Juliane Kronsbein

Relevance of human metapneumovirus in exacerbations of COPD

Background and methodsHuman metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.ResultsWe analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.ConclusionHMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.

Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

Objective Human bocavirus (HBoV) is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Methods We retrospectively tested 212 COPD patients, 141 (66.5%) with AE-COPD and 71 (33.5%) with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA). The specificity of positive polymerase chain reaction results was confirmed by sequencing. Results Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%). Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8%) and stable COPD (2.9%). HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain. Conclusion HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely.

No evidence for WU polyomavirus infection in chronic obstructive pulmonary disease

Human polyomaviruses are known to cause persistent or latent infections, which are reactivated under immunosuppression. Polyomaviruses have been found to immortalize cell lines and to possess oncogenic properties. Moreover, the recently discovered Merkel cell polyomavirus shows a strong association with human Merkel cell carcinomas. Another novel human polyomavirus, WU polyomavirus (WUPyV), has been identified in respiratory specimens from patients with acute respiratory tract infections (ARTI). WUPyV has been proposed to be a pathogen in ARTI in early life and immunocompromised individuals, but so far its role as a causative agent of respiratory disease remains controversial.The objective of our study was to determine the prevalence of WUPyV infections in adult hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and to establish its potential clinical relevance by comparison to patients with stable COPD hospitalized for other reasons than acute exacerbation of COPD (AE-COPD).A total of 378 respiratory specimens, each 189 induced sputum and nasal lavage samples from 189 patients, who had been recruited in a prospective 2:1 ratio case-control set-up between 1999 and 2003, were evaluated for the presence of WUPyV DNA by real-time PCR.In the present study we could not detect WUPyV DNA in 378 respiratory specimens from 189 adult hospitalized patients with AE-COPD and stable COPD in four consecutive years.Persistence of viral replication or reactivation of latent WUPyV infection did not occur. WUPyV may not play a major role in adult immunocompetent patients with AE-COPD and stable COPD.

The role of respiratory infections in chronic obstructive pulmonary disease

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Endothelin receptor-antagonists suppress lipopolysaccharide-induced cytokine release from alveolar macrophages of non-smokers, smokers and COPD subjects

Smoking-induced COPD is characterized by chronic airway inflammation, which becomes enhanced by bacterial infections resulting in accelerated disease progression called exacerbation. Alveolar macrophages (AM) release endothelin-1 (ET-1), IL-6, CCL-2 and MMP-9, all of which are linked to COPD pathogenesis and exacerbation. ET-1 signals via ETA- and ETB-receptors (ETAR, ETBR). This is blocked by endothelin receptor antagonists (ERAs), like bosentan, which targets both receptors, ETAR-selective ambrisentan and ETBR-specific BQ788. Therefore, ERAs could have anti-inflammatory potential, which might be useful in COPD and other inflammatory lung diseases. We hypothesized that ERAs suppress cytokine release from AM of smokers and COPD subjects induced by lipopolysaccharide (LPS), the most important immunogen of gram-negative bacteria. AM were isolated from the broncho-alveolar lavage (BAL) of n=29 subjects (11 non-smokers, 10 current smokers without COPD, 8 smokers with COPD), cultivated and stimulated with LPS in the presence or absence of ERAs. Cytokines were measured by ELISA. Endothelin receptor expression was investigated by RT-PCR and western blot. AM expressed ETAR and ETBR mRNA, but only ETBR protein was detected. LPS and ET-1 both induced IL-6, CCL-2 and MMP-9. LPS-induced IL-6 release was increased in COPD versus non-smokers and smokers. Bosentan, ambrisentan and BQ788 all partially reduced all cytokines without differences between cohorts. Specific ETBR inhibition was most effective. LPS induced ET-1, which was exclusively blocked by BQ788. In conclusion, LPS induces ET-1 release in AM, which in turn leads to CCL-2, IL-6 and MMP-9 expression rendering AM sensitive for ERAs. ERAs could have anti-inflammatory potential in smoking-induced COPD.

Viral colonization in intubated patients: initial pathogen pattern and follow-up

Introduction:  Colonization of the lower respiratory tract is an independent risk factor for ventilator‐associated pneumonia. Little is known about the frequency of viral colonization on intubation and during mechanical ventilation.

Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.

Die Rolle von Atemwegsinfektionen bei der chronisch-obstruktiven Lungenerkrankung@@@The Role of Respiratory Infections in Chronic Obstructive Pulmonary Disease

ZusammenfassungDie Morbiditäts- und Mortalitätsraten der chronisch-obstruktiven Lungenerkrankung (COPD) sind heute schon erheblich und werden in naher Zukunft noch weiter ansteigen. Somit gewinnt diese Erkrankung zunehmend an volkswirtschaftlicher Bedeutung. Die Kenntnisse der zugrundeliegenden Mechanismen erscheinen daher von besonderer Relevanz, vor allem weil bislang noch keine kurativen Therapieansätze vorhanden sind.Atemwegsinfektionen wurden in den letzten Jahren zunehmend als wesentliche Auslöser der Exazerbation der Erkrankung objektiviert. Es zeigt sich aber auch, dass ihnen eine wichtige Bedeutung bei der Pathogenese der Erkrankung zukommen könnte, was zu neuen therapeutischen Perspektiven führen würde.Ziel dieser Übersicht ist es daher, die Atemwegsentzündung bei der COPD zu beschreiben und die besondere Rolle von Atemwegsinfektionen darzustellen.AbstractMorbidity and mortality of chronic obstructive pulmonary disease (COPD) are considerable and still increasing. The disease is gaining increasing socioeconomic importance. The knowledge of underlying mechanisms is of special relevance because of the lack of a curative therapy.Respiratory infections have been identified as the most important triggers of acute exacerbations but recent data suggest that they might also play an important role in COPD pathogenesis. This knowledge might offer new therapeutic perspectives in the future.The aim of this review is, therefore, to describe the inflammatory processes involved and to specify the role of respiratory infections in this context.