Experimental rhinovirus infection in COPD: Implications for antiviral therapies

Abstract

Chronic obstructive pulmonary disease (COPD) is a major public health problem and will be one of the leading global causes of mortality over the coming decades. Much of the morbidity, mortality and health care costs of COPD are attributable to acute exacerbations, the commonest causes of which are respiratory infections. Respiratory viruses are frequently detected in COPD exacerbations but direct proof of a causative relationship has been lacking. We have developed a model of COPD exacerbation using experimental rhinovirus infection in COPD patients and this has established a causative relationship between virus infection and exacerbations. In addition it has determined some of the molecular mechanisms linking virus infections to COPD exacerbations and identified potential new therapeutic targets. This new data should stimulate research into the role of antiviral agents as potential treatments for COPD exacerbations. Testing of antiviral agents has been hampered by the lack of a small animal model for rhinovirus infection and experimental rhinovirus infection in healthy volunteers has been used to test treatments for the common cold. Experimental rhinovirus infection in COPD subjects offers the prospect of a model that can be used to evaluate the effects of new treatments for virus-induced COPD exacerbations, and provide essential data that can be used in making decisions regarding large scale clinical trials.

C-reactive protein level and microbial aetiology in patients hospitalised with acute exacerbation of COPD

“…In addition, the changes in inflammatory profile, less frequent detection in steady state and the seasonal changes in exacerbation rate suggest that viral acquisition is causally related to exacerbation [9][10][11][12]. Furthermore, recent challenge studies with human rhinovirus in patients with COPD have replicated the symptoms and inflammatory profile changes associated with naturally occurring exacerbations [13]. Studies examining bacterial and viral co-infection in COPD exacerbations have suggested a synergistic relationship between the two [12,14], with a recent study demonstrating a quantitative change in bacteria in the lower respiratory tract of COPD patients following experimental rhinovirus challenge [15].…”

Exacerbation of Chronic Obstructive Pulmonary Disease

“…It is estimated that viral or bacterial infections or combination of both are responsible from two thirds to three quarters of all COPD exacerbations [11,34]. The role of respiratory viruses as pathogens provoking the majority is increasingly recognized [35][36][37]. Owing to clinical availability of multiplex PCR, detection of respiratory viruses has been greatly facilitated in the recent years.…”

Resveratrol inhibits rhinovirus replication and expression of inflammatory mediators in nasal epithelia

“…Several drug candidates have been progressed into clinical trials, including a viral 3C protease inhibitor, and different compounds that prevent virus attachment and entry into cells by binding to the viral capsid (Gunawardana et al, 2014). However, none of these candidates were commercialized due to unacceptable side effects or lack of efficacy when applied to the natural setting [10].…”