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Learning from Corticosteroid Resistance in Asthma

I was doing some research recently and came across a newly published study that highlighted the discovery of a molecule that underlies corticosteroids are not effective in a particular asthma population.1

Asthma is becoming more and more recognized as a disease with lots of phenotypes, they all have their own unique molecular mechanisms, natural history, and response to therapy.2,3,5,6 The paper discusses the importance of this discovery in helping to identify a phenotype that is corticosteroid resistant,

The new discovery is thought to be really important because it highlights that inhaled corticosteroids, which are a pillar of airway inflammation treatment but have been found to be ineffective in 5 to 10% of severe asthma patients. Researchers are working hard to better understand asthma in this particular population of asthmatics. Researchers are making progress by previously identifying that increased levels of the inflammatory protein interferon gamma in the airways and its role as being important in asthma.6 The paper examined mouse models, I which identified that interferon gamma was responsible for poor lung function. Interferon gamma signaling is hypothesized as being the culprit for poor responses to corticosteroid therapy in some severe asthmatics. Research have focused specifically on a protein CXCL 10 that is produced by interferon gamma that recruits immune cells that produce it causing a perpetuating cycle of inflammation.4,5

Research found that CXCL 10 was identified in about half of severe asthma patients treated by inhaled corticosteroids. They were also higher in severe asthma patients than in milder asthmatics. This is important as it helps researchers to be able to develop a picture of who has CXCL identified in their cells and their steroid responsiveness. Researchers were able to identify that CXCL 10 can be classified into those that are high CXCL 10 and those that are low CXCL 10.

What do researcher think the relationship between CXCL 10 and corticosteroid response is?

While ongoing and future research will be needed to further understand the relationship in more detail. Researchers have been able to culture immune cells that showed that corticosteroid failed to suppress CXCL gene expression in immune cells. This has allowed researchers to recognize that corticosteroids have limited value in patients with high CXCL 10 values from interferon gamma. Researchers are working on identifying a way to block the inflammatory loop by CXCL 10 and interferon gamma. They also hope to develop a biomarker that can be used in a clinic setting that will assist in identifying patients who will not respond to corticosteroids, which will prevent them from experiencing related side effects.4

I hope this will provide a bit of good news to people that are not responders to corticosteroids and hopefully there will soon be away to keep physicians from prescribing them to this population of asthmatics.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The Asthma.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–725.
  2. Gauthier M, Ray A, Wenzel SE. Evolving Concepts of Asthma. Am J Respir Crit Care Med. 2015;192(6):660–668.
  3. Ray A, Oriss TB, Wenzel SE. Emerging molecular phenotypes of asthma. Am J Physiol Lung Cell Mol Physiol. 2015;308(2):L130–L140.
  4. Woodruff PG, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–395
  5.  https://www.sciencedaily.com/releases/2017/07/170706114602.htm
  6. Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias. Marc Gauthier,1 Krishnendu Chakraborty,1 Timothy B. Oriss1, Mahesh Raundhal,1 Sudipta Das,1 Jie Chen,1 Rachael Huff,1Ayan Sinha,1 Merritt Fajt,1,2 Prabir Ray,1,2,3 Sally E. Wenzel,1,2,3 and Anuradha Ray1,2,3

Comments

  • cali
    1 year ago

    This article really hit home…..thank you! I’ve had adult onset asthma for 37 years along with a super sensitive/reactive system. Steroids and corticosteroids have yielded awful side effects but never the relief others seemed to experience, so for many years I’ve lived on rescue inhalers and random trips to the ER. Last year brought two rounds of pneumonia and thankfully, I recoved from both. Unfortunately, my asthma is now Severe with lung function of 25% (no improvement with steroids). It’s daunting and I pray options will be found for all those whose treatment doesn’t fit inside “the box”.

  • Leon Lebowitz, RRT moderator
    1 year ago

    Hi Cali and thanks for sharing your asthma experience with the community. We’re so glad this article resonated so highly for you. Thanks for being par of our online community! All the best, Leon (site moderator)

  • Katheryn48808
    2 years ago

    Corticosteroids are not useable for me. They cause uncontrollable vomiting, massive weight gain, and there is a rebound issue… they let in so many allergens that I cannot breathe.
    Not only that but corticosteroids cause thinning of tissues… explain to me why you want thinned lung tissue?
    This is a bad medication that should be removed from the market.

  • Leon Lebowitz, RRT moderator
    2 years ago

    Hi Katheryn48808 – I too am sorry to hear corticosteroids are not an option for you. I would underscore John’s comments and hope that you and your physician can find an alternate form of treatment.
    I thought you might find it helpful and interesting to review John’s recent publication on this very subject: https://asthma.net/living/steroid-injections-a-pain-in-the-butt/.
    All the best,
    Leon (site moderator)

  • John Bottrell, RRT moderator
    2 years ago

    Hi. Katheryn48808. Sorry to hear you had such a bad experience with corticosteroids. It is so true they do not work for everyone. It’s also important to note that about 90% of asthmatics do respond well to them, and it’s for this reason they are recommended as a top-line option for asthma. So, it’s pretty good odds they will remain on the market. In the meantime, I certainly hope that you and your doctor were able to find an alternative medicine (or medicines) to help you control your asthma. John. Site Moderator.

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