Irmgard Borg

Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study

Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. Methods: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. Results: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). Conclusion: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.

Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases

Respiratory syncytial virus (RSV) is known to cause acute lower respiratory tract infections (ARI) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (COPD) in adults. The role of RSV in stable COPD and the viral load in different respiratory diseases has not been investigated to date. The present authors established and evaluated a quantitative TaqMan® real-time polymerase chain reaction assay specific for RSV subgroup A. Absolute quantification for the determination of viral load input was achieved using a control plasmid. The assay allowed for a quantification over a >6-log range and a detection limit of <10 RSV copies per reaction mixture. The assay was 30 times more sensitive than conventional nested polymerase chain reaction assays. Interassay sd was 1.3 and coefficient of variation 4.7% on average. Clinical specimens from infants with ARI (n=62) and elderly adults with COPD (n=125) were compared for viral loads. A total of 47% RSV-positive samples were found in the ARI study group and 28% in the COPD study group. The viral load of both study groups was found to differ significantly. In the ARI study group the viral load was increased almost 2000-fold, suggesting acute infection in this group and former or latent infection in the COPD group. Respiratory syncytial virus-A specific TaqMan® real-time polymerase chain reaction assay is a sensitive and rapid method for the determination of viral load in clinical samples. It enables differential statements concerning the involvement of respiratory syncytial virus in acute lower respiratory tract infections and chronic obstructive pulmonary disease to be achieved.

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.

Inflammatory Response in Acute Viral Exacerbations of COPD

Background:Respiratory viruses are important triggers of acute exacerbations of COPD (AE-COPD). However, the inflammatory response in virus-positive exacerbations is still not fully understood.Methods:We investigated CRP, IL-6, IL-8, IL-10, IFN-γ, blood and sputum cells in patients with acute exacerbation (n = 36) and in stable disease (n = 20) and correlated these parameters to virus detection in respiratory secretions.Results:Similar to other studies we found a significant increase in systemic CRP and absolute numbers of blood leukocytes in AE-COPD patients. Sputum IL-6 levels and sputum eosinophils tended to be higher during exacerbation. In patients with detection of respiratory viruses in nasal lavage, local IL-6 production in sputum was significantly increased; FEV1 was significantly decreased and both parameters were inversely correlated to each other.Conclusion:This study supports previous findings of both, increased local and systemic inflammation in acute exacerbation of COPD. In virus-associated exacerbations, IL-6 is significantly increased and negatively correlated to FEV1 indicating a relation between virus-induced inflammation and airway obstruction. However, regarding our finding and previous data, it is becoming increasingly clear that the mediators investigated so far do not permit identifying the etiology of AE-COPD. Hence, further studies are needed to better define the inflammatory response in AE-COPD in general and in viral exacerbations in particular.

Soluble Interleukin-5 Receptor Alpha Is Increased in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background: During chronic obstructive pulmonary disease (COPD) exacerbations (AE-COPD), an influx of eosinophils into the bronchial mucosa has been described. Eosinophilic cationic protein (ECP) and soluble interleukin-5 receptor α (sIL5Rα) are secreted by eosinophils and increased in eosinophilic airway diseases. Methods: We studied ECP and sIL5Rα expression in patients with COPD compared to healthy controls and smokers and investigated a possible association to viral exacerbations of COPD. Expression of sIL5Rα in serum was analyzed by ELISA and ECP by the Uni-Cap system. Induced sputum from patients with COPD was analyzed for six different respiratory viruses by nested PCR. Results: ECP and sIL5Rα were significantly elevated in AE-COPD subjects (n = 54) compared to healthy controls (n = 11, p = 0.018). Furthermore, there was a significant increase in sIL5Rα, but not in ECP, in 30 patients with virus-associated AE-COPD compared to smokers without COPD (n = 16) and healthy controls. The increase in FEV1 after resolution of the AE-COPD correlated with the decrease in sIL5Rα (r = 0.269, p = 0.034). Conclusions: sIL5Rα is increased in AE-COPD and not affected by smoking like ECP. sIL5Rα is increased in patients with virus-associated AE-COPD compared to smokers and controls. Concentrations of sIL5Rα mirror changes in the clinical status and lung function. These data support the involvement of eosinophils in acute exacerbations of COPD.

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.

Levels of soluble triggering receptor expressed on myeloid cells 1 in infectious exacerbations of chronic obstructive pulmonary disease

Background: Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is an activating receptor on inflammatory cells upregulated by microbial products. Elevated levels of sTREM-1 have been associated with the diagnosis and prognosis of patients with sepsis, severe pneumonia and chronic obstructive pulmonary disease (COPD). Objectives: The aim of this study was to define the role of sTREM-1 in acute exacerbations of COPD (AE-COPD) and to investigate the ability of sTREM-1 to differentiate between infectious triggers of AE-COPD. Methods: Smokers without COPD (SM), patients with stable COPD (sCOPD) and patients with AE-COPD were prospectively recruited. sTREM-1 levels were determined by ELISA in serum. Potentially pathogenic bacteria were analyzed by sputum culture, and polymerase chain reaction was used to determine the presence of respiratory viruses. Results: One hundred and ninety-five subjects were included: 64 sCOPD patients, 118 AE-COPD patients and 13 SM. In 62 (52.6%) AE-COPD patients, a respiratory pathogen was detected. Serum levels of sTREM-1 were barely detectable in SM but were significantly increased in patients with sCOPD [97.5 (interquartile value 76.6) pg/ml] and AE-COPD [110.9 (98.5) pg/ml; p < 0.001]. There was no significant difference in sTREM-1 between sCOPD and AE-COPD (p = 0.277). However, in AE-COPD, sTREM-1 was significantly lower in patients with virus detection [87.5 (97.3) pg/ml] compared to those without [120.3 (99.7) pg/ml; p = 0.015]. No difference was found in AE-COPD patients with or without bacterial detection. Conclusions: The present study shows an increase in sTREM-1 in patients with COPD compared to SM but not in AE-COPD compared to sCOPD. Viral exacerbations showed significantly lower sTREM-1 levels than non-viral exacerbations.

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.

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.