Examining Asthma Exacerbation within Children and Disease Management

Dr Chad Oh, Director Respiratory & Inflammatory Diseases, MedImmune speaks to Pharma IQ about asthma exacerbations in children and therapeutic approaches, ahead of the 2nd Asthma & COPD conference to be held the 28th -30th June Philadelphia, PA.

Please give some background about your company. What is your role, and what does it entail?

MedImmune is a biotechnology company and has expanded through the key acquisitions of U.S. Bioscience in 1999 and Aviron in 2002, as well as the integration with Cambridge Antibody Technology and becoming a wholly owned subsidiary of AstraZeneca PLC in 2007. MedImmune has established itself as an innovator within the biotechnology sector as a result of several firsts. These include:

• Development and commercialization of Synagis® (palivizumab), the first monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for an infectious disease. To date, more than 1 million patients have received Synagis
• Development and commercialization of FluMist® (Influenza Vaccine Live, Intranasal), the first advance in flu vaccine technology in more than 60 years and the only live, attenuated influenza vaccine to be approved in the United States

One of the major areas MedImmune has been focusing on is respiratory diseases. As a medical director of the respiratory team, I have been working on developing novel therapeutic modalities for asthma through clinical studies.

What are the symptoms of asthma? How many people have asthma, and why is it especially common in children?

Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, airflow obstruction, and bronchospasm.  Symptoms include wheezing, cough, chest tightness, and shortness of breath.

Asthma affects approximately 34.1 million Americans and a total of 300 million worldwide.

Asthma is known to be more common in children and almost 9 million children in the United States alone suffer from asthma. The causes of asthma exacerbation in children are similar to the causes of asthma exacerbation in adults. Children are more prone to developing chronic asthma due to their underdeveloped respiratory system and small airways.

Why has the number of people with asthma grown recently?

Evidence shows that the prevalence of asthma is increasing, especially in children. One of the most popular explanations at the moment for the increase in asthma is the "hygiene hypothesis." This blames increasing asthma rates on cleaner homes, which mean that children get fewer infections than they used to. Some scientists think that childhood infections help to build up the immune system. So, since children are getting fewer infections, they have less protection against asthma. Body weight also contributes to asthma, and the steady rise in childhood obesity likely contributes, too.

What causes asthma exacerbations in children? What are some of the therapeutic approaches to control this?

As mentioned above, the causes of asthma exacerbation in children are similar to the causes of asthma exacerbation in adults. Asthma exacerbation is the result of or triggered by an exposure to allergens such as dust and pollens, or smoke, pollution, a change in weather conditions, respiratory infections, and emotional disturbance. Children are more prone to developing chronic asthma due to their underdeveloped respiratory system and small airways.

Essential components of successful asthma management include

• Pharmacotherapy
• Allergen avoidance
• Patient education
• Use of a standardized diagnostic questionnaire, use of an asthma control test
   

Which medicines are currently used for treatments, and what are some of their side effects?

The most effective treatment for asthma is identifying triggers, such as cigarette smoke, pets, or aspirin, and eliminating exposure to them. If trigger avoidance is insufficient, medical treatment is recommended. Current asthma guidelines recommend the stepwise pharmacotherapy. Bronchodilators are recommended for short-term relief of symptoms. For occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks per week), low-dose inhaled corticosteroids or alternatively, an oral leukotriene modifier or cromolyn sodium is recommended. For those who suffer daily attacks, a higher dose of glucocorticoid is used. In a severe asthma exacerbation, oral glucocorticoids are added to these treatments. Anti-immunoglobulin E (IgE) antibodies (omalizumab) can be used to treat moderate to severe persistent asthma.

Long-term use of corticosteroids can have many side effects, including a redistribution of fat, increased appetite, blood glucose problems, and weight gain. High doses of steroids may cause osteoporosis. These side effects are generally not seen with inhaled steroids, when used in conventional doses for control of asthma, due to the smaller dose which is targeted to the lungs. Leukotriene modifiers or cromolyn sodium in general do not cause any significant side effect.

What are some of the options for pharmacotherapy in pediatric asthma?

The approach to pharmacotherapy in pediatric asthma in many ways is similar to pharmacotherapy in adult asthma, except for treatment with anti-IgE antibody, which is approved for patients 12 years of age or older in the United States and 6 years of age or older in the European Union. However, dosage and delivery methods need to be modified by age group.

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Please describe Pediatrics Investigational Plans (PIP). What is meant by this?

PIP is the basis for the development and authorization of a medicinal product for pediatric population subsets in the European Union. PIP includes details of the timing and the measures proposed to demonstrate quality, safety, and efficacy. PIP is to be agreed upon and/or amended by the Pediatric Committee (PDCO) in the European Union.

Is there anything you’d like to add?

Despite optimized standard therapy according to the NHLBI/GINA guidelines, there are patients who have inadequately controlled asthma, require significant use of health services, and are at risk of severe exacerbations, highlighting an important unmet need. The Th2 pathway plays a key role in the development of airway inflammation, mucus production, and airway hyperresponsiveness in asthma. Biological compounds targeting these molecules, including IL-5, IL-9, and IL-13, are under development and may ultimately provide a new therapeutic modality for patients with uncontrolled severe asthma.

Interview conducted by Jessica Livingston