Dr Konstantinos Kostikas: Back to basics with management of allergic asthma

Asthma

27 May 2019

Dr. Konstantinos Kostikas

The limbic had the opportunity to sit down recently and talk about allergic asthma with Dr. Konstantinos Kostikas, Associate Professor of Respiratory Medicine and Head of the Respiratory Medicine Department of the University Hospital of Ioannina, Greece. Dr. Kostikas was in Australia for the TSANZSRS 2019 Annual Scientific Meeting on the Gold Coast.

The limbic: How do you define allergic asthma?

My clinical definition of allergic asthma is the presence of allergic symptoms in patients with a diagnosis of asthma. So by allergic symptoms I mean symptoms that are related to specific exposures, either perennial or seasonal, usually aeroallergens and allergic manifestations beyond the lower airway symptoms. These patients have upper airways symptoms, they have allergic rhinitis, hay fever and/or atopic dermatitis. If a patient presents with any of these symptoms plus a picture of asthma, this is allergic asthma.

The limbic: How prevalent is the allergic phenotype compared to other forms of asthma?

In children this is probably 60-70%; in adults 50-60%. It is the most common phenotype of asthma. I would say the 50-60% in adults is rather conservative and it is related to the fact that we are still not extremely good at diagnosing allergy and allergic asthma in primary care even though patients complain about allergic symptoms. This is something we certainly need to improve.

The limbic: How is allergic asthma differentiated from other types of asthma in the clinic?

A careful history taking from the patient is the first step to identify allergies. Patients usually are very happy to tell the allergic story because they’ll say ‘I came close to a cat and I started sneezing’. They all have a story like that. So we probably need to take a more careful history in asthmatic patients and try to identify some things that they may be sensitised to. In children it could be food allergy and then they are more likely to have allergic asthma. In adults, it is usually aeroallergens or even perennial allergens like house dust mites.

Diagnosis is also based on symptoms and many patients have increased total IgE in their blood – a marker of atopy – and also these patients may have and are likely to have positive skin prick tests or allergen-specific IgEs in their blood. As a pulmonologist running a severe asthma clinic, I do a basic battery of 20 skin prick tests and if I find anything I am not sure about, then I refer to allergist to do more extensive, targeted tests.

The limbic: What’s the role or significance of IgE in allergic asthma?

IgE is the central mediator in allergic asthma because it comes very early in the allergic cascade, and blocking IgE will not only block the late phase reaction that we block when we block eosinophils, but also the early phase reaction – the typical nasal allergies, hay fever, etcetera. The key about intervening on IgE is going both for the allergic symptoms plus the asthma symptoms and the exacerbations, which is not the case with other biologics because they intervene in a later part of the pathway.

The limbic: What’s the current evidence that targeting IgE pathway helps?

The INNOVATE1 study gave us the basic evidence and was the study used by the regulators, but we need to understand this study happened many years ago and it was not targeting patients with a lot of exacerbations.

The additional study that I consider as very important in our understanding is the EXTRA2 study. This study evaluated the treatment response based on biomarkers.

They were able to show that patients with higher blood eosinophils and patients with higher fractional exhaled nitric oxide (FeNO) have very significant reductions in exacerbations. FeNO and blood eosinophils are markers of type 2 inflammation so they are the ones that actually show which patients will respond best in terms of exacerbations on omalizumab.

The limbic: How should clinicians approach the management of a patient who they suspect has allergic asthma?

The major discussion in biologics today is which pathway do we go? Should we treat with the anti-IgE or anti-IL-5? The answer to that is simpler than we would be expecting. It goes back to the phenotype of the patients.

If a patient has early onset asthma, predominately allergic phenotype with allergic rhinitis, hay fever, etc. – that patient will respond much better to an anti-IgE treatment.

In frequently exacerbating patients with late onset asthma, with high blood eosinophils, potentially nasal polyps and without atopy, they will most likely respond to an anti-IL-5. You have to have frequent exacerbations.

Do these two simple definitions cover everybody? No. We will still have some overlapping patients and the obvious question then, is which is the predominant phenotype. And this is how we make the decision.

 

This article was sponsored by Novartis, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Novartis.

Disclosure: Dr. Kostikas has previously worked as an employee of Novartis.

References:

  1. Humbert M et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005; 60(3):309-16. https://www.ncbi.nlm.nih.gov/pubmed/15679715
  2. Hanania N et al. Exploring the Effects of Omalizumab in Allergic Asthma An Analysis of Biomarkers in the EXTRA Study. AJRCCM 2013; 187(8):804-11. https://www.atsjournals.org/doi/full/10.1164/rccm.201208-1414OC

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