Current Concepts: Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease

Division of Pulmonary and Critical Medicine, Department of Medicine, University at Buffalo, State University of New York, and Department of Veterans Affairs Western New York Healthcare System, Buffalo 14215, USA.
New England Journal of Medicine (Impact Factor: 55.87). 12/2008; 359(22):2355-65. DOI: 10.1056/NEJMra0800353
Source: PubMed


New molecular, cellular, and immunologic techniques used to study host-pathogen interactions have led to a reexamination of the role of infection in chronic obstructive pulmonary disease (COPD). There is now considerable evidence that infection plays a major role in the pathogenesis and clinical course of COPD. A vicious circle of infection and inflammation is thought to lead to exacerbations of the disease.

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    • "" Inflamm-aging " often takes place and is associated with immunosuppression and low grade inflammation [69]. When secondary pulmonary infection occurs as a result of impaired host response, secondary inflammation develops [73]. "
    Mediators of Inflammation 06/2015; 2015(692546):1. · 3.24 Impact Factor
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    • "Acute and chronic inflammation and infection of the lung also contribute to tissue destruction and loss of lung function in COPD and CF [1,5]. Bacterial and viral infections are associated with exacerbations of COPD [1,6]. In CF, ongoing inflammation and activation of immune mechanisms is evoked by colonizing bacteria, such as P. aeruginosa[7]. "
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    ABSTRACT: Background Moxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. The antimicrobial activity of quinolones against Gram-positive and Gram-negative bacteria is based on their ability to inhibit topoisomerases. Quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model. Methods Mice were treated with moxifloxacin or saline for two consecutive days and were subsequently intranasally infected with viable or heat-inactivated bacterial pathogens (Streptococcus pneumoniae, Pseudomonas aeruginosa) for 6 and 24 hours. Measurements of cytokines in the lungs and plasma were performed. Alveolar cells were determined in bronchoalveolar lavage fluits. Results The inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria. Numbers of total immune cells and neutrophils and concentrations of inflammatory mediators (e.g. KC, IL-1β, IL-17A) were significantly reduced in lungs of moxifloxacin-treated mice infected with inactivated and viable bacterial pathogens as compared to infected control mice. Plasma concentrations of inflammatory mediators were significantly reduced in moxifloxacin-treated mice. Immunohistochemistry showed a stronger infiltrate of TNF-α-expressing cells into lungs of saline-treated mice infected with viable P. aeruginosa as compared to moxifloxacin-treated mice. Conclusions These data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.
    Respiratory Research 07/2014; 15(1):82. DOI:10.1186/1465-9921-15-82 · 3.09 Impact Factor
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    • "Therefore, a novel systemic biomarker with genetic and mechanistic correlations to the etiology of COPD and/or its exacerbation is needed (Carter et al. 2011, 2013). Most cases of COPD exacerbation are thought to be triggered by airway infection (Sethi and Murphy 2008). In a previous genotype–phenotype correlation study, we found that COPD patients without Siglec-14 were less prone to exacerbation (Angata et al. 2013). "
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    ABSTRACT: We have previously demonstrated that chronic obstructive pulmonary disease (COPD) patients who do not have Siglec-14 are less prone to exacerbation of the disease. Siglec-14 is a myeloid cell protein that recognizes bacteria and triggers inflammatory responses. Therefore, soluble mediators secreted by myeloid cells responding to Siglec-14 engagement could be involved in the pathogenesis of exacerbation and could potentially be utilized as biomarkers of exacerbation. To find out, we sought genes specifically induced in Siglec-14+ myeloid cells and evaluated their utility as biomarkers of COPD exacerbation. Using DNA microarray, we compared gene expression levels in Siglec-14+ and control myeloid cell lines stimulated with or without nontypeable Haemophilus influenzae to select genes that were specifically induced in Siglec-14+ cells. The expressions of several cytokine and chemokine genes were specifically induced in Siglec-14+ cells. The concentrations of seven gene products were analyzed by multiplex bead array assays in paired COPD patient sera (n = 39) collected during exacerbation and stable disease states. Those gene products that increased during exacerbation were further tested using an independent set (n = 32) of paired patient sera. Serum concentration of interleukin-27 (IL-27) was elevated during exacerbation (discovery set: P = 0.0472; verification set: P = 0.0428; combined: P = 0.0104; one-sided Wilcoxon matched-pairs signed-rank test), particularly in exacerbations accompanied with sputum purulence and in exacerbations lasting more than a week. We concluded that IL-27 might be mechanistically involved in the exacerbation of COPD and could potentially serve as a systemic biomarker of exacerbation.
    07/2014; 2(7). DOI:10.14814/phy2.12069
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