Non-smoking Controls Research Articles

MiRNA Signatures in Alveolar Macrophages Related to Cigarette Smoke: Assessment and Bioinformatics Analysis

Cigarette smoke (CS) is a driver of many respiratory diseases, including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several regulatory pathways. Previously, we monitored the expressions of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p, and 106a-5p in AMs derived from the bronchoalveolar lavage (BAL) of subjects with NSCLC, COPD, and smoker and non-smoker control groups. Here, we investigated the capability of CS conditionate media to modulate the abovementioned miRNAs in primary AMs obtained in the same 43 sex-matched subjects. The expressions of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p were assessed before and after in vitro CS exposure by RT-PCR. In addition, a comprehensive bioinformatic analysis of miRNAs KEGGS and PPI linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is worth noting that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both smokers and non-smokers, 106a-5p in non-smokers, and 20a-5p in smokers, shifted towards those found in individuals with COPD, suggesting them as a risk factor in developing this lung condition. Moreover, CS-focused sub-analysis identified miRNA which exhibited CS-dependent pattern and modulated mRNA involved in the immune system or AMs property regulation. In conclusion, our study uncovered miRNA signatures in AMs exposed to CS, indicating that CS might modify epigenetic patterns that contribute to macrophage activation and lung disease onset and progression.

Trimethylamine N-Oxide (TMAO) and TNF-α Levels in Periodontal Disease Associated With Smoking.

Trimethylamine N-oxide (TMAO) is a compound involved in the pathogenesis of various systemic inflammatory diseases, including cardiovascular conditions. The aim of this study was to determine differences in saliva and serum levels of TMAO between periodontitis and healthy patients according to smoking status. The study included four systemically healthy groups: periodontally healthy non-smokers (NS-Control; n = 25), non-smokers with Stage-III-Grade-B periodontitis (NS-Periodontitis; n = 25), periodontally healthy smokers (S-Control; n = 25), and smokers with Stage-III Grade-C periodontitis (S-Periodontitis; n = 25). Periodontal parameters were recorded. TMAO levels were determined in saliva and serum samples using liquid chromatography-mass spectrometry (LC-MS/MS). TNF-α levels were measured by the ELISA method. Salivary TNF-α and TMAO levels were significantly elevated in the smoking periodontitis group compared to other groups (p < 0.001 and p = 0.003, respectively). Serum TMAO levels were also significantly higher in the smoking periodontitis group compared to non-smoking controls and non-smoking periodontitis. TMAO/SFR ratios were notably higher in the smoking periodontitis group compared to other groups, and a strong positive correlation was observed between salivary TMAO and TNF-α levels (r = 0.892, p < 0.001). The data suggested that TMAO and TNF-α are associated with inflammatory mechanisms of periodontitis in cases where periodontitis coexists with smoking. NCT06580431.

NLRP3 is a BMI-independent mediator of stable COPD

PurposeThe inflammatory response in animal models of chronic obstructive pulmonary disease (COPD) is activated by the NLR-family-pyrin-domain-containing-3 (NLRP3) inflammasome pathway, which is also known to play a role in obesity-related inflammation. The NLRP3/caspase-1/interleukin (IL)-1β pathway might be involved in the progression of COPD with increasing body mass index. To our knowledge, no previous studies have explored the role of NLRP3 inflammasome markers in linking COPD and obesity. Here, we aim to investigate this potential connection by examining levels of NLRP3, caspase-1, IL-1β, and IL-17A and to provide additional data on the expression of these molecules in relation to smoking status and COPD severity.MethodsA case‒control study was conducted between July 2020 and March 2023. Peripheral blood mononuclear cells were isolated, and total RNA was extracted for real-time quantitative polymerase chain reaction (qPCR) analysis to measure the expression levels of inflammasome molecules.Results29 subjects who were diagnosed with stable COPD and 32 controls were included in the data analysis. NLRP3 and IL-17A but not caspase-1 or IL-1β expression was significantly greater in the COPD group than in the control group. We detected a significant increase in NLRP3 levels in the smoker COPD group (p = 0.009) and nonsmoker COPD group (p = 0.045) compared with those in the nonsmoker control group. There was no significant correlation between BMI and the inflammasome markers.ConclusionAs proinflammatory biomarkers, NLRP3 and IL-17A are prominent in stable COPD patients. Smoking may trigger NLRP3-mediated inflammation in stable COPD patients. The expression levels of NLRP3 inflammasome molecules did not differ in terms of disease severity or BMI.Graphical

High BMP7 Expression May Worsen Airway Disease in COPD by Altering Epithelial Cell Behavior.

Airway disease is the main pathological basis of chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are unknown. Bone morphogenetic protein-7 (BMP7) is a multi-functional growth factor that belongs to the transforming growth factor superfamily, which affects the regulation of proliferation, differentiation, and apoptosis. Previous research has shown that BMP7 is highly expressed in the airway epithelia of patients with COPD, but its role in airway disease has not been fully elucidated. A lung tissue cohort and a sputum cohort were included in the study. BMP7 expression in the airway epithelium and the BMP7 level in sputum supernatants were detected. Human primary bronchial epithelial cells (HPBECs) were isolated by bronchoscopy from healthy individuals. The functional consequences of adding recombinant human BMP7 or BMP7 overexpression to HPBECs were explored. BMP7 expression in bronchial epithelial cells of patients with COPD was significantly higher than that in smoking and nonsmoking controls. The expression of BMP7 in the bronchial epithelia of patients with COPD was negatively correlated with the airway counts measured by quantitative computed tomography, positively correlated with airway wall thickness, and negatively correlated with FEV1. The BMP7 level in the induced sputum of patients with COPD was higher than that in controls, and was related to the levels of interleukin-6 (IL-6), IL-8, and IL-1β. The addition of rhBMP7 (100 ng/mL) inhibited the proliferation of HPBECs and promoted squamous metaplasia and inhibit ciliated cell differentiation in human bronchial epithelial cells. BMP7 overexpression promotes apoptosis in human bronchial epithelial cells, through regulating MKK7/JNK2 signaling pathway and activating the caspase-3 pathway. High expression of BMP7 in the bronchial epithelia may play a crucial role in airway disease of COPD through inhibiting proliferation and promoting abnormal differentiation and excessive apoptosis of human bronchial epithelial cells.

The effect of tobacco use on clinical outcomes in total knee arthroplasty patients

Introduction Previous research has established that smoking significantly increases the complication rate of total knee arthroplasty (TKA). Risk of infection, prosthetic loosening, fractures, wound healing issues, and revisions are increased in smokers, but research is limited on the long-term clinical outcomes of pain, range of motion, stability, and functionality between smokers, nonsmokers, and former smokers, specifically utilizing Knee Society Scores (KSS). Methods This was a retrospective chart review of primary TKA patients (n = 203) at a single university hospital. The patients were divided by smoking status: nonsmoker, current smoker, or former smoker. One-way analysis of variance with associated f ratios was performed to assess variance in KSS by smoking status over time. Relative risk ratio analyses were employed to assess patients’ predictive risk of acquiring postoperative infection and requiring additional surgery following TKA based on smoking status. Results Postoperative KSS were significantly lower in the smoker group compared to nonsmokers and former smokers at 6 weeks and 1 year. For every 20 months a former smoker used tobacco, an approximate 1-point decrease in KSS was expected. The relative risk ratios for postoperative infection rates and patients requiring additional surgery were 2.13 and 1.44, respectively, when current smokers were compared to nonsmokers. Conclusions This analysis found that current smokers had lower KSS and higher infection rates following TKA when compared to nonsmoking controls. In addition, increased duration of smoking was correlated with poorer outcomes within the former smoker group.

Integrating Metabolomics Domain Knowledge with Explainable Machine Learning in Atherosclerotic Cardiovascular Disease Classification.

Metabolomic data often present challenges due to high dimensionality, collinearity, and variability in metabolite concentrations. Machine learning (ML) application in metabolomic analyses is enabling the extraction of meaningful information from complex data. Bringing together domain-specific knowledge from metabolomics with explainable ML methods can refine the predictive performance and interpretability of models used in atherosclerosis research. In this work, we aimed to identify the most impactful metabolites associated with the presence of atherosclerotic cardiovascular disease (ASCVD) in cross-sectional case-control studies using explainable ML methods integrated with metabolomics domain knowledge. For this, a subset from the FLEMENGHO cohort with metabolomic data available was used as the training cohort, including 63 patients with a history of ASCVD and 52 non-smoking controls matched by age, sex, and body mass index from the same population. First, Partial Least Squares Discriminant Analysis (PLS-DA) was applied for dimensionality reduction. The selected metabolites' correlations were analyzed by considering their chemical categorization. Then, eXtreme Gradient Boosting (XGBoost) was used to identify metabolites that characterize ASCVD. Next, the selected metabolites were evaluated in an external cohort to determine their effectiveness in distinguishing between cases and controls. A total of 56 metabolites were selected for ASCVD discrimination using PLS-DA. The primary identified metabolites' superclasses included lipids, organic acids, and organic oxygen compounds. Upon integrating these metabolites with the XGBoost model, the classification yielded a test area under the curve (AUC) of 0.75. SHAP analyses ranked cholesterol, 3-methylhistidine, and glucuronic acid among the most impactful features and showed the diversity of metabolites considered for building the ASCVD discriminator. Also using XGBoost, the selected metabolites achieved an AUC of 0.93 in an independent external validation cohort. In conclusion, the combination of different metabolites has the potential to build classifiers for ASCVD. Integrating metabolite categorization within the SHAP analysis further enhanced the interpretability of the model, offering insights into metabolite-specific contributions to ASCVD risk.

Exploring the Relationship Between VMAT2 and DAT Expression, Psychotic Experiences, Craving, and Treatment Motivation in Male Patients with Methamphetamine Use Disorder.

Objectives: We aimed to examine the relationship of Dopamine transporter (DAT) and vesicular monoamine transporter (VMAT-2) gene and protein levels with psychic experiences and other clinical parameters in individuals with Methamphetamine Use Disorder (MUD). Methods: This study included 50 males diagnosed with MUD and 50 males as a smoking control (SC) and nonsmoking control (NSC). Community Assessment of Psychic Experiences (CAPE) was administered to patients and controls; Addiction Profile Index, Treatment Motivation Questionnaire, and Substance Craving Scale were administered only to the patient group. DAT and VMAT2 gene and protein levels were determined in blood obtained from the controls and patient groups. Results: CAPE positive, depressive, total, and distress scores were significantly higher in the patient group. DAT protein level and VMAT2 gene and protein levels were lower in the patient group compared to the controls. The DAT gene expression level was higher in the patient group compared to the controls. There was no correlation between any clinical variables and expression levels. A low VMAT2 gene expression level could diagnose MUD with a 5% probability when NSCs were used as a reference. A high DAT gene expression level could diagnose tobacco use disorder (TUD) with a 99.9% probability when NSCs were used as a reference. Conclusions: The patient group showed more psychic experiences than healthy people. The low expression of the VMAT2 gene was identified as a predictor of MUD, while the high expression of the DAT gene was predictive of TUD.

Mitochondrial dysfunction and impaired DNA damage repair through PICT1 dysregulation in alveolar type II cells in emphysema

BackgroundAlveolar type II (ATII) cells have a stem cell potential in the adult lung and repair the epithelium after injury induced by harmful factors. Their damage contributes to emphysema development, characterized by alveolar wall destruction. Cigarette smoke is the main risk factor for this disease development.MethodsATII cells were obtained from control non-smoker and smoker organ donors and emphysema patients. Isolated cells were used to study the role of PICT1 in this disease. Also, a cigarette smoke-induced murine model of emphysema was applied to define its function in disease progression further.ResultsDecreased PICT1 expression was observed in human and murine ATII cells in emphysema. PICT1 was immunoprecipitated, followed by mass spectrometry analysis. We identified MRE11, which is involved in DNA damage repair, as its novel interactor. PICT1 and MRE11 protein levels were decreased in ATII cells in this disease. Moreover, cells with PICT1 deletion were exposed to cigarette smoke extract. This treatment induced cellular and mitochondrial ROS, cell cycle arrest, nuclear and mitochondrial DNA damage, decreased mitochondrial respiration, and impaired DNA damage repair.ConclusionsThis study indicates that PICT1 dysfunction can negatively affect genome stability and mitochondrial activity in ATII cells, contributing to emphysema development. Targeting PICT1 can lead to novel therapeutic approaches for this disease.

Effect of smoking on meibomian gland among Nepalese population

Purpose of study: To investigate the effects of cigarette smoking on meibomian gland and tear function test. Methods: It was a hospital-based cross-sectional study, which enrolled examined 30 subjects with a smoking history of at least 1 year (study group) alongside 25 healthy non-smokers (control group). Each participant’s symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire. A comprehensive ophthalmological evaluation followed, which included the non-invasive tear breakup time (NITBUT) and Schirmer test (with anesthesia). Additionally, we conducted a detailed analysis of the meibomian glands in both the upper and lower eyelids using meibography, employing the advanced Sirius anterior segment analysis system. Results: Participants in the study group averaged a smoking history of 6.94 ± 6.73 pack years. The mean OSDI score was 36.45 ± 10.60 in the study group, compared to 31.41 ± 8.12 in the control group (P = 0.05). For the NITBUT and Schirmer test, the study group recorded values of 9.54 ± 5.89 seconds and 14.77 ± 9.39 mm, respectively, while the control group showed 9.95 ± 6.15 seconds and 19.08 ± 7.08 mm (P = 0.85 and P = 0.03, respectively). Upper lid meibography revealed a 55.40 ± 10.10% gland loss in the study group, significantly higher than the 46.33 ± 14.70% observed in the control group (P = 0.01). However, no statistically significant difference was found in lower lid meibomian gland loss between the groups, with the study group at 54.08 ± 9.71% and the control group at 51.41 ± 17.24% (P = 0.49). Conclusion: Smoking results in meibomian gland damage which may be a risk factor for dry eye. In cases of ocular surface disorders related to chronic smoking, meibomian gland damage should be taken into consideration.

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

TGFβ1, SMAD and β-catenin in pulmonary arteries of smokers, patients with small airway disease and COPD: potential drivers of EndMT.

We previously reported pulmonary arterial remodelling and active endothelial-to-mesenchymal transition (EndMT) in smokers and patients with early chronic obstructive pulmonary disease (COPD). In the present study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-β1 (P<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (P<0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared with NC. Total β-catenin expression was significantly higher in smoking groups across arterial sizes (P<0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total β-catenin was positively correlated with total S100A4 in small and medium arteries (r = 0.35, 0.50; P=0.02, 0.01, respectively), with Vimentin in medium arteries (r = 0.42, P=0.07), and with arterial thickness of medium and large arteries (r = 0.34, 0.41, P=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-β1 in smokers, SAD, and COPD patients. Increased expression of β-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway.

Differentiation and Growth-Arrest-Related lncRNA (DAGAR): Initial Characterization in Human Smooth Muscle and Fibroblast Cells.

Vascular smooth muscle cells (SMCs) can transition between a quiescent contractile or "differentiated" phenotype and a "proliferative-dedifferentiated" phenotype in response to environmental cues, similar to what in occurs in the wound healing process observed in fibroblasts. When dysregulated, these processes contribute to the development of various lung and cardiovascular diseases such as Chronic Obstructive Pulmonary Disease (COPD). Long non-coding RNAs (lncRNAs) have emerged as key modulators of SMC differentiation and phenotypic changes. In this study, we examined the expression of lncRNAs in primary human pulmonary artery SMCs (hPASMCs) during cell-to-cell contact-induced SMC differentiation. We discovered a novel lncRNA, which we named Differentiation And Growth Arrest-Related lncRNA (DAGAR) that was significantly upregulated in the quiescent phenotype with respect to proliferative SMCs and in cell-cycle-arrested MRC5 lung fibroblasts. We demonstrated that DAGAR expression is essential for SMC quiescence and its knockdown hinders SMC differentiation. The treatment of quiescent SMCs with the pro-inflammatory cytokine Tumor Necrosis Factor (TNF), a known inducer of SMC dedifferentiation and proliferation, elicited DAGAR downregulation. Consistent with this, we observed diminished DAGAR expression in pulmonary arteries from COPD patients compared to non-smoker controls. Through pulldown experiments followed by mass spectrometry analysis, we identified several proteins that interact with DAGAR that are related to cell differentiation, the cell cycle, cytoskeleton organization, iron metabolism, and the N-6-Methyladenosine (m6A) machinery. In conclusion, our findings highlight DAGAR as a novel lncRNA that plays a crucial role in the regulation of cell proliferation and SMC differentiation. This paper underscores the potential significance of DAGAR in SMC and fibroblast physiology in health and disease.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder

BackgroundStudies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. MethodsUsing dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. ResultsCompared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LimitationsThis study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. ConclusionrTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

Expression of human Interferon Regulatory Factor 3 (IRF-3) in alveolar macrophages relates to clinical and functional traits in COPD.

IntroductionChronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.AimTo evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed.MethodsLung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry.ResultsA significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001).ConclusionsSmoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease.

Multimodal 7T imaging reveals enhanced functional coupling between salience and frontoparietal networks in young adult tobacco cigarette smokers.

Tobacco cigarette smoking is associated with disrupted brain network dynamics in resting brain networks including the Salience (SN) and Fronto parietal (FPN). Unified multimodal methods [Resting state connectivity analysis, Diffusion Tensor Imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and cortical thickness analysis] were employed to test the hypothesis that the impact of cigarette smoking on the balance among these networks is due to alterations in white matter connectivity, microstructural architecture, functional connectivity and cortical thickness (CT) and that these metrics define fundamental differences between people who smoke and nonsmokers. Multimodal analyses of previously collected 7 Tesla MRI data via the Human Connectome Project were performed on 22 people who smoke (average number of daily cigarettes was 10 ± 5) and 22 age- and sex-matched nonsmoking controls. First, functional connectivity analysis was used to examine SN-FPN-DMN interactions between people who smoke and nonsmokers. The anatomy of these networks was then assessed using DTI and CT analyses while microstructural architecture of WM was analyzed using the NODDI toolbox. Seed-based connectivity analysis revealed significantly enhanced within network [p = 0.001 FDR corrected] and between network functional coupling of the salience and R-frontoparietal networks in people who smoke [p = 0.004 FDR corrected]. The network connectivity was lateralized to the right hemisphere. Whole brain diffusion analysis revealed no significant differences between people who smoke and nonsmokers in Fractional Anisotropy, Mean diffusivity and in neurite orienting and density. There were also no significant differences in CT in the hubs of these networks. Our results demonstrate that tobacco cigarette smoking is associated with enhanced functional connectivity, but anatomy is largely intact in young adults. Whether this enhanced connectivity is pre-existing, transient or permanent is not known. The observed enhanced connectivity in resting state networks may contribute to the maintenance of smoking frequency.

A Comparative Study of Biomarker Levels for Iraqi Individuals’ Smokers and Non-Smokers Depending on the Duration of Smoking

Smoking is a widespread public health challenge globally, impacting societal health and economy while elevating the risk of cardiovascular and peripheral vascular diseases. This study aims to examine hematological parameters (HB, PCV%, WBC, RBC, PLT, ESR), liver and kidney function, lipid profile, and electrolytes (K+, Na+, Ca++) in male smokers aged 20-55 from Baghdad City, subdivided by smoking duration (≥5 years and &lt;5 years), compared to non-smoking controls. A total of sixty participants were recruited across three areas (Diyala Bridge, Mada'in, Talbieh), with each group comprising thirty individuals. Venipuncture was performed for blood sample collection. Results revealed statistically significant elevations in total WBC and RBC counts, hematocrit, hemoglobin, total cholesterol, and liver enzymes (GOT, GPT, ALP) among smokers compared to non-smokers (p&lt;0.05 or p&lt;0.001). Serum uric acid, urea, and creatinine levels were significantly higher in smokers (p&lt;0.001), while triglyceride levels showed no significant difference (p&gt;0.05) between groups. Smokers with longer duration (&gt;5 years) exhibited higher HB, triglyceride, and Na+ levels compared to shorter-term smokers. Sensitivity analysis indicated Na+ as a potentially effective biomarker for smoking-related health impacts, complementing PCV% and urea sensitivity. The study underscores the association between smoking and oxidative stress, notably reflected in elevated GOT and GPT levels, suggesting implications for antioxidant therapies in managing smoking-induced oxidative damage. These findings contribute novel insights into biomarker responses influenced by smoking duration and advocate for targeted public health strategies and further research into antioxidant interventions to mitigate smoking-associated health risks effectively.

Assessing the Consequences of Smoking Tobacco Products with Consideration of the Forced Oscillation Technique.

BACKGROUND The effects of cigarette smoking on the health of active smokers and passive smokers have long been known, in contrast to the effects of alternative forms of nicotine intake that are gaining popularity. The aim of the study was to assess the effects of smoking traditional cigarettes and alternative forms of nicotine intake on the functional state of the respiratory system of smokers and non-smokers. MATERIAL AND METHODS Study participants (n=60) were divided into 3 groups: non-smokers (control group), cigarette smokers, and nicotine alternative users. Respiratory function testing (spirometry), forced oscillation technique, and measurement of respiratory muscle strength (PImax, PEmax) were performed. All of the above respiratory function tests were performed in accordance with European Respiratory Society and American Thoracic Society recommendations. RESULTS Smokers and those using alternative forms of nicotine intake had significantly higher values, including resistance at 5 Hz% and 11 Hz%, among others. CONCLUSIONS Smokers and users of alternative forms of nicotine are characterized by reduced flow through the small bronchioles, as evidenced by a reduction in maximal expiratory flow at 25% of vital capacity. Smokers and users of alternative forms of nicotine have higher resistance values at the height of small and medium bronchioles. Assessment method of technical forced oscillation parameters is simple to perform to detect early airway changes and is an important element in the early diagnosis of changes in smokers. The correlation analysis showed a significant correlation between age of smoking initiation/use of alternative forms of nicotine and changes in mid bronchial resistance.

Potential role of serum copeptin among smoker T2DM patients with emphasis to ACE I/D gene polymorphism predicting DN

Diabetic nephropathy represents one of the main long-term complications in T2DM patients. Cigarette smoking represents one of modifiable renal risk factors to kidney damage due to lead (Pb) exposure in these patients. Our goal is to investigate serum copeptin and Kidney injury molecule-1 (KIM-1) and urinary lead (UPb) in type 2 diabetes mellitus (T2DM) patients even smokers and non-smokers groups and compared to corresponding health controls and assess its associations with Angiotensin-Converting enzyme Insertion/Deletion polymorphism [ACE (I/D)] polymorphism in diabetic nephropathy progression in those patients. In present study, 106 T2DM patients and 102 healthy control individuals were enrolled. Serum glucose, copeptin, KIM-1, total cholesterol (TChol), triglycerides (TG), estimated glomerular filtration rate (eGFR) and UPb levels and ACE (I/D) polymorphisms were assessed in both groups. Results mentioned to significant variations in all parameters compared to in T2DM group compared to control group. Serum copeptin and UPb demonstrated significant difference in diabetic smokers (DS) and diabetic non-smokers (DNS) groups while KIM-1 exhibited significant change between DNS and healthy control non-smokers (CNS) groups. Positive relation was recorded between serum glucose and KIM-1 while negative one was found between serum copeptin and TChol. D allele was associated with significant variation in most parameters in T2DM, especially insertion/deletion (ID) polymorphism. ROC curve analysis (AUC) for serum copeptin was 0.8, p < 0.044 and for Kim-1 was 0.54, p = 0.13 while for uPb was 0.71, p < 0.033. Serum copeptin and UPb might be a prognostic biomarker for renal function decline in smoker T2DM patients while KIM-1 was potent marker in non-smoker T2DM with association with D allele of ACE I/D gene polymorphism.

Chronic e-cigarette use in young adults is associated with reduced cardiopulmonary function at rest and during exercise

E-cigarette aerosols produce contaminant particles that have the potential to impair cardiopulmonary function. However, the current understanding of the impact of e-cigarette use on cardiopulmonary function remains inconclusive. Exercise represents a stress on the cardiopulmonary system and may help identify cardiopulmonary dysfunction in chronic e-cigarette users. Consequently, the purpose of this study was to investigate if e-cigarette users exhibit cardiopulmonary abnormalities under physiological stress of exercise. To further investigate pulmonary vascular responses, the secondary purpose of the study was to examine how diffusing capacity (DLCO), pulmonary capillary blood volume (VC), and membrane diffusing capacity (DM) respond to positional changes, as the transition from the upright to supine position should increase DLCO, VC, and DM, secondarily to increased perfusion pressure. We hypothesized that e-cigarette users would exhibit impaired cardiopulmonary function during exercise and reduced pulmonary vascular responsiveness to postural changes. Six chronic e-cigarette (e-cig) users (age: 24±5yrs, 5±2 years of e-cigarette use) with &lt;5 pack years of traditional cigarette smoking history and six non-smoking controls who were age-, height-, and sex-matched completed two experimental trials. Day 1: Pulmonary function test and cardiopulmonary exercise test. Day 2: multiple fraction of inspired oxygen DLCO technique to quantify DLCO, VC, and DM at rest in the upright and supine positions. Resting pulmonary function was not significantly different between groups. The change in DLCO from upright to supine was significantly lower in e-cig users compared to controls (Control: 7.61±2.32 ml/min/mmHg vs. E-cig: 3.17±2.09 ml/min/mmHg; p=0.01), due to a smaller change in VC ( p=0.03), which suggests reduced pulmonary vascular distention in e-cig users. V̇O2peak was significantly lower in e-cig users compared to controls (Control: 4.4±1.2 L/min vs. E-cig: 2.6 ±0.7 L/min; p=0.01). E-cig users exhibited significantly elevated V̇E/ V̇CO2nadir ( p=0.02) indicating worse ventilatory effciency, and greater dyspnea relative to power output ( p=0.02) compared to controls. Preliminary findings suggest that e-cigarette use is associated with normal resting lung function but reduced pulmonary vascular distensibility. Further, e-cigarette users demonstrate ventilatory ineffciency and greater exertional dyspnea along with exercise intolerance. Canadian Institutes of Health Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Upregulation of Notch Signaling and Cell-Differentiation Inhibitory Transcription Factors in Stable Chronic Obstructive Pulmonary Disease Patients.

Notch signaling is involved in the prevention of cell differentiation and cell fate in various organs, including the lungs. We aimed to determine the transcriptomic and protein expression of Notch receptors, their ligands, and related transcription factors in stable COPD. The expression and localization of Notch receptors, their ligands, and related transcription factors were measured in bronchial biopsies of individuals with stable mild/moderate (MCOPD) (n = 18) or severe/very severe (SCOPD) (n = 16) COPD, control smokers (CSs) (n = 13), and control nonsmokers (CNSs) (n = 11), and in the lung parenchyma of those with MCOPD (n = 13), CSs (n = 10), and CNSs (n = 10) using immunohistochemistry, ELISA tests, and transcriptome analyses. In the bronchial biopsies, Notch4 and HES7 significantly increased in the lamina propria of those with SCOPD compared to those with MCOPD, CSs, and CNSs. In the peripheral lung bronchiolar epithelium, Notch1 significantly increased in those with MCOPD and CSs compared to CNSs. ELISA tests of lung parenchyma homogenates showed significantly increased Notch2 in those with MCOPD compared to CSs and CNSs. Transcriptomic data in lung parenchyma showed increased DLL4 and HES1 mRNA levels in those with MCOPD and CSs compared to CNSs. These data show the increased expression of the Notch pathway in the lungs of those with stable COPD. These alterations may play a role in impairing the regenerative-reparative responses of diseased bronchioles and lung parenchyma.