Lung Emphysema Research Articles

Influence and distinctions of particulate matter exposure across varying etiotypes in chronic obstructive pulmonary disease (COPD) mouse model

BackgroundAir pollution, notably particulate matter (PM), significantly impacts chronic respiratory disease such chronic obstructive pulmonary disease (COPD). Although asthma-COPD overlap (ACO), considered one of the COPD etiotype, is associated with greater severity in both symptoms and outcomes, effects of PM exposure remain unclear. Thus, this study aimed to evaluate impact of PM on chronic airway disease animal models.MethodsWe established two distinct COPD etiotypes, cigarette smoking-related COPD (COPD-C) and COPD with asthma (COPD-A), using porcine pancreatic elastase (PPE) for COPD-C and a combination of PPE with ovalbumin for COPD-A. To reflect smoking influence, cigarette smoking extract was administered to both disease models. To assess impact of PM exposure, bronchoalveolar lavage fluid (BALF), proinflammatory cytokines, lung histology, and cellular damage mechanisms were analyzed.ResultsIn the COPD-A model, cell counts and type 2 cytokines were elevated in BALF independent of PM exposure. All models exhibited increased lung inflammation and emphysema due to PM exposure. Expression levels of apoptosis-related protein B-cell lymphoma protein 2 (Bcl-2) associated X (Bax) showed an inclination to increase with PM exposure. In the COPD-A model, decreased expression of basal nuclear factor erythroid-derived 2-like 2 (Nrf-2) and increased production of reactive oxygen species (ROS) due to PM exposure were noted.ConclusionWe developed two distinct models for the etiotypes of COPD and found increased vulnerability to cell damage in COPD-A after PM exposure. Moreover, the control group displayed escalated airway inflammation and emphysema due to PM exposure, substantiating the risk of respiratory diseases.

The prevalence of respiratory symptoms and diseases and declined lung function among foundry workers.

Foundry workers are occupationally exposed to a variety of inhalable chemical substances. Occupational exposure to vapors, gases, dusts, and fumes can lead to adverse health effects on the respiratory system and cause chronic respiratory diseases, such as interstitial lung diseases (ILDs), chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. Research on respiratory symptoms, diseases, and lung function in foundry workers over the past few decades has been limited. The aim of this cross-sectional study was to assess the prevalence of respiratory symptoms and diseases and declined lung function of current foundry workers, ex-foundry workers, and unexposed controls. We assessed respiratory symptoms, diseases, and lung function among 335 current foundry workers, 64 ex-foundry workers, and 161 unexposed controls. The cumulative dust exposure (mg-y) of each participant was calculated, and the median cumulative dust exposure according to the main places of exposure was determined. A higher prevalence of chronic bronchitis, as reported in a questionnaire, was found among current and ex-foundry workers compared to unexposed controls, even after adjusting for pack-years of smoking (p = 0.009). Additionally, cough and wheezing in adulthood without respiratory infection, and chronic rhinitis symptoms were more common among current and ex-foundry workers compared to unexposed controls. These differences remained significant even after adjusting for pack-years of smoking and body mass index (BMI) (p = 0.007 and p < 0.001, respectively). Impaired lung function was more prevalent among both ex-foundry workers (29.7%) and current foundry workers (15.5%) compared to the unexposed controls (8.7%), with the difference remaining significant even after adjusting for the pack-years of smoking and BMI (p = 0.009). According to the questionnaire, the number of physician-diagnosed cases of chronic obstructive pulmonary disease (COPD) or chronic bronchitis was unexpectedly low compared to the indications from the symptom questionnaire and lung function test results, suggesting a potential underdiagnosis. The prevalence of silicosis was low (0.8%) among current and ex-foundry workers. Respiratory symptoms are common among foundry workers. Current and ex-foundry workers exhibited lower lung function in spirometry compared to unexposed controls. There is a potential underdiagnosis of COPD and chronic bronchitis among foundry workers.

Environmental and inflammatory factors influencing concurrent gut and lung inflammation.

Crohn's disease and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases that affect the gut and lung respectively and can occur comorbidly. Using the SHIP-1-/- model of Crohn's-like ileitis and chronic lung inflammation, the two diseases were co-investigated. Contrary to prior literature, Crohn's-like ileitis was not fully penetrant in SHIP-1-/- mice, and housing in a specific pathogen-free facility was completely protective. Indeed, ileal tissue from SHIP-1-/- mice without overt ileitis was similar to control ilea. However, SHIP-1-/- mice with ileitis exhibited increased granulocytes in ileal tissue together with T cell lymphopenia and they lacked low abundance Bifidobacteria, suggesting this bacterium protects against ileitis. Lung disease, as defined by inflammation in lung washes, emphysema, and lung consolidation, was present in SHIP-1-/- mice regardless of ileitis phenotype; however, there was a shift in the nature of lung inflammation in animals with ileitis, with increased G-CSF and neutrophils, in addition to type 2 cytokines and eosinophils. Deficiency of G-CSF, which protects against lung disease, protected against the development of ileitis in SHIP-1-/- mice. These studies have defined environmental, immune, and inflammatory factors that predispose to ileitis, and have identified that comorbid lung disease correlates with a granulocyte signature.

Оценка влияния пандемии COVID‑19 на распространённость эмфиземы по данным компьютерной томографии с применением технологии искусственного интеллекта

Respiratory diseases represent the most prevalent class of diseases in the Russian Federation, accounting for up to 25.0% of the total morbidity structure according to various authors. Several authors suggest that the proportion of patients with chronic obstructive pulmonary disease (COPD) with emphysema has increased in recent years. One of the reasons for the rising prevalence of emphysema is the aftermath of COVID‑19. The aim of this study is to analyze the changes in the incidence of emphysema before, during, and after the COVID‑19 pandemic. Materials and methods. The study included the results of chest computed tomography (CT) scans processed using artificial intelligencebased software, enabling the assessment of the volume of emphysematous lung tissue damage. Patient samples were divided into four periods: the «pre-COVID period» (625 studies), the «COVID period» (6,809 studies), the «post-COVID2023» period (101,872 studies), and the «post-COVID2024» period (78,539 studies). Results. The proportion of studies indicating emphysema in the pre-COVID period was 5.60%, increasing to 9.37% during the COVID period, and then decreasing to 6.63% in the first post-COVID year (2023), with a subsequent increase to 7.67% in the second post-COVID year (2024). Statistically significant differences in the percentage of emphysema were found in 2022, 2023, and 2024 when analyzed pairwise. Notably, when categorized by the severity of the disease, significant emphysema (&gt;6% lung involvement) was more prevalent in 2024, with an average percentage of 25.79% in this group. Conclusion. Our study confirms a significant increase in cases of emphysema in the population in recent years, which may be associated with the impact of the COVID‑19 pandemic. The proportion of patients with signs of emphysema in 2024 was 7.67%, which is 1% higher than in 2023.

Effect of HIV on Lung Function and Structure: A Systematic Review and Meta-analysis.

Obstructive lung disease (OLD) pathogenesis includes inhalational (e.g., smoking) and non-inhalational mechanisms (e.g., infections). HIV has been suggested as a novel OLD risk factor. Substantial data have recently emerged about its effects on lung function and structure, especially in low-to-middle-income countries and regarding longitudinal lung function. To assess the association of HIV infection with OLD, impaired gas exchange, and emphysema. In this systematic review and meta-analysis, we searched PubMed, EMBASE, CENTRAL, CDSR, WoS, Scopus, CINAHL, and GIM through April 2023 for controlled and observational studies of people living with and without HIV reporting pulmonary function and/or emphysema. Primary outcomes were OLD by spirometry, gas exchange impairment by diffusing capacity for carbon monoxide, and visual emphysema by computed tomography. We performed random-effects meta-analyses using odds ratios (OR) with 95% confidence intervals (CIs). This study was registered in PROSPERO (CRD42021268498). We included 95 publications pertaining to 43 unique studies. HIV was associated with OLD (OR 1.29; 95% CI 1.02-1.63), impaired gas exchange (OR 2.63; 95% CI 0.96-7.24), emphysema (OR 1.46; 95% CI 1.02-2.09), and faster lung function decline. OLD risk was greatest in Africans with HIV. There were no gas exchange or emphysema data from Africa. Certainty of evidence was low to very low, primarily due to studies' observational design. People living with HIV have increased risk for OLD, gas exchange impairment, faster lung function decline, and emphysema. OLD risk in HIV varies regionally. We recommend both spirometry and DLCO be measured in people living with HIV and respiratory symptoms. Future studies should develop and validate HIV-specific screening and case-finding strategies for chronic lung disease.

Swyer – James – McLeod syndrome in an adult male

Swyer – James syndrome, also called Swyer – James – MacLeod syndrome (SJMS), is a rare acquired disorder characterized by pulmonary artery hypoplasia, unilateral hyperlucent lungs, and usually also bronchiectasis. Adults with SJMS are often diagnosed with and treated for chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumothorax, or pulmonary embolism due to the similar clinical manifestations. Underestimation of an important radiological sign – unilateral “impoverishment” of the pulmonary pattern and hyperlucent lung – leads to erroneous diagnosis and inadequate treatment. Diagnosis of SJMS involves a computed tomography scan of the chest.The aim of this work was to familiarize readers with aspects of diagnosis and detail the clinical, radiological, and other characteristics of a patient with McLeod syndrome. The described adult man was diagnosed with SJMS at the age of 32. Some typical mistakes in examinations of such patients and the lack of vigilance of radiologists in case of unilateral hyperlucent lung are presented.Conclusion. Using the example of a rare clinical case of SJMS, we demonstrated the need to consider this syndrome when diagnosing adults with unjustified shortness of breath and a history of frequently recurrent pulmonary infections, with radiological signs of unilateral pulmonary emphysema and hyperlucent lung. According to the literature and our observations, computed tomography of the chest organs is a fast and reliable method for establishing the diagnosis of SJMS.

Clinical Improvements after Endoscopic Lung Volume Reduction with Valves in Patients with advanced Emphysema and a 6-Minute-Walk-Test ≤140 m at Baseline

BackgroundData regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with very low 6-Minute Walk Test (6-MWT) is limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6-MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutics benefits and increased complication risk.Study Designs and MethodsThis study utilized data from the Lungenemphysemregister e.V., a large German national multi-center prospective open label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6-MWT ≤140 m and dyspnea primarily attributed to hyperinflation.ResultsFifty-four patients with a baseline 6-MWT ≤140 m and 365 patients with a baseline 6-MWT between 140 m and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6-MWT ≤140 m at baseline had a lower FEV1, DLCO and higher symptom burden. In the 3-month-follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6-MWT ≤140 m at baseline showed significantly more 6-MWT improvement compared to patients with baseline 6-MWT between 140 m–450 m. Moreover, complication rates were similar in both groups.InterpretationIn summary, the data indicates that ELVR may be an effective and safe treatment for emphysema patients with a very low 6-MWT ≤140 m, if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6-MWT.

12556 Medullary Thyroid Cancer With Persistent Elevation Of Carcinoembryonic Antigen: Case Report

Abstract Disclosure: M.S. Campana: None. Introduction: Medullary thyroid Cancer (MTC) is a rare neuroendocrine tumor that originates from thyroid parafollicular C-cells and represents 5 % of all thyroid cancers. MTC can be sporadic (75%) or hereditary (25%) associated with multiple endocrine neoplasia type 2 syndrome (MEN2). Serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) are its tumor markers. We report a case of persistently elevated CEA levels despite an undetectable Ctn in a patient with MTC after initial thyroid lobectomy. Description of the case: A 42-year-old woman self-identified a neck lump after intentional weight loss. A neck US showed a right lobe thyroid nodule which resulted as suspicious for malignancy (Bethesda V) with subsequent right lobectomy. Pathology reported a 2.6 cm unexpected MTC with negative surgical margins, extrathyroidal extension, angioinvasion, and lymphatic invasion. No cervical lymph nodes (LNs) were removed. Immunohistochemistry was positive for CEA, chromogranin A, synaptophysin, and Ctn. T2 Nx. One month after lobectomy, the Ctn was 10.5 (0-3.0 pg/mL) and CEA 205.2 (0-3.0 ng/mL Non-smoker; 0-5.0 ng/mL smoker). The patient was then referred to our clinic for further management. Laboratories showed normal serum calcium, PTH, and fractionated plasma metanephrine/normetanephrine. A 2-month post-operative Ctn was undetectable, but CEA was elevated at 24.5. Subsequently, we broaden imaging studies to include neck US, CT neck /chest with contrast, and MRI abdomen pelvis with contrast. The only remarkable finding was a 6.7 cm pelvic mass with normal Ca-125. Genetic testing was negative for germline RET, ruling out MEN2. Patient underwent completion left lobectomy with prophylactic bilateral central neck dissection. Pathology showed benign thyroid parenchyma with multinodular hyperplasia and 0/12 LNs. Because of concerning pelvic mass, the patient was referred to OB/GYN. She underwent a laparoscopic bilateral salpingo-oophorectomy. Pathology showed a follicular ovarian cyst, negative for malignancy. A year post-completion total thyroidectomy Ctn remains undetectable, and a CEA is normal at 1.3. Discussion: Because Ctn was already undetectable 1 month after lobectomy with persistent elevated CEA a complete total thyroidectomy with prophylactic bilateral central neck dissection was indicated to achieve operative cure. Ctn is specific to MTC but variable. CEA is more reproducible with less variability; however, it is not specific to MTC and can also be elevated in smokers, benign breast and genitourinary disease, emphysema, cirrhosis, and cancer of colon, rectum, liver, genitourinary, and lung. If residual disease is present, Ctn tends to be proportionally more elevated than CEA. When the opposite occurs, poorly differentiated MTC with possibility of distant metastases vs. a second primary malignancy vs. a distant benign neoplasm known to elevate CEA need to be ruled out. Presentation: 6/2/2024

Citrullination, a novel posttranslational modification of elastin, is involved in COPD pathogenesis.

Elastin is an extracellular matrix protein (ECM) that supports elasticity of the lung, and in patients with chronic obstructive pulmonary disease (COPD) and emphysema, the structural changes that reduce the amount of elastic recoil, lead to loss of pulmonary function. We recently demonstrated that elastin is a target of peptidyl arginine deiminase (PAD) enzyme-induced citrullination, thereby leading to enhanced susceptibility of this ECM protein to proteolysis. This study aimed to investigate the impact of PAD activity in vivo and furthermore assessed whether pharmacological inhibition of PAD activity protects against pulmonary emphysema. Using a Serpina1a-e knockout mouse model, previously shown to develop inflammation-mediated emphysema, we validated the involvement of PADs in airway disease. In line with emphysema development, intratracheal administration of lipopolysaccharide in combination with PADs provoked significant airspace enlargement (P < 0.001) and diminished lung function, including loss of lung tissue elastance (P = 0.0217) and increases in lung volumes (P = 0.0463). Intraperitoneal treatment of mice with the PAD inhibitor, BB-Cl-amidine, prevented PAD/LPS-mediated lung function decline and emphysema and reduced levels of citrullinated airway elastin (P = 0.0199). These results provide evidence for the impact of PADs on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.NEW & NOTEWORTHY This study provides evidence for the impact of peptidyl arginine deiminase (PAD) enzymes on lung function decline, indicating promising potential for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.

Emphysema and lung cancer risk.

With increasing significance of lung cancer screening programs, it is essential to determine the group of participants, who would benefit the most from screening. In our study, we aimed to establish the correlation between lung emphysema and lung cancer risk. The study design was cross-sectional. Low-dose computed tomography (LDCT) scans of 896 subjects from MOLTEST-BIS lung cancer screening program, including 100 subjects with detected lung cancer, were visually evaluated for the presence, type and severity of emphysema. Quantitative emphysema evaluation was performed with Siemens syngo.via Pulmo 3D application. Visually detected presence of centrilobular emphysema (CLE) correlated with male gender (P=0.02), age (P<0.001) and pack-years of smoking (P=0.004), as well as with quantitative assessment of Emphysema Index (EI) (P=0.008), and with emphysema clusters of given size (Clas 1-4) Clas 1, Clas 3 and Clas 4 (P<0.001). Visually assessed severity grade of emphysema correlated with age (P<0.001), pack-years of smoking history (P=0.002) and EI (P<0.001). There was a correlation between lung cancer occurrence and pack-years (P<0.001), age (P<0.001), and presence of CLE (P<0.001) but no correlation with gender (P=0.88) and EI (P=0.32) was found. In the logistic regression model pack-years, age, qualitative severity of CLE and Clas 1 were significant factors correlated with lung cancer occurrence (P<0.001). Qualitative and quantitative emphysema evaluation correlate with each other. Both, presence and severity of CLE correlate with higher incidence of lung cancer. Severity of visually assessed emphysema, age and pack-years of smoking are significant predictors of lung cancer occurrence.

Cigarette smoke-induced exosomal miR-221-3p facilitates M1 macrophage polarization via the STAT3 pathway in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is marked by irreversible airflow limitations stemming from small airway constriction and lung emphysema. The advancement of COPD is greatly influenced by the M1 polarization of macrophages. The mechanisms governing macrophage polarization in inflammation conditions in COPD are not yet fully understood. To investigate the interplay between exosomes triggered by cigarette smoke and the polarization of macrophages, we utilized a combination of flow cytometry, quantitative real-time reverse transcription PCR, and western blot analysis. Our research reveals that cigarette smoke (CS) exposure induces the secretion of exosomes from human bronchial epithelial cells, with exosomal miR-221-3p identified as a key player in modulating the polarization of M1 macrophages. The evidence indicates that cigarette smoke promotes exosome secretion in these cells, with exosomal miR-221-3p targeting SOCS3 and regulating the STAT3 signaling pathway to facilitate M1 macrophage polarization. This research delves into the molecular pathways through which miR-221-3p facilitates the polarization of M1 macrophages, presenting a groundbreaking approach for potential targeted therapy in COPD.

Sex-biased Regulation of Extracellular Matrix Genes in COPD.

Compared to men, women often develop COPD at an earlier age with worse respiratory symptoms despite lower smoking exposure. However, most preventive, and therapeutic strategies ignore biological sex differences in COPD. Our goal was to better understand sex-specific gene regulatory processes in lung tissue and the molecular basis for sex differences in COPD onset and severity. We analyzed lung tissue gene expression and DNA methylation data from 747 individuals in the Lung Tissue Research Consortium (LTRC), and 85 individuals in an independent dataset. We identified sex differences in COPD-associated gene regulation using gene regulatory networks. We used linear regression to test for sex-biased associations of methylation with lung function, emphysema, smoking, and age. Analyzing gene regulatory networks in the control group, we identified that genes involved in the extracellular matrix (ECM) have higher transcriptional factor targeting in females than in males. However, this pattern is reversed in COPD, with males showing stronger regulatory targeting of ECM-related genes than females. Smoking exposure, age, lung function, and emphysema were all associated with sex-specific differential methylation of ECM-related genes. We identified sex-based gene regulatory patterns of ECM-related genes associated with lung function and emphysema. Multiple factors including epigenetics, smoking, aging, and cell heterogeneity influence sex-specific gene regulation in COPD. Our findings underscore the importance of considering sex as a key factor in disease susceptibility and severity.

E-cigarette use and respiratory illnesses among U.S. adults: An analysis of the Population Assessment of Tobacco and Health Study

IntroductionElectronic cigarettes (e-cigarette) entered the United States marketplace in 2007. Because of the chemical composition of e-cigarette liquid, there are concerns related to its effects on respiratory illnesses. MethodsUsing Wave 4 (2016–2018) of the adult (≥18 years of age) Population Assessment of Tobacco and Health study, logistic regression was used to quantify the association between e-cigarette use and any respiratory illness (asthma, chronic bronchitis, COPD, emphysema, or other lung or respiratory conditions). Age, gender, and the use of other tobacco products were assessed as modifiers of this relationship via interactions on the additive and multiplicative scales. ResultsAfter adjustment, ever e-cigarette use was associated with a 1.32 (95 % confidence intervals [CI]:1.03, 1.69) greater odds of any respiratory illness compared with never e-cigarette users among U.S. adults. When comparing ever and never e-cigarette users, older adults (Odds Ratio [OR] = 1.65, 95 %CI:1.20, 2.26), and ever users of other tobacco products (OR = 1.77, 95 %CI:1.37, 2.29) had greater odds of reporting any respiratory illness than younger adults and those who never used other tobacco products. Among never e-cigarette users, men (OR = 1.51, 95 %CI:1.12, 2.04) were less likely to report any respiratory illness than women. Only the joint effect of age and e-cigarette use on any respiratory illness was statistically significant, suggesting this effect was greater than expected on the additive and multiplicative scales. ConclusionThese findings suggest that the relationship between e-cigarette use and any respiratory illness varies with age. Interventions and policies to reduce e-cigarette use should target high-risk groups for any respiratory illness.

Aucubin Alleviates Chronic Obstructive Pulmonary Disease by Activating Nrf2/HO-1 Signaling Pathway.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high death rates. Aucubin is an iridoid glycoside extracted from Eucommia ulmoides with antioxidative and anti-inflammatory properties in human diseases. This study aimed to investigate its specific function in mouse and cell models of COPD. The COPD mouse model was established by exposing mice to a long-term cigarette smoke (CS). The number of inflammatory cells and the contents of inflammatory factors tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-8 in bronchoalveolar lavage fluid (BALF) of CS-exposed mice were measured. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) in the lung tissues were estimated. Masson staining and hematoxylin-eosin (H&E) staining were utilized to evaluate pulmonary fibrosis and emphysema in CS-treated mice. Cell apoptosis in the lung tissues was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blot was applied to quantify protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and apoptotic markers. COPD cell model was established by exposing mouse lung epithelial cells (MLE12) with cigarette smoke extract to further verify the properties of aucubin in vitro. Aucubin reduced the number of inflammatory cells and decreased the contents of TNF-α, IL-6, and IL-8 in BALF of CS-treated mice. The oxidative stress, lung emphysema, fibrosis, and lung cell apoptosis induced by CS exposure were ameliorated by aucubin administration. Aucubin activated the Nrf2/HO-1 signaling pathway in vitro and in vivo. Pretreatment with ML385, a specific Nrf2 inhibitor, antagonized the protective effects of aucubin on inflammation, oxidative stress, fibrosis, and cell apoptosis in COPD. Aucubin alleviates inflammation, oxidative stress, apoptosis, and pulmonary fibrosis in COPD mice and CSE-treated MLE12 cells by activating the Nrf2/HO-1 signaling pathway.

FEATURES OF ANESTHESIA IN PATIENTS WITH SPECIAL NEEDS. PART 1

The non-medical use of cannabis can negatively impact the morpho-functional state of almost all organs and systems of the human body. During acute intoxication and established drug dependence, it can unevenly distort the effects of drugs for local and general anesthesia, leading to life-threatening complications. Part 1 of this review presents the results of acute and chronic cannabis use on homeostasis. Cerebral vasospasm and atherosclerosis are identified as major etiological factors for cannabis-related cerebrovascular diseases. Young to middle-aged individuals (30–50 years), male gender (male-to-female ratio 3.7:1), and chronic use (86%) are significant independent predictors of neurovascular toxicity, cerebral hypoperfusion, and stroke. Cannabis smoking causes damage to the respiratory mucosa similar to tobacco. Regular cannabis smokers can expect irritation of the upper respiratory tract, swelling, obstruction, chronic cough, bronchitis, lung emphysema, and bronchospasm. Some reports advocate the use of dexamethasone during surgery to alleviate these symptoms. The detrimental effects of chronic cannabis use on liver and kidney functions are somewhat overstated. Disturbances in immune system, thermoregulation, blood clotting, and carbohydrate metabolism in the absence of anesthetic precautions can significantly complicate the patient's condition in the perioperative period. Cannabinoids can interact with drugs from various groups. Awareness of the pathophysiological and biochemical consequences of cannabis use allows anesthesiologists to anticipate and effectively manage perioperative complications in this patient category

Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project

BackgroundThe PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry.MethodDemographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables.ResultsThe study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL.ConclusionsWe found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels.Trial registrationwww.clinicaltrials.gov (ID: NCT04180319).

Repurposing nitrofurantoin as a stimulant of fibroblast extracellular matrix repair for the treatment of emphysema

Emphysema is a respiratory disease that causes the progressive loss of lung extracellular matrix (ECM) organisation, subsequently undermining lung integrity and reducing lung function. Fibroblasts must constantly repair damage to the lungs to preserve lung health, however, fibroblast ECM repair is reduced during emphysema, causing ECM damage to outweigh fibroblast ECM maintenance. Current treatments for emphysema fail to address the root causes of emphysematous progression, highlighting the need for novel methods of treating emphysema. Nitrofurantoin is a broad-spectrum antibiotic indicated for the treatment of urinary tract infections that also displays potential as a novel avenue of emphysema treatment. Nitrofurantoin is known to potentially cause fibrotic effects that could be repurposed to increase fibroblast repair and outweigh the progressive ECM damage of the emphysematous lung. Therefore, this study examined the effects of nitrofurantoin treatment on primary human lung fibroblasts derived from emphysema patients to determine if the drug holds potential as a novel treatment for emphysema. Nitrofurantoin was shown to stimulate migration and alter fibroblast morphology by increasing cell area and reducing roundness, suggesting that it could induce an ECM-repair primed phenotype in fibroblasts. Interestingly, nitrofurantoin treatment did not alter collagen-IV, perlecan, periostin or tenascin-C deposition, though fibronectin deposition was significantly upregulated at a higher dosage (20 μg/mL). This study highlighted the nitrofurantoin induced changes to fibroblast motility and morphology that facilitate ECM repair. Thus, nitrofurantoin induced pulmonary fibrosis could be caused by a change in cell phenotype that subsequently upregulates ECM repair, indicating its potential as a treatment for emphysema.

A Lactobacillus Combination Ameliorates Lung Inflammation in an Elastase/LPS-induced Mouse Model of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is the world's leading lung disease and lacks effective and specific clinical strategies. Probiotics are increasingly used to support the improvement of the course of inflammatory diseases. In this study, we evaluated the potential of a lactic acid bacteria (LAB) combination containing Limosilactobacillus reuteri GMNL-89 and Lacticaseibacillus paracasei GMNL-133 to decrease lung inflammation and emphysema in a COPD mouse model. This model was induced by intranasal stimulation with elastase and LPS for 4weeks, followed by 2weeks of oral LAB administration. The results showed that the LAB combination decreased lung emphysema and reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) in the lung tissue of COPD mice. Microbiome analysis revealed that Bifidobacterium and Akkermansia muciniphila, reduced in the gut of COPD mice, could be restored after LAB treatment. Microbial α-diversity in the lungs decreased in COPD mice but was reversed after LAB administration, which also increased the relative abundance of Candidatus arthromitus in the gut and decreased Burkholderia in the lungs. Furthermore, LAB-treated COPD mice exhibited increased levels of short-chain fatty acids, specifically acetic acid and propionic acid, in the cecum. Additionally, pulmonary emphysema and inflammation negatively correlated with C. arthromitus and Adlercreutzia levels. In conclusion, the combination of L. reuteri GMNL-89 and L. paracasei GMNL-133 demonstrates beneficial effects on pulmonary emphysema and inflammation in experimental COPD mice, correlating with changes in gut and lung microbiota, and providing a potential strategy for future adjuvant therapy.

Comparative Analysis of Particulate Content in Cigarette Smoke: Implications for Respiratory Health of Active and Passive Smokers

Cigarette smoke is a heterogeneous mixture of gases, uncondensed vapours and liquid particulate matter with millions of particles per cubic centimetre. Cigarette smoking can negatively impact the health of smokers and non-smokers. As such, there is a need to constantly assess the quantity of toxic substances emanating from smoking cigarettes. This study investigated the total amount of particulates to which smokers and non-smokers are exposed and identified the chemical compositions of total particulates in cigarette smoke from some selected cigarette brands obtained from Nagongera town council shops in Uganda. To achieve this, we made use of an apparatus that mimics the smoking process of a human being and a passive smoker by connecting this set to another set-up containing a cigarette to be burnt. Qualitative tests for chemical composition were conducted using conventional tests for organic functional groups. It was found that Sportsman and locally cured tobacco had the highest total particulate content (116 mg and 73 mg) while Supermatch and Safari had the lowest total amount of particulates 45.5 mg and 40.3 mg, respectively. The investigated cigarettes were found to be composed of the following functional groups: aromatics, phenolics, nitrosamines and alkaloids. However, aldehyde and ketonic groups were not identified. The cigarette composition results in cigarette smoke composition either in the mainstream or the side stream causing disease to a respiratory system like lung cancer, emphysema and cancers in the mouth cavity and oesophagus. This study confirmed that the brand of cigarette smoked could determine the quantity of particulate smokers and non-smokers of cigarettes might be exposed to and that functionalities and/or chemical compositions vary amongst Ugandan cigarette brands