The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease-a systematic review

BACKGROUND: Despite the increasing knowledge on the role of viruses in exacerbations of COPD (AECOPD), it is less clear which viruses are involved and to what extent they contribute to exacerbations. This review aims to systematically combine and evaluate the available literature of the prevalence of respiratory viruses in patients with AECOPD, detected by PCR. METHODS: An electronic search strategy was performed on PubMed and Embase and reference lists were screened for eligible studies. Cross-sectional, prospective studies and case-control studies were included. The primary outcome measure was the prevalence of respiratory viruses (adenovirus, bocavirus, coronavirus, EBV, hMPV, influenza, parainfluenza, rhino-/enterovirus, RSV) in respiratory secretions of patients during an AECOPD. Secondary outcomes were the odds of the presence of the viruses in different respiratory secretions and the odds of the presence of viruses in upper and lower respiratory tract (URT/LRT) samples. RESULTS: Nineteen studies with 1728 patients were included. Rhino-/enteroviruses (16.39%), RSV (9.90%) and influenza (7.83%) were the most prevalent viruses detected with lower detection rates of coronaviruses (4.08%) and parainfluenza (3.35%). Adenovirus (2.07%), hMPV (2.78%) and bocaviruses (0.56%) appear to be rare causative agents of AECOPD. Definitive conclusions regarding the role of EBV cannot be made. Seven of the eight analyzed viruses had a higher prevalence in LRT samples. Coronaviruses were detected more frequently in the URT. CONCLUSIONS: Respiratory viruses are frequently detected in both URT and LRT samples in AECOPD with rhino-/enteroviruses, RSV and influenza viruses the most prevalent viruses. Detection rates vary between the two sites for different viruses

Similar matrix alterations in alveolar and small airway walls of COPD patients

BACKGROUND: Remodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling. The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-beta signalling in COPD patients of different GOLD stages. METHODS: Lung tissue sections of 14 smoking controls, 16 GOLD II and 19 GOLD IV patients were included and stained for elastin and collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2. RESULTS: Elastin was significantly decreased in COPD patients not only in alveolar, but also in small airway walls. Interestingly, both collagen and hyaluronan were increased in alveolar as well as small airway walls. The matrix changes were highly comparable between GOLD stages, with collagen content in the alveolar wall increasing further in GOLD IV. A calculated remodelling index, defined as elastin divided over collagen and hyaluronan, was decreased significantly in GOLD II and further lowered in GOLD IV patients, suggesting that matrix component alterations are involved in progressive airflow limitation. Interestingly, there was a positive correlation present between the alveolar and small airway wall stainings of the matrix components, as well as for pSMAD2. No differences in pSMAD2 staining between controls and COPD patients were found. CONCLUSIONS: In conclusion, remodelling in the alveolar and small airway wall in COPD is markedly similar and already present in moderate COPD. Notably, alveolar collagen and a remodelling index relate to lung function

Cigarette smoke extract induces the release of extracellular vesicles by airway epithelial cells via cellular carbonyl stress

Introduction: Secreted extracellular vesicles (EVs) participate in multiple processes by transferring proteins and RNA between cells. Yet, their contribution to chronic inflammation in the lungs is largely unexplored. We determined if exposure of airway epithelial cells (AEC) to cigarette smoke extract (CSE) results in release of pro-inflammatory EVs. Using the CSE components H2O2 and acrolein, we determined whether reactive oxygen species or thiol-reactive carbonyl compounds account for CSE-induced EV release.Methods: AEC were exposed for 24h to different concentrations of CSE, H2O2 or acrolein, in some experiments in the presence of the thiol-group bearing antioxidant N-acetylcysteine (NAC). Relative levels of CD63+CD81+ EVs in conditioned media were measured by bead-coupled flow cytometry. Oxidized and total GSH were assessed using a GSH reductase cycling assay.Results: CSE induced EV release in a concentration-dependent manner up to 2.3-fold at 1.5% CSE. This was paralleled by increases in cellular oxidized (3.1 fold) and total (5.8 fold) GSH. Incubation of CSE with GSH resulted in complete GSH oxidation, confirming direct thiol reactivity of CSE. NAC prevented CSE-induced EV-release, likely by scavenging thiol-reactive components of CSE. Similar to CSE, acrolein, but not H2O2, induced EV release in a NAC-reversible manner. Exposure of naïve macrophages to CSE-induced EVs resulted in increased release of TNFα.Conclusion: AEC release an increased quantity of EVs when exposed to CSE. This is likely mediated by reactive carbonyl compounds. These EVs exert pro-inflammatory effects that may contribute to the pathogenesis of COPD

Supplementary Material for: Predictors of 1-Year Mortality at Hospital Admission for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

<b><i>Background:</i></b> Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are related to high mortality, especially in hospitalized patients. Predictors for severe outcomes are still not sufficiently defined. <b><i>Objectives:</i></b> To assess the mortality rate and identify potential determinants of mortality in a cohort of patients hospitalized for AE-COPD. <b><i>Methods:</i></b> A retrospective, observational cohort study including all consecutive patients admitted between January 1, 2009, and April 1, 2010, for AE-COPD. Potential predictors were assessed at initial presentation at the emergency room. The primary outcome was mortality during 1-year follow-up. Univariate and multivariate time-to-event analyses using Cox proportional hazard models were employed for statistical analysis. <b><i>Results:</i></b> A total of 260 patients were enrolled in this study. Mean age was 70.5 ± 10.8 years, 50.0% were male and 63.4% had severe COPD. The in-hospital mortality rate was 5.8% and the 1-year mortality rate was 27.7%. Independent risk factors for mortality were age [hazard ratio (HR) = 1.04; 95% confidence interval (CI) = 1.01–1.07], male sex (HR = 2.00; 95% CI = 1.15–3.48), prior hospitalization for AE-COPD in the last 2 years (HR = 2.56; 95% CI = 1.52–4.30), prior recorded congestive heart failure (HR = 1.75; 95% CI = 1.03–2.97), Paco₂ ≥6.0 kPa (HR = 2.90; 95% CI = 1.65–5.09) and urea ≥8.0 mmol/l (HR = 2.38; 95% CI = 1.42–3.99) at admission. <b><i>Conclusions:</i></b> Age, male sex, prior hospitalization for AE-COPD in the last 2 years, prior recorded congestive heart failure, hypercapnia and elevated levels of urea at hospital admission are independent predictors of mortality within the first year after admission

Shift in bacterial etiology from the CAPNETZ cohort in patients with community-acquired pneumonia: data over more than a decade

To determine the most relevant pathogens for CAP in Germany, patients with radiologically confirmed pulmonary infiltrates and at least one clinical sign of lung infection were prospectively recruited within the CAPNETZ cohort from 2004 until 2016. In 990 out of 4.672 patients (21%) receiving complete diagnostics the most prominent change of pathogens was a decrease of S. pneumoniae (58% in 2004 to 37.5% in 2016; p ≤ 0.001, ρ =  − 0.148) and an increase of H. influenzae (12.2% to 20.8%; p = 0.001, ρ = 0.104)

Therapy with proton-pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD

Background and objective: Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD. Methods: A total of 638 patients with stable COPD for ≥6 weeks, ≥10 pack-years of smoking and Global Initiative for Chronic Obstructive Lung Disease II–IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations-COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death. Results: A total of 85 (13.3%) of COPD patients were on anti-GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF-36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6-min walking distance (P = 0.0004) and a higher adjusted Charlson score (P &lt; 0.0001). Anti-GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37–3.08). Using three multivariable Cox-regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26–2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04–2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04–2.53). Conclusion: These findings suggest that patients with stable COPD receiving acid-suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations. © 2016 Asian Pacific Society of Respirolog