Early-life house dust mite aeroallergen exposure augments cigarette smoke-induced myeloid inflammation and emphysema in mice.

BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.

Environmental pollutants exposure-derived extracellular vesicles: crucial players in respiratory disorders.

BACKGROUND: Individual exposure to environmental pollutants, as one of the most influential drivers of respiratory disorders, has received considerable attention due to its preventability and controllability. Considering that the extracellular vesicle (EV) was an emerging intercellular communication medium, recent studies have highlighted the crucial role of environmental pollutants derived EVs (EPE-EVs) in respiratory disorders. METHODS: PubMed and Web of Science were searched from January 2018 to December 2023 for publications with key words of environmental pollutants, respiratory disorders and EVs. RESULTS: Environmental pollutants could disrupt airway intercellular communication by indirectly stimulating airway barrier cells to secrete endogenous EVs, or directly transmitting exogenous EVs, mainly by biological pollutants. Mechanistically, EPE-EVs transferred specific contents to modulate biological functions of recipient cells, to induce respiratory inflammation and impair tissue and immune function, which consequently contributed to the development of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary hypertension, lung cancer and infectious lung diseases. Clinically, EVs could emerged as promising biomarkers and biological agents for respiratory diseases attributed by their specificity, convenience, sensibility and stability. CONCLUSIONS: Further studies of EPE-EVs are helpful to understand the aetiology and pathology of respiratory diseases, and facilitate the precision respiratory medicine in risk screening, early diagnosis, clinical management and biotherapy.

The 2021 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and the outpatient management: Examining physician adherence and its effects on patient outcome.

Background: Chronic obstructive pulmonary disease (COPD) is a common preventable illness that carries a large global economic and social burden. The global initiative for chronic obstructive lung disease (GOLD) guidelines has been utilized as a global strategy for the continued COPD diagnosis, assessment, and treatment. We aimed to determine if the adherence to the 2021 GOLD guideline directed management influenced outcomes. Materials and Methods: Retrospective medical records review of adult patients with COPD, who received care in our office during the entire year of 2021. Patients managed as per the 2021 GOLD guidelines were compared with those who received usual care. Results: Among 242 patients, 171 (70.7%) were GOLD management adherent (GA) and 71 (29.3%) were GOLD non-adherent (GNA). Certain comorbidities were associated with higher frequencies in the GA group, such as allergic rhinitis (63.2 vs. 18.3%; P < 0.001), coronary artery disease (55.9 vs. 38.0%; P = 0.011), GERD (63.2 vs. 32.4%; P < 0.001), anemia (38.6 vs. 19.7%; P = 0.004), malignancy (34.5 vs. 19.7%; P = 0.023), and immunodeficiency (12.3 vs. 1.4%; P = 0.007). There was no significant difference in the mortality between the GA and GNA groups (5.3 vs. 9.9%; P = 0.254). Although the frequency of number of exacerbations was greater in the GA group, the difference in the mean number of exacerbations was not statistically significant (0.39 ± 1.08 vs. 0.39 ± 1.14; P = 0.984). Conclusion: We found no significant difference in the patient outcomes, such as number of exacerbations of COPD and mortality, when comparing the 2021 GOLD guideline adherent versus GOLD guideline non-adherent management of COPD.

Guggulsterone protects against cigarette smoke-induced COPD linked lung inflammation.

Recently, we have shown that guggulsterone is the principal constituent responsible for protective effects of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease (COPD)-linked inflammation/emphysema. Given that cigarette smoke (CS) exposure is a primary risk factor for COPD and beneficial effects of guggulsterone have not been investigated in CS-induced COPD-linked lung inflammation. The present work was designed to validate the potential of guggulsterone in amelioration of COPD-linked lung inflammation by using a CS-based mouse model of the condition. Male BALB/c mice were exposed to 9 cigarettes/day with 1 h interval for 4 days daily. Guggulsterone was administered daily at a dose of 10 mg/kg orally for 4 consecutive days, 1 h before initiation of CS exposure. Mice were subjected to measurement of lung function followed by procurement of bronchoalveolar lavage fluid (BALF)/lung tissue. BALF was analyzed for inflammatory cells and pro-inflammatory cytokines. Lung tissue was subjected to RT-PCR for gene expression analysis. Data showed that CS exposure resulted in a significant increase in total BALF cells, predominantly neutrophils, and macrophages. Interestingly, guggulsterone administration significantly blunted CS-induced inflammation as reflected by reduced neutrophil and macrophage count. Further, the compound inhibited CS-induced gene expression of pro-inflammatory mediators TNF-α/ IL-1ß/ G-CSF/and KC in lungs along with the production of pro-inflammatory mediators TNF-α/ IL-1ß/ IL-6/ G-CSF/ KC/and MCP-1 in BALF. Further, guggulsterone improved the lung function parameters upon CS exposure. Analysis of mRNA expression of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 suggests that guggulsterone may restore the fine balance between matrix-degrading proteases and its inhibitor in lung tissue upon CS exposure, which may contribute in the development of emphysema at later stages. Overall, our data show that guggulsterone protects against CS-induced COPD-linked lung inflammation by modulating relevant molecular players. Based on the potential effects of guggulsterone in the amelioration of CS-induced lung inflammation, we speculate that guggulsterone might alter chronic CS-induced emphysema.

Gut Microbiome and Transcriptomic Changes in Cigarette Smoke-Exposed Mice Compared to COPD and CD Patient Datasets.

Chronic obstructive pulmonary disease (COPD) patients and smokers have a higher incidence of intestinal disorders. The aim of this study was to gain insight into the transcriptomic changes in the lungs and intestines, and the fecal microbial composition after cigarette smoke exposure. Mice were exposed to cigarette smoke and their lung and ileum tissues were analyzed by RNA sequencing. The top 15 differentially expressed genes were investigated in publicly available gene expression datasets of COPD and Crohn's disease (CD) patients. The murine microbiota composition was determined by 16S rRNA sequencing. Increased expression of MMP12, GPNMB, CTSK, CD68, SPP1, CCL22, and ITGAX was found in the lungs of cigarette smoke-exposed mice and COPD patients. Changes in the intestinal expression of CD79B, PAX5, and FCRLA were observed in the ileum of cigarette smoke-exposed mice and CD patients. Furthermore, inflammatory cytokine profiles and adhesion molecules in both the lungs and intestines of cigarette smoke-exposed mice were profoundly changed. An altered intestinal microbiota composition and a reduction in bacterial diversity was observed in cigarette smoke-exposed mice. Altered gene expression in the murine lung was detected after cigarette smoke exposure, which might simulate COPD-like alterations. The transcriptomic changes in the intestine of cigarette smoke-exposed mice had some similarities with those of CD patients and were associated with changes in the intestinal microbiome. Future research could benefit from investigating the specific mechanisms underlying the observed gene expression changes due to cigarette smoke exposure, focusing on identifying potential therapeutic targets for COPD and CD.

Extracellular vesicle dynamics in COPD: understanding the role of miR-422a, SPP1 and IL-17 A in smoking-related pathology.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) induced by smoking poses a significant global health challenge. Recent findings highlight the crucial role of extracellular vesicles (EVs) in mediating miRNA regulatory networks across various diseases. This study utilizes the GEO database to uncover distinct expression patterns of miRNAs and mRNAs, offering a comprehensive understanding of the pathogenesis of smoking-induced COPD. This study aims to investigate the mechanisms by which extracellular vesicles (EVs) mediate the molecular network of miR-422a-SPP1 to delay the onset of COPD caused by smoking. METHODS: The smoking-related miRNA chip GSE38974-GPL7723 was obtained from the GEO database, and candidate miRs were retrieved from the Vesiclepedia database. Downstream target genes of the candidate miRs were predicted using mRNA chip GSE38974-GPL4133, TargetScan, miRWalk, and RNA22 databases. This prediction was integrated with COPD-related genes from the GeneCards database, downstream target genes predicted by online databases, and key genes identified in the core module of WGCNA analysis to obtain candidate genes. The candidate genes were subjected to KEGG functional enrichment analysis using the "clusterProfiler" package in R language, and a protein interaction network was constructed. In vitro experiments involved overexpressing miRNA or extracting extracellular vesicles from bronchial epithelial cell-derived exosomes, co-culturing them with myofibroblasts to observe changes in the expression levels of the miR-422a-SPP1-IL-17 A regulatory network, and assessing protein levels of fibroblast differentiation-related factors α-SMA and collagen I using Western blot analysis. RESULTS: The differential gene analysis of chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Subsequently, an intersection was taken among the prediction results from TargetScan, miRWalk, and RNA22 databases, the COPD-related gene retrieval results from GeneCards database, the WGCNA analysis results of chip GSE38974-GPL4133, and the differential gene analysis results. This intersection, combined with KEGG functional enrichment analysis, and protein-protein interaction analysis, led to the final screening of the target gene SPP1 and its upstream regulatory gene miR-422a. KEGG functional enrichment analysis of mRNAs correlated with SPP1 revealed the IL-17 signaling pathway involved. In vitro experiments demonstrated that miR-422a inhibition targets suppressed the expression of SPP1 in myofibroblasts, inhibiting differentiation phenotype. Bronchial epithelial cells, under cigarette smoke extract (CSE) stress, could compensate for myofibroblast differentiation phenotype by altering the content of miR-422a in their Extracellular Vesicles (EVs). CONCLUSION: The differential gene analysis of Chip GSE38974-GPL7723 and the retrieval results from the Vesiclepedia database identified candidate miRs, specifically miR-422a. Further analysis involved the intersection of predictions from TargetScan, miRWalk, and RNA22 databases, gene search on COPD-related genes from the GeneCards database, WGCNA analysis from Chip GSE38974-GPL4133, and differential gene analysis, combined with KEGG functional enrichment analysis and protein interaction analysis. Ultimately, the target gene SPP1 and its upstream regulatory gene miR-422a were selected. KEGG functional enrichment analysis on mRNAs correlated with SPP1 revealed the involvement of the IL-17 signaling pathway. In vitro experiments showed that miR-422a targeted inhibition suppressed the expression of SPP1 in myofibroblast cells, inhibiting differentiation phenotype. Furthermore, bronchial epithelial cells could compensate for myofibroblast differentiation phenotype under cigarette smoke extract (CSE) stress by altering the miR-422a content in their extracellular vesicles (EVs).

sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking: Differences according to the rs3134940 AGER variant.

The receptor for advanced glycation end products (RAGE) and its gene (AGER) have been related to lung injury and inflammatory diseases, including chronic obstructive pulmonary disease (COPD). We aimed to evaluate the association of rs2071288, rs3134940, rs184003, and rs2070600 AGER single-nucleotide variants and the soluble-RAGE plasma and sputum levels with COPD secondary to biomass-burning smoke (BBS) and tobacco smoking. Four groups, including 2189 subjects, were analyzed: COPD secondary to BBS exposure (COPD-BBS, n = 342), BBS-exposed subjects without COPD (BBES, n = 774), tobacco smoking-induced COPD (COPD-TS, n = 434), and smokers without COPD (SWOC, n = 639). Allelic discrimination assays determined the AGER variants. The sRAGE was quantified in plasma (n = 240) and induced-sputum (n = 72) samples from a subgroup of patients using the ELISA technique. In addition, a meta-analysis was performed for the association of rs2070600 with COPD susceptibility. None of the studied genetic variants were found to be associated with COPD-BBS or COPD-TS. A marginal association was observed for the rs3134940 with COPD-BBS (p = 0.066). The results from the meta-analysis, including six case-control studies (n = 4149 subjects), showed a lack of association of rs2070600 with COPD susceptibility (p = 0.681), probably due to interethnic differences. The sRAGE plasma levels were lower in COPD-BBS compared to BBS and in COPD-TS compared to SWOC. The sRAGE levels were also lower in sputum samples from COPD-BBS than BBES. Subjects with rs3134940-TC genotypes exhibit lower sRAGE plasma levels than TT subjects, mainly from the COPD-BBS and SWOC groups. The AGER variants were not associated with COPD-BBS nor COPD-TS, but the sRAGE plasma and sputum levels are related to both COPD-BBS and COPD-TS and are influenced by the rs3134940 variant.

COPD: Iron Deficiency and Clinical Characteristics in Patients With and Without Chronic Respiratory Failure.

Background: The prevalence of iron deficiency in patients with COPD varies in previous studies. We aimed to assess its prevalence according to three well-known criteria for iron deficiency, its associations with clinical characteristics of COPD and mortality. Methods: In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 non-COPD controls, ferritin, TSat and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses. Results: The prevalence of iron deficiency in the study population was 10-43% according to diagnostic criteria, and was consistently higher in COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with FEV1 (OR 0.33 per liter increase), smoking (OR 3.2) and cardiovascular disease (OR 4.7). TSat < 20% was associated with BMI (OR 1.1 per kg/m2 increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV1 (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (HR 1.2-1.8) in adjusted analyses. Conclusion: The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking and cardiovascular disease, while TSat < 20% was associated with reduced level of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.

18-ß-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-ß-glycyrrhetinic acid (18-ß-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-ß-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1ß), mimicking what happens in smokers and COPD patients. Treatment with 18-ß-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1ß levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-ß-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample.

BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are associated with unfavorable outcomes following coronary artery bypass grafting (CABG). The purpose of this study was to compare in-hospital outcomes of patients with COPD alone versus OSA-COPD overlap after CABG. METHODS: Data of adults ≥ 18 years old with COPD who received elective CABG between 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS). Patients were divided into two groups: with OSA-COPD overlap and COPD alone. Propensity score matching (PSM) was employed to balance the between-group characteristics. Logistic and linear regression analyses determined the associations between study variables and inpatient outcomes. RESULTS: After PSM, data of 2,439 patients with OSA-COPD overlap and 9,756 with COPD alone were analyzed. After adjustment, OSA-COPD overlap was associated with a significantly increased risk of overall postoperative complications (adjusted odd ratio [aOR] = 1.12, 95% confidence interval [CI]: 95% CI: 1.01-1.24), respiratory failure/prolonged mechanical ventilation (aOR = 1.27, 95%CI: 1.14-1.41), and non-routine discharge (aOR = 1.16, 95%CI: 1.03-1.29), and AKI (aOR = 1.14, 95% CI: 1.00-1.29). Patients with OSA-COPD overlap had a lower risk of in-hospital mortality (adjusted odd ratio [aOR] = 0.53, 95% CI: 0.35-0.81) than those with COPD only. Pneumonia or postoperative atrial fibrillation (AF) risks were not significantly different between the 2 groups. Stratified analyses revealed that, compared to COPD alone, OSA-COPD overlap was associated with increased respiratory failure/prolonged mechanical ventilation risks among patients ≥ 60 years, and both obese and non-obese subgroups. In addition, OSA-COPD overlap was associated with increased risk of AKI among the older and obese subgroups. CONCLUSION: In US adults who undergo CABG, compared to COPD alone, those with OSA-COPD are at higher risks of non-routine discharge, AKI, and respiratory failure/prolonged mechanical ventilation, but a lower in-hospital mortality. No increased risk of AF was noted.

GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway.

BACKGROUND: Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is a significant process during the occurrence of airway remodelling. Increasing evidence suggests that glucose transporter 3 (GLUT3) is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in the airway epithelial cells of COPD patients remains unclear. METHODS: We detected the levels of GLUT3 in the peripheral lung tissue of COPD patients and cigarette smoke (CS)-exposed mice. Two Gene Expression Omnibus GEO datasets were utilised to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect GLUT3 expression. In addition, we used the AAV9-GLUT3 inhibitor to reduce GLUT3 expression in the mice model. Masson's staining and lung function measurement were used detect the collagen deposition and penh in the mice. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot, and immunofluorescence were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65, and ZEB1. RESULTS: Based on the GEO data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover, GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research revealed that down-regulation of GLUT3 significantly alleviated airway remodelling in vivo and in vitro. Lung function measurement showed that GLUT3 reduction reduced airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulating the NF-κB/ZEB1 pathway. CONCLUSION: We demonstrate that CS enhances the expression of GLUT3 in COPD and further confirm that GLUT3 may regulate airway remodelling in COPD through the NF-κB/ZEB1 pathway; these findings have potential value in the diagnosis and treatment of COPD. The down-regulation of GLUT3 significantly alleviated airway remodelling and reduced airway resistance in vivo. Our observations uncover a key role of GLUT3 in modulating airway remodelling and shed light on the development of GLUT3-targeted therapeutics for COPD.

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions.

BACKGROUND AND OBJECTIVE: Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients. METHODS: A total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro. RESULTS: Endothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05). CONCLUSION: NP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Risk of chronic obstructive pulmonary disease in a large cohort of Ontario, Canada workers.

Although several occupational exposures have been linked to the risk of COPD; limited data exists on sex-specific differences. This study aimed to identify at-risk occupations and sex differences for COPD risk. Cases were identified in a large surveillance system established through the linkage of former compensation claimants' data (non-COPD claims) to physician visits, ambulatory care data, and hospital inpatient data (1983-2020). Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CI) for occupation groups (occupation at time of claim), stratified by sex. HRs were indirectly adjusted for cigarette smoking using another population dataset. A total of 29,445 male and 14,693 female incident cases of COPD were identified. Increased risks were observed in both sexes for construction (HRmale 1.15, 95% CI 1.12-1.19; HRfemale 1.54, 95% CI 1.29-1.83) transport/equipment operating (HRmale 1.32, 95% CI 1.28-1.37; HRfemale 1.53, 95% CI 1.40-1.68) farming (HRmale 1.23, 95% CI 1.15-1.32; HRfemale 1.19, 95% CI 1.04-1.37) and janitors/cleaners (HRmale 1.31, 95% CI 1.24-1.37; HRfemale 1.40, 95% CI 1.31-1.49). Increased risks were observed for females employed as chefs and cooks (HR 1.44, 95% CI 1.31-1.58), bartenders (HR 1.38, 95% CI 1.05-1.81), and those working in food/beverage preparation (HR 1.34, 95% CI 1.24-1.45) among other occupations. This study demonstrates elevated risk of COPD among both male and female workers potentially exposed to vapours, gases, dusts, and fumes, highlighting the need for occupational surveillance of COPD.

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

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

Atrial Myxoma in a Patient With Chronic Obstructive Pulmonary Disease (COPD): Unmasking Overlapping Symptomatology.

Atrial myxoma, though the most common primary cardiac tumor, often presents with nonspecific symptoms that can obscure its diagnosis. This case report details an unusual presentation of dyspnea on exertion (DOE) in a patient initially considered to have chronic obstructive pulmonary disease (COPD), a common pulmonary etiology of DOE. The diagnostic journey underscores the critical importance of considering atrial myxoma in patients with DOE, especially when symptoms are not fully explained by apparent pulmonary conditions. Our findings highlight the necessity of a comprehensive diagnostic approach, including the early use of resting transthoracic echocardiogram, to unveil less common causes like atrial myxoma. This case reinforces the pivotal role of considering alternative diagnoses in complex presentations of DOE, thereby guiding more accurate and tailored patient management.

Characteristics of Patients With Alpha-1 Antitrypsin Deficiency From Rural Appalachia: A Retrospective Single-Center Study.

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant inherited condition, significantly impacts lung and liver functions, with mutations in the SERPINA1 gene, notably the Z allele, playing a pivotal role in disease susceptibility. This retrospective descriptive study from a rural Eastern Kentucky pulmonary clinic aimed to characterize patients with AAT deficiency, focusing on demographic, clinical, and laboratory parameters extracted from electronic health records (EHR) of Appalachian Regional Healthcare (ARH). Among 100 patient encounters, 56 were analyzed, revealing notable sex-based differences in smoking rates and co-existing conditions, with males showing higher rates of black lung and chronic obstructive pulmonary disease. In comparison, females exhibited higher rates of asthma, COVID-19, pneumothorax, and obstructive sleep apnea. The study emphasizes the importance of understanding genotype-phenotype correlations and demographic factors in assessing AAT deficiency, advocating for further research to refine management strategies and elucidate causal relationships.

The role of vasculature and angiogenesis in respiratory diseases.

In European countries, nearly 10% of all hospital admissions are related to respiratory diseases, mainly chronic life-threatening diseases such as COPD, pulmonary hypertension, IPF or lung cancer. The contribution of blood vessels and angiogenesis to lung regeneration, remodeling and disease progression has been increasingly appreciated. The vascular supply of the lung shows the peculiarity of dual perfusion of the pulmonary circulation (vasa publica), which maintains a functional blood-gas barrier, and the bronchial circulation (vasa privata), which reveals a profiled capacity for angiogenesis (namely intussusceptive and sprouting angiogenesis) and alveolar-vascular remodeling by the recruitment of endothelial precursor cells. The aim of this review is to outline the importance of vascular remodeling and angiogenesis in a variety of non-neoplastic and neoplastic acute and chronic respiratory diseases such as lung infection, COPD, lung fibrosis, pulmonary hypertension and lung cancer.

Discriminative potential of exhaled breath condensate biomarkers with respect to chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. METHODS: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. RESULTS: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. CONCLUSIONS: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future.

DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways, it is characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 expression has a detrimental role in numerous disorders. However, its role in COPD remains understudied. This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated mice airway inflammation and lung function decline caused by CS, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion in 16 HBE cells after CSE simulation, respectively. Nuclear factor erythroid 2-related factor 2 (NRF2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking COPD patients when compared to nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

Distinct trajectories of lung function from childhood to mid-adulthood.

RATIONALE: Life course trajectories of lung function development and decline influence the risk for lung disease but are poorly documented. OBJECTIVE: To document lung function trajectories from childhood to mid-adult life. METHODS: We modelled forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC at ages 9, 11, 13, 15, 18, 21, 26, 32, 38 and 45 years from a population-based cohort using latent profile analysis to identify distinct subgroups of participants with similar lung function trajectories. Regression analyses were used to assess associations between the trajectories, early life factors and postbronchodilator airflow obstruction at age 45. RESULTS: Among 865 participants with ≥6 measures of lung function, we identified 10 distinct FEV1 trajectories. Most were approximately parallel except for a childhood airway hyper-responsiveness-related persistently low trajectory (3% of study population); two accelerated-decline trajectories, one of which (8%) was associated with smoking and higher adult body mass index (BMI) and a catch-up trajectory (8%). Findings for FEV1/FVC trajectories were similar. Nine trajectories were identified for FVC: most were also approximately parallel except for a higher BMI-related accelerated-decline trajectory. The three FEV1 trajectories leading to the lowest FEV1 values comprised 19% of the cohort but contributed 55% of airflow obstruction at age 45. CONCLUSIONS: Lung function trajectories to mid-adult life are largely established before adolescence, with a few exceptions: a childhood airway hyper-responsiveness-related persistently low trajectory, which starts low and gets worse with age, and accelerated adult decline trajectories associated with smoking and obesity. Adverse trajectories are associated with a high risk of airflow obstruction in mid-adult life.