ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19

AbstractIntroductionCoronavirus disease 2019 (COVID-19) is a respiratory infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus uses the angiotensin converting enzyme II (ACE-2) as the cellular entry receptor to infect the lower respiratory tract. Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID-19, we determined whether ACE-2 expression in the lower airways was related to COPD and cigarette smoking.MethodsUsing RNA-seq, we determined gene expression levels in bronchial epithelia obtained from cytologic brushings of 6th to 8th generation airways in individuals with and without COPD. We eternally validated these results from two additional independent cohorts, which used microarray technologies to measure gene expression levels from 6th to 12th generation airways.ResultsIn the discovery cohort (n=42 participants), we found that ACE-2 expression levels were increased by 48% in the airways of COPD compared with non-COPD subjects (COPD=2.52±0.66 log2 counts per million reads (CPM) versus non-COPD= 1.70±0.51 CPM, p=7.62×10−4). There was a significant inverse relationship between ACE-2 gene expression and FEV1% of predicted (r=-0.24; p=0.035). Current smoking also significantly increased ACE-2 expression levels compared with never smokers (never current smokers=2.77±0.91 CPM versus smokers=1.78±0.39 CPM, p=0.024). These findings were replicated in the two eternal cohorts.ConclusionsACE-2 expression in lower airways is increased in patients with COPD and with current smoking. These data suggest that these two subgroups are at increased risk of serious COVID-19 infection and highlight the importance of smoking cessation in reducing the risk.

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Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease

Scientific Reports ◽

10.1038/s41598-021-01950-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

J. M. Kiszałkiewicz ◽

S. Majewski ◽

W. J. Piotrowski ◽

P. Górski ◽

D. Pastuszak-Lewandoska ◽

...

Keyword(s):

Gene Expression ◽

Mirna Expression ◽

Induced Sputum ◽

Control Group ◽

Chronic Obstructive ◽

Expression Levels ◽

Stat3 Pathway ◽

Copd Patients ◽

Mirna 106B ◽

Gene Expression Levels

AbstractCOPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miRNA-1, miRNA-106b, miRNA-155, in patients with COPD. Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2021 (A–D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. In induced sputum IL6 was significantly down-regulated in COPD group compared with control (p = 0.0008), while IL6ST were up-regulated (p = 0.05). The results were also statistically significant for STAT3 (p = 0.04) and miRNA-155 (p = 0.03) with higher expression in the current smokers compared to ex-smokers. Higher expression levels for IL6ST (p = 0.03) in COPD patients with the exacerbation history compared to COPD patients without the exacerbation history were noted. Compared induced sputum and PB lymphocytes we observed higher expression of IL6 (p = 0.0003), STAT3 (p = 0.000001) miRNA-106b (p = 0.000069 and miRNA-155 (p = 0.000016) in induced sputum with lower expression of PIAS3 (p = 0.006), IL6ST (p = 0.002) and miRNA-1 (p = 0.001). Differences in gene expression levels of the IL-6/IL6ST/STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

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Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-98749-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Donato Lacedonia ◽

Giulia Scioscia ◽

Carla Santomasi ◽

Paolo Fuso ◽

Giovanna Elisiana Carpagnano ◽

...

Keyword(s):

Clinical Course ◽

Current Data ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Increased Risk ◽

All Cause Mortality ◽

Former Smokers ◽

Never Smokers ◽

The Impact

AbstractThe prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

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Clinical and functional peculiarities at patients with bronchial asthma, chronic obstructive pulmonary disease and overlap of asthma-chronic obstructive pulmonary disease

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2020-24-4-80-86 ◽

2020 ◽

Vol 24 (4) ◽

pp. 80-86

Author(s):

V. I. Trofimov ◽

D. Z. Baranov

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Bronchial Asthma ◽

Blood Test ◽

Chronic Obstructive ◽

Inflammation Markers ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Functional Features ◽

Lower Airways

BACKGROUND: a comparative analysis of laboratory and instrumental tests at patients with bronchial obstructive diseases seems very actual due to the wide prevalence of these diseases. THE AIM: to evaluate characteristics of spirometry as well as allergic (total IgE, sputum eosinophils) and infectious (blood and sputum leucocytes, ESR, CRP, fibrinogen) inflammation markers at patients with bronchial obstructive diseases. PATIENTS AND METHODS: 104 case histories of patients with bronchial asthma, chronic obstructive pulmonary disease and overlap were analyzed including age, duration of smoking (pack-years), laboratory (clinical blood test, biochemical blood test, general sputum analysis, sputum culture) and instrumental (spirometry, body plethysmography, echocardiography) tests. Data were processed statistically with non-parametric methods. RESULTS: COPD patients were older than other groups’ patients, had the highest pack-years index. ACO patients were marked with maximal TLC and Raw, minimal FEV1, FEF25-75, FEV1/FVC. Patients with COPD had the highest inflammation markers (leucocyte count, CRP, fibrinogen). CONCLUSION: high active inflammation may cause severe lower airways possibility disorders at patients with COPD. Data related to a possible role of K. pneumoniaе in the pathogenesis of eosinophilic inflammation in lower airways are of significant interest. Patients with ACO occupy an intermediate position between asthma and COPD patients based on clinical and functional features.

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LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01579-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaoman Zhou ◽

Yunjun Zhang ◽

Yutian Zhang ◽

Quanni Li ◽

Mei Lin ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Genetic Polymorphisms ◽

Chronic Obstructive ◽

Nucleotide Polymorphisms ◽

Obstructive Pulmonary Disease ◽

Logistic Analysis ◽

Copd Patients ◽

Increased Risk ◽

And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

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Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Human Molecular Genetics ◽

10.1093/hmg/ddz067 ◽

2019 ◽

Vol 28 (15) ◽

pp. 2477-2485 ◽

Cited By ~ 1

Author(s):

Diana A van der Plaat ◽

Judith M Vonk ◽

Natalie Terzikhan ◽

Kim de Jong ◽

Maaike de Vries ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Occupational Exposure ◽

Health Effects ◽

Mineral Dust ◽

Occupational Exposures ◽

Expression Levels ◽

Adverse Health Effects ◽

Never Smokers ◽

Gene Expression Levels

Abstract Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.

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Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease

Journal of Applied Physiology ◽

10.1152/japplphysiol.00577.2006 ◽

2007 ◽

Vol 102 (5) ◽

pp. 1976-1984 ◽

Cited By ~ 29

Author(s):

Shlomit Radom-Aizik ◽

Naftali Kaminski ◽

Shlomo Hayek ◽

Hillel Halkin ◽

Dan M. Cooper ◽

...

Keyword(s):

Gene Expression ◽

Chronic Obstructive Pulmonary Disease ◽

Exercise Training ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Muscle Gene Expression ◽

Copd Patients ◽

Before And After ◽

Ubiquitin Proteasome ◽

Muscle Gene

Exercise capacity and training response are limited in chronic obstructive pulmonary disease (COPD), but the extent to which this is related to altered skeletal muscle function is not fully understood. To test the hypothesis that muscle gene expression is altered in COPD, we performed needle biopsies from the vastus lateralis of six COPD patients and five sedentary age-matched healthy men, before and after 3 mo of exercise training. RNA was hybridized to Affymetrix U133A Genechip arrays. In addition, peak O2 uptake and other functional parameters (e.g., 6-min walk) were measured before and after training. The 6-min walk test increased significantly following training in both groups (53.6 ± 18.6 m in controls, P = 0.045; 37.1 ± 6.7 m in COPD, P = 0.002), but peak O2 uptake increased only in controls (19.4 ± 4.5%, P = 0.011). Training significantly altered muscle gene expression in both groups, but the number of affected genes was lower in the COPD patients (231) compared with controls (573). Genes related to energy pathways had higher expression in trained controls. In contrast, oxidative stress, ubiquitin proteasome, and COX gene pathways had higher expression in trained COPD patients, and some genes (e.g., COX11, COX15, and MAPK-9) were upregulated by training only in COPD patients. We conclude that both COPD and control subjects demonstrated functional responses to training but with somewhat different patterns in muscle gene expression. The pathways that are uniquely induced by exercise in COPD (e.g., ubiquitin proteasome and COX) might indicate a greater degree of tissue stress (perhaps by altered O2 and CO2 dynamics) than in controls.

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Chronic obstructive pulmonary disease and rheumatic diseases: A systematic review on a neglected comorbidity

Journal of Comorbidity ◽

10.1177/2235042x18820209 ◽

2019 ◽

Vol 9 ◽

pp. 2235042X1882020 ◽

Cited By ~ 3

Author(s):

Irini Gergianaki ◽

Ioanna Tsiligianni

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Primary Sjögren Syndrome ◽

Copd Patients ◽

Increased Risk ◽

Health Quality

Background: Although, both chronic obstructive pulmonary disease (COPD) and rheumatic diseases (RDs) are common, and each has significant impact on patients’ overall health/quality of life, their co-occurrence has received little attention, while 15% of COPD remains undiagnosed in RDs. Objective: To update the information regarding the comorbid state of RD/COPD (prevalence, incidence), to examine whether patients with RD have increased risk of developing COPD and vice versa, and what implications this comorbidity has on patients’ outcomes (mortality, hospitalizations, exacerbations). Methods: We performed a systematic literature review regarding the comorbidity of an RD (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), primary Sjogren syndrome disease (pSS), and systemic sclerosis (SSc)) with COPD. From 2803 reports retrieved, 33 articles were further screened. Finally, 27 articles were included. Results: Robust evidence supports that COPD develops up to 68% more frequently in patients with RA, as compared to the general population. Similarly, COPD is increased in every other RD that was studied. Further, self-referred arthritis is more common in COPD patients versus non-COPD controls and a predictor of worst self-rated health status. Patients with inflammatory arthritis/COPD have increased mortality (threefold in RA-COPD, irrespectively of which is first diagnosed), hospitalizations, and emergency visits. Conclusion: COPD is more common in patients with RA, AS, PsA, SLE, pSS, and SSc; yet, the association, vice versa, warrants further investigation. Nevertheless, COPD/RDs coexistence has significant prognostic value for worst outcomes; therefore, awareness is required to track early identification, especially in primary care.

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Increased respiratory symptoms in COPD patients living in the vicinity of livestock farms

European Respiratory Journal ◽

10.1183/13993003.00265-2015 ◽

2015 ◽

Vol 46 (6) ◽

pp. 1605-1614 ◽

Cited By ~ 47

Author(s):

Floor Borlée ◽

C. Joris Yzermans ◽

Christel E. van Dijk ◽

Dick Heederik ◽

Lidwien A.M. Smit

Keyword(s):

Respiratory Symptoms ◽

Respiratory Health ◽

Personal Characteristics ◽

Chronic Obstructive ◽

Livestock Farming ◽

Obstructive Pulmonary Disease ◽

Livestock Farm ◽

Copd Patients ◽

Increased Risk ◽

Livestock Farms

Several studies have investigated the effect of livestock farm emissions on the respiratory health of local residents, but results are inconsistent. This study aims to explore associations between the presence of livestock farms and respiratory health in an area of high-density livestock farming in the Netherlands. We focused especially on associations between farm exposures and respiratory symptoms within subgroups of potentially susceptible patients with a pre-existing lung disease.In total, 14 875 adults (response rate 53.4%) completed a questionnaire concerning respiratory health, smoking habits and personal characteristics. Different indicators of livestock farm exposures relative to the home address were computed using a geographic information system.Prevalence of chronic obstructive pulmonary disease (COPD) and asthma was lower among residents living within 100 m of a farm (OR 0.47, 95% CI 0.24–0.91 and OR 0.65, 95% CI 0.45–0.93, respectively). However, >11 farms in 1000 m compared to fewer than four farms in 1000 m (fourth quartileversusfirst quartile) was associated with wheezing among COPD patients (OR 1.71, 95% CI 1.01–2.89). Using general practitioners' electronic medical records, we demonstrated that selection bias did not affect the observed associations.Our data suggest a protective effect of livestock farm emissions on the respiratory health of residents. Nonetheless, COPD patients living near livestock farms reported more respiratory symptoms, suggesting an increased risk of exacerbations.

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Differential Genomic Profile in TERT, DSP, and FAM13A Between COPD Patients With Emphysema, IPF, and CPFE Syndrome

Frontiers in Medicine ◽

10.3389/fmed.2021.725144 ◽

2021 ◽

Vol 8 ◽

Author(s):

Javier Guzmán-Vargas ◽

Enrique Ambrocio-Ortiz ◽

Gloria Pérez-Rubio ◽

Marco Antonio Ponce-Gallegos ◽

Rafael de Jesus Hernández-Zenteno ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Association Studies ◽

Genetic Association Studies ◽

Simultaneous Presentation ◽

Chronic Obstructive ◽

Nucleotide Polymorphisms ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Increased Risk ◽

Comparison Groups

Background: Genetic association studies have identified single nucleotide polymorphisms (SNPs) associated with lasting lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF), as well as the simultaneous presentation, known as Combined Pulmonary Fibrosis and Emphysema (CPFE) Syndrome. It is unknown if these diseases share genetic variants previously described in an independent way. This study aims to identify common or differential variants between COPD, IPF, and CPFE.Materials and methods: The association analysis was carried out through a case-control design in a Mexican mestizo population (n = 828); three patients' groups were included: COPD smokers (COPD-S, n = 178), IPF patients (n = 93), and CPFE patients (n = 16). Also, two comparison groups were analyzed: smokers without COPD (SWOC, n = 367) and healthy subjects belonging to the Mexican Pulmonary Aging Cohort (PAC, n = 174). Five SNPs in four genes previously associated to interstitial and obstructive diseases were selected: rs2609255 (FAM13A), rs2736100 (TERT), rs2076295 (DSP) rs5743890, and rs111521887 (TOLLIP). Genotyping was performed by qPCR using predesigned Taqman probes.Results: In comparing IPF vs. PAC, significant differences were found in the frequency of the rs260955 G allele associated with the IPF risk (OR = 1.68, p = 0.01). Also, the genotypes, GG of rs260955 (OR = 2.86, p = 0.01) and TT of rs2076295 (OR = 1.79, p = 0.03) were associated with an increased risk of IPF; after adjusting by covariables, only the rs260955 G allele remain significant (p = 0.01). For the CPFE vs. PAC comparison, an increased CPFE risk was identified since there is a difference in the rs2736100 C allele (OR = 4.02, p < 0.01; adjusted p < 0.01). For COPD-S, the rs2609255 TG genotype was associated with increased COPD risk after adjusting by covariables.Conclusion: The rs2736100 C allele is associated with decreased IPF risk and confers an increased risk for CPFE. Also, the rs2076295 TT genotype is associated with increased IPF risk, while the GG genotype is associated with CFPE susceptibility. The rs2609255 G allele and GG genotype are associated with IPF susceptibility, while the TG genotype is present in patients with emphysema.

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Influence of Insulin-Like Growth Factor 1 Gene Expression in Women with Breast Cancer: A Systematic Review

10.21203/rs.3.rs-69892/v1 ◽

2020 ◽

Author(s):

Danylo Rafhael Costa-Silva ◽

Francisco Adelton Alves-Ribeiro ◽

Maria da Conceição Barros-Oliveira ◽

Larysse Cardoso Campos-Verdes ◽

Renato de Oliveira Pereira ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Systematic Review ◽

Growth Factor ◽

Expression Patterns ◽

Insulin Like Growth Factor ◽

Expression Levels ◽

Cancer Support ◽

Increased Risk ◽

Gene Expression Levels

Abstract Background: Breast cancer, the leading cause of cancer death among women worldwide, one of the major risk factors for breast cancer is genetic changes. Changes in the expression levels of the insulin-like growth factor 1 (IGF-1) gene have been associated with increased risk and aggressiveness of breast cancer. The IGF-1 gene encodes the IGF-1 peptide that is present in most human tissues, as in the normal and neoplastic mammary gland. Here, we conducted a systematic review to investigate the influence of IGF-1 gene expression levels in women with breast cancer.Methods: PubMed, Scopus, and Web of Science databases were searched for relevant studies published between February 2 and May 15, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find association between IGF-1gene expression and breast cancer.Results: A growing number of studies in women with breast cancer support, with controversial results, the influence of IGF-1 gene expression levels on clinical-pathological factors, disease-free survival, overall survival, and resistance to tamoxifen.Conclusions: Therefore, the elucidation of IGF-1 gene expression patterns through further studies may enable the characterization of women at high risk for breast cancer, as well as the development of effective prognostic and therapeutic strategies.

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