non-COPD Smokers Research Articles

Clinical characteristics of chronic obstructive pulmonary disease according to smoking status.

COPD can be caused by various factors, including lung infections, asthma, air pollution, childhood growth disorders, and genetic factors, although smoking is a predominant risk factor. The main pathological mechanisms in COPD involve small airway disease, emphysema, mucus hypersecretion, and vascular disorders. COPD in non-smokers is characterized by normal FEV1 decline, equal distribution of sex, younger age of onset, fewer comorbidities, milder airflow obstruction, normal diffusing capacity of the lungs for carbon monoxide (DLCO) and radiological features such as more air-trapping and less severe emphysema, compared to COPD in smokers. COPD in non-smokers is still accompanied by a high prevalence of acute exacerbation almost equal to COPD in smokers. Moreover, COPD per se is an independent risk factor for the development of lung cancer, irrespective of smoking status. Considering that COPD coexists with numerous comorbidities, effective management of these comorbidities is essential, and multifaceted efforts are required for the comprehensive treatment of COPD.

The severity of non-smoking chronic obstructive pulmonary disease is correlated with biomass fuel exposure and COPD assessment test score.

Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

Evaluation of Salivary Biomarkers and Spirometry for Diagnosing COPD in Non-Smokers and Smokers of Polish Origin.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however, traditional diagnostic methods (based on spirometry) show limitations, prompting the search for predictive biomarkers and modern diagnostic techniques. This study explored the validation of COPD-related biomarkers (C-reactive protein, procalcitonin, neutrophil elastase, and alpha-1 antitrypsin) in saliva. A diverse cohort, including healthy non-smokers, healthy smokers, and COPD patients of Polish origin, underwent spirometry and marker analysis. The data correlated with clinical factors, revealing noteworthy relations. Firstly, salivary biomarker levels were compared with serum concentrations, demonstrating notable positive or negative correlations, depending on the factor. Further analysis within healthy individuals revealed associations between biomarker levels, spirometry, and clinical characteristics such as age, sex, and BMI. Next, COPD patients exhibited an enhanced concentration of biomarkers compared to healthy groups. Finally, the study introduced a breathing assessment survey, unveiling significant associations between self-perceived breathing and spirometric and tested parameters. Outcomes emphasized the relevance of subjective experiences in COPD research. In conclusion, this research underscored the potential of salivary biomarkers as diagnostic tools for COPD, offering a non-invasive and accessible alternative to traditional methods. The findings paved the way for improved modern diagnostic approaches.

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.

Prevalence of chronic obstructive pulmonary disease among non-smokers in rural areas of Lucknow district, Uttar Pradesh, India

Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive disease of the airways and lung parenchyma and the risk factors include both genetic and environmental factors. Tobacco smoking has remained the most important risk factor associated with it. The occurrence of COPD in non-smokers is not widely appreciated, even though its relative burden is higher in developing countries than developed countries. There is limited information on the risk factors associated with spirometrically confirmed COPD in non-smokers in the general population and more data from population-based studies are needed. Hence, the objective of this study was to determine the prevalence of COPD and associated risk factors among non-smokers in rural areas of Lucknow district, Uttar Pradesh, India. Methods: This cross-sectional study with multi-stage random sampling was conducted among 552 non-smoking participants aged 18 years and above in rural areas of Lucknow. It was conducted using pre-designed questionnaire for data collection. COPD assessments were done using a combination of clinical history and portable spirometry. Data collected was analysed using SPSS 23.0 version. Results: FEV1/FVC &lt;0.7 was used to define COPD which yielded a prevalence of 8.5 percent among non-smoking participants. Gender, occupation, type of family, presence of ex-smoker, presence of dampness and livestock in the house were the risk factors that showed statistically significant association with COPD. Conclusions: The higher prevalence noted in this study highlights the need for enhanced community-based screening programme for secondary prevention of COPD among adults.

Identification of AHNAK expression associated with the pathogenesis of chronic obstructive pulmonary disease by bioinformatic analysis.

Chronic obstructive pulmonary disease (COPD) was a risk factor for lung cancer tumorigenesis. This study aimed to discover novel diagnostic biomarkers for COPD patients and determine their underlying pathogenetic mechanisms. Differentially expressed genes (DEGs) in COPD samples and normal controls were analyzed and utilized to construct a network associated with a high risk for COPD occurrence. Enrichment analysis was applied on the strength of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The RT-qPCR analysis was performed to determine 10 hub genes in COPD. ELISA assay was utilized to measure IL-1β, IL-6, and IL-10 levels. Spearman's correlation analysis was conducted to detect the correlation between inflammatory cytokines and AHNAK expression. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry assays. AHNAK was significantly increased in COPD serum samples compared with non-COPD smokers and strongly correlated with inflammation. AHNAK level could also discriminate COPD from non-COPD with high accuracy. AHNAK may be a feasible biomarker playing crucial functions in the diagnosis and progression of COPD.

Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis.

Nonsmokers with chronic obstructive pulmonary disease (COPD) are neglected despite constituting half of all cases in studies from the developed world. Herein, we systematically reviewed the prevalence of COPD among nonsmokers in India. We searched Embase, Scopus, and PubMed databases for studies examining the prevalence of COPD among nonsmokers in India. We used the Joanna Briggs Institute (JBI) checklist to assess included studies' quality. Meta-analysis was performed using random-effects model. Seven studies comprising 6,903 subjects were included. The quality of the studies ranged from 5/9 to 8/9. The prevalence of COPD varied between 1.6 and 26.6 %. Studies differed considerably in demographics and biomass exposure profiles of subjects. Among the four studies that enrolled both middle-aged and elderly Indian nonsmokers not screened based on biomass fuel exposure, the pooled prevalence of COPD was 3 % (95 % CI, 2-3 %; I2=50.52 %, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10 % (95 % CI, 2-18 %; I2=98.8 %, p<0.001). Limited evidence suggests a sizable burden of COPD among nonsmokers and biomass fuel-exposed individuals in India. More epidemiological studies of COPD in nonsmokers are needed from low and middle-income countries.

Profiling of Microbial Landscape in Lung of Chronic Obstructive Pulmonary Disease Patients Using RNA Sequencing.

The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD. We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients. We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis. This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.

COPD in Non-Smokers in South Asia: An Under Estimated and Unrecognized Condition

COPD is an acronym used for chronic obstructive pulmonary disease. Globally, it is one of the leading causes of morbidity and mortality. It is among the significant causes of death in the developing countries of the world too. A major established causal risk factor for COPD is tobacco smoking.

Nucleic acid sensor STING drives remodeling and its inhibition enhances steroid responsiveness in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often associated with double-stranded DNA release which potentially activates DNA-sensing pathways, such as STING. This study, therefore, analyzed the role of STING pathway in inducing pulmonary inflammation, steroid resistance, and remodeling in COPD. Primary cultured lung fibroblasts were isolated from healthy non-smoker, healthy smoker, and smoker COPD individuals. The expression of STING pathway, remodeling, and steroid resistance signatures were investigated in these fibroblasts upon LPS stimulation and treatment with dexamethasone and/or STING inhibitor, at both mRNA and protein levels using qRT-PCR, western blot, and ELISA. At baseline, STING was elevated in healthy smoker fibroblasts and to a higher extent in smoker COPD fibroblasts when compared to healthy non-smoker fibroblasts. Upon using dexamethasone as monotherapy, STING activity was significantly inhibited in healthy non-smoker fibroblasts but showed resistance in COPD fibroblasts. Treating both healthy and COPD fibroblasts with STING inhibitor in combination with dexamethasone additively inhibited STING pathway in both groups. Moreover, STING stimulation triggered a significant increase in remodeling markers and a reduction in HDAC2 expression. Interestingly, treating COPD fibroblasts with the combination of STING inhibitor and dexamethasone alleviated remodeling and reversed steroid hyporesponsiveness through an upregulation of HDAC2. These findings support that STING pathway plays an important role in COPD pathogenesis, via inducing pulmonary inflammation, steroid resistance, and remodeling. This raises the possibility of using STING inhibitor as a potential therapeutic adjuvant in combination with common steroid treatment.

Identification of Molecular Markers Associated with COPD in non-smokers and smokers: A Bioinformatics Analysis

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) often associated with cigarette smoking. However, increasing evidence suggests that non-smoking COPD is much higher than previously thought. This study aims to identify a nonsmoking COPD biomarker and examined its value in diagnosis and prediction of acute exacerbation. A total of 35 stable COPD patients, 70 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients and 35 healthy control subjects were included. Plasma α 2 macroglobulin (A2M) and matrix metalloproteinase-9 (MMP-9) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method on all participants. Their association with clinical characteristics and lung function parameters were determined by regression analysis. Receiver operating characteristic (ROC) curve was used to determine the diagnostic sensitivity and specificity. Correlation coefficients were evaluated using Pearson's correlation. Plasma A2M concentration was decreased and MMP-9 concentration, MMP-9/A2M ratio were elevated in stable COPD patients compared with control groups. And MMP-9 expression was significantly higher in AECOPD patients. A2M level was increased in AECOPD patients with infection compared with those without. In addition, there was no statistical difference in A2M levels between smokers and nonsmokers COPD or healthy control subjects. Furthermore, A2M, MMP-9 and MMP-9/A2M were correlated with forced expiratory volume in one second (FEV1)%, FEV1/ forced vital capacity (FVC), CAT and mMRC score in COPD patients, but had no correlation with fraction of exhaled nitric oxide (FeNO) and concentration of alveolar nitric oxide (CaNO). A2M is altered in peripheral blood of COPD patients and correlated with severity and infection. Moreover, there was no significant correlation between the change in A2M and smoking, FeNO and CaNO, suggesting A2M may reflect the overall rather than local inflammation in COPD patients and serve as a potential biomarker for nonsmoking COPD patients.

Association of Respiratory Functional Indices and Smoking with Pleural Movement and Mean Lung Density Assessed Using Four-Dimensional Dynamic-Ventilation Computed Tomography in Smokers and Patients with COPD.

To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index. Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13-17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25-75% using Spearman's rank coefficients. MPMVND/D was highest in non-smokers (0.819±0.464), followed by non-COPD smokers (0.405±0.131) and patients with COPD (-0.219±0.900). GCRND/D in non-smokers (1.003±1.384) was higher than that in patients with COPD (-0.164±1.199). MLDCR in non-COPD smokers (0.105±0.028) was higher than that in patients with COPD (0.078±0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p<0.001), and FEF25-75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25-75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=-0.398, p=0.006). We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.

A comparative study of lung functions in non-smoker COPD patients from various localities with healthy subjects

Background &amp; Objectives: Chronic Obstructive Pulmonary Disease (COPD) is the illness with airflow obstruction caused by emphysema, chronic bronchitis, or a combination of both the disorders. It is the third leading cause of death worldwide. Between 20 and 40% of all COPD patients across the globe are never smokers. The primary objective of this study was to evaluate Pulmonary Function Tests (PFTs) in non-smoker COPD patients and compare their results with normal healthy subjects. The study also intended to check the variations in lung function of COPD patients living in urban &amp; rural areas.&#x0D; Materials &amp; Methods: The study was conducted by performing PFTs in 50 non-smoker COPD patients (28 from urban &amp; 22 from rural areas) &amp; comparing them with 50 non-smoker healthy subjects of same age group excluding ex-smokers. Various parameters of PFTs like FVC, FEV1, FEV1/FVC, PEFR &amp; MVV were assessed &amp; compared. For statistical data analysis unpaired t-Test was applied.&#x0D; Results: The mean values of PFT parameters such as FVC, FEV1, FEV1/FVC, PEFR &amp; MVV are very significantly differed between COPD patients &amp; healthy subjects (p&lt;0.01). Although the data is not statistically significant between total COPD patients, urban &amp; rural COPD patients, mean values of above PFT parameters are higher in total COPD patients than urban while higher in rural compared to total COPD patients (p&gt;0.05). The mean values of above PFT parameters are not significant statistically between urban &amp; rural COPD patients (p&gt;0.05).&#x0D; Conclusion: The study indicates that as compared to normal subjects, in patients of COPD there is great reduction in mean values for FVC, FEV1, PEFR, FEV1/FVC%, &amp; MVV irrespective of their residing location which is suggestive of an increase air way obstruction with reduced values of various PFT parameters. The study also shows that there is no significant difference in mean values of various parameters between urban &amp; rural areas.

ВЛИЯНИЕ КУРЕНИЯ НА ПОКАЗАТЕЛИ ОКИСИ УГЛЕРОДА И ОКСИДА АЗОТА В ВЫДЫХАЕМОМ ВОЗДУХЕ У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ

To date, points of view regarding the effect of smoking on the indicators of exhaled air are very contradictory, especially with regard to the examination of patients with chronic obstructive pulmonary disease (COPD) suffering from tobacco dependence. Basically, a comparative analysis is carried out by researchers solely on the fact of the presence of tobacco dependence, without taking into account the indicator of the smoking index (CI), as such, or the data obtained from the examination of smoking COPD patients and healthy volunteers are compared. Objective: to evaluate the change in the concentration of carbon monoxide (CO), nitric monoxide (NO) and carboxyhemoglobin (COHb) in the exhaled air of patients with COPD, depending on the status of smoking and CI. Material and research methods. 96 patients with COPD were examined, the average age of which was 54.6±5.9 years, the duration of the disease was 15±4.8 years. 70 patients (72.9%) who participated in the study suffered from tobacco dependence, while CI ≤10 pack-year was observed in 2.8% of them, 11-20 pack-year in 42.9%, 21-30 pack-year in 40.0% and &gt;30 pack-year in 14.3%. As part of a comprehensive examination, all patients underwent determination of CO (ppm) and COHb (%) in exhaled air using the MicroCO device (Micro medica, UK) and the level of NO was assessed using the Niox Mino analyzer (Aerocline, Sweden). The results of the study. During the analysis of the obtained data, we noted an increase in the average concentration of CO in the exhaled air in all smoking patients, while the increase in the indicator was directly proportional to the CI. A similar picture was observed with respect to the COHb level. The concentration of NO in the exhaled air, on the contrary, showed a tendency to decrease with increasing CI. A comparative analysis of the obtained data was carried out in three groups: I - non-smoking patients with COPD (n=26), II - patients with COPD with an IC of 11-20 pack-years (n=30) and III – patients with COPD with an IC of 21-30 pack-years (n=28). In terms of peripheral blood saturation, significant differences compared with the group of non-smokers were found in patients with IC 11-20 pack-years and with IC 21-30 pack-years, while there were no statistically significant differences between these groups of smoking patients. The CO level in smokers, regardless of CI, was significantly higher than in non-smokers, while in COPD patients with CI 21-30 pack-year it was also significantly higher than in patients with CI 11-20 pack-year. The COHb index in smokers with COPD was also significantly higher than in non-smokers, but when comparing data in the group with IC 11-20 pack-years and IC 21-30 pack/years, no statistically significant differences were found. In terms of NO in exhaled air, statistically significant differences were noted when comparing data in the group of non-smoking patients with COPD with the results obtained in groups of patients with IC 11-20 pack-years and with IC 21-30 pack-years, as well as when comparing data in these groups of smokers among themselves. Conclusions. The study revealed a statistically significant increase in the level of CO in the exhaled air, depending on the status of smoking and CI. It was determined that the smoking factor in COPD patients affects the level of NO in the exhaled air, causing its significant decrease in COPD patients with CI &gt;10 pack-year compared to non-smoking COPD patients.

Chronic Obstructive Pulmonary Disease among non-Smokers

Since tobacco use has been linked to COPD for more than 50 years, this population has served as the foundation for almost all of our knowledge regarding the clinical, physiological, pathological, and radiological aspects of the disease as well as the rates of lung function loss and the effectiveness of various treatments. We stated in 1990 that 25 to 45% of COPD cases among never smokers. According to the 2017 Global Burden of Disease report, smoking is only responsible for 35% of the burden of COPD worldwide, with the majority of cases occurring in high-income nations. Most of the world's remaining 65% of nonsmokers with COPD live in low- and middle-income nations. Other non-smoking risk factors for COPD include exposure to biomass smoke while cooking in poorly ventilated homes, high ambient air pollution levels, occupational exposures to dust and gases, ambient ozone exposure, poverty, recurrent respiratory tract infections in childhood, poorly controlled chronic persistent asthma, and prior tubercular lung disease. Worldwide, non-tobacco-related risk factors, which vary by geographic region, are to blame for around half of all instances of COPD. Inflammation, oxidative stress, airway remodelling, and accelerated lung ageing are potential factors for the development of COPD in never-smokers. Never-smokers with COPD had less severe chronic respiratory symptoms, little to no emphysema, less airflow limitation, and fewer comorbidities than smokers who acquire COPD; however, exacerbations can still happen often. More research- including epidemiological, translational, clinical, and implementation studies- is required to fill in knowledge gaps and promote viable solutions to lessen the burden of COPD in never-smokers. Clinical history and spirometry can be used to diagnose Chronic Obstructive Pulmonary Disease (COPD), but identifying its risk factors is time-consuming and crucial because doing so can stop the disease's progression. Contrary to popular belief, smoking cigarettes is only one of the numerous risk factors for COPD. We have examined the etiology of nonsmoker COPD through this review in an effort to identify the causative risk factor and reduce the disease's morbidity and mortality.

MicroRNA-101-3p Suppresses mTOR and Causes Mitochondrial Fragmentation and Cell Degeneration in COPD

Cigarette smoke is assumed to cause the loss of airway wall structure in chronic obstructive pulmonary disease (COPD) by reducing airway smooth muscle cell (ASMC) function. It also modifies mTOR activity, microRNA (miR)-101-3p expression, and mitochondria function. Here, the link between miR-101-3p and mTOR-regulated mitochondria integrity and ASMC deterioration was assessed. Disease-specific miR-101-3p expression was determined by RT-PCR in primary ASMC (non-COPD smokers: n = 6; COPD: n = 8; healthy: n = 6). The regulatory effect of miR-101-3p modification on mTOR expression, mitochondrial fragmentation, and remodeling properties (α-SMA, fibronectin, MTCO2, and p70S6 kinase) was assessed in ASMC (healthy nonsmokers: n = 3; COPD: n = 3) by Western blotting and immunofluorescence microscopy. MiR-101-3p was modified by specific mimics or inhibitors, in ASMC stimulated with TNF-α (10 ng/ml) or cigarette smoke extract (CSE). MiR-101-3p expression was significantly higher in ASMC of COPD patients, compared to ASMC of healthy or active smokers. MiR-101-3p expression was increased by TNF-α or CSE. TNF-α or miR-101-3p deteriorated ASMC and mitochondria, while decreasing mTOR signaling, α-SMA, fibronectin, and MTCO2. MiR-101-3p inhibition reduced ASMC deterioration and mitochondrial fragmentation. Constitutive high miR-101-3p expression characterizes COPD-ASMC, causing increased mitochondrial fragmentation and ASMC deterioration. Thus, reactivation mTOR or blocking miR-101-3p presents a potential new strategy for COPD therapy.

The Role of Chitinases in Chronic Airway Inflammation Associated with Tobacco Smoke Exposure

Chitinases and chitinase-like proteins are thought to play a role in innate inflammatory responses. Our study aimed to assess whether chitinase concentration and activity in induced sputum (IS) of patients exposed to tobacco smoke are related to the level of airway inflammation including the level and activity of chitinases and chitinase-like proteins. The study included 22 patients with chronic obstructive pulmonary disease (COPD), 12 non-COPD smokers, and nine nonsmoking subjects. Sputum CHIT1 and YKL-40 levels and chitinolytic activity were compared with sputum IL-6, IL-8, IL-18, and MMP-9 levels. A hierarchical cluster analysis was also performed. Sputum YKL-40 was higher in COPD patients than in the control groups. Sputum CHIT1 and YKL-40 levels correlated with IS inflammatory cell count as well as with MMP-9 and IL-8 levels. Two main clusters were revealed: Cluster 1 had lower chitinase levels and activity, lower IS macrophage and neutrophil count, and lower IS IL-8, IL-18, and MMP-9 than Cluster 2. Comparison of COPD patients from both clusters revealed significant differences in the IS inflammatory profile despite comparable clinical and functional data. Our findings seem to confirm the involvement of chitinases in smoking-associated chronic airway inflammation and show that airway chitinases may be a potential novel marker in COPD phenotyping.

Increased risk of open-angle glaucoma in non-smoking women with obstructive pattern of spirometric tests

To investigate differences in the prevalence of open-angle glaucoma (OAG) between different pulmonary function types. A population-based, cross-sectional analysis was conducted using Korean National Health and Nutrition Examination Surveys from 2008 to 2011. A total of 8941 subjects ≥ 40 years of age were analyzed. Chronic obstructive pulmonary disease (COPD) was defined as the ratio between first second of forced expiration (FEV1) and forced vital capacity (FVC) below 70%. The prevalence of glaucoma, as defined by the International Society of Geographical and Epidemiological Ophthalmology, was the main outcome. OAG was more prevalent in women with COPD (8.0% vs. 4.8% normal, P = 0.001) compared to women with normal pulmonary function. Intraocular pressure (IOP) of women with COPD were 13.3 (0.2) mmHg (13.9 (0.1) mmHg for normal function, P = 0.182). Never-smokers were more prevalent in women with COPD and glaucoma (92.9% vs. 52.4% normal function; P < 0.001). COPD was found to increase the risk of glaucoma in women (OR 2.077, P = 0.017) and even further in non-smoking women (OR 2.711, P = 0.003). Women with COPD showed a higher glaucoma prevalence despite similar IOP in comparison to women with normal pulmonary function. Non-smoking COPD is significantly associated with open-angle glaucoma in women.

Prediction of COPD acute exacerbation in response to air pollution using exosomal circRNA profile and Machine learning.

Ambient fine particulate matter (PM2.5) is linked to an increased risk of chronic obstructive pulmonary disease (COPD) exacerbations, which significantly increase the risk of mortality in COPD patients. Identifying the subtype of COPD patients who are sensitive to environmental aggressions is necessary. Using in vitro and in vivo PM2.5 exposure models, we demonstrate that exosomal hsa_circ_0005045 is upregulated by PM2.5 and binds to the protein cargo peroxiredoxin2, which functionally aggravates hallmarks of COPD by recruiting neutrophil elastase and triggering in situ release of tumor necrosis factor (TNF)-α by inflammatory cells. The biological function of hsa_circ_0005045 associated with aggravation of COPD is validated using exosome-transplantation and conditional circRNA-knockdown murine models. By sorting the major components of PM2.5, we find that PM2.5-bound heavy metals, which are distinguishable from the components of cigarette smoke, trigger the elevation of exosomal hsa_circ_0005045. Finally, using machine learning models in a cohort with 327 COPD patients, the PM2.5 exposure-sensitive COPD patients are characterized by relatively high hsa_circ_0005045 expression, non-smoking, and group C (mMRC 0-1 (or CAT<10) and≥2 exacerbations (or≥1 exacerbation leading to hospital admission) in the past year). Thus, our results suggest that environmental reduction in PM2.5 emission provides a targeted approach to protecting non-smoking COPD patients against air pollution-related disease exacerbation.