnormal quality-of-life scores, there was CT evidence of airway remodelling, similar to ex-smokers and patients with COPD, but there was no evidence of pulmonary vascular remodelling.Clinical Trial Registration: www.clinicaltrials.gov NCT05014516 and NCT02279329.

Adventures with the ß2-adrenoceptor Receptor: A Career Long Interest in Agonising One of the Most Widely Studied GPCRs.

Drug discovery is a multi-disciplinary effort in which groups with expertise in a range of areas combine in a unified way to achieve a common goal: to deliver a clinical candidate to evaluate a hypothesis for improving human health. As a medicinal chemist this environment has provided multiple opportunities to be involved in cross-discipline interactions that have been both rewarding and led to outcomes that would not have been possible without an intimate interdisciplinary curiosity. Within this article I aim to share some of my experiences with the ß2-adrenoceptor that have fostered such synergistic relationships with several disciplines, but in particular with in vitro pharmacologists looking at different ways to stimulate this G protein-coupled receptor (GPCR). This interest now spans over a quarter of a century and has been intertwined with the delivery of three clinical candidates.

OSGIN1 regulates PM2.5-induced fibrosis via mediating autophagy in an in vitro model of COPD.

Fine particulate matter (PM2.5) has been identified as a significant contributing factor to the exacerbation of chronic obstructive pulmonary disease (COPD). It has been observed that PM2.5 may induce lung fibrosis in COPD, although the precise molecular mechanism behind this remains unclear. In a previous study, we demonstrated that PM2.5 upregulates OSGIN1, which in turn leads to injury in airway epithelial cells, thereby, suggesting a potential link between PM2.5 exposure and COPD. Based on this, we hypothesized that OSGIN1 plays a role in PM2.5-induced fibrosis in COPD. Human bronchial epithelial (HBE) cells were treated with cigarette smoke extract (CSE) to construct an in vitro model of COPD. Our findings revealed that PM2.5 increased fibrosis indicators and upregulated OSGIN1 in CSE-stimulated HBE cells (CSE-HBEs), and that knockdown of OSGINA reduced the expression of fibrosis indicators. Through the use of microRNA target prediction software and the Gene Expression Omnibus database, we predicted miRNAs that targeted OSGIN1 in COPD. Subsequently, real-time polymerase chain reaction and western blot analysis confirmed that PM2.5 modulated miR-654-5p to regulate OSGIN1 in CSE-HBEs. Western blot demonstrated that OSGIN1 induced autophagy, thereby exacerbating fibrosis in CSE-HBEs. In summary, our results suggest that PM2.5 upregulates OSGIN1 through miR-654-5p, leading to increased autophagy and fibrosis in CSE-HBEs.

Investigating the Utility of Red Blood Cell Distribution Width as a Prognostic Indicator for Deterioration of Patients with Chronic Obstructive Pulmonary Disease Within One Year.

BackGround: Considerable studies have demonstrated a significant association between red blood cell distribution width (RDW) and clinical adverse events in cardiovascular or respiratory diseases, infections, and pulmonary embolism. However, there are limited data on prognostic predictions for patients suffering from chronic obstructive pulmonary disease (COPD). Methods: This study conducted a retrospective cohort analysis using data gathered from patients who diagnosed with COPD in the respiratory department of The Central hospital of Enshi Tujia and Miao Autonomous Prefecture between 2018 and 2021. Specifically, the RDW was recorded on their first admission. Multivariate logistic regression analysis were employed to examine the correlation between RDW and deterioration of COPD within one-year period. Results: The cohort of 1799 patients in the study comprised 74.7% male and had an average age of 68.9 ± 9.9 years. The fully adjusted model revealed that, the RDW-middle group (≤13.7,>12.8; OR 1.5, 95% CI 1.0-2.3, p=0.055) and the RDW-high group (>13.7; OR 1.7, 95% CI 1.1-2.6, p=0.013) had a 50% and 70% increased risk of deterioration within 1 year, respectively, in comparison with the RDW-low group (≤12.8). Subgroup analysis indicated that this trend was more significant in patients with hypertension (p for interaction = 0.016), and the probability of deterioration within 1 year in the RDW-high group was 3.3 times higher compared to the RDW-low group (OR 3.3, 95% CI 1.4-7.9, p=0.008). Conclusion: A significant association was observed between the increase in RDW and the heightened risk of deterioration within a year in patients diagnosed with COPD. Most importantly, our findings suggested the importance of RDW in enhancing the risk stratification and prevention of deterioration of COPD.

Development and validation of a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality. Methods: In a retrospective study, we used probabilistic graphs to analyse clinical cross-sectional data (COPDGene cohort), including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data. COPDGene recruited current and former smokers, aged 45-80 years with >10 pack-years smoking history, from across the USA (Phase 1, 11/2007-4/2011) and invited them for a follow-up visit (Phase 2, 7/2013-7/2017). ECLIPSE cohort recruited current and former smokers (COPD patients and controls from USA and Europe), aged 45-80 with smoking history >10 pack-years (12/2005-11/2007). We applied graphical models on multi-modal data COPDGene Phase 1 participants to identify factors directly affecting all-cause and COPD-specific mortality (primary outcomes); and on Phase 2 follow-up cohort to identify additional molecular and social factors affecting mortality. We used penalized Cox regression with features selected by the causal graph to build VAPORED, a mortality risk prediction model. VAPORED was compared to existing scores (BODE: BMI, airflow obstruction, dyspnoea, exercise capacity; ADO: age, dyspnoea, airflow obstruction) on the ability to rank individuals by mortality risk, using four evaluation metrics (concordance, concordance probability estimate (CPE), cumulative/dynamic (C/D) area under the receiver operating characteristic curve (AUC), and integrated C/D AUC). The results were validated in ECLIPSE. Findings: Graphical models, applied on the COPDGene Phase 1 samples (n = 8610), identified 11 and 7 variables directly linked to all-cause and COPD-specific mortality, respectively. Although many appear in both models, non-lung comorbidities appear only in the all-cause model, while forced vital capacity (FVC %predicted) appears in COPD-specific mortality model only. Additionally, the graph model of Phase 2 data (n = 3182) identified internet access, CD4 T cells and platelets to be linked to lower mortality risk. Furthermore, using the 7 variables linked to COPD-specific mortality (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ration, FVC %predicted, age, history of pneumonia, oxygen saturation, 6-min walk distance, dyspnoea) we developed VAPORED mortality risk score, which we validated on the ECLIPSE cohort (3-yr all-cause mortality data, n = 2312). VAPORED performed significantly better than ADO, BODE, and updated BODE indices in predicting all-cause mortality in ECLIPSE in terms of concordance (VAPORED [0.719] vs ADO [0.693; FDR p-value 0.014], BODE [0.695; FDR p-value 0.020], and updated BODE [0.694; FDR p-value 0.021]); CPE (VAPORED [0.714] vs ADO [0.673; FDR p-value <0.0001], BODE [0.662; FDR p-value <0.0001], and updated BODE [0.646; FDR p-value <0.0001]); 3-year C/D AUC (VAPORED [0.728] vs ADO [0.702; FDR p-value 0.017], BODE [0.704; FDR p-value 0.021], and updated BODE [0.703; FDR p-value 0.024]); integrated C/D AUC (VAPORED [0.723] vs ADO [0.698; FDR p-value 0.047], BODE [0.695; FDR p-value 0.024], and updated BODE [0.690; FDR p-value 0.021]). Finally, we developed a web tool to help clinicians calculate VAPORED mortality risk and compare it to ADO and BODE predictions. Interpretation: Our work is an important step towards improving our identification of high-risk patients and generating hypotheses of potential biological mechanisms and social factors driving mortality in patients with COPD at the population level. The main limitation of our study is the fact that the analysed datasets consist of older people with extensive smoking history and limited racial diversity. Thus, the results are relevant to high-risk individuals or those diagnosed with COPD and the VAPORED score is validated for them. Funding: This research was supported by NIH [NHLBI, NLM]. The COPDGene study is supported by the COPD Foundation, through grants from AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.

Strengthening Clinician-Researchers' Communication and Knowledge Translation Skills: An Innovative Game Model From the Breathe Well Group.

Communication is a core component of a clinician's role; however, when clinicians conduct research, communicating the emerging findings and recommendations to different types of stakeholders can be unfamiliar territory. Communicating research to advocate for change can be even more challenging. Clinician researchers seeking to be agents for change need to conceive and craft specific, evidence-based messages and communicate these effectively to different stakeholders to negotiate action. As part of a global health research program, we developed and tested a novel game-based model to strengthen the communication skills of clinician researchers, from 4 countries, for improving services for chronic obstructive pulmonary disease. This model focused on communication with 3 key stakeholder groups for knowledge translation: Patients/carers, healthcare providers and policy makers/healthcare managers. Delivered through a series of facilitated, online meetings, this model consisted of 2 parts: developing and rehearsing advocacy messages with coaching support, and then testing them with a panel of 3 representative stakeholders, and an audience of fellow researchers. All the country teams reported increased confidence in crafting advocacy messages for specific stakeholders and have applied lessons learned from the model. Delivering this model within a global health research program requires mentoring, time, commitment, resources and translation support to address language barriers. It offers an exemplar to build the communication skills of clinician and non-clinician researchers so that they can go beyond dissemination toward translation of evidence into policy and practice.

Tricuspid Annular Plane Systolic Excursion (TAPSE) in COPD Patients, A Systematic Review and Meta-Analysis.

Introduction: Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic parameter that serves as a prognostic indicator for severity of COPD clinical course. This study, consisting of a systematic review and meta-analysis, evaluates the current literature to elucidate the relationship between TAPSE measurement in COPD patients versus control subjects to discern baseline evidence of right heart strain. Methods: PubMedTM, ScopusTM, CINAHL, Web of Science, and Cochrane Review databases were searched from their beginning through November 1, 2023, for eligible studies. Outcomes included the difference of TAPSE measurement and right ventricular wall thickness between COPD patients and control patients. The Newcastle-Ottawa Scale was applied to assess risk of bias; Q-statistics and I2 values were used to assess for heterogeneity; and Egger's and Begg's test used to assess for publication bias. Results: The search yielded eleven studies reporting TAPSE values involving 1671 patients, 800 (47.9%) patients with COPD. The unadjusted mean TAPSE values for COPD patients was 18.9 mm (SD+/- 4), while the mean TAPSE value for control patients was 22.2 mm (SD+/- 0.8). The presence of COPD was significantly associated with decreased TAPSE values with the meta-analysis reporting the mean difference of TAPSE value between COPD and control patients was -3.0 (95% CI -4.3 to -1.7, P=0.001). Six studies reported the RV free wall thickness. The unadjusted mean RV free wall thickness for COPD patients was 4.9 mm (SD+/- 1.2), and control patients was 3.4 mm (SD+/- 0.7), respectively. Conclusions: This meta-analysis demonstrated statistically-significantly lower TAPSE values and thicker RV free wall among COPD patients versus control patients.

Self-report underestimates the frequency of the acute respiratory exacerbations of COPD but is associated with BAL neutrophilia and lymphocytosis: an observational study.

RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001). DISCUSSION: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis.

New-onset obstructive airway disease following COVID-19: a multicenter retrospective cohort study.

BACKGROUND: The study assessed the association between COVID-19 and new-onset obstructive airway diseases, including asthma, chronic obstructive pulmonary disease, and bronchiectasis among vaccinated individuals recovering from COVID-19 during the Omicron wave. METHODS: This multicenter retrospective cohort study comprised 549,606 individuals from the U.S. Collaborative Network of TriNetX database, from January 8, 2022, to January 17, 2024. The hazard of new-onset obstructive airway diseases between COVID-19 and no-COVID-19 groups were compared following propensity score matching using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: After propensity score matching, each group contained 274,803 participants. Patients with COVID-19 exhibited a higher risk of developing new-onset asthma than that of individuals without COVID-19 (adjusted hazard ratio (aHR), 1.27; 95% CI, 1.22-1.33; p < 0.001). Stratified analyses by age, SARS-CoV-2 variant, vaccination status, and infection status consistently supported this association. Non-hospitalized individuals with COVID-19 demonstrated a higher risk of new-onset asthma (aHR, 1.27; 95% CI, 1.22-1.33; p < 0.001); however, no significant differences were observed in hospitalized and critically ill groups. The study also identified an increased risk of subsequent bronchiectasis following COVID-19 (aHR, 1.30; 95% CI, 1.13-1.50; p < 0.001). In contrast, there was no significant difference in the hazard of chronic obstructive pulmonary disease between the groups (aHR, 1.00; 95% CI, 0.95-1.06; p = 0.994). CONCLUSION: This study offers convincing evidence of the association between COVID-19 and the subsequent onset of asthma and bronchiectasis. It underscores the need for a multidisciplinary approach to post-COVID-19 care, with a particular focus on respiratory health.

Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

Awareness of COPD in low-and middle-income countries and implications for treatment.

INTRODUCTION: COPD is the 3rd leading cause of death worldwide, affecting an estimated 212.3 million people. More than 80% of this burden occurs in low- and middle-income countries. One of the major reasons for this growing burden, is the lack of awareness of COPD among all levels. AREAS COVERED: In this review article, we studied the level of awareness of COPD among lay people, health care providers and policy makers in the LMICs. Search engines including Google Scholar, PubMed, and Scopus were used for relevant articles. Articles spanning from 1990 to March 2024 were screened on COPD awareness in LMICs and its treatment implications using a combination of key words. EXPERT OPINION: We report that the overall awareness of COPD is low at all levels. There are several reasons such as poverty, illiteracy, societal beliefs, cultural beliefs, and misconceptions. This is associated with increase in suffering, deaths, and economic loss, due to poor adaption correct prescription and compliance to treatment. And very little is being done to improve the current status. COPD needs to be highlighted in the national programs in LMICs.

Unveiling the Long-Term Lung Consequences of Smoking and Tobacco Consumption: A Narrative Review.

Smoking and tobacco use present significant public health challenges due to their association with high morbidity and mortality rates worldwide. Despite reductions in smoking rates in many developed countries, global tobacco consumption remains high, especially in developing regions. This review examines the chronic effects of smoking on the respiratory system, detailing the pathological changes in the lungs and the resultant respiratory illnesses such as chronic obstructive pulmonary disease and lung cancer. Additionally, the review explores the impact of smoking on other body systems, including cardiovascular, immune, gastrointestinal, nervous, and reproductive systems. The extensive health implications of smoking emphasize the need for comprehensive public health interventions to reduce tobacco use and mitigate its adverse effects on health.

Causal Relationship Between Gut Microbiota and Chronic Obstructive Pulmonary Disease: A Bidirectional Two-Sample Mendelian Randomization Study.

Background: The associations between gut microbiota and chronic obstructive pulmonary disease (COPD) have gained increasing attention and research interest among scholars. However, it remains unclear whether gut microbiota serves as a causal factor for COPD or if it is a consequence of the disease. Therefore, we investigated the causal relationship between COPD and gut microbiota, with intention of providing novel insights and references for clinical diagnosis and treatment. Methods: Based on the genome-wide association study (GWAS) data, we employed MR-Egger regression, random-effects inverse variance-weighted (IVW) method, and weighted median method for bidirectional Mendelian randomization (MR) analysis. We conducted Cochran's Q test for heterogeneity assessment and performed multivariable analysis, sensitivity analysis, and heterogeneity testing to validate the reliability and stability of results. Results: Utilizing MR analysis, mainly employing the IVW method, we detected a collective of 11 gut microbiota species that exhibited associations with COPD. Among them, Bacteroidia, family XIII, Clostridium innocuum group, Barnesiella, Collinsella, Lachnospiraceae NK4A136 group, Lachnospiraceae UCG004, Lachnospiraceae UCG010, and Bacteroidales were found to be protective factors for COPD. On the other hand, Holdemanella and Marvinbryantia were identified as risk factors for COPD. Individuals with elevated levels of Holdemanella exhibited a 1.141-fold higher risk of developing COPD compared to their healthy counterparts, and those with increased levels of Marvinbryantia had a 1.154-fold higher risk. Reverse MR analysis yielded no evidence indicating a causal relationship between gut microbiota and COPD occurrence. Conclusion: Our study established a causal link between 11 specific gut microbiota species and COPD, offering novel insights and valuable references for targeted therapies in the clinical management of COPD. However, our results were mainly based on the analysis of database, and further clinical studies are needed to clarify the effects of gut microbiota on COPD and its specific protective mechanism.

Remote Patient Monitoring and Machine Learning in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Dual Systematic Literature Review and Narrative Synthesis.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with high mortality, morbidity, and poor quality of life and constitute a substantial burden to patients and health care systems. New approaches to prevent or reduce the severity of AECOPD are urgently needed. Internationally, this has prompted increased interest in the potential of remote patient monitoring (RPM) and digital medicine. RPM refers to the direct transmission of patient-reported outcomes, physiological, and functional data, including heart rate, weight, blood pressure, oxygen saturation, physical activity, and lung function (spirometry), directly to health care professionals through automation, web-based data entry, or phone-based data entry. Machine learning has the potential to enhance RPM in chronic obstructive pulmonary disease by increasing the accuracy and precision of AECOPD prediction systems. OBJECTIVE: This study aimed to conduct a dual systematic review. The first review focuses on randomized controlled trials where RPM was used as an intervention to treat or improve AECOPD. The second review examines studies that combined machine learning with RPM to predict AECOPD. We review the evidence and concepts behind RPM and machine learning and discuss the strengths, limitations, and clinical use of available systems. We have generated a list of recommendations needed to deliver patient and health care system benefits. METHODS: A comprehensive search strategy, encompassing the Scopus and Web of Science databases, was used to identify relevant studies. A total of 2 independent reviewers (HMGG and CM) conducted study selection, data extraction, and quality assessment, with discrepancies resolved through consensus. Data synthesis involved evidence assessment using a Critical Appraisal Skills Programme checklist and a narrative synthesis. Reporting followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: These narrative syntheses suggest that 57% (16/28) of the randomized controlled trials for RPM interventions fail to achieve the required level of evidence for better outcomes in AECOPD. However, the integration of machine learning into RPM demonstrates promise for increasing the predictive accuracy of AECOPD and, therefore, early intervention. CONCLUSIONS: This review suggests a transition toward the integration of machine learning into RPM for predicting AECOPD. We discuss particular RPM indices that have the potential to improve AECOPD prediction and highlight research gaps concerning patient factors and the maintained adoption of RPM. Furthermore, we emphasize the importance of a more comprehensive examination of patient and health care burdens associated with RPM, along with the development of practical solutions.