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      The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

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          ABSTRACT

          COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD ( AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe– COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.

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          Most cited references151

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          Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis.

          Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD. A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV(1)) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-alpha (TNF-alpha), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model. Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-alpha levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)). Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.
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            The natural history of chronic airflow obstruction.

            A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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              Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

              The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.
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                Author and article information

                Contributors
                schotirmall@ntu.edu.sg
                Journal
                Respirology
                Respirology
                10.1111/(ISSN)1440-1843
                RESP
                Respirology (Carlton, Vic.)
                John Wiley & Sons, Ltd (Chichester, UK )
                1323-7799
                1440-1843
                25 March 2017
                May 2017
                : 22
                : 4 ( doiID: 10.1111/resp.2017.22.issue-4 )
                : 634-650
                Affiliations
                [ 1 ] Centre for Heart Lung Innovation Vancouver British Columbia Canada
                [ 2 ] Division of Respiratory Medicine, St Paul's Hospital University of British Columbia Vancouver British Columbia Canada
                [ 3 ] Department of Respiratory and Critical Care Medicine Singapore General Hospital Singapore
                [ 4 ] Lee Kong Chian School of Medicine Nanyang Technological University Singapore
                [ 5 ] Priority Research Centre for Healthy Lungs University of Newcastle Newcastle New South Wales Australia
                [ 6 ] Hunter Medical Research Institute Newcastle New South Wales Australia
                Author notes
                [*] [* ]Correspondence: Sanjay H. Chotirmall, Lee Kong Chian School of Medicine, Nanyang Technological University, Clinical Sciences Building, Novena Campus, Singapore 308232, Singapore. Email: schotirmall@ 123456ntu.edu.sg
                [†]

                J.M.L. and P.Y.T. are joint first authors

                Author information
                http://orcid.org/0000-0002-1726-7700
                http://orcid.org/0000-0003-0417-7607
                Article
                RESP13032
                10.1111/resp.13032
                7169176
                28342288
                5903ce4e-f49e-4c18-90b1-846eceba5b4b
                © 2017 Asian Pacific Society of Respirology

                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
                : 22 September 2016
                : 09 February 2017
                : 09 February 2017
                Page count
                Figures: 3, Tables: 3, Pages: 17, Words: 17283
                Funding
                Funded by: Singapore Ministry of Health's National Medical Research Council
                Award ID: NMRC/TA/0048/2016
                Funded by: National Health and Medical Research Council of Australia
                Funded by: Rainbow Foundation
                Categories
                Invited Review Series: Unravelling the Many Faces of COPD to Optimize Its Care and Outcomes
                INVITED REVIEW SERIES
                Unravelling the Many Faces of COPD to Optimize its Care and Outcomes
                Custom metadata
                2.0
                May 2017
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Respiratory medicine
                acute exacerbations of chronic obstructive pulmonary disease,chronic obstructive pulmonary disease,colonization,infection,microbiome

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