Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model

Mosquera, Ricardo A.; Jesus-Rojas, W. De; Stark, James M.; Yadav, Aravind; Jon, Cindy; Atkins, Constance L.; Samuels, Cheryl; Gonzales, Traci; McBeth, K.; Hashmi, Syed; Garolalo, Roberto; Colasurdo, Giuseppe N.

doi:10.1002/ppul.23956

Cited by 28 publications

(28 citation statements)

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“…Therefore, it is necessary to find low-toxic and effective drugs to treat excessive inflammation caused by virus. The excessive inflammation caused by RSV infection is worthy of attention (Shi et al, 2016;Mosquera et al, 2018). There is growing evidence that certain natural products may be able to keep mice away from viral pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

et al. 2020

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“…A variety of animal models exist to research respiratory viruses such as influenza [124][125][126], RSV [127][128][129][130][131][132][133][134][135][136][137], HRV [22,[138][139][140]. No single animal offers a platform for all respiratory viruses that infect humans, and different animal models exist for the same virus, which can give different, often conflicting results.…”

Section: The History Of the Human Viral Challenge Modelmentioning

confidence: 99%

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

et al. 2018

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The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics.Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies.We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development.The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics.Future applications of the model are also explored.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.

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“…We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with CLD as evidenced by a reduction in the days with unscheduled face-to-face provider encounters based on the preliminary results from our laboratory study that indicated that prophylactic azithromycin can effectively reduce airway inflammation and disease severity in a RSV-infected mouse model. 6 7 Recent studies have shown that the high morbidity rate of respiratory virus infections is a result of a neutrophilic overactive inflammatory response. 5 Macrolides downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections and may reduce virus-related exacerbation.…”

Section: Discussionmentioning

confidence: 99%

“… 5 Recent studies, including a study performed in our laboratory with elderly BALB/c mice infected with respiratory syncytial virus (RSV), have shown that the high mortality rate of respiratory virus infections is a result of an overactive neutrophilic inflammatory response. 6 7 A recently published study examined the inflammatory response in hospitalised infants with RSV and evaluated the predictive value of cytokines in nasopharyngeal aspirate in comparison to disease severity and found an increase in Th1 and Th2 cytokines. 8 Respiratory viral infections are characterised by the appearance of cytokine storms which involve an extreme production and secretion of numerous proinflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial

et al. 2016

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IntroductionRecent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade.Methods and analysisA randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3–6 months during two respiratory syncytial virus (RSV) seasons (2015–2016 and 2016–2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach.DiscussionWe predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters.Ethics and disseminationThis research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published.Trial registration numberNCT02544984.

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Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model

Abstract: Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

Cited by 28 publications

References 30 publications

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial

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