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While all eukaryotic cells are dependent on mitochondria for function, in a complex tissue, which cell type and which cell behavior are more sensitive to mitochondrial deficiency remain unpredictable. Here, we show that in the mouse airway, compromising mitochondrial function by inactivating mitochondrial protease gene Lonp1 led to reduced progenitor proliferation and differentiation during development, apoptosis of terminally differentiated ciliated cells and their replacement by basal progenitors and goblet cells during homeostasis, and failed airway progenitor migration into damaged alveoli following influenza infection. ATF4 and the integrated stress response (ISR) pathway are elevated and responsible for the airway phenotypes. Such context-dependent sensitivities are predicted by the selective expression of Bok, which is required for ISR activation. Reduced LONP1 expression is found in chronic obstructive pulmonary disease (COPD) airways with squamous metaplasia. These findings illustrate a cellular energy landscape whereby compromised mitochondrial function could favor the emergence of pathological cell types.

BackgroundSkeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.MethodsForty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.ResultsAbnormal myofibre proportion was defined in males with COPD (n = 29) as 22% type IIx/IIax fibres and in females with COPD (n = 17) as 12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.ConclusionsOur findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

Fine particulate matter (PM 2.5) has been identified as a significant contributing factor to the exacerbation of chronic obstructive pulmonary disease (COPD). It has been observed that PM 2.5 may induce lung fibrosis in COPD, although the precise molecular mechanism behind this remains unclear. In a previous study, we demonstrated that PM 2.5 upregulates oxidative stress induced growth inhibitor 1 (OSGIN1), which in turn leads to injury in airway epithelial cells, thereby, suggesting a potential link between PM 2.5 exposure and COPD. Based on this, we hypothesized that OSGIN1 plays a role in PM 2.5 -induced fibrosis in COPD. Human bronchial epithelial cells (HBEs) were treated with cigarette smoke extract (CSE) to construct an in vitro model of COPD. Our findings revealed that PM 2.5 increased fibrosis indicators and upregulated OSGIN1 in CSE-stimulated HBEs (CSE-HBEs), and knockdown of OSGIN1 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 PM 2.5 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 PM 2.5 upregulates OSGIN1 through inhibiting miR-654–5p, leading to increased autophagy and fibrosis in CSE-HBEs. • PM 2.5 promotes fibrosis in CSE-HBEs. • PM 2.5 regulates OSGIN1 to modulate fibrosis in CSE-HBEs. • miR-654–5p negatively regulates OSGIN1 in PM 2.5 -treated CSE-HBEs. • OSGIN1 modulates autophagy in PM 2.5 -treated CSE-HBEs. [ABSTRACT FROM AUTHOR]

The varied treatment response to inhaled corticosteroids (ICS) in patients with COPD and the associated increased risk of pneumonia necessitate a personalized 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. Does (1) BEC measured on ICS treatment (2) BEC measured off ICS treatment, or (3) the change in BEC during ICS treatment best predict treatment response to ICS in COPD? The Fluticasone Salmeterol on COPD Exacerbations Trial (FLAME), a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing BEC before and after the run-in period 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. Our study showed that LABA/LAMA combination was superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS, higher 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 was not predictive of treatment effects on lung function and health status. 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. ClinicalTrials.gov; No.: NCT01782326 ; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Airway mucus plugs are frequently identified on CT scans of patients with COPD with a smoking history without mucus-related symptoms (ie, cough, phlegm [silent mucus plugs]). In patients with COPD, what are the risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease? We identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and ≥ 3). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models. Of 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT scan. Risk factors of silent mucus plugs (compared with symptomatic mucus plugs) were older age (OR, 1.02), female sex (OR, 1.40), and Black race (OR, 1.93) (all P values <.01). Among those without cough or phlegm, silent mucus plugs (vs absence of mucus plugs) were associated with worse 6-min walk distance, worse resting arterial oxygen saturation, worse FEV 1 % predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models. Mucus plugs are common in patients with COPD without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural, and clinical measures of disease. CT scan-identified mucus plugs can complement the evaluation of patients with COPD. [Display omitted] [ABSTRACT FROM AUTHOR]

Although there are many sleep-related complaints in chronic obstructive pulmonary disease (COPD) patients, nocturnal leg cramps have not been adequately and extensively studied. This study fills a significant gap in the literature by determining the prevalence and influencing factors of nocturnal leg cramps in COPD patients. However, our findings also underscore the need for further research, inspiring future studies and interventions in this area. This study was conducted with a rigorous methodology, employing a comprehensive approach to evaluate the probability of experiencing nocturnal leg cramps in 215 COPD and 215 control group patients matched for age and gender. Logistic regression analysis was used, supplemented by artificial neural networks, to identify the influencing factors. This robust methodology ensures the reliability and validity of our findings. The findings of this study are not only significant but also enlightening, shedding light on the prevalence and influencing factors of nocturnal leg cramps in COPD patients. The frequency of experiencing these cramps was found to be 40.9% in chronic obstructive pulmonary patients and 21.9% in the control group (p <.05). In COPD patients, factors such as milk group food consumption, blood erythrocyte level, the cover used while sleeping, blood creatinine level, the presence of coronary artery disease, the diagnosis of diabetes mellitus, the upper mid-arm muscle area, and use of drugs with methylxanthine active ingredient methylxanthine were found to affect the occurrence of these cramps. Our findings not only call for further research but also have immediate practical implications. They highlight the crucial role of nurses in managing nocturnal leg cramps in COPD patients. By controlling patients' cold stress, the bed covers they use, and their dairy product consumption, nurses can significantly contribute to managing these cramps, thereby improving the quality of life for these patients. This underscores the importance of their role in patient care and management. [ABSTRACT FROM AUTHOR]

Family caregivers care for individuals in the home environment. Family caregivers of individuals with chronic obstructive pulmonary disease (COPD) observe breathlessness in the care recipient. Breathlessness is a main symptom of COPD, and watching breathlessness creates emotional distress and a toll on family caregivers. The purpose of this integrative review was to explore the literature on family caregivers and witnessed breathlessness in individuals with COPD. An understanding of family caregiver experiences of breathlessness will allow for further development of evidence-based practice and research. An integrative review was performed using the five-step process of the Whittemore and Knafl Integrative Review Model. Literature search results were reported using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. An overarching theme of constant care and burden resulted from the 18 studies on family caregivers and witnessed breathlessness in individuals with COPD. Three themes: psychosocial implications of caregivers, response ambiguity, and knowledge of interventions represented family caregivers and breathlessness in the care recipient among the studies. This integrative review provides insight on family caregivers and witnessed breathlessness in individuals with COPD. An understanding of the family caregiver perception of breathlessness in the care recipient can help home healthcare professionals empathize with and offer support specific to the needs of family caregivers of individuals with breathlessness from COPD, heart failure, and other chronic diseases. [ABSTRACT FROM AUTHOR]

Background and Objective: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. Methods: Based on visual CT assessment, patients with mucus plugs in 0, 1–2 and ≥3 lung segments were assigned to no‐, low‐ and high‐mucus groups. Loss of health‐related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto–Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. Results: Of 199 and 96 patients in the Kyoto–Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high‐mucus group than in the no‐mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. Conclusion: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health‐related independence and mortality in patients with COPD. [ABSTRACT FROM AUTHOR]

Aim: To explore experiences of patients affiliated to a cross‐sectorial outgoing lung team. Background: The outgoing lung team consisted of respiratory nurses from the hospital and community nurses. The lung team offered 24/7 help to patients with advanced chronic obstructive pulmonary disease (COPD) through visits and/or treatment in the patients' home. Affiliation to the lung team reduced both hospitalizations and length of hospital stay due to acute exacerbation of COPD. However, based on questionnaires on health‐related quality of life, no significant differences were found between patients affiliated to the lung team and patients receiving usual care. Design: A qualitative interview study. Methods: In total, 16 patients, aged 61–88 years were interviewed between February 2019 and July 2021. They had been affiliated to the outgoing lung team for 1–3 years. Semi‐structured interviews were conducted in the patients' home and audio‐recorded after informed consent was obtained. The interviews were transcribed verbatim and analysed, inspired by systematic text condensation by Malterud. Findings: Four themes emerged from the analysis: (1) feeling safe, (2) improvements in living with COPD, (3) avoiding hospitalization and (4) satisfied with staying at home. Conclusion: Affiliation to the cross‐sectorial outgoing lung team gave the patients peace of mind and improved their ability to live with advanced COPD. The patients preferred contacting the lung team because they could stay at home and receive treatment, and thus avoid hospitalization. Impact: The findings from this study support that municipalities should consider implementing an outgoing lung team, as it has the potential to bring several benefits, including improving patient self‐management. Reporting Method: The manuscript adhered to Consolidated criteria for reporting qualitative research (COREQ) guideline. Patient or Public Contribution: Patients were interviewed. Additionally, no patient or public contributed to the design or conduction of the study, analysis, or interpretation of the data. [ABSTRACT FROM AUTHOR]

Background: Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and response to therapy in obstructive lung diseases. Aim: To investigate the delta values between expiratory and inspiratory resistance and reactance, measured using respiratory oscillometry and its correlation with air trapping and symptoms in subjects with obstructive lung diseases. Methods: Four hundred and seventy‐one subjects (96 with chronic obstructive pulmonary disease [COPD], 311 with asthma, 30 healthy smokers and 34 healthy subjects) were included. Spirometry, body plethysmography and respiratory oscillometry measurements were performed and the differences between the expiratory and inspiratory respiratory oscillometry values (as delta values) were calculated. Questionnaires regarding symptoms and quality of life were administered. Results: Patients with COPD and healthy smokers had an increased delta resistance at 5 Hz (R5) compared with patients with asthma (p < 0.0001 and p = 0.037, respectively) and healthy subjects (p = 0.0004 and p = 0.012, respectively). Patients with COPD also had higher values of ΔR5–R19 than healthy subjects (p = 0.0001) and patients with asthma (p < 0.0001). Delta reactance at 5 Hz (X5) was significantly more impaired in COPD patients than in asthma and healthy subjects (p < 0.0001 for all). There was a correlation between the ratio of residual volume and total lung capacity and ΔR5 (p = 0.0047; r = 0.32), ΔR5–R19 (p = 0.0002; r = 0.41) and ΔX5 (p < 0.0001; r = −0.44), for all subjects. ΔX5 correlated with symptoms in COPD, healthy smokers and patients with asthma. In addition, ΔR5 correlated with asthma symptoms. Conclusion: EFL was most prominent in parameters measuring peripheral resistance and reactance and correlated with air trapping and airway symptoms. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease characterised by irreversible airways obstruction associated with chronic airways inflammation and remodelling, while the pathogenesis and the mechanistic differences between patients remain to be fully elucidated. We previously reported that alarmin cytokine IL‐33 may contribute to the production of autoantibodies against respiratory epithelial cells. Here we expand the hypothesis that pulmonary autoimmune responses induced by airway microbiota also contribute to the progression of COPD. We focused on Edwardsiella tarda which we detected uniquely in the induced sputum of patients with acute exacerbations of COPD. Pernasal challenge of the airways of WT mice with supernatants of cultured E. tarda induced marked, elevated expression of IL‐33 in the lung tissues. Immunisation of animals with supernatants of cultured E. tarda resulted in significantly elevated airways inflammation, the formation of tertiary lymphatic structures and significantly elevated proportions of T follicular helper T cells in the lung tissue and mediastinal lymph nodes. Interestingly, such challenge also induced production of IgG autoantibodies directed against lung tissue lysate, alveolar epithelial cell proteins and elastin fragment, while putrescine, one of metabolites generated by the bacterium, might play an important role in the autoantibody production. Furthermore, all of these effects were partly but significantly abrogated in mice with deletion of the IL‐33 receptor ST2. Collectively, these data support the hypothesis that COPD is progressed at least partly by airways microbiota such as E. tarda initiating autoimmune attack of the airways epithelium mediated at least partly through the IL‐33‐ST2 axis. [ABSTRACT FROM AUTHOR]

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24-$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005-March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Home noninvasive ventilation (NIV) may improve chronic hypercarbia in COPD and patient-important outcomes. The efficacy of home high-flow nasal cannula (HFNC) as an alternative is unclear. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov for randomized trials of subjects from inception to March 31, 2023, and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We analyzed randomized controlled trials (RCTs) comparing NIV, HFNC, or standard care in adult subjects with COPD with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (St George Respiratory Questionnaire [SGRQ]). RESULTS: We analyzed 24 RCTs (1,850 subjects). We found that NIV may reduce the risk of death compared to standard care (relative risk 0.82 [95% CI 0.66-1.00]) and probably reduces exacerbations (relative risk 0.71 [95% CI 0.58-0.87]). HFNC probably reduces exacerbations compared to standard care (relative risk 0.77 [0.68-0.88]), but its effect on mortality is uncertain (relative risk 1.20 [95% CI 0.63-2.28]). HFNC probably improves SGRQ scores (mean difference -7.01 [95% CI -12.27 to -1.77]) and may reduce hospitalizations (relative risk 0.87 [0.69-1.09]) compared to standard care. No significant difference was observed between HFNC and NIV in reducing exacerbations. CONCLUSIONS: Both NIV and HFNC reduce exacerbation risks in subjects with COPD compared to standard care. HFNC may offer advantages in improving quality of life. [ABSTRACT FROM AUTHOR]

To assess validity and responsiveness of the Extended Rehabilitation Complexity Scale (RCS-E v13) to in-hospital pulmonary rehabilitation (PR) in individuals with chronic respiratory diseases (CRD). Cross-sectional, multicentric study. Assessments in individuals attending units on 2 nonconsecutive days. Fourteen in-hospital PR units. Five hundred forty-seven individuals (59.2% male, age 72y [range, 65-78y]): 317 with chronic respiratory failure because of various causes (CRF); 96 with chronic obstructive pulmonary disease without CRF (COPD), 39 tracheostomized and ventilated (TX/V), and 95 with other diseases (Miscellaneous). Assessment of RCS-E v13 before and after the PR program. RCS-E v13 and outcome measures: Barthel Index (BI), Barthel Index Dyspnea (BiD), Medical Research Council scale for dyspnea (MRC), COPD Assessment Test (CAT), Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT). The highest RCS-E v13 admission values (median [interquartile range]) were found in TX/V (17 [15-18]) as compared with other groups (8 [7-10], 10 [9-12], and 8 [8-10] in COPD, CRF, and Miscellaneous, respectively, P <.001). At admission and discharge, RCS-E v13 correlated strongly with BI, 6MWT, and SPPB and moderately with MRC and BiD (r =.43-.60). After the program, RCS-E v13 as well as all outcome measures improved significantly in all groups (P <.001 for all). The size of improvement was different among groups according to the different variables. In the overall group, the effect size was high for changes in RCS-E v13 (Cohen's d =−2.0984), CAT (d =−1.1937), MRC (d =−1.0505), BiD (d =−.9364), and SPPB (d =.9231) whereas it was moderate for 6MWT (d =.7670) and BI (d =.6574). RCS-E v13 varies according to different CRD, is responsive to PR, has good construct and concurrent validity, and correlates with most of the accepted outcome measures of PR. Its scoring may provide useful information on the care burden of individuals undergoing PR. [ABSTRACT FROM AUTHOR]

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18. [ABSTRACT FROM AUTHOR]

Cigarette smoking causes serious complications and diseases in a person's life, such as Chronic Obstructive Pulmonary Disease (COPD) and some cancers, including lung cancer. On the other hand, studies have shown that smokers do not have a real understanding of the health hazards of smoking. This study was conducted to determine the perceived risk of lung cancer and COPD in current smokers. This cross-sectional study which was conducted between January-May 2023, recruited 380 current smokers by convenience sampling in community setting. The data were collected face to face using three questionnaires (1) the risk perception for lung cancer and COPD questionnaire, (2) the smoking stage of change questionnaire, and (3) the Fagerström test for nicotine dependence. We examined the relationship between the included variables and the smokers' perceived risk of lung cancer and COPD by using multiple linear regression. We found that lower education (coefficient = 3.60, 95%CI [1.00, 6.19], P < 0.0001) for elementary level and (coefficient = 2.81, 95% CI [0.36, 5.26], P < 0.05) for secondary level had greater lung cancer perceived risk. Besides, smoking age onset for 20 + years (coefficient=-1.36, 95%CI [-2.42, -3.17], P < 0.0001) lower than those who started before the age of 20 were associated with lower perceived risk for lung cancer. Regarding COPD, results indicated that lower education (coefficient = 4.54, 95% CI [1.87, 7.21], p < 0001) for elementary level (coefficient = 3.35, 95% CI [0.83, 5.87], p < 0.001) for secondary level and (coefficient = 3.03, 95% CI[-0.67, 4.25], P < 0.05) for high school dropout, and employment status (coefficient = 3.62, 95% CI[0.66, 6.59], p < 0.05) of employer and (coefficient = 3.23, 95% CI [0.14, 6.33], p < 0.05) for homemaker reported greater perceived risk. This study's results showed that participants' perceived risk was relatively low. It seems necessary to carry out interventions to inform about the harms of smoking and to enhance public awareness about the heightened risks of diseases such as lung cancer and COPD among cigarette smokers. [ABSTRACT FROM AUTHOR]

Ambroxol hydrochloride is a pharmaceutical compound that is primarily used to treat respiratory disorders characterized by excessive mucus production. It is a mucolytic agent used in treating various respiratory conditions, including bronchitis, asthma, COPD (Chronic Obstructive Pulmonary Disease), and cystic fibrosis. The standard industrial‐scale synthesis involves Schiff's base formation followed by reduction; this method is widely adopted due to its efficiency and cost‐effectiveness. Apart from this, various patented methodologies have emerged recently, along with novel therapeutic applications, where it is used for treating Parkinson's and Alzheimer's diseases, including anti‐inflammatory and antioxidant properties. These findings open new avenues for its use in various medical treatments. The current review aims to assess the industrial scale processes in the current market, examine its pharmacological action, and explore recently evaluated therapeutic applications, offering a comprehensive overview of its potential in modern medicine. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by pulmonary and systemic inflammation. Inflammatory mediators show relationships with shortness of breath, exercise intolerance and health related quality of life. Pulmonary rehabilitation (PR), a comprehensive education and exercise training programme, is the most effective therapy for COPD and is associated with reduced exacerbation and hospitalization rates and increased survival. Exercise training, the primary physiological intervention within PR, is known to exert a beneficial anti‐inflammatory effect in health and chronic diseases. The question of this review article is whether exercise training can also make such a beneficial anti‐inflammatory effect in COPD. Experimental studies using smoke exposure mice models suggest that the response of the immune system to exercise training is favourably anti‐inflammatory. However, the evidence about the response of most known inflammatory mediators (C‐reactive protein, tumour necrosis factor α, interleukin 6, interleukin 10) to exercise training in COPD patients is inconsistent, making it difficult to conclude whether regular exercise training has an anti‐inflammatory effect in COPD. It is also unclear whether COPD patients with more persistent inflammation are a subgroup that would benefit more from hypothesized immunomodulatory effects of exercise training (i.e., personalized treatment). Nevertheless, it seems that PR combined with maintenance exercise training (i.e., lifestyle change) might be more beneficial in controlling inflammation and slowing disease progress in COPD patients, specifically in those with early stages of disease. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionOxidative stress plays a crucial role in the development of multiple chronic respiratory diseases. Oxidative Balance Score (OBS) composing of 16 dietary factors and 4 lifestyle factors has been developed to evaluate the effect of oxidants/antioxidants produced by dietary intake and lifestyle habits on the overall oxidative balance. However, the relationships between OBS with asthma, COPD, and asthma-COPD overlap (ACO) are still unclear.A total of 10,942 adults aged 20 years and older from the 2013-2018 National Health and Nutrition Examination Survey were included in the analyses. ANOVA and chi-square tests were used to compare characteristics between different OBS subgroups.Multiple multivariate logistic regression was used to analyze the associations between OBS and asthma, COPD, and ACO.RCS curves were used to describe the dose-response effect of the associations. Subgroup analyses and interaction effects were employed to reflect the stability of the associations.In the fully adjusted models, OBS was found to be negatively associated with asthma, COPD, and ACO. OBS at Q2, Q3, and Q4 (OR: 0.66, 95% CI: 0.46-0.97) were negatively associated with the risk of asthma. OBS at Q2 and Q4 were negatively associated with the risk of COPD. OBS at Q2 and Q4 were negatively associated with the risk of ACO. The RCS curves reflected the negative dose-response trend of association. Moreover, the associations were stable in various subgroups.The negative associations between OBS and asthma, COPD, and ACO were found in American adults, providing evidence for dietary and lifestyle prevention. [ABSTRACT FROM AUTHOR]

Background: Protective measures applied during the Covid-19 pandemic had a marked impact on the incidence of pneumonia. However, systematic data are lacking for hospitalizations for pneumonia and acute exacerbations of chronic obstructive lung diseases (AECOPD) not caused by SARS-CoV-2 in Switzerland. We aimed to compare the incidences of hospitalization for these entities between 2020/2021 and prepandemic years. Methods: This retrospective study examined all nationwide hospitalizations for non-Covid-19-pneumonia and AECOPD listed as primary diagnoses based on ICD-10 codes between 2015 and 2021 in a publicly available hospitalization database of the Swiss Federal Statistical Office. Hospitalizations for acute coronary syndrome (ACS) and stroke were used as controls. Changes of monthly incidences of hospitalizations, length of stay (LOS) and mortality were compared between 2020/2021 and the average of 2015–2019. Results: The incidences of hospitalizations for AECOPD and for pneumonia showed seasonal variations from 2015 to 2019 followed by significant and almost identical decreases in 2020/2021 (incidence rate ratio [IRR] 0.59, 95% CI: 0.45–0.77, p < 0.001, and IRR: 0.62, 95% CI: 0.52–0.74, p < 0.001, respectively). Hospital-mortality was slightly higher in 2020/2021 for AECOPD (2015–2019: 3.8%; 2020/2021: 4.2%, odds ratio [OR] 1.24, 95% CI: 1.07–1.44, p = 0.004) and for pneumonia (2015–2019: 4.5%, 2020/2021: 4.6%, odds ratio [OR] 1.17, 95% CI: 1.07–1.28, p < 0.001). Median LOS slightly decreased for AECOPD (2015–2019: 8 [IQR: 5–14] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001) but slightly increased for pneumonia (2015–2019: 7 [IQR: 4–11] days; 2020/2021: 7 [IQR: 4–13] days, Wilcoxon test: p < 0.001). Throughout 2020/2021, there were no significant fluctuations observed in the incidences of ACS and stroke. (IRR: 0.98, 95% CI: 0.83–1.16, p = 0.810, IRR: 0.96, 95% CI: 0.81–1.14, p = 0.636, respectively). Conclusion: The first two years of the Covid-19 pandemic showed a marked decrease in incidences in AECOPD and non-Covid-19 pneumonia hospitalizations in Switzerland. It is likely that this effect is associated with the society-based, at first vigorous, social distancing measures. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a complex respiratory condition influenced by environmental and genetic factors. Using next-generation sequencing, we aimed to identify dysregulated genes and potential therapeutic targets for COPD. Methods: Peripheral blood leukocyte RNA profiles from COPD patients and healthy controls were analyzed using next-generation sequencing. Key genes involved in COPD pathogenesis were identified through protein–protein interaction network analysis. In vitro, bronchial epithelial cells treated with cigarette smoke extract (CSE) were used to study the effects on gene expression, cell viability, apoptosis, and ferroptosis. Additionally, Lipocalin 2 (LCN2) inhibition experiments were conducted to elucidate its role in COPD-related cellular processes. Results: Analysis of RNA profiles revealed consistent downregulation of 17 genes and upregulation of 21 genes across all COPD groups. Among these, Cathelicidin Antimicrobial Peptide(CAMP), Defensin Alpha 4(DEFA4), Neutrophil Elastase(ELANE), LCN2 and Lactotransferrin(LTF) were identified as potentially important players in COPD pathogenesis. Particularly, LCN2 exhibited a close association with COPD and was found to be involved in cellular processes. In vitro experiments demonstrated that CSE treatment significantly increased LCN2 expression in bronchial epithelial cells in a concentration-dependent manner. Moreover, CSE-induced apoptosis and ferroptosis were observed, along with alterations in cell viability, Glutathione content, Fe2 + accumulation, ROS: Reactive Oxygen Species and Malondialdehyde levels, Lactate Dehydrogenase(LDH) release and Glutathione Peroxidase 4(GPX4) expression. Inhibition of LCN2 expression partially reversed these effects, indicating the pivotal role of LCN2 in COPD-related cellular processes. Conclusion: Our study identified six candidate genes: CAMP, DEFA4, ELANE, LCN2, and LTF were upregulated, HSPA1B was downregulated. Notably, LCN2 emerges as a significant biomarker in COPD pathogenesis, exerting its effects by promoting apoptosis and ferroptosis in bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Background and Objective Methods Results Conclusion Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV1, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18‐month measures of disease progression associated with 18–54‐month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort.Analysing data of 1364 patients from the German observational COSYCONET‐cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models.Increased risk of 18–54‐month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV1 (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18‐month disease progression occurring in ~52% and ~46% of patients, respectively. IL‐6 and CRP thresholds exhibited significant associations with medium‐ and long‐term disease measures.In a multicentric cohort of COPD, new markers of current disease activity predicted mid‐term mortality and could not be anticipated by baseline biomarkers. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD. Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation. Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8–10.9] and 41.6 [5.6–307.9], respectively). Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD. [ABSTRACT FROM AUTHOR]

Background: The pan-immune-inflammation value (PIV) is an emerging biomarker quantitatively reflecting the systemic immune-inflammatory status. The predictive value of PIV has been well-established across various clinical settings. However, its role in chronic obstructive pulmonary disease (COPD) remains unclear and necessitates further investigation. Methods: Data from NHANES 1999-2018 were filtered. Logistic regression analyses were used to assess the correlation between COPD prevalence and PIV in all participants. COX regression analyses and Kaplan-Meier survival curves were used to investigate the relationship between COPD all-cause mortality and PIV in COPD patients. Restricted cubic spline (RCS) analyses and piecewise linear regression analyses were additionally employed to explore the correlation between PIV and COPD. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were employed to assess the robustness of the results. Results: A total of 28,485 participants aged 40 years and older were recruited for this study. After fully adjusting for covariates, higher PIV levels were independently associated with increased COPD prevalence (OR = 1.67; 95% CI: 1.39-2.01) and all-cause mortality (HR = 2.04; 95% CI: 1.41-2.95). The COPD prevalence curve exhibited an inflection point at Log10-PIV of 2.24, showing no significant correlation on the left side (OR = 0.86; 95% CI: 0.45-1.64) but a positive correlation on the right side (OR = 2.00; 95% CI: 1.57-2.55). The COPD allcause mortality curve displayed an inflection point at Log10-PIV of 2.38, indicating a negative correlation on the left side (HR = 0.23; 95% CI: 0.12-0.44) and a positive correlation on the right side (HR = 4.12; 95% CI: 2.62-6.48). Subgroup analyses with interaction tests showed that the strength of the correlation between PIV and COPD prevalence was influenced by race, smoking status, and BMI (all p for interaction <0.05). The relationship between PIV and COPD all-cause mortality was unaffected by any covariates (all p for interaction >0.05). Conclusion: Elevated PIV levels are associated with increased COPD prevalence. COPD patients with either elevated or reduced PIV levels experience higher allcause mortality. Further large-scale, longitudinal studies are required to corroborate these findings. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is an irreversible and progressive chronic inflammatory lung disease which affects millions of people worldwide. Activated fibroblasts are observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition. In this study, we identified that miR-1307-5p expression was significantly increased in lung fibroblasts derived from COPD patients. Mechanistically, we found that upregulation of miR-1307-5p promoted TGF-β induced lung fibroblast activation and transdifferentiation. We also identified FBXL16 as a direct target for miR-1307-5p mediated myofibroblast activation in COPD. Knockdown of FBXL16 by siRNA prominently increased the expression of myofibroblast markers in MRC-5 fibroblasts after TGF-β administration. Ectopic expression of FBXL16 in MRC-5 counteracted miR-1307-5p agomir-induced fibroblast transdifferentiation. Furthermore, We found that miR-1307-5p promoted pulmonary fibroblast transdifferentiation through FBXL16 regulated HIF1α degradation. In general, our findings indicate that miR-1307-5p is important for COPD pathogenesis, and may serve as a potential target for COPD treatment. [ABSTRACT FROM AUTHOR]

Background: IL-26 is a key mediator of pulmonary host defense given its abundant expression in human airways and its established antibacterial properties. Moreover, recent studies indicate that IL-26 can also inhibit viral replication. Along these lines, we have previously reported an increase in the plasma concentration of IL-26 among patients with acute COVID-19 that is linked to harmful hyperinflammation. Nevertheless, it is still unclear whether this systemic increase in IL-26 relates to disease severity, sex, comorbidities, viral load, or the innate immune response in acute COVID-19. Methods: IL-26 was quantified using ELISA in plasma samples from a large cohort of well-characterized patients with acute COVID-19 (n=178) and healthy controls (n=30). The plasma concentrations of SARS-CoV-2 nucleocapsid and spike protein, as well as those of IFN-α2α, IFN-β, and IFN-γ, were determined using electrochemiluminescence immunoassay. The concentration of double-stranded DNA was determined using fluorometry. Results: The plasma concentration of IL-26 was increased in patients with severe/critical COVID-19, particularly among males and patients with comorbid obstructive lung disease. Moreover, the concentration of IL-26 displayed positive correlations with length of hospital stay, as well as with systemic markers of viral load, antiviral immunity, and extracellular DNA. Conclusions: Systemic IL-26 is involved in severe COVID-19, especially in males and patients with comorbid obstructive lung disease. These findings argue that systemic IL-26 has pathogenic and antiviral relevance, as well as biomarker potential. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa (PA) isolation in patients with chronic obstructive pulmonary disease (COPD) has been associated with a poor prognosis. This meta-analysis aimed to determine significant risk factors for PA isolation among patients with COPD. Methods: A systematic literature retrieval from PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) was conducted, including studies from January 2003 to September 2024. Case-control and cohort studies exploring the risk factors for PA isolation in patients with COPD were included in this analysis. A random-effects model was applied to estimate the pooled adjusted odds ratio (paOR) or hazard ratio (paHR) with the corresponding 95% confidence intervals (CI). Results: Thirteen eligible studies with a total of 25,802 participants were included in this meta-analysis. Prior systemic steroid therapy (paOR: 2.67; 95% CI: 1.29–5.53; P = 0.008), previous antibiotic treatment (paOR: 2.83; 95% CI: 1.14–6.97; P = 0.02), high "Body mass index, airflow Obstruction, Dyspnea, Exercise capacity" (BODE) index (paOR: 4.13; 95% CI: 1.67–10.23; P = 0.002), 6-min walking distance (6MWD) < 250 m (paOR: 4.27; 95% CI: 2.59–7.01; P < 0.001), COPD assessment test (CAT) score > 20 points (paOR: 2.49; 95% CI: 1.46–4.23; P = 0.001), hypoproteinemia (paOR: 2.62; 95%CI: 1.32–5.19; P = 0.006), hospitalizations in the previous year (paOR: 3.74; 95%CI: 1.22–11.49; P = 0.021), Bronchiectasis (paOR = 4.81; 95% CI: 3.66–6.33; P < 0.001) and prior PA isolation (paOR: 16.39; 95% CI: 7.65–35.10; P < 0.001) were associated with PA isolation in patients with COPD. Conclusions: Our study identified nine risk factors associated with an increased risk of PA isolation in COPD patients. These findings are significant for the early identification of patients at risk for PA isolation, which might contribute to reducing mortality and improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. Methods: We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA). The two treatments were compared concerning systemic corticosteroids, antibiotics, salbutamol, antifungal prescriptions, and number of emergency room visits/hospitalizations (ERV/Hs). We studied 292 MITT patients (Group A) during 2019, switching to SITT in 2020, and 366 subjects (Group B) who took SITT during 2019, and 206 MITT individuals (Group C) in 2020. Results: ICS/LABA + LAMA (MITT) package use was 8.2 ± 4.2 and 7.85 ± 4 in 2019, switching to 11.2 ± 3.2 when patients shifted to SITT in 2020 (p = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, p = 0.0001; Group B). Throughout 2020, Group C (10.3 ± 6.1 packs) adherence to ICS/LABA was similar to SITT adherence in Group A (p = 0.270), whereas LAMA package use (9.1 ± 5) was lower (p = 0.0038). Patients using systemic corticosteroids/antibiotics were fewer in SITT in 2020, compared to the MITT results in 2019. Subjects with fewer ERV/Hs were observed with SITT rather than with MITT. Particularly, 13.8% of patients needed ≥2 ERV/Hs when treated with SITT, whereas 19.2% needed ≥2 ERV/Hs with MITT in 2019 (p = 0.08). Multivariate analysis, adjusted for all confounding factors including treatment adherence, showed that MITT (vs. SITT) can have an increased risk of at least one ERV/H (subjects receiving MITT during 2019 passing to SITT in 2020, OR: 1.718 [1.010–2.924], p = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973–3.153], p = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018–3.577], p = 0.044). Conclusions: SITT therapy may promote treatment adherence more effectively, therefore, reducing COPD exacerbations better than MITT. A possible synergistic effect of ICS/LABA/LAMA intake with a single device might be another cause of SITT's greater efficacy. [ABSTRACT FROM AUTHOR]

IntroductionMethodResultsDiscussionChronic obstructive pulmonary disease (COPD) is a condition characterized by airflow obstruction which can lead to physical and psychosocial challenges, with a higher prevalence in developing countries. Non-pharmacological interventions for this group of people include pulmonary rehabilitation as well as music interventions. Although music technology was recommended to adjust to the user’s breathing capacity for music-making and to gather information about their performance, music therapy trials used acoustic wind instruments for their rehabilitation. This interdisciplinary project aims to develop a dedicated electronic wind instrument for people with COPD.This project follows a systematic prototype methodology that includes product research, instrument development, and user validation. Based in Brazil, our team has decided on an electronic ocarina based on its cultural features, its popularity as a digital application, and its potential for respiratory training. Unlike existing technologies, the prototype intends to be dedicated and a low-cost solution.The development process includes decision making about the appropriate mouthpiece, sensors, Arduino, pushbuttons, 3-D printing projects, building a MIDI interface and a dedicated software. This is an ongoing project, and our team is in the MIDI interface development stage. We aim to run the first hardware trial with users so that we can integrate their feedback into the functional prototype and the dedicated software for the following trials.This project’s strengths rely on the innovation of building viable electronic wind instruments that can facilitate self-management of people with COPD in developing countries, where access to healthcare can be challenging. [ABSTRACT FROM AUTHOR]

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

Background: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. Methods: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. Results: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. Conclusions: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung abnormality (ILA) has been recognized as a pertinent factor in the development and prognosis of various pulmonary conditions. However, its correlation with co-morbidities remains understudied. The current study endeavors to elucidate the association between ILA and both clinical features and co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort comprising 1131 hospitalized patients diagnosed with COPD was examined in this observational study. Patients were dichotomously classified based on the presence or absence of ILA, and subsequent analyses scrutinized disparities in demographic, clinical, and laboratory profiles, alongside co-morbid conditions, between the two subgroups. Results: Of the 1131 COPD patients, 165 (14.6%) exhibited ILA. No statistically significant differences were discerned between COPD patients with and without ILA concerning demographic, clinical, or laboratory parameters, except for levels of circulating fibrinogen and procalcitonin. Nevertheless, a notable discrepancy emerged in the prevalence of multiple co-morbidities. Relative to COPD patients devoid of ILA, those presenting with ILA manifested a diminished prevalence of lung cancer (OR = 0.50, 95% CI: 0.30–0.83, p = 0.006), particularly of the lung adenocarcinoma (OR = 0.32, 95% CI: 0.15–0.71, p = 0.005). Additionally, the presence of ILA in COPD was positively associated with heart failure (OR = 1.75, 95% CI: 1.04-3.00, p = 0.040) and cancers other than lung cancer (OR = 2.27, 95% CI: 1.16–4.39, p = 0.012). Conclusion: These findings demonstrate that the presence of ILA is associated with co-morbidities of COPD, particularly lung cancer. [ABSTRACT FROM AUTHOR]

Background: Pulmonary rehabilitation (PR) is widely recommended for short-term benefits in chronic respiratory diseases, yet long-term outcomes remain uncertain. This retrospective cohort study addresses this gap, comparing 20-year mortality rates between PR participants and matched controls, and hypothesizing that the short-term benefits of PR contribute to improved long-term survival. Methods: The 20-year mortality of stable chronic respiratory patients who participated in an outpatient PR program was compared with a matched control group based on the type of lung disease. Demographic and clinical variables, and the dates of deaths, were extracted and compared between two groups with two sample t-test and chi-square tests. Kaplan-Meier plots and Cox regression analyses were employed to evaluate survival differences. Results: Between 2000 and 2002, 238 individuals enrolled in a pulmonary rehabilitation (PR) program (58% male, mean age ± SD: 69 ± 8 years, mean FEV1% predicted ± SD: 46 ± 21%). An equal number of people with comparable lung disease were selected as controls (88% COPD, 5% ILD). Controls had lower FEV1% predicted values (mean ± SD: 39 ± 17%, P < 0.001), smoked more (mean ± SD: 48 ± 35 pack-years, P = 0.032), and no differences in age, BMI, sex, and Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). Median (IQR) follow-up time was 68 months (34–123), with 371 (78%) deaths. Univariable (HR = 1.71, p < 0.001) and multivariable (HR = 1.64, p < 0.001) Cox regression found higher mortality risk in controls. Subgroup analysis for COPD replicated these findings (HR = 1.70, P < 0.001). Discussion: Despite some methodological limitations, our study suggests that clinically stable patients with chronic respiratory disease who undertake PR may have lower mortality than matched controls. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Hospital readmissions pose a challenge for modern healthcare systems. Our aim was to assess the efficacy of telemedicine incorporating telemonitoring of patients' vital signs in decreasing readmissions with a focus on a specific patient population particularly prone to rehospitalization: patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) through a comparative effectiveness systematic review. Methods: Three major electronic databases, including PubMed, Scopus, and ProQuest's ABI/INFORM, were searched for English-language articles published between 2012 and 2023. The studies included in the review employed telemedicine incorporating telemonitoring technologies and quantified the effect on hospital readmissions in the HF and/or COPD populations. Results: Thirty scientific articles referencing twenty-nine clinical studies were identified (total of 4,326 patients) and were assessed for risk of bias using the RoB2 (nine moderate risk, six serious risk) and ROBINS-I tools (two moderate risk, two serious risk), and the Newcastle-Ottawa Scale (three good-quality, four fair-quality, two poor-quality). Regarding the primary outcome of our study which was readmissions: the readmission-related outcome most studied was all-cause readmissions followed by HF and acute exacerbation of COPD readmissions. Fourteen studies suggested that telemedicine using telemonitoring decreases the readmission-related burden, while most of the remaining studies suggested that it had a neutral effect on hospital readmissions. Examination of prospective studies focusing on all-cause readmission resulted in the observation of a clearer association in the reduction of all-cause readmissions in patients with COPD compared to patients with HF (100% vs. 8%). Conclusions: This systematic review suggests that current telemedicine interventions employing telemonitoring instruments can decrease the readmission rates of patients with COPD, but most likely do not impact the readmissionrelated burden of the HF population. Implementation of novel telemonitoring technologies and conduct of more high-quality studies as well as studies of populations with =2 chronic disease are necessary to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: To assess the effect of pneumonia on the risk of mortality and other clinical outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: PubMed, EMBASE and Scopus were screened for observational cohort and case-control studies that reported outcomes in AECOPD patients with and without pneumonia. Pooled effect sizes were reported as relative risks (RR) or hazard ratio (HR) for categorical outcomes and as weighted mean difference (WMD) for continuous outcomes. The primary outcome was mortality. Secondary outcomes were risk of admission to intensive care unit (ICU), need for assisted ventilation and readmission as well as duration of stay at the hospital. The certainty of the evidence was assessed using the GRADE approach. Results: Thirteen studies were included. AECOPD patients with pneumonia had significantly higher risk of in-hospital mortality (RR 2.29, 95% CI: 1.40, 3.73), mortality at 1 month (RR 1.84, 95% CI: 1.09, 3.13), and 1 year or more of follow-up (HR 2.30, 95% CI: 1.15, 4.61) compared to AECOPD patients without pneumonia. Pneumonia was associated with significantly higher risk of admission to ICU (RR 2.79, 95% CI: 1.47, 5.28), need for assisted ventilation (RR 2.02, 95% CI: 1.52, 2.67), and longer hospital stay (in days) (WMD 3.31, 95% CI: 2.33, 4.29). The risk of readmission was comparable in the two groups of patients (RR 1.07, 95% CI: 0.97, 1.19). The overall quality of evidence for the outcomes was judged to be "Low". Conclusion: Pneumonia during acute exacerbation of COPD may lead to increases in both short-term and long-term mortality as well as increased hospital stay, need for ventilatory support and admission to ICU. Our findings suggest the need for close monitoring, early intervention, and long-term follow-up, to improve the outcomes in AECOPD patients with concurrent pneumonia. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in the management of asthma and chronic obstructive pulmonary disease (COPD), patients still experience suboptimal disease control largely due to medication non-adherence and inappropriate use of inhaler. This study evaluates the impact of pharmacist-led intervention in medication adherence and inhaler usage on asthma and COPD control among out-patients attending the premier tertiary hospital in Nigeria. Method: A quasi-experimental study carried-out among eligible out-patients attending pulmonology clinic of University College Hospital, Ibadan. Baseline questionnaire explored medication adherence using a comprehensive-medication-adherence-assessment-scale (CMAAS-12) developed by the study co-investigators, use of pressurized-metered-dose (pMDI) and Diskus inhalers, as well as asthma/COPD control using validated asthma control test (ACT) and COPD assessment test (CAT). Subsequently, patients were allocated into control (n = 65) or intervention group (n = 65) using odd or even number. Intervention group received 2-month follow-up educational and/or cognitive-behavioural interventions to resolve identified adherence barriers, while control group continued with traditional care. Descriptive statistics, Chi-square and Wilcoxon-signed-ranked tests were used for analysis at p < 0.05. Results: Overall, patients with optimal adherence were 11(18.6%) and 16(27.1%), p = 0.132 (control), but 20(33.3%) and 38(63.3%), p < 0.001 (intervention) at baseline and post-baseline, respectively. Specifically, in the intervention group, the identified adherence barriers at baseline were summarized into knowledge (120;40.4%), practical (115;38.7%) and attitudinal (62;20.9%). Patients with correct use of pMDI were 11(21.6%) baseline and 19(36.5%) post-baseline, p = 0.011 (control), but 13(22.8%) and 46(80.7%) respectively, p < 0.001 (intervention). Correct use of Diskus inhaler were 5(50.0%) and 4(40.0%), p = 0.157 (control), but 7(35.0%) and 14(70.0%), p = 0.025 (intervention) at baseline and post-baseline, respectively. Patients with 'well-controlled asthma' were 25(44.6%) and 26 (47.3%), p = 0.025 (control), but 18(35.3%) and 32(60.4%), p < 0.001 (intervention) at baseline and post-baseline, respectively. The COPD-specific health status indicated that 0(0.0%) and 1(14.3%), p = 0.059 (control), but 0(0.0%) and 7(50.0%), p < 0.001 (intervention) at baseline and post-baseline, respectively, belonged to 'low COPD impact'. Conclusion: Pharmacist-led intervention significantly enhanced medication adherence and appropriate use of inhaler among the intervention cohort, with subsequent significant improvement in asthma control and reduced COPD impact compared with the control group. This underscores the need for active involvement of pharmacists in collaborative management of patients with chronic respiratory diseases in clinical practice. Trial registration: ClinicalTrials.gov identifier: NCT06417931. Retrospectively-registered. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic airway inflammation has been detected in up to 40% of chronic obstructive pulmonary disease (COPD) patients during stable periods of the disease, and increased sputum eosinophil count was associated with better lung function, more future exacerbations, and symptoms that responded better to treatment with inhaled and oral corticosteroids. The aim of this work was to investigate the relationship of blood eosinophils and plasma periostin with lung function changes related to ICS and long-acting beta2-agonist combination treatment in stable COPD patients for 3 months. Methods: This prospective experimental study was carried out on 50 COPD patients with post-bronchodilator FEV1/FVC ratio < 70%. Patients collected from outpatient clinics of Chest Department Tanta University Hospitals, Tanta Chest Hospital, and Mansoura Chest Hospital from February 2020 to February 2022. Patients were subjected to complete history taking, and clinical examinations including general and local examinations and laboratory investigations (complete blood count to assess eosinophilic count, arterial blood gases, and plasma periostin) and spirometry were done for all patients pre- and post-treatment. All patients received 3 months of treatment with a fixed dose of combined inhalers of ICS and LABA, and then they were classified into FEV1 responder and FEV1 non-responder according to improvement in FEV1 at least 12% and 200 mL from baseline of 3 months of combined treatment with ICS/LABA. Results: Blood eosinophil count had a significant positive correlation with smoking index (pack/year), negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC ratio. Plasma periostin concentration had significant positive correlation with blood eosinophil count, COPD grade, and FVC actual value (L) and significant negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC. Cutoff values of blood eosinophil count > 265 cell/µL, plasma periostin concentration > 15.747 ng/mL, and FEV1% < 40.5% were associated with posttreatment FEV1 response. Conclusions: COPD patients with poor lung functions regarding FEV1/FVC ratio, FEV1 actual value (L), and FEV1% of predicted as well as high blood eosinophil count and high plasma periostin concentration are predicted to have FEV1 response with fixed-dose ICS/LABA combination treatment. [ABSTRACT FROM AUTHOR]

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

Chronic obstructive pulmonary disease (COPD) ranks among the world's three leading causes of mortality, owing to the increased smokers and aging populations. Previous studies showed that gut microbiota could help to ameliorate respiratory diseases. Hence, the current study aims to evaluate the effects of probiotics, prebiotics, or yogurt on the prevalence of COPD. A cross‐sectional study was carried out by investigating data from three consecutive NHANES cycles during 2007–2012. Individuals who met the inclusion and exclusion criteria were studied. Prescription medications and dietary were reviewed to identify the intake of probiotics, prebiotics, or yogurt. The included participants were then divided into two groups depending on their consumption of probiotics, prebiotics, or yogurt. Multivariate logistic regression analysis was conducted to analyze the effects of probiotics, prebiotics, or yogurt consumption on the prevalence of COPD. Out of 7486 enrolled participants, 1656 (22.12%) were categorized into the probiotics, prebiotics, or yogurt intake group. This study indicated that consuming probiotics, prebiotics, or yogurt were correlated with a lower incidence of COPD, even when factors like gender, age, education, moderate‐intensity activities, vigorous activities, hypertension, asthma, diabetes, smoking and alcohol consumption were accounted for (Model 1: OR, 0.68, 95% CI, 0.53–0.87; Model 2: OR, 0.77, 95% CI, 0.59–0.99; Model 3: OR, 0.75, 95% CI, 0.57–0.98). The findings reveal that consuming probiotics, prebiotics, or yogurt might play a beneficial role in preventing COPD. [ABSTRACT FROM AUTHOR]

Bacterial Lysates are immunostimulants clinically prescribed for the prevention of respiratory tract infections (RTIs). It has been shown that Bacterial Lysates upregulate the immune system, acting both on innate and adaptive reactions. In fact, there are demonstrations of their efficacy in restoring the integrity and immune function of epithelial barriers, activating ILC3 and dendritic cells with an enhanced Th1 response, and producing serum IgG and serum and salivary IgA specific to the administered bacterial antigens. The activated immune system also protects against other bacteria and viruses due to a trained immunity effect. Most studies show that the number of RTIs and their severity decrease in Bacterial Lysates-pretreated patients, without relevant side effects. The Bacterial Lysates treatment, in addition to reducing the number of RTIs, also prevents the deterioration of the underlying disease (i.e., COPD) induced by repeated infections. Despite these positive data, the most recent meta-analyses evidence the weakness of the studies performed, which are of low quality and have an inadequate number of patients, some of which were non-randomized while others were without a control group or were performed contemporarily in different clinical conditions or with different ages. The high heterogeneity of the studies does not allow us to state Bacterial Lysates' effectiveness in preventing RTIs with sufficient certainty. To completely define their indications, double-blind, placebo-controlled, multicenter, randomized clinical trials should be performed for each product and for each indication. The study population should be adequate for each indication. For this purpose, an adequate run-in phase will be necessary. [ABSTRACT FROM AUTHOR]

Background: The ComEx3 community‐based extended maintenance pulmonary rehabilitation (PR) randomised controlled trial (RCT) aimed to determine the optimal strategy for maintaining the benefits of exercise for people with chronic obstructive pulmonary disease (COPD). We conducted a process evaluation of this RCT to determine if the trial was implemented per protocol, and to explore the barriers and facilitators of the trial, and mechanisms of impact. Methods: This was a mixed methods study consisting of analysis of PR class records, study diaries and interviews of those involved in the trial. We developed a reporting framework from available literature and performed a content analysis. Results: Eleven of the 12 participants in the intervention group attended ≥70% of available classes before the trial was terminated due to the COVID‐19 pandemic. Analysis of the study diaries found that adherence to the home exercise program was higher in the intervention than the control group. Analyses of interviews (n = 21) highlighted the complexity of standardising the processes across multiple sites, but revealed behaviour change amongst class physiotherapists who were able to conform with the required processes. Facilitators of participation included the desire to improve function and quality of life, while barriers included illnesses and lack of motivation. Mechanisms of impact included confidence in exercising and benefits from the education sessions. Conclusions: The ComEx3 RCT was implemented as planned largely due to commitment by the research team and the desire by patients to improve their quality of life by attending a PR program that they are familiar with. Successful implementation of PR RCTs requires good organisational skills, clear and consistent trial documentation, broad understanding of participant needs while being conscious of challenges experienced by people with COPD, and dedication by everyone involved in the RCT. So What?: This article shows the importance of running a process evaluation alongside an RCT. Although this RCT did not progress to completion, this process evaluation which was guided by a robust framework, will provide guidance for future interventions in this area. [ABSTRACT FROM AUTHOR]

There are nearly 3 billion people exposed to biomass smoke worldwide. Biomass represents approximately 50% of deaths from chronic obstructive pulmonary disease (COPD) in developing countries; mainly affecting women, who are exposed during all stages of their life. The cumulative effect and inhalation characteristics determine a predominantly small airway condition, different from the radiological findings of COPD in smoking patients. The radiological characteristics (morphological and quantitative) allow the appropriate identification of these patients, their follow-up and appropriate treatment. [ABSTRACT FROM AUTHOR]

The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions. Fostair™ and Trimbow™, two pressurized metered dose inhalers, have emerged as noteworthy therapeutic options for treating both asthma and COPD. Fostair combines an inhaled corticosteroid, specifically beclometasone dipropionate, with a long-acting beta2-agonist, formoterol fumarate dihydrate, offering a dual-action approach to mitigate airway inflammation and bronchoconstriction. Conversely, Trimbow integrates a tri-particulate formulation consisting of beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide, providing a comprehensive strategy to target the pathophysiology of COPD and asthma. Recent clinical trials have underscored Trimbow's superior efficacy compared with Fostair, particularly in terms of reducing exacerbation rates and enhancing lung function. However, despite their therapeutic promise, both inhalers encounter challenges, including limited generalizability of study findings and a disparity between in vitro and human trial results. This literature review offers an in-depth analysis of Fostair and Trimbow, delving into their mechanisms of action, clinical applications, and outcomes in human studies for asthma and COPD. Additionally, the review discusses the role of combination therapy in managing respiratory diseases and underscores the necessity for further research to address existing knowledge gaps and optimize therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Background: Magnesium plays an important role in bronchodilation and has anti-inflammatory effects. Hypomagnesaemia has been associated with increased risk of acute exacerbations in chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the relationship between serum magnesium levels and clinical outcomes in patients hospitalized for acute exacerbation of COPD (AECOPD). Methods: This prospective observational study enrolled 45 patients admitted with AECOPD. Serum magnesium levels were measured at admission. Patients were followed until discharge, and duration of hospital and intensive care unit (ICU) stay were recorded. The association between serum magnesium and length of stay was analyzed using correlation and regression analyses. Results: The mean age of study participants was 69.9±10.2 years. The mean duration of COPD was 9.13±4.7 years. The mean serum magnesium level was 2± 0.48 mg/dL. Lower serum magnesium levels correlated with longer hospital stay (r = -0.517, p < 0.001) and ICU stay (r = -0.570, p < 0.001). Conclusions: Hypomagnesaemia at admission is associated with longer hospital and ICU stays in patients hospitalized for AECOPD. Serum magnesium levels may serve as a prognostic biomarker, and magnesium supplementation warrants further study as a potential intervention to improve clinical outcomes during COPD exacerbations. [ABSTRACT FROM AUTHOR]

Aim:To study clinico-demographic and lung spirometry profile between non-smoker and smoker COPD patients. Material & Methods: The present cross-sectional observational study was conducted among 200 clinically diagnosed COPD patients attending the Pulmonary Medicine Department at tertiary care centre, Bhopal, Madhyapradesh. Upon diagnosis of COPD, detailed past medical history and any previous exposures was recorded. Patients aged <18 years and patients who do not provide consent were excluded from the patients. Informed consent was taken from all the patients and ethical clearance was obtained form institutional ethical committee. Result: Out of 200 COPD patients, 134(67%) were non smokers and 66(33%) were smokers. Out of 200 COPD patients, 150 were male & 50 were female. Smokers experienced a higher frequency of acute exacerbations (3-5 times) compared to non-smokers, suggesting that smoking exacerbates the severity and recurrence of COPD episodes.(P=0.001) Smokers had a significantly higher mean CAT score compared to non-smokers, indicating more severe COPD symptoms and a greater impact on daily life for smokers.(P=0.001) Smokers had more severe shortness of breath (higher mMRC grades) compared to nonsmokers, indicating a greater impact of smoking on the severity of COPD symptoms. Conclusion: Present study found that an Environmental and occupational exposures are significant contributors to COPD among non-smokers, with biofuel smoke and second-hand smoke being primary risk factors. [ABSTRACT FROM AUTHOR]

Introduction: Dynamic hyperinflation in chronic obstructive pulmonary disease (COPD) results in intrinsic positive end‐expiratory pressure (auto‐PEEP). Automatic tube compensation (ATC) is used to increase airway pressure in COPD and overcome endotracheal tube (ETT)–imposed respiratory workload. We aim to investigate effects of ATC activation on auto‐PEEP decrease in COPD. Methods: ATC was activated three times a day (1 min duration) in the morning, evening, and night shift. Auto‐PEEP was measured for the 1 min period (every 6 s) following ATC activation. Linear mixed model (LMM) was used to measure changes in auto‐PEEP and compare with baseline value. Age, gender, and COPD types were inserted in model as covariates and analyzed using SPSS. Results: A total of 60 patients including COPD (n = 40) and COPD with exacerbation (n = 20) were included. Compared with exacerbated COPD, baseline auto‐PEEP in COPD was significantly lower in morning (p = 0.011), evening (p = 0.043), and night shift (p = 0.007). After ATC activation, auto‐PEEP decreased significantly in COPD in morning, evening, and night (p = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (p = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto‐PEEP in morning (β = −0.27, p = 0.001), evening (β = −0.16, p = 0.001), and night (β = −0.26, p = 0.001). Conclusion: The activation of ATC mode in COPD patients under mechanical ventilation could decrease the value of auto‐PEEP. Nevertheless, COPD patients with an exacerbation appear to benefit less from ATC activation. [ABSTRACT FROM AUTHOR]

Background: PM2.5 has been associated with various adverse health effects, particularly affecting lung function and chronic respiratory diseases. However, the genetic causality relationship between PM2.5 exposure and lung function as well as chronic respiratory diseases remains poorly understood. Method: We conducted a two-sample Mendelian randomization analysis to investigate the causal impact of PM2.5 on lung function and chronic respiratory diseases. Instrumental variables were carefully selected, with significance thresholds (P < 5 × 10− 8), and linkage disequilibrium with an r2 value below 0.001. Additionally, SNPs with an F-statistic exceeding 10 were included to mitigate potential bias stemming from weak instrumental variables. The primary analytical approach employed the Inverse Variance Weighted method, supplemented by the Weighted Median, MR-Egger, Simple Model, and Weighted Model. Furthermore, pleiotropy and heterogeneity were evaluated through the MR-Egger intercept test and Cochrane's Q test, with a sensitivity analysis conducted using the leave-one-out method. Results: Eight SNPs significantly associated with PM2.5 exposure were identified as Instrumental variables. Mendelian randomization analysis revealed a significant causal association between PM2.5 exposure and lung function (FEV), with an OR of 0.7284 (95% CI: 0.5799–0.9150). Similarly, PM2.5 exposure demonstrated a substantial causal effect on asthma, with an OR of 1.5280 (95% CI: 1.0470–2.2299). However, no causal association was observed between PM2.5 exposure and chronic obstructive pulmonary disease, with an OR of 1.5176 (95% CI: 0.8294–2.7768). Conclusion: These findings emphasize the necessity for continued research efforts in environmental health to develop effective strategies for the prevention and management of chronic respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress plays an important role in the pathophysiology of bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO), but its relevance has not been fully elucidated. The aim of this study was to measure the levels of oxidative stress and investigate its clinical significance in patients with BA, COPD, or ACO. Methods: We recruited 214 patients between June 2020 and May 2023 (109 patients with BA, 63 with COPD, and 42 with ACO). To assess clinical conditions, we evaluated patient characteristics, results of respiratory function tests and blood tests, and administered several questionnaires. We evaluated oxidative stress using the test for derivatives–reactive oxygen metabolites (d–ROMs) in serum. Results: The d–ROMs levels were significantly higher in patients with COPD or ACO than in patients with BA. There was no difference in serum d–ROMs levels between the COPD and ACO groups. In BA, d–ROMs levels were positively correlated with interleukin (IL)-6, IL-8, serum amyloid A (SAA), and C-reactive protein (CRP) levels; white blood cell (WBC) and neutrophil counts; and St. George's Respiratory Questionnaire (SGRQ) scores, and they were negatively correlated with forced expiratory volume in 1 s (%FEV1) and asthma control test (ACT) score. In COPD, d–ROMs levels were positively correlated with IL-6, SAA, and CRP levels; WBC, neutrophil, and eosinophil counts; and COPD assessment test (CAT) and SGRQ scores, and they were negatively correlated with forced vital capacity (%FVC), %FEV1, and %FEV1/FVC scores. In ACO, d–ROMs levels were positively correlated with IL-6, SAA, tumor necrosis factor alpha (TNF-α), and CRP levels; and CAT and SGRQ scores, and they were negatively correlated with %FVC and %FEV1 scores. Conclusions: Serum d–ROMs levels may serve as a marker reflecting clinical conditions such as systemic inflammation, symptom severity, and airflow limitation in patients with BA, COPD, and ACO. [ABSTRACT FROM AUTHOR]

COPD and asthma are lung diseases that cause considerable burden to more than 800 million people worldwide. As both lung diseases are so far incurable, it is mandatory to understand the mechanisms underlying disease development and progression for developing novel therapeutic approaches. Exposures to environmental cues such as cigarette smoke in earliest life are known to increase disease risks in the individual's own future. To explore the pathomechanisms leading to later airway disease, mammalian models are instrumental. However, such in vivo experiments are time-consuming and burdensome for the animals, which applies in particular to transgenerational studies. Along this line, the fruit fly Drosophila melanogaster comes with several advantages for research in this field. The short lifespan facilitates transgenerational studies. A high number of evolutionary conserved signaling pathways, together with a large toolbox for tissue-specific gene modification, has the potential to identify novel target genes involved in disease development. A well-defined airway microbiome could help to untangle interactions between disease development and microbiome composition. In the following article, Drosophila melanogaster is therefore presented and discussed as an alternative in vivo model to investigate airway diseases that can complement and/or replace models in higher organisms. [ABSTRACT FROM AUTHOR]

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. β2-adrenergic receptor (β2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. β2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of β2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of β2AR during viral infections or prolonged therapy with β2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies. [ABSTRACT FROM AUTHOR]