An analysis of exogenous harmful substance exposure as risk factors for COPD and hypertension co-morbidity using PSM.

Background: Some occupational and environmental exposures could increase the risk of chronic obstructive pulmonary disease (COPD) and hypertension in various work and living environments. However, the effect of exposure to multiple exogenous harmful substances on COPD and hypertension co-morbidities remains unclear. Methods: Participants were selected from eight hospitals in five provinces in China using a multistage cluster sampling procedure. Participants' demographic, exposure, and disease information were collected through questionnaires, spirometry, and blood pressure examinations. Demographic data were used as matching factors, and 1:1 matching between the exposed and non-exposed groups was performed by employing propensity score matching (PSM) to minimize the influence on the results. A one-way chi-squared analysis and multifactorial logistic regression were used to analyze the association between the exposure to exogenous harmful substances (metals and their compound dust, inorganic mineral dust, organic chemicals, and livestock by-products) and the co-morbidity of COPD and hypertension. Results: There were 6,610 eligible participants in the final analysis, of whom 2,045 (30.9%) were exposed to exogenous harmful substances. The prevalence of co-morbidities of COPD and hypertension (6.0%) in the exposure group was higher than their prevalence in the total population (4.6%). After PSM, exogenous harmful substance exposure was found to be a risk factor for the co-morbidity of COPD and hypertension [odds ratio (OR) = 1.347, 95% confidence interval (CI): 1.011-1.794], which was not statistically significant before PSM (OR = 1.094, 95% CI: 0.852-1.405). Meanwhile, the results of different outcomes showed that the association between hypertension and exogenous harmful substance exposure was not statistically significant (OR = 0.965, 95% CI: 0.846-1.101). Smoking (OR = 4.702, 95% CI: 3.321-6.656), history of a respiratory disease during childhood (OR = 2.830, 95% CI: 1.600-5.006), and history of respiratory symptoms (OR = 1.897, 95% CI: 1.331-2.704) were also identified as risk factors for the co-morbidity of COPD and hypertension. Conclusion: The distribution of exogenous harmful substance exposure varies in the population, and the prevalence of co-morbidities is generally higher in susceptible populations. Exposure to exogenous harmful substances was found to be a key risk factor after adjusting for demographic confounders.

Insufficient Pulmonary Rehabilitation Uptake After Severe Exacerbation of COPD: A Multicentre Study in the South West Region of France.

Purpose: Pulmonary rehabilitation (PR) is a type of multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD). Recently, a national French study reported a very low rate of PR uptake (8.6%); however, important clinical data were missing. Here, we aimed to identify the main factors associated with insufficient PR uptake after hospitalisation for COPD exacerbation. Patients and Methods: This multicentre retrospective study included patients hospitalised with COPD exacerbation between 1 January 2017 and 31 December 2018, as identified by both coding and a detailed review of medical records. PR was defined as inpatient care in a specialised centre or unit within 90 days of discharge. Multivariate logistic regression was used to identify associations between PR uptake and patient characteristics, such as comorbidities, non-invasive ventilation (NIV), inhaled treatment, and forced expiratory volume in 1 second (FEV1). Results: Among the 325 patients admitted for severe COPD exacerbation, 92 (28.3%) underwent PR within 90 days of discharge. In univariate analysis, relative to those who underwent PR, patients without PR had significantly more comorbidities, were less often treated with triple bronchodilator therapy or NIV, and had a higher FEV1. In multivariate analysis, variables independently associated with the lack of PR uptake were the presence of comorbidities (adjusted odds ratio (aOR) = 1.28 [1.10-1.53], p = 0.003) and a higher FEV1 (aOR = 1.04 [1.02-1.06], p < 0.001). There was no significant correlation between PR uptake and departmental PR centre capacity (notably, some departments had no PR facilities). Conclusion: These data highlight the lack of PR in the early stages of COPD. Collaboration among all healthcare providers involved in patient management is crucial for improved PR uptake.

Pulmonary rehabilitation (PR) is multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD); however, referral remains very low in France. We have shown, in three French centres, that early-stage COPD and associated comorbidities are the main factors contributing to insufficient PR after hospitalisation for exacerbation. Collaboration among all healthcare providers involved in patient management is crucial to improve PR uptake in the years ahead because physical medicine and rehabilitation professionals play key roles in the promotion and early initiation of PR programs.

Pain prevalence and pain relief in end-of-life care - a national registry study.

BACKGROUND: Despite pain control being a top priority in end-of-life care, pain continues to be a troublesome symptom and comprehensive data on pain prevalence and pain relief in patients with different diagnoses are scarce. METHODS: The Swedish Register of Palliative Care (SRPC) was used to retrieve data from 2011 to 2022 about pain during the last week of life. Data were collected regarding occurrence of pain, whether pain was relieved and occurrence of severe pain, to examine if pain differed between patients with cancer, heart failure, chronic obstructive pulmonary disease (COPD) and dementia. Binary logistic regression models adjusted for sex and age were used. RESULTS: A total of 315 000 patients were included in the study. Pain during the last week of life was more commonly seen in cancer (81%) than in dementia (69%), heart failure (68%) or COPD (57%), also when controlled for age and sex, p < 0.001. Severe forms of pain were registered in 35% in patients with cancer, and in 17-21% in non-cancer patients. Complete pain relief (regardless of pain intensity) was achieved in 73-87% of those who experienced pain, depending on diagnosis. The proportion of patients with complete or partial pain relief was 99.8% for the whole group. CONCLUSIONS: The occurrence of pain, including severe pain, was less common in patients with heart failure, COPD or dementia, compared to patients with cancer. Compared with cancer, pain was more often fully relieved for patients with dementia, but less often in heart failure and COPD. As severe pain was seen in about a third of the cancer patients, the study still underlines the need for better pain management in the imminently dying. TRIAL REGISTRATION: No trial registration was made as all patients were deceased and all data were retrieved from The Swedish Register of Palliative Care database.

Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

Improvement in Inhaler Techniques After Training and Counseling in Patients With Chronic Obstructive Pulmonary Disease or Asthma.

Background Chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma significantly impair quality of life and impose a substantial burden on healthcare systems. Proper inhalation technique is important for effective management of these diseases, yet remains poorly performed by many patients. This study evaluated the impact of structured counseling and training sessions on inhaler use among patients with COPD and asthma, aiming to enhance technique correctness and disease control. Methodology This cross-sectional study analyzed 150 patients with asthma and COPD who fulfilled the inclusion criteria for inhalation techniques. Patients were counseled regarding the proper seven-step inhalation technique for each inhaler type [metered-dose inhaler (MDI), MDI with spacer, and dry powder inhaler (DPI)] through practical demonstration at baseline visits. Correct use of inhalers was assessed by a predefined checklist for each inhaler device at the baseline visit and after three months. The correctness of the inhalation technique was evaluated by scoring each of the seven steps. The disease control assessment was done using the COPD assessment test (CAT) and asthma control test (ACT) at the baseline visit and after three months. Results In this study of 150 patients, there were 97 (64.7%) males and 53 (35.3%) females. In total, 67 (44.7%) were diagnosed with asthma and 83 (55.3%) with COPD. The mean age was 45.33 ± 12.62 years. Post-counseling improvements in inhaler technique were marked, with MDI users enhancing their technique score from an average of 4.4 to 6.1, MDI with spacer from 4.56 to 6.26, and DPI from 4.92 to 6.24 (p < 0.001 for all). Disease control also showed significant gains; CAT scores decreased for MDI users from 23.4 to 20.5, MDI with spacer from 23.92 to 20.96, and DPI from 24.89 to 21.96. Concurrently, ACT scores increased for MDI users from 16.4 to 18.0 (p = 0.002), MDI with spacer from 17.29 to 19.04, and DPI from 16.42 to 18.37 (p < 0.001 for both), reflecting substantive advances in managing COPD and asthma symptoms. Furthermore, patients with primary education exhibited a significant boost in technique mastery post-counseling (p < 0.001), underscoring the potential of well-crafted counseling to transcend educational barriers in promoting effective inhaler use. Conclusions Post-counseling, inhaler technique improved significantly across all types, with MDI with spacer users demonstrating the most progress. Technique scores increased notably (p < 0.001), and disease control scores for COPD and asthma, measured by CAT and ACT, also showed significant improvements (p < 0.001). Remarkably, primary education level participants exhibited substantial technique gains post-intervention, emphasizing the effectiveness of counseling irrespective of initial educational status in enhancing inhaler use and disease management.

Emotion Regulation Difficulties and Smoking Behavior among Adults with Chronic Obstructive Pulmonary Diseases.

COPD is one of the leading causes of death in the United States and results in increased healthcare costs and disability. Smoking is the main determinant of COPD development and continued use increases mortality as compared to those who have stopped smoking. Research has indicated that cigarette smoking may play a role in attempts to regulate distressing emotional experiences and thus, may be an important transdiagnostic process underlying continued smoking behavior among adults with COPD. The current study investigated the role of ER difficulties in relation to smoking status and cigarettes smoked per day among adults with COPD. This cross-sectional study included a sample was adults with COPD (N = 320). Participants self-reported current smoking status, daily smoking, and the Difficulties in Emotion Regulation Scale. All analyses were adjusted for age, sex, probable depression, probable anxiety, and dyspnea severity. DERS total scores were associated with greater odds of current smoking. With the exception of impulsivity, all other dimensions of emotion regulation were significantly associated with current smoking. Greater difficulties in emotional awareness were associated with greater cigarettes smoked per day. However, neither the DERS total score nor any other dimensions of emotional regulation were significantly associated with cigarettes smoked per day. The present study provides preliminary data linking ER difficulties to smoking behavior among adults with COPD. If corroborated by future research, these findings suggest that ER might be a potential target for smoking cessation programs among adults with COPD.

Residential radon decay products are associated with cough and phlegm in patients with COPD.

Radon decay products attach to particulate matter (referred to as particle radioactivity, PR) has been shown to be potential to promote airway damage after inhalation. In this study, we investigated associations between PR with respiratory symptoms and health-related quality of life (HRQL) in patients with COPD. 141 male patients with COPD, former smokers, completed the St. George's Respiratory Questionnaire (SGRQ) after up to four 1-week seasonal assessments (N=474) of indoor (home) and ambient (central site) particulate matter ≤ 2.5 µm in diameter (PM2.5) and black carbon (BC). Indoor PR was measured as α-activity (radiation) on PM2.5 filter samples. The ratio of indoor/ambient sulfur in PM2.5 (a ventilation surrogate) was used to estimate α-PR from indoor radon decay. SGRQ responses assessed frequent cough, phlegm, shortness of breath, wheeze, and chest attacks in the past 3 months. Multivariable linear regression with generalized estimating equations accounting for repeated measures was used to explore associations, adjusting for potential confounders. Median (IQR) indoor α-PR was 1.22 (0.62) mBq/m3. We found that there were positive associations between α-PR with cough and phlegm. The strongest associations were with estimated α-PR of indoor origin for cough (31.1 % increase/IQR, 95 %CI: 8.8 %, 57.8 %), and was suggestive for phlegm (13.0 % increase/IQR, 95 %CI: -2.5 %, 31.0 %), similar adjusting for indoor BC or PM2.5. α-PR of indoor origin was positively associated with an increase in SGRQ Symptoms score [1.2 units/IQR; 95 %CI: -0.3, 2.6] that did not meet conventional levels of statistical significance. Our results suggested that exposure to indoor radon decay products measured as particle radioactivity, a common indoor exposure, is associated with cough, and suggestively associated with phlegm and worse HRQL symptoms score in patients with COPD.

Association of volatile organic compound levels with chronic obstructive pulmonary diseases in NHANES 2013-2016.

Volatile organic compounds (VOCs) represent a significant component of air pollution. However, studies evaluating the impact of VOC exposure on chronic obstructive pulmonary disease (COPD) have predominantly focused on single pollutant models. This study aims to comprehensively assess the relationship between multiple VOC exposures and COPD. A large cross-sectional study was conducted on 4983 participants from the National Health and Nutrition Examination Survey. Four models, including weighted logistic regression, restricted cubic splines (RCS), weighted quantile sum regression (WQS), and the dual-pollution model, were used to explore the association between blood VOC levels and the prevalence of COPD in the U.S. general population. Additionally, six machine learning algorithms were employed to develop a predictive model for COPD risk, with the model's predictive capacity assessed using the area under the curve (AUC) indices. Elevated blood concentrations of benzene, toluene, ortho-xylene, and para-xylene were significantly associated with the incidence of COPD. RCS analysis further revealed a non-linear and non-monotonic relationship between blood levels of toluene and m-p-xylene with COPD prevalence. WQS regression indicated that different VOCs had varying effects on COPD, with benzene and ortho-xylene having the greatest weights. Among the six models, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest predictive power, with an AUC value of 0.781. Increased blood concentrations of benzene and toluene are significantly correlated with a higher prevalence of COPD in the U.S. population, demonstrating a non-linear relationship. Exposure to environmental VOCs may represent a new risk factor in the etiology of COPD.

Rethinking Blood Eosinophils for Assessing ICS Response in COPD: A Post-Hoc Analysis from FLAME.

BACKGROUND: The varied treatment response to inhaled corticosteroids (ICS) in COPD, and the increased risk of pneumonia necessitate a personalised ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment. RESEARCH QUESTION: Does BEC measured on or off ICS treatment or the change in BEC during ICS treatment, best predict treatment response to ICS in COPD? STUDY DESIGN AND METHODS: FLAME, a 52-week, double-blind RCT compared LABA/LAMA versus LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing pre- and post-run-in period BEC to represent BEC on and off ICS, respectively. In this post-hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS containing regimen. RESULTS: Our study confirms that LABA/LAMA combination is superior, or at least non-inferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off and BEC on ICS and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time-to-first exacerbation, and time-to-first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥200 cells/µL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC were not predictive of treatment effects on lung function and health status. INTERPRETATION: This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response. CLINICAL TRIAL REGISTRATION: NCT01782326.

Association of COPD with adverse outcomes in heart failure patients with preserved ejection fraction.

We performed a systematic review and meta-analysis to detect the impact of chronic obstructive pulmonary disease (COPD) on the prognosis of heart failure patients with preserved ejection fraction (HFpEF). We systematically screened eligible literature from three electronic databases, PubMed, EMBASE and Cochrane Library, up to April 2023. Two researchers participated in data collection independently. Risk ratios (RRs) from included studies with 95% confidence intervals (CIs) were pooled in the Review Manager version 5.40 software using a random-effects model for analysis. A total of 11 studies (3 post hoc analyses of RCTs and 8 observational studies) with 18 602 participants were included in this meta-analysis. After pooling all the data from eligible studies, our results indicated that COPD was associated with an increased risk of hospitalization (RR = 1.66, 95% CI, 1.47-1.87, P < 0.00001), mortality (RR = 1.62, 95% CI, 1.34-1.95, P < 0.00001), and the composition of hospitalization or mortality (RR = 1.84, 95% CI, 1.35-2.51, P < 0.001) in patients with HFpEF. In a subgroup analysis, the risks of cardiovascular-related mortality (RR = 1.59, 95% CI, 1.30-1.93, P < 0.00001) and post-discharge mortality risk (RR = 2.57, 1.34-4.93, P < 0.01) were increased in HFpEF patients comorbid with COPD, and these associations were also detected in HF-caused hospitalization (RR = 1.64, 95% CI, 1.44-1.87, P < 0.00001). Evidence from existing studies supported that COPD was an independent prognostic risk factor for patients with HFpEF. Developing rapid clinical diagnostic indicators and early use of novel drugs such as SGLT-2 and ARNI may improve the prognosis of this population, deserving further study.

Rare intercostal herniation of abdominal organs in COPD patient managed non-operatively.

Nontraumatic intercostal and intrathoracic herniation of intra-abdominal organs is rare and has been sparsely reported in the literature. They are defined as protrusion of intra-abdominal contents through defects in the chest wall. The cases reported in the literature mostly involved herniation of intra-abdominal contents and the lungs through the defect. In this case report, we describe a case of intra-abdominal contents herniation through an intercostal defect with subsequent improvement in patient's respiratory status related to the hernia.

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

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

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

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

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

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

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

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

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

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

Characterization and Mortality Risk of Impaired Left Ventricular Filling in COPD.

BACKGROUND: In COPD, impaired left ventricular (LV) filling might be associated with coexisting HFpEF or due to reduced pulmonary venous return indicated by small LV size. We investigate the all-cause mortality associated with small LV or HFpEF and clinical features discriminating between both patterns of impaired LV filling. METHODS: We performed transthoracic echocardiography (TTE) in patients with stable COPD from the COSYCONET cohort to define small LV as LVEDD below the normal range and HFpEF features according to recommendations of the European Society of Cardiology. We assessed the E/A and E/e' ratios, NT-pro-BNP, hs-Troponin I, FEV1, RV, DLCo, and discriminated patients with small LV from those with HFpEF features or no relevant cardiac dysfunction as per TTE (normalTTE). The primary outcome was all-cause mortality after four and a half year. RESULTS: In 1752 patients with COPD, the frequency of small LV, HFpEF-features, and normalTTE was 8%, 16%, and 45%, respectively. Patients with small LV or HFpEF features had higher all-cause mortality rates than patients with normalTTE, HR: 2.75 (95% CI: [1.54 - 4.89]) and 2.16 (95% CI: [1.30 - 3.61]), respectively. Small LV remained an independent predictor of all-cause mortality after adjusting for confounders including exacerbation frequency and measures of RV, DLCo, or FEV1. Compared to normalTTE, patients with small LV had reduced LV filling, as indicated by lowered E/A. Yet in contrast to patients with HFpEF-features, patients with small LV had normal LV filling pressure (E/e') and lower levels of NT-pro-BNP and hs-Troponin I. CONCLUSION: In COPD, both small LV and HFpEF-features are associated with increased all-cause mortality and represent two distinct patterns of impaired LV filling.

L-shaped association between serum chloride levels with 90-day and 365-day all-cause mortality in critically ill patients with COPD: a retrospective cohort study.

This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P < 0.05), accompanied by lower 90-day and 365-day mortality (P < 0.05). Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile after adjusting for confounders (90-day HR = 0.54, 365-day HR = 0.52, both P < 0.05). An L-shape relationship was observed, with risks of death decreasing as serum chloride levels increased, although the magnitude decreased when levels reached 102 mmol/L. This study demonstrated an independent L-shaped association between serum chloride levels and all-cause mortality in critically ill patients with COPD. This finding helps us to understand the prognostic value of serum chloride levels in critically ill patients with COPD.

Psoralen attenuates cigarette smoke extract-induced inflammation by modulating CD8+ T lymphocyte recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.