Saturday, July 21, 2012

Are Allergies Contributing to My Asthma?

Studies demonstrate that at least 60% of adults with asthma and 80% of children with asthma are sensitized to one or more common environmental allergens. But what is allergic sensitization, and how might being allergic to something contribute to asthma?

Allergies are the result of the immune system, a complex and diverse group of cells in the body, many of which start of in the bone marrow, then circulate in the blood as white blood cells, and eventually leave the blood to enter body tissues like the lungs and the gastrointestinal tract. It is believed that the immune system’s main function is to defend the body against danger. Most often, that danger is from infection – the invasion of the body by micro-organisms like bacteria, viruses, parasites, and fungi. The immune system is not only like a combined armed forces, police, and fire department (defending the healthy “citizens” of the body), but also a like a border guard, checking the identity of things that enter into the body every day when we breath, eat, and drink – weeding out the “terrorists” from the “tourists.”

Although a precise understanding of the molecular and cellular details is incomplete, a popular hypothesis is that allergies result when the immune system mistakenly identifies a harmless substance (such as dust mite or cat dander protein) as if it were dangerous. The immune response against these substances constitutes an allergic reaction. Among the many cells involved in such reactions, the mast cell is a powerful central player in allergies. Armed with claw-like molecules called “IgE antibodies,” mast cells in the airways can bind to allergenic proteins, which triggers the release of mast cell inflammatory chemicals like histamine, leukotrienes, and cytokines that bring about many of the features of asthma. Mast cell activation by allergens can lead to airway spasm (bronchoconstriction), mucus hypersecretion, and the influx of other inflammatory cells such as eosinophils. This allergic inflammation results in asthma symptoms like wheezing, cough, and breathlessness.

Allergies such as “hay fever” (known in medical parlance as “allergic rhinitis”) are common. Knowing whether allergies contribute to asthma can be an important part of prevention and treatment. If allergies are part of what drives your asthma, avoidance of allergic triggers, treatment with allergy medications, and the use of allergy immunotherapy (“allergy shots”) to reprogram the immune system away from its mistaken attack against common harmless substances may help. Allergy testing –blood testing or skin testing – in conjunction with a careful history and physical exam at a visit with an allergist can answer the question of whether or not allergies are contributing to your asthma.

Saturday, July 14, 2012

Long-Acting Beta Agonists (LABAs) - Why All the Fuss?

Every package insert of a medication containing salmeterol (Serevent) or formoterol (Foradil), including the very popular and effective bronchodilator-steroid combinations, Advair, Symbicort, and Dulera, includes a black-box warning about serious potential risks from these long-acting beta-agonist bronchodilators. In persons with asthma, the warning notes, use of these medications is associated with an increased risk of death and near-death (requiring ICU care) from an asthma attack.

Therein lies a major dilemma. Highly effective medications used to control asthma, recommended by national and international panels of experts in their Guidelines for optimal management of asthma, may pose a risk of causing a fatal or near-fatal asthma attack. Why do we say “may” pose a risk? Evidence from a large study (26,000 subjects) indicated an increase in asthma deaths and near-fatal asthma attacks among persons treated with salmeterol compared to placebo, but it did not control what other medications persons participating in this study were taking. Most of the subjects were not taking an inhaled steroid. It is well accepted that a long-acting beta agonist without a medication to control the inflammation of the bronchial tubes in asthma is a bad idea. But what about patients who take an inhaled steroid (such as those combined with a long-acting bronchodilator in Advair, Symbicort, and Dulera)? Are they then safe from any increased risk of severe asthma attacks?

This question is central to the future of asthma care. The answer is too important to leave to speculation and opinion. So the FDA has mandated that a large-scale study be performed in which all subjects (more than 45,000 to be recruited) will receive an inhaled steroid. In addition, half will also receive a long-acting beta-agonist bronchodilator and half will receive a placebo. Participants will be observed for 6 months to determine whether the two groups have any differences in their rates of hospitalization, respiratory failure, or death from asthma. And then – around 2017 – we will know the answer.

In the meantime, we rely on hunch, intuition, and best guess based on information currently available. Our bias is that the long-acting beta-agonist bronchodilators when used in combination with an inhaled steroid will prove to be safe as well as effective.

P.S. Long-acting beta-agonists in patients with COPD are not associated with any increase in respiratory-related deaths or near-deaths from COPD.