“Viral Infection & Asthma Exacerbations” presented by Prof. John Upham

As part of our ongoing seminar series, the Centre of Excellence in Severe Asthma hosted Prof. John Upham, for a webinar “Viral Infection & Asthma Exacerbations” on 13 June 2019.

Presentation Summary

Prof. John Upham provides an overview of the impact of virus infection as an important cause of asthma attacks. He discusses data that links virus infections with a worsening of asthma symptoms and possible immune mechanisms that may explain this connection. Finally, Prof. Upham provides an overview of current treatment options available to reduce the effects of virus-induced disease exacerbations.

More information about severe asthma attacks is also available in the Severe Asthma Toolkit – click here

• Virus infections are a major cause of asthma attacks / exacerbations and have a significant burden on people with asthma, their families and the healthcare system
• How infections cause exacerbations is not clear and relates to the effects of both the virus and the resulting immune response
• Studies identified correlations between virus infection and asthma exacerbations, in particular RNA-based viruses (most commonly human rhinoviruses)
• Rates of virus infection are similar for people with asthma and those without asthma, but the effects of infection are worse in people with asthma (e.g. symptoms, virus clearance; Corne et al. 2002 Lancet)
• Factors that may explain the link between virus infection and asthma include reduced lung function, airway abnormalities (e.g. barrier function, mucous) and immune mis-regulation or immune deficiency
• Synergy exists between allergic status and virus infections, in the initial development of asthma and disease exacerbations, but why this occurs is unclear. This link may result from a single underlying factor, allergy may alter responses to infection and/or virus infection may alter immune responses and lead to development of allergy
• Inhaled corticosteroid treatment prevents both viral and non-viral exacerbations, but the mechanism of how this occurs remains unclear. Corticosteroid treatment is typically thought to minimise allergic responses.
• Immune defence against infection requires a combination of efficient barrier function by structural cells and highly mobile immune cells with specialised functions
• Immune alterations in people with asthma impact responses to virus infection, including deficient interferon (IFN) production, altered blood plasmacytoid cells (pDCs), altered T cell responses and altered epithelial cell responses
• Cells isolated from people with asthma often produce less IFN when exposed to virus (ie. IFN deficiency). IFN deficiency may only be present in a subset of asthma patients, which may depend on disease phenotype (e.g. neutrophilic asthma), asthma severity and treatment dose (e.g. high dose inhaled corticosteroids) or other factors (Simpson et al. 2016 CHEST)
• Plasmacytoid dendritic cells (pDCs) are a type of circulating immune cell that produces large amounts of interferons in response to infection. Low numbers of pDCs in early life is predictive of later asthma development (Upham et al. 2009 JACI) and pDCs isolated from adults with asthma produce less IFN (Tversky et al. 2008 CEA; Gill et al. 2010 JI)
• When exposed to virus, T cells from people with asthma produce less IFN and more Type-2 cytokines (e.g. IL-5, IL-13) (Message et al. 2008 PNAS)
• Recent data suggests roles for interleukin 33 (IL-33), a cytokine that guides production of Type-2 cytokines, is associated with asthma risk, produced by epithelial cells and highly expressed in asthma. Exposure of immune cells to IL-33 before virus infection increases Type-2 cytokine production in people with asthma, but not healthy controls (Jurak et al. 2018 Frontiers Immunology)
• Management strategies to reduce the impact of virus infections in asthma include good hand hygiene, antiviral medications, inhaled interferon treatment, vaccination, biological therapies (e.g. monoclonal antibodies) and macrolide antibiotics
• Good hand hygiene is the most practical intervention that can be applied immediately in the hospital and home to limit virus infections
• Antiviral medications to block or treat rhinovirus infection have had limited effects
• Inhaled interferon treatment within 24-hours of developing a cold had no overall effect on asthma symptoms, although there was a possible benefit in people with difficult-to-treat asthma (Djukanovic et al. 2014 AJRCCM)
• Vaccination against infection has limited efficacy. Seasonal influenza vaccination is moderately effective and is recommended for people with asthma. Vaccines for rhinovirus are not available.
• Biological therapy (e.g. monoclonal antibody) treatment with anti-IgE (omalizumab) before peaks of virus infection protected from asthma exacerbations in a subset of children with unstable asthma (Teach et al. 2015 JACI) and reduced the number of rhinovirus infections (Esquivel et al. 2017 AJRCCM)
• Long-term macrolide antibiotic treatment (e.g. azithromycin) reduces asthma exacerbations (Gibson et al. 2017 Lancet) and has anti-inflammatory and anti-viral effects
• It is important to optimise asthma control to limit the effects of virus infection, particularly before peak virus infection seasons

More information about severe asthma attacks is also available in the Severe Asthma Toolkit – click here

To view other webinars on Severe Asthma please click here