scholarly journals Dysregulation of COVID-19 related gene expression in the COPD lung

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alastair Watson ◽  
◽  
Lisa Öberg ◽  
Bastian Angermann ◽  
C. Mirella Spalluto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renin Angiotensin System ◽  
Chronic Obstructive ◽  
Angiotensin Ii Receptor ◽  
Ras Gene ◽  
Obstructive Pulmonary Disease ◽  
Expression Of Genes ◽  
Increased Risk ◽  
Bronchial Biopsies ◽  
The Impact

Abstract Background Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection. Methods We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects. Results ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of –0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES. Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively). Conclusion This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.

The impact of comorbidities on COVID -19 severity and mortality in Egypt (Preprint)

2021 ◽  
Author(s):  
Shereen Elghazaly ◽  
Hanaa Abu El Sood ◽  
Sahar Samy ◽  
Mohamad AbdelFatah ◽  
Mohamed Hassany ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Severe Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Disease Surveillance System ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Risk Of Disease ◽  
The Impact ◽  
Epidemiologic Characteristics

BACKGROUND Older population and people of any age with underlying certain comorbidities such as diabetes mellitus, cardiovascular, lung disease, kidney disease, liver disease and cancer are at higher risk of severe disease course and death if they become infected with COVID-19. Identifying risky group and risk factors for COVID-19 severity and mortality is important for guiding efficient and appropriate prevention and management of patients with COVID-19. OBJECTIVE This study aims at describing demographics and epidemiologic characteristics of confirmed COVID-19 cases in Egypt and determine the impact of different comorbidities on patients’ outcomes. METHODS Data of all confirmed COVID-19 patients admitted to 408 governmental hospitals allover Egypt February-May 2020 were collected retrospectively from the National Egyptian Disease Surveillance System. Cases were confirmed using RT-PCR. RESULTS Overall, 28,415 patients (55.0% males, 45.0% females) were identified. Their median age was 44 years. Of those, 743(2.6%) were admitted to ICU, 408(1.4%) required ventilator and 1,045(3.7%) died. Of 21,617(76.1%) patients with completed data, 4,687(21.7%) had comorbidities. Overall, 11.8% had diabetes, 5.3% cardiovascular disease and 4.3% chronic obstructive pulmonary disease. Those with one comorbidity were more likely to die (OR = 2.83), admitted to ICU (OR = 6.36) and need ventilator (OR = 5.95) compared to patients with no comorbidities. Having multiple comorbidities increased risk of mortality (OR = 3.53), ICU admission (OR = 8.62), and requiring ventilator (OR = 9.06). CONCLUSIONS COVID-19 Patients with comorbidities had higher risk of disease severity and mortality. Multiple comorbidities further increase the risk to higher extent. All necessary precautions should be taken for patients with comorbidities to avoid COVID-19 infection to prevent the worst prognosis.

scholarly journals 804. Impact of Azithromycin Prophylaxis in Lung Transplant Recipients on the Risk of Nontuberculous Mycobacterial Infections

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S288-S288
Author(s):  
Adrienne Workman ◽  
Vaidehi Kaza ◽  
Scott Bennett ◽  
Pearlie Chong
Keyword(s):  
Lung Transplant ◽  
Bronchiolitis Obliterans Syndrome ◽  
Chronic Obstructive ◽  
Transplant Recipients ◽  
Multivariable Logistic Regression Model ◽  
Obstructive Pulmonary Disease ◽  
Clinical Criteria ◽  
Increased Risk ◽  
Lung Transplant Recipients ◽  
The Impact

Abstract Background Azithromycin has been shown to improve FEV1 in lung transplant recipients (LTR) with bronchiolitis obliterans syndrome (BOS). The impact of azithromycin use on the incidence of infections due to Mycobacterium avium complex (MAC) and M. abscessus in LTR is currently unknown. Methods We conducted a nested case–control study of a retrospective cohort of adult LTR transplanted between 2007 and 2017. Cases were defined as LTR with nontuberculous mycobacterial (NTM) infections due to MAC and/or M. abscessus. Controls were defined as LTR without NTM infections. NTM infection was defined by presence of pulmonary symptoms and radiographic changes (clinical criteria) in addition to positive cultures from ≥2 sputa or ≥1 bronchial specimens (microbiological criteria) according to the IDSA/ATS criteria. LTR who meet microbiological, but not clinical criteria were considered colonized and not included for analysis. Azithromycin use was defined as ≥90 days for BOS treatment. Results Among 538 LTR, 60% (321/538) were male and 81% (434/538) received double LTs. Indication for LT was idiopathic pulmonary fibrosis (28% [152/538]), chronic obstructive pulmonary disease (23% [121/538]), cystic fibrosis [CF] (13% [68/538]), and other (37% [197/538]). The overall incidence of NTM infections was 4.3% (23/538); of which 65.2% (15/23), 17.4% (4/23), and 17.4% (4/23) were due to MAC, M. abscessus and polymicrobial infections, respectively. Thirty-one percent (165/538) of LTR received azithromycin. LTR who received azithromycin prophylaxis had 0.21 times the odds of developing NTM infections compared with LTR who did not receive azithromycin prophylaxis (OR: 0.21, 95% CI: 0.02 – 0.86, P = 0.02). Age (P = 0.88), type of LT (P = 0.81), pretransplant NTM colonization (P = 0.46), and CF (P = 0.22) were evaluated as possible risk factors, but were not associated with increased risk of developing NTM infections in bivariable analyses. In a multivariable logistic regression model, azithromycin prophylaxis was independently associated with decreased risk of NTM infections after adjusting for CF and pretransplant NTM colonization (aOR: 0.20, 95% CI: 0.05–0.88, P = 0.01). Conclusion Azithromycin use was associated with lower risk of NTM infections due to M. abscessus and MAC in our LTR. Disclosures All authors: No reported disclosures.

scholarly journals InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dave Singh ◽  
Gerard J. Criner ◽  
Mark T. Dransfield ◽  
David M. G. Halpin ◽  
MeiLan K. Han ◽  
...  
Keyword(s):  
Predictive Biomarker ◽  
Chronic Obstructive ◽  
Severe Exacerbation ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Increased Risk ◽  
Rate Ratios ◽  
Post Hoc ◽  
The Impact ◽  
The Relationship

Abstract Background Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. Methods 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). Results Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. Conclusions Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. Trial registration: NCT02164513

Impact of Chronic Obstructive Pulmonary Disease on Postoperative Complications Following Simultaneous Bilateral Total Knee Arthroplasty

2019 ◽  
Author(s):  
Alex Gu ◽  
Shitong Wu ◽  
Fabio Mancino ◽  
Jiabin Liu ◽  
Michael P. Ast ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Total Knee Arthroplasty ◽  
Chronic Obstructive ◽  
Thromboembolic Complications ◽  
Bilateral Total Knee Arthroplasty ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
Total Knee ◽  
The Impact ◽  
Simultaneous Bilateral Tka

AbstractFor patients who qualify, simultaneous bilateral total knee arthroplasty (TKA) is a viable option for the treatment of bilateral symptoms. However, the incidence of chronic obstructive pulmonary disease (COPD) has been steadily rising over the past few decades and may impact those who qualify as candidates for bilateral TKA. As such, the aim of this study was to determine the impact of COPD on postoperative outcomes in patients who receive simultaneous bilateral TKA. A retrospective cohort study was conducted utilizing data provided through the American College of Surgeons National Surgical Quality Improvement Program. All patients who had undergone simultaneous bilateral TKA between 2007 and 2016 were identified and further stratified into groups based upon the COPD status. Incidence of adverse events after TKA in the acute postoperative period was evaluated with univariate and multivariate analyses. COPD was found to be an independent risk factor for the development of major (odds ratio [OR]: 2.5; p = 0.015), renal (OR: 5.1; p = 0.02), and thromboembolic complications (OR: 2.5; p = 0.027). In addition, patients with COPD were at increased risk for having an extended hospital length of stay (LOS; p < 0.001) and development of urinary tract infections (p < 0.001). Patients with COPD are at higher risk for development of overall major complications, as well as renal and thromboembolic complications after simultaneous bilateral TKA. Interestingly, patients were not at increased risk for the development of pulmonary or wound complications. When considering a staged versus simultaneous bilateral TKA, surgeons should be aware of the impact COPD status has on the postoperative complication rate.

scholarly journals Lung Cancer Screening in Patients with COPD—A Case Report

Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 364
Author(s):  
Roxana Amirahmadi ◽  
Avnee J. Kumar ◽  
Mark Cowan ◽  
Janaki Deepak M.B.B.S.
Keyword(s):  
Lung Cancer ◽  
Case Report ◽  
Cancer Screening ◽  
Lung Cancer Screening ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
Poor Functional Status ◽  
The Impact

We present two cases demonstrating the nuances that must be considered when determining if a patient could benefit from low dose computed tomography (LDCT) lung cancer screening. Our case report discusses the available literature, where it exists, on lung cancer screening with special attention to the impact of chronic obstructive pulmonary disease (COPD), and poor functional status. Patients with COPD and concurrent smoking history are at higher risk of lung cancer and may therefore benefit from lung cancer screening. However, this population is at increased risk for complications related to biopsies and lobar resections. Appropriate interventions other than surgical resection exist for COPD patients with poor pulmonary reserve. Risks and benefits of lung cancer screening are unique to each patient and require shared decision-making.

ACE Inhibitor—Induced Bronchial Reactivity in Patients with Respiratory Dysfunction

2002 ◽  
Vol 36 (6) ◽  
pp. 1058-1067 ◽  
Author(s):  
Kathleen A Packard ◽  
Richard L Wurdeman ◽  
Amy J Arouni
Keyword(s):  
Heart Failure ◽  
Chronic Obstructive Pulmonary Disease ◽  
Congestive Heart Failure ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Chronic Obstructive ◽  
Angiotensin Ii Receptor ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Responsiveness ◽  
Increased Risk

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are often associated with an increased incidence of cough and bronchial responsiveness that may cause further deterioration of patients with impaired pulmonary function. OBJECTIVE: To review the available literature on the incidence of cough and bronchial responsiveness associated with ACE-inhibitor therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). DATA SOURCES: Literature was accessed through MEDLINE (1985–September 2001). Key search terms included cough, bronchospasm, asthma, congestive heart failure, chronic obstructive pulmonary disease, ACE inhibitors, and angiotensin II receptor blockers. DATA SYNTHESIS: The literature reports several cases of increased bronchial responsiveness associated with ACE inhibitors. Larger, controlled studies evaluating the increased risk in patients with pulmonary dysfunction are limited. Data from these trials are summarized in this article. CONCLUSIONS: The literature shows that patients with primary airway disease such as asthma and COPD are not at an increased risk of developing cough or bronchoconstriction as a result of ACE-inhibitor therapy. Despite the ability of ACE inhibitors to improve exercise tolerance, perfusion, and gas transfer, patients with CHF may be at higher risk of developing cough than the general population. Whether this cough is attributed to ACE inhibition or increased left-ventricular dysfunction remains uncertain. If increased bronchial responsiveness does occur, angiotensin II receptor antagonists are another reasonable option.

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

2020 ◽  
Author(s):  
Janice M. Leung ◽  
Chen X. Yang ◽  
Anthony Tam ◽  
Tawimas Shaipanich ◽  
Tillie-Louise Hackett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Current Smoking ◽  
Expression Levels ◽  
Copd Patients ◽  
Increased Risk ◽  
Lower Airways ◽  
Never Smokers ◽  
Gene Expression Levels

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.

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 Respiratory Aspergillus Colonization Was Associated With Relapse of Acute Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Analysis of Data From A Retrospective Cohort Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi-xing Wu ◽  
Yi-hui Zuo ◽  
Qi-jian Cheng ◽  
Yi Huang ◽  
Zhi-yao Bao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Acute Exacerbation ◽  
Retrospective Cohort ◽  
Invasive Pulmonary Aspergillosis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
Short Period ◽  
The Impact

Background: Patients with chronic obstructive pulmonary disease (COPD) are more susceptible to Aspergillus colonization or infection. Several studies have demonstrated that invasive pulmonary Aspergillosis (IPA) and Aspergillus hypersensitivity (AH) have a detrimental effect on COPD. However, it remains to be clarified whether Aspergillus colonization is associated with acute exacerbation of COPD (AECOPD). This study aimed to explore the impact of Aspergillus colonization in the lower respiratory tract on AECOPD.Method: Patients with Aspergillus colonization were identified from a retrospective cohort of hospitalized AECOPD from 2011 to 2016 in eight centers in Shanghai, China. The demographic information, conditions of the stable stage, clinical characteristics during hospitalization, and 1-year follow-up information after discharge were collected and compared to participants without fungi colonization.Result: Twenty-six hospitalized AECOPD patients with Aspergillus colonization and 72 controls were included in the final analysis after excluding patients with other fungi isolation and matching. The rates of recurrence of acute exacerbation within 90 days and 180 days after discharge in the patients with Aspergillus colonization were both significantly higher than that in the fungi negative patients (90 days: 19.2 vs. 4.2%, p = 0.029; 180 days: 23.1 vs. 4.2%, p = 0.010), and the all-cause mortality within 1 year was also higher (11.5 vs. 0.0%, p = 0.017). Multivariate logistic regression analysis showed that Aspergillus colonization was an independent risk factor for the recurrence of acute exacerbation within 90 days and 180 days (90 days: OR = 8.661, 95% CI: 1.496-50.159, p = 0.016; 180 days: OR =10.723, 95% CI: 1.936-59.394, p = 0.007).Conclusion:Aspergillus colonization may predict poor prognosis of AECOPD while leading to an increased risk of recurrent AECOPD in a short period.

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