Asthma is a disease of the lung airways. It is different from all other diseases of the lungs in that no other contributory factors are involved. So theoretically, once the restriction of the airways is resolved, the lungs retain normal structure and performance. Aside from the tightening of the muscle layers of the airway, which causes contraction, there is also an inflammatory reaction that causes a thickening of the inner layer of the airways. The net result is a narrowing of the inner space of the airways. This makes it much harder to move air deep into the lungs. That is the essence of the shortness of breath that accompanies asthma.
The treatment strategy for asthma is to prevent this inflammation before it happen, or resolve the inflammation when it does occur. To do that, one must understand the complicated process that involves many cells, chemicals, and protein antibodies at many different levels, causing the inflammation.
Years ago when lecturing medical students using some very busy and complicated slides, showing all these reactions in sequence, I said that the day will come where we could have a medicine or an injection to suppress each of these steps. I was wrong.
In the past 15 years only one medication has been developed. It’s called Omazilumab (Xolair). It’s an injection that interferes with the binding of the receptor of immunoglobulin E (IgE). This is the antibody that is responsible for allergies. The problem is that the drug just prevents the IgE from binding at the receptor site. It doesn’t prevent the protein from circulating loose in the blood stream.
The whole idea of developing these agents was abandoned and asthma was just treated with steroid inhalers and inhalers are known as bronchodilators. Essentially all the new drugs for asthma were just imitators of old ones. In the meantime, the concept of directed therapy with these “biological “ agents was pursued successfully in other areas such as cancer and rheumatoid arthritis.
Biologicals for asthma
Recently there’s been a lot of attention in the media for agents known as biologicals, or biopharmaceuticals. These are medications that inhibit inflammatory proteins by binding to their receptor sites. You may be familiar with some of the names of these biologicals, including Humira, Embrel, and Arava, because thanks to advertisers they have become household names. They have been very successful in the treatment of Rheumatoid Arthritis and Cancer.
Finally, there has been a new biological agent developed specifically for asthma. It’s called Mepolizumab (Nucala). It’s an injection that contains an antibody to the inflammatory agent called interleukin 5 (Il-5). Interleukins are a series of substances that cause inflammation in various disease processes including asthma.
What makes this medication effective in asthma is that it counteracts the activity of cells known as eosinophils, which are also responsible for allergic reactions that can lead to asthma inflammation. One can easily see the complementary action that this drug would have with the previous agent discussed, Omazilumab, since both of these will act on different levels of the inflammatory reaction causing asthma. It’s a one-two punch against the inflammatory process.
The promise of biologicals is that they may have the potential to personalize the treatment to select individual pathways of disease processes. Biologicals treat the source of asthma rather than the symptoms (once an asthma attack has occurred). The key to treatment success is identifying the patients that are likely to benefit from drugs like biologicals. After all, they are much more expensive.
Healthcare professionals, like myself, are becoming aware that asthma is a very broadly used term and the diagnosis often applies to every person who at some point has narrowing of the airways and shortness of breath. The individuals who would benefit for this targeted therapy will be those who have the ongoing inflammatory process, even when they don’t feel it. If allowed to continue, this sometimes asymptomatic process will cause permanent, irreversible damage.
Rising to the challenge of identifying patients who can benefit from this new class of treatment drugs will elevate the diagnosis and treatment of asthma to more specificity and greater prevention.
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