Asthma Research: Looking Beyond the Genes

James Thompson, MD Health Pro
  • Asthma is a complex disorder which may begin in the first year of life and last a lifetime. Modern medicine has focused on controlling this disease by reducing airway inflammation with inhalers. Although death rates from asthma have decreased steadily over the past 20 years, morbidity (the suffering associated with it) has changed very little for those who have moderate to severe disease.



    Tens of millions of dollars have been spent on research to define the genetic profile of asthma patients in order to develop the best treatment. For unexplained reasons, some people respond well to certain asthma medications while others don’t.

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    The study of genetic information and how it relates to drug therapy is called pharmacogenetics. Our genetic makeup is the blueprint for what makes us who we are. Our cells, body organs, bones, muscles, and nerves are formed as a result of genes (located on chromosomes) that provide vital information for growth and development. In recent years some interest has shifted from gene studies to phenotype studies.



    We can’t see or identify genes with the naked eye or even a powerful microscope. But we can see the outcome of our genetic makeup which is called “phenotype”. For example, the color of our skin, hair and eyes is the “phenotypic expression” of certain genes. There are many different genes found to be associated with allergy and asthma. The phenotypic expression of these genes has allowed the identification of certain asthma subtypes.



    A recent clinical study reported on a phenotype of severe asthma patients. They were called “frequent exacerbators,” which meant they had frequent severe flare-ups of asthma. The one-year study analyzed characteristics of 93 patients with severe asthma and 76 with mild to moderate asthma. The question was how they differed with respect to lung function, inhaled steroid use, cells in their sputum, certain blood test factors, tobacco use, and exhaled nitric oxide levels.



    Exhaled nitric oxide (ENO) has been available for many years as a means of measuring the level of inflammation in the lungs at a given time. The patient blows into a mouthpiece which analyzes the breath for nitric oxide. Higher breath levels of nitric oxide correlate with higher levels of inflammation in the lungs.

    Lung function tests were also done in order to measure the severity of asthma in the study patients. Lung function was measured by spirometry (a type of breathing test based on forced exhalation of air into a mouthpiece) which is a component of pulmonary function testing.



    Study results showed two major differences between patients with severe asthma (frequent exacerbators) and patients with milder asthma. First, a higher number of patients with severe asthma had a history of smoking tobacco. Second, ENO levels were significantly higher in the severe asthma group compared to the milder asthma group.



    What are the take-home messages in this study?


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    Actually, there are no surprises in the study findings. It’s understandable and expected that people who have more severe and difficult-to-control asthma will require more or stronger medication, have more abnormal breathing tests, and more likely have a smoking history compared to milder asthmatics. But the take home messages for me are:


    1)    Pulmonary function testing (spirometry) and/or peak flow rate monitoring have been a mainstay in routine assessment of asthma for many years. ENO has recently emerged as an additional tool to objectively measure inflammation. This study further supports the inclusion of ENO in the management of asthma.


    2)    ENO may assist in identifying patients who may require closer monitoring (follow-up appointments) and adjustment of their medications based on serial ENO and lung function tests.


    3)    Tobacco cessation counseling is an essential component of asthma management for those who continue to smoke.


    4)    Greater strides should be taken with older children and young adults to discourage them from ever smoking. Informing them (and parents) early on about the future risk of more severe and hard-to-control asthma may be a helpful deterrent.


    5)    Asthma has many different faces (phenotypes), which explain why treatment plans should be individualized based on historical factors, familial information, trials of medication and follow-up assessments. The above study further highlights the importance of a comprehensive evaluation by an asthma care provider in order to best manage this treatable disease.





    Kupczyk M, ten Brinke A, Sterk PJ, et al et al: Frequent exacerbators--a distinct phenotype of severe asthma.



Published On: July 28, 2014