Recognizing the Importance of Respiratory Syncytial Virus in Chronic Obstructive Pulmonary Disease

Ramaswamy, Murali; Groskreutz, Dayna J.; Look, Dwight C.

doi:10.1080/15412550902724024

Cited by 28 publications

(20 citation statements)

References 133 publications

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“…The fact that the poly(I:C)-and RSV-induced IFN-b and ISG expression is not perturbed by IL-17 stimulation may be due to expression of antiviral genes being sustained indirectly via type I IFN signaling induced by the IFN-b generated in response to poly(I:C). RSV infection has recently been associated with chronic obstructive pulmonary disease (COPD), which is characterized by severe inflammation in the respiratory system (34). At the same time, Th17 cells and IL-17 levels are increased in COPD patients (35,36).…”

Section: Discussionmentioning

confidence: 92%

IL-17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells

Ryzhakov

Lai

Blazek

et al. 2011

The Journal of Immunology

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Excessive inflammation during bacterial and viral infections is destructive to the host and involves elevated production of proinflammatory cytokines. It is especially deleterious in organs with space constraints such as lung and the CNS. Indeed, a number of viruses that infect lungs, such as avian influenza virus, SARS-associated coronavirus, and respiratory syncytial virus, elicit a very high level of proinflammatory cytokines; however, it is unclear what triggers their production. In this study, we show that IL-17 commonly produced during viral infection specifically augments a proinflammatory response by directly synergizing with antiviral signaling. Costimulation of primary human fibroblasts with IL-17 greatly enhanced respiratory syncytial virus-induced or synthetic dsRNA-based viral mimic polyinosinic:polycytidylic acid-induced expression of proinflammatory genes without affecting expression of IFN-β–stimulated or IFN-stimulated genes. Knockdown of expression of known mediators of the antiviral signaling pathway revealed that the IL-17–poly(I:C) synergy depends on the presence of the transcriptional factors RelA and IFN regulatory factor 3 and IκB kinases. Moreover, this synergy was blocked by an IκB kinase inhibitor, BAY 11-7082. These findings shed light on the molecular mechanisms behind IL-17–dependent immunopathology observed in viral infections.

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Section: Discussionmentioning

confidence: 92%

IL-17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells

Ryzhakov

Lai

Blazek

et al. 2011

The Journal of Immunology

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“…Respiratory syncytial virus (RSV) is an increasingly recognized cause of illness in adults, particularly among adults with chronic obstructive pulmonary disease (COPD) (1)(2)(3)(4)(5). COPD is a progressive syndrome of expiratory airfl ow limitation caused by chronic infl ammation of the airways and destruction of lung parenchyma (6).…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Respiratory Syncytial Virus Illness Among Patients with Chronic Obstructive Pulmonary Disease

Mehta¹,

Walsh

Mahadevia³

et al. 2013

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Respiratory syncytial virus (RSV), although not typically considered an important pathogen in adults, may cause acute exacerbation of chronic obstructive pulmonary disease (COPD). It is unclear which COPD patients are at highest risk for developing serious RSV illness. Our objective was to identify risk factors for RSV illness among adult patients with COPD. We conducted a pooled analysis of data from COPD patients in 2 previously published longitudinal studies that examined RSV infection in high risk adults for ≤ 2 RSV seasons. Risk factors for RSV illness studied included age, sex, race, smoking status, exposure to children, home oxygen use, inhaled or oral steroid use, instrumental activities of daily living scores, and co-morbid conditions. Outcomes studied included symptomatic and medically attended RSV illness. Logistic regression was used to identify significant risk factors for RSV illness among older adults with COPD. Among 379 patients with COPD, the rate of symptomatic RSV illness was 11.1% (42/379); almost half (20/42) of whom required medical attention. In multivariable analyses, congestive heart failure (odds ratio [OR] = 4.18; 95% CI: 1.38, 12.69) and exposure to children (OR = 2.38; 95% CI: 1.03, 5.51) were risk factors for symptomatic RSV illness. Congestive heart failure (OR = 4.16; 95% CI: 1.02, 17.01) was the only significant risk factor for developing medically attended RSV illness. Exposure to children and congestive heart failure are risk factors for RSV illness among adult patients with COPD. Future prospective, well-designed studies are needed to corroborate these findings and examine other risk factors, including history of exacerbations.

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“…Furthermore, RSV infection is a trigger for acute exacerbations in chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (3–4), and is a risk factor for recurrent wheezing in children post infection (5). Despite the substantial morbidity and mortality associated with RSV infection, treatment remains primarily supportive, and antiviral agents have not proved to be an effective therapy for severe RSV disease.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus

Kong

Clancy

Peng

et al. 2013

European Respiratory Journal

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Hypothesis RSV infection is a potent stimulus for airway epithelial expression of MMP-9, and MMP-9 activity in vivo is a predictor of disease severity in children with RSV-induced respiratory failure (RSV-RF). Methods Human airway epithelial cells were infected with RSV A2 strain, and analyzed for MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1, a natural inhibitor of MMP-9) release. In addition, endotracheal samples from children with RSV-RF and controls (non-RSV pneumonia and non-lung disease controls) were analyzed for MMP-9, TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) activity. Results RSV infection of airway epithelia was sufficient to rapidly induce MMP-9 transcription and protein release. Pulmonary MMP-9 activity peaked at 48 hours in infants with RSV-RF compared to controls. In the RSV group, MMP-9 activity and MMP-9:TIMP-1 ratio imbalance predicted higher oxygen requirement and worse Pediatric Risk of Mortality scores. Highest levels of HNE and MPO were measured in the RSV cohort but unlike MMP-9, these neutrophil markers failed to predict disease severity. Conclusions These results support the hypothesis that RSV is a potent stimulus for MMP-9 expression and release from human airway epithelium, and that MMP-9 is an important biomarker of disease severity in mechanically ventilated children with RSV lung infection.

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Recognizing the Importance of Respiratory Syncytial Virus in Chronic Obstructive Pulmonary Disease

Cited by 28 publications

References 133 publications

IL-17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells

IL-17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells

Risk Factors for Respiratory Syncytial Virus Illness Among Patients with Chronic Obstructive Pulmonary Disease

Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus

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