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      Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease

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          Abstract

          Objective

          To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection.

          Methods

          This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty‐one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus‐positive (+) group and AECOPD virus‐negative (−) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum.

          Results

          A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus− group. However, serum concentrations of interferon‐inducible protein‐10 (IP‐10) and interferon‐gamma (IFN‐γ) in virus+ AECOPD patients were significantly higher than those in the virus− AECOPD, stable COPD and healthy control groups ( P < .05).

          Conclusion

          Viral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP‐10 and IFN‐γ levels might be value to indicate viral infection in AECOPD.

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          Most cited references40

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

          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. 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. 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). 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.
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            Effect of Interactions Between Lower Airway Bacterial and Rhinoviral Infection in Exacerbations of COPD

            Study objectives The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. Design Prospective cohort study. Setting Outpatient Department, London Chest Hospital, London, UK. Patients Thirty-nine patients with COPD. Measurements We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. Results A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. Conclusions The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.
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              Is Open Access

              Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

              Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.
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                Author and article information

                Contributors
                ywhu0117@126.com
                jiezjlxh@163.com
                Journal
                Clin Respir J
                Clin Respir J
                10.1111/(ISSN)1752-699X
                CRJ
                The Clinical Respiratory Journal
                John Wiley and Sons Inc. (Hoboken )
                1752-6981
                1752-699X
                15 June 2017
                March 2018
                : 12
                : 3 ( doiID: 10.1111/crj.2018.12.issue-3 )
                : 1228-1239
                Affiliations
                [ 1 ] Department of Respiratory Medicine, the Fifth People's Hospital of Shanghai Fudan University Shanghai China
                [ 2 ] Department of Internal Medicine, Wannan Medical College Wuhu China
                [ 3 ] Department of Pathogen Diagnosis and Biosafety Shanghai Public Health Clinical Center Shanghai China
                Author notes
                [*] [* ] Correspondence

                Zhijun Jie, Department of Respiratory

                Medicine, The Fifth People's Hospital of

                Shanghai, Fudan University, Shanghai,

                China.

                Email: jiezjlxh@ 123456163.com

                or

                Yunwen Hu, Department of Pathogen

                Diagnosis and Biosafety, Shanghai Public

                Health Clinical Center, Shanghai, China.

                Email: ywhu0117@ 123456126.com

                [†]

                Tiping Yin and Zhaoqin Zhu both contributed in this study.

                Author information
                http://orcid.org/0000-0002-9410-1827
                Article
                CRJ12656
                10.1111/crj.12656
                7162408
                28586150
                16b47c83-537d-4801-ae80-f8aea314d1d5
                © 2017 John Wiley & Sons Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 21 November 2016
                : 12 April 2017
                : 09 May 2017
                Page count
                Figures: 4, Tables: 4, Pages: 12, Words: 7169
                Funding
                Funded by: Science and Technology Commission of Shanghai Natural Fund , open-funder-registry 10.13039/501100003399;
                Award ID: 134119b1200
                Funded by: Training Plan of Outstanding academic leader of health system in Shanghai
                Award ID: XBR2013078
                Funded by: Key Department of Shanghai Fifth Peopleˊs Hospital
                Award ID: 2017WYZDZK07
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                March 2018
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Respiratory medicine
                acute exacerbation of chronic obstructive pulmonary disease,chronic obstructive pulmonary disease,cytokine,ip‐10,viral infection

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