Learning from Corticosteroid Resistance in Asthma
RATE

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.

view references
  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
advertisement
SubscribeJoin 5,000 subscribers to our weekly newsletter.

Your username will be visible to others.


Reader favorites