scholarly journals Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking

2019 ◽  
Author(s):  
Chen Xi Yang ◽  
Henry Shi ◽  
Irving Ding ◽  
Cheng Wei Tony Yang ◽  
Edward Kyoo-Hoon Kim ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Epidemiological Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Increased Risk ◽  
Former Smokers

ABSTRACTEpidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females at baseline and in response to smoking. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n=68; current smokers n=143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules’ level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic COPD risk and presentation potentially enabling a precision medicine approach to COPD.

scholarly journals Widespread Sexual Dimorphism in the Transcriptome of Human Airway Epithelium in Response to Smoking

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chen Xi Yang ◽  
Henry Shi ◽  
Irving Ding ◽  
Stephen Milne ◽  
Ana I. Hernandez Cordero ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Epidemiological Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Increased Risk ◽  
Former Smokers

AbstractEpidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females, as well the sex-by-smoking interaction. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n = 68; current smokers n = 143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules’ level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic effect of smoking, potentially enabling a precision medicine approach to smoking related lung diseases.

scholarly journals Peripheral blood microbial signatures in current and former smokers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jarrett D. Morrow ◽  
Peter J. Castaldi ◽  
Robert P. Chase ◽  
Jeong H. Yun ◽  
Sool Lee ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Interaction Analysis ◽  
Smoking Status ◽  
Meta Analysis ◽  
Human Microbiome ◽  
Independent Set ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Dyspnea Score ◽  
Former Smokers

AbstractThe human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.

scholarly journals Fibronectin-Binding Proteins of Staphylococcus aureus Are Involved in Adherence to Human Airway Epithelium

2002 ◽  
Vol 70 (2) ◽  
pp. 620-630 ◽  
Author(s):  
Emmanuel Mongodin ◽  
Odile Bajolet ◽  
Jérôme Cutrona ◽  
Noël Bonnet ◽  
Florence Dupuit ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Airway Epithelium ◽  
Molecular Mechanisms ◽  
Binding Capacity ◽  
Primary Cultures ◽  
Xenograft Model ◽  
Airway Epithelial Cells ◽  
Regulatory Pathways ◽  
Human Airway ◽  
Human Airway Epithelium

ABSTRACT This study was designed to investigate the molecular mechanisms of Staphylococcus aureus adherence to human airway epithelium. Using a humanized bronchial xenograft model in the nude mouse and primary cultures of human airway epithelial cells (HAEC), we showed that S. aureus adhered mainly to undifferentiated HAEC whereas weak adherence (11- to 20-fold lower) to differentiated HAEC was observed (P < 0.01). A fibronectin (FN)-binding protein (FnBP)-deficient strain of S. aureus had a fivefold-lower adherence level to undifferentiated HAEC than did the parental strain (P < 0.005), suggesting that S. aureus FN-binding capacity is involved in the adherence to HAEC. We also showed that 97% of 32 S. aureus clinical strains, isolated from the airway secretions of cystic fibrosis patients (n = 18) and patients with nosocomial pneumonia (n = 14), possessed the two fnb genes. The strains from pneumonia patients had a significantly (P < 0.05) higher FN-binding capacity than did the strains from CF patients. This result was confirmed by the expression of FnBPs, investigated by Western ligand affinity blotting. Our results suggest a major role of FnBPs in the colonization of the airways by S. aureus and point to the importance of the adhesin regulatory pathways in the staphylococcal infectious process.

scholarly journals Glucocorticoids Elevate Pseudomonas aeruginosa Binding to Airway Epithelium by Upregulating Syndecan-1 Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Dong Liu ◽  
Ying-Ying Zeng ◽  
Meng-Meng Shi ◽  
Jie-Ming Qu
Keyword(s):  
Airway Epithelium ◽  
Inhaled Corticosteroids ◽  
Glycogen Synthase ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Enhancer Binding Protein ◽  
Increased Risk ◽  
Gsk 3Β

Glucocorticoids are commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids are associated with a significantly increased risk of pneumonia. Syndecan-1 (SDC1) located in the cell membrane of airway epithelial cell is the crucial molecule mediating infections by P. aeruginosa (PA). In the present study, we found that SDC1 expression was upregulated and the adhesion of PA to human bronchial epithelial (HBE) cells increased to 125 and 138%, respectively, after stimulation by dexamethasone or budesonide. The HBE cells knocking down SDC1 showed lower affinity to PA compared with control. CCAAT-enhancer-binding protein β (C/EBP β) and its phosphorylated form participated in the regulation of glucocorticoid to SDC1 for interfering C/EBP β or inhibiting phosphorylation of C/EBP β by LiCl and BIO, which are inhibitors of glycogen synthase kinase 3β (GSK-3β), and could prevent glucocorticoids from upregulating SDC1 expression. One should be cautious in administering glucocorticoids in chronic lung disease because of their property of increasing the expression of SDC1 and PA binding to the airway epithelium.

scholarly journals Lung Function Impairment and the Risk of Incident Dementia: The Rotterdam Study

2021 ◽  
pp. 1-10
Author(s):  
Tian Xiao ◽  
Sara R.A. Wijnant ◽  
Silvan Licher ◽  
Natalie Terzikhan ◽  
Lies Lahousse ◽  
...  
Keyword(s):  
Lung Function ◽  
Sex Education ◽  
Smoking Status ◽  
Apoe Genotype ◽  
Chronic Obstructive ◽  
Rotterdam Study ◽  
Obstructive Pulmonary Disease ◽  
Incident Dementia ◽  
Increased Risk ◽  
Impaired Lung Function

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia. Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia. Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 <  80%) and in participants with COPD (FEV1/FVC <  0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80%). Hazard ratios (HRs) with 95%confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype. Results: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95%CI, 1.53–4.75; adjusted HRCOPD 1.03; 95%CI, 0.61–1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC%predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95%CI, 1.31–3.98), as well as Alzheimer’s disease (AD; adjusted HR 2.13; 95%CI, 1.13–4.02). Conclusion: Participants with PRISm or a low FVC%predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC%predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.

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

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.

scholarly journals Anemia, sarcopenia, physical activity, and the risk of tuberculosis in the older population: a nationwide cohort study

2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Jung Eun Yoo ◽  
Dahye Kim ◽  
Hayoung Choi ◽  
Young Ae Kang ◽  
Kyungdo Han ◽  
...  
Keyword(s):  
Physical Activity ◽  
Screening Program ◽  
Chronic Obstructive ◽  
Older Population ◽  
Timed Up And Go ◽  
Obstructive Pulmonary Disease ◽  
Mild Anemia ◽  
Increased Risk ◽  
Male Sex

Background: The aim of this study was to investigate whether physical activity, sarcopenia, and anemia are associated an with increased risk of tuberculosis (TB) among the older population. Methods: We included 1,245,640 66-year-old subjects who participated in the National Screening Program for Transitional Ages for Koreans from 2009 to 2014. At baseline, we assessed common health problems in the older population, including anemia and sarcopenia. The subjects’ performance in the timed up-and-go (TUG) test was used to predict sarcopenia. The incidence of TB was determined using claims data from the National Health Insurance Service database. Results: The median follow-up duration was 6.4 years. There was a significant association between the severity of anemia and TB incidence, with an adjusted hazard ratio (aHR) of 1.28 [95% confidence interval (CI), 1.20–1.36] for mild anemia and 1.69 (95% CI, 1.51–1.88) for moderate to severe anemia. Compared with those who had normal TUG times, participants with slow TUG times (⩾15 s) had a significantly increased risk of TB (aHR 1.19, 95% CI, 1.07–1.33). On the other hand, both irregular (aHR 0.88, 95% CI 0.83–0.93) and regular (aHR 0.84, 95% CI, 0.78–0.92) physical activity reduced the risk of TB. Male sex, lower income, alcohol consumption, smoking, diabetes, and asthma/chronic obstructive pulmonary disease increased the risk of TB. Conclusion: The risk of TB among older adults increased with worsening anemia, sarcopenia, and physical inactivity. Physicians should be aware of those modifiable predictors for TB among the older population.

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

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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