Pro: the illegitimate crusade against corticosteroids for severe H1N1 pneumonia.

American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.04). 05/2011; 183(9):1125-6. DOI: 10.1164/rccm.201102-0345ED
Source: PubMed
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    ABSTRACT: Since December 2011, influenza virologists and biosecurity experts have been engaged in a controversial debate over research on the transmissibility of H5N1 influenza viruses. Influenza virologists disagreed with the NSABB's recommendation not to publish experimental details of their findings, whereas biosecurity experts wanted the details to be withheld and future research restricted. The virologists initially declared a voluntary moratorium on their work, but later the NSABB allowed their articles to be published, and soon transmissibility research will resume. Throughout the debate, both sides have had understandable views, but both have overlooked the more important question of whether anything could be done if one of these experimentally derived viruses or a naturally occurring and highly virulent influenza virus should emerge and cause a global pandemic. This is a crucial question, because during the 2009 H1N1 influenza pandemic, more than 90% of the world's people had no access to timely supplies of affordable vaccines and antiviral agents. Observational studies suggest that inpatient statin treatment reduces mortality in patients with laboratory-confirmed seasonal influenza. Other immunomodulatory agents (glitazones, fibrates and AMPK agonists) improve survival in mice infected with influenza viruses. These agents are produced as inexpensive generics in developing countries. If they were shown to be effective, they could be used immediately to treat patients in any country with a basic health care system. For this reason alone, influenza virologists and biosecurity experts need to join with public health officials to develop an agenda for laboratory and clinical research on these agents. This is the only approach that could yield practical measures for a global response to the next influenza pandemic.
    Human vaccines & immunotherapeutics. 02/2013; 9(5).
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    ABSTRACT: Secondary bacterial pneumonia is a significant cause of morbidity and mortality during influenza, despite routine use of standard antibiotics. Antibiotic-induced immunopathology associated with bacterial cell wall lysis has been suggested to contribute to these poor outcomes. Using Streptococcus pneumoniae in a well-established murine model of secondary bacterial pneumonia (SBP) following influenza, we stratified disease severity based on pneumococcal load in the lungs via in vivo bioluminescence imaging. Ampicillin treatment cured mice with mild pneumonia but was ineffective against severely pneumonic mice, despite effective bacterial killing. Adjunctive dexamethasone therapy improved ampicillin-induced immunopathology and improved outcomes in mice with severe SBP. However, early dexamethasone therapy during primary influenza infection impaired lung adaptive immunity as manifest by increased viral titers, with an associated loss of its protective functions in SBP. These data support adjunctive clinical use of corticosteroids in severe cases of community-acquired pneumonia.
    The Journal of Infectious Diseases 11/2013; · 5.85 Impact Factor
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    ABSTRACT: Statins not only reduce levels of LDL-cholesterol, they counteract the inflammatory changes associated with acute coronary syndrome and improve survival. Similarly, in patients hospitalized with laboratory-confirmed seasonal influenza, statin treatment is associated with a 41% reduction in 30-day mortality. Most patients of any age who are at increased risk of influenza mortality have chronic low-grade inflammation characteristic of metabolic syndrome. Moreover, differences in the immune responses of children and adults seem responsible for the low mortality in children and high mortality in adults seen in the 1918 influenza pandemic and in other acute infectious and non-infectious conditions. These differences probably reflect human evolutionary development. Thus the host response to influenza seems to be the major determinant of outcome. Outpatient statins are associated with reductions in hospitalizations and deaths due to sepsis and pneumonia. Inpatient statins are also associated with reductions in short-term pneumonia mortality. Other immunomodulatory agents - ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), PPARγ and PPARα agonists (glitazones and fibrates) and AMPK agonists (metformin) - also reduce mortality in patients with pneumonia (ACEIs, ARBs) or in mouse models of influenza (PPARγ and AMPK agonists). In experimental studies, treatment has not increased virus replication. Thus effective management of influenza may not always require targeting the virus with vaccines or antiviral agents. Clinical investigators, not systems biologists, have been the first to suggest that immunomodulatory agents might be used to treat influenza patients, but randomized controlled trials will be needed to provide convincing evidence that they work. To guide the choice of which agent(s) to study, we need new types of laboratory research in animal models and clinical and epidemiological research in patients with critical illness. These studies will have crucial implications for global public health. During the 2009 H1N1 influenza pandemic, timely and affordable supplies of vaccines and antiviral agents were unavailable to more than 90% of the world's people. In contrast, statins and other immunomodulatory agents are currently produced as inexpensive generics, global supplies are huge, and they would be available to treat patients in any country with a basic health care system on the first pandemic day. Treatment with statins and other immunomodulatory agents represents a new approach to reducing mortality caused by seasonal and pandemic influenza. This article forms part of a symposium in Antiviral Research on ''Treatment of influenza: targeting the virus or the host.''
    Antiviral research 07/2013; · 3.61 Impact Factor