What Are Subgroups, Phenotypes, And Endotypes?

Asthma is now considered an umbrella term under which various asthma subgroups fall. Modern terms for subgroups are phenotypes and endotypes. So, what are subgroups, phenotypes, and endotypes anyway? Here are some basics to know.

What is a subgroup (subtype)?

It’s a way of lumping asthmatics who present with similar clinical presentations together. For instance, two older subgroups are Extrinsic (allergic) and Intrinsic (non-allergic).The former is now the asthma subgroup: Allergic Asthma

The later is now subdivided into a variety of subgroups that include:

Two other older subgroups were adult-onset and childhood-onset asthma. These are now recognized as early-onset and late-onset asthma.Early-onset means it’s diagnosed before the age of 12. It’s almost always Allergic Asthma. It responds well to corticosteroids. Late-onset means it’s diagnosed after the age of 12. It’s usually any other subgroup listed above other than Allergic Asthma. These late-onset subgroups are more likely to become Severe Asthma

What is a phenotype?

It’s a new term for a subgroup. It’s defined as:
“Observable properties of an organism that are produced by the interactions of the genotype and the environment.”3-4 Or, worded another way:“Patients with common characteristics are grouped together in an attempt to guide therapy and management.”5 At the present time, this is the most common method of subgrouping. There are three problems with clinical phenotyping. One, there is no specific test that says, “You have this phenotype or you have that phenotype.” So, a diagnosis is usually left to the judgment of the physician or researcher.Two, there is no set agreed upon definition to specific subgroups. For this reason, less well-understood subgroups may go undiagnosed and untreated. Examples of this are psychological induced asthma and premenopausal asthma.Three, a person’s phenotype may change over time. This makes it hard for doctors to understand a person’s asthma, making it hard to treat.2, 8 Still, phenotyping is very useful for studying, diagnosing, and treating asthma. But, someday there will be a shift to endotypes.

What is an endotype?

It’s defined as:
“A specific biological pathway is identified that explains the observable properties of a phenotype.”4It’s defining subgroups or phenotypes by specific cells or molecules in blood or sputum. It’s a more specific, more accurate, way of defining subgroups.6Here are two examples of endotypes.

Eosinophilic Asthma.

Eosinophils cause airway inflammation. They are what makes asthma persistent. Their levels increase when you’re exposed to your asthma triggers, and then decrease (Allergic). When they stay elevated between attacks they can cause severe asthma. In either case, it’s diagnosed by a sputum or blood test. It responds well to corticosteroids and other traditional asthma medicines.

Neutrophilic Asthma.

Neutrophils also cause airway inflammation. This endotype is not well understood. Still, it’s diagnosed by a sputum or blood test. It does not respond well to corticosteroids and other traditional asthma medicines. This tends to make it a subgroup of severe asthma. Asthma-COPD Overlap Syndrome is one subgroup that falls under this endotype. Another is Occupational Asthma.

Endotypes do not change with time or treatment.8 This is because the types of cells, or the type of inflammation present, will not change. The problem with endotypes is they are not well defined or understood. This is because researchers remain on the cutting edge of genetic research. They are still learning about asthma genes and how they cause asthma.

What will the future bring?

In the short term, you can expect doctors to continue using phenotypes. This is because they are easier to understand given what we know today. In the future, you should expect to hear more about endotypes. This will happen as researchers learn more about asthma genes and how they cause asthma. In the meantime, I will continue to use the term subgroup. This is because this term pretty much covers both phenotypes and endotypes.

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View References
  1. “Genotype,” Merriam-Webster, https://www.merriam-webster.com/dictionary/genotype, accessed 9/25/17
  2. Lockey, Richard F., “Defining Phenotypes: Expanding Our Understanding of Asthma Challenges in Treating Heterogeneous Asthma,” NHLBI, slideshow, http://www.worldallergy.org/UserFiles/file/NHLBI%20Asthma%20Phenotypes-Lockey.pdf, accessed 3/3/17
  3. “Phenotype,” Merriam-Webster, https://www.merriam-webster.com/dictionary/phenotype, accessed 9/25/17
  4. Wenzel, Sally, “Asthma phenotypes: the evolution from clinical to molecular approaches,” Nature Medicine, 2012, May, Vol. 18, No. 5, pages 716-725, http://www.healthylungs.com.au/resources/WenzelAstham-Phenotypes.pdf, accessed 10/31/16
  5. Brasier, Alan R., editor, “Heterogeneity In Asthma,” 2014, New York, Springer, pages 5-13
  6. Agache, Iona, Cezmi A. Akdis, “Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine, Allergology International, 2016, July, http://www.sciencedirect.com/science/article/pii/S132389301630048X, accessed 9/25/17
  7. Asthma Phenotypes, AAAAI.org, http://www.aaaai.org/ask-the-expert/asthma-phenotypes, accessed 9/23/17
  8. Robinson, D. et al, “Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications,” Clinical And Experimental Allergy, 2017, January 30, http://onlinelibrary.wiley.com/doi/10.1111/cea.12880/full, accessed 9/23/17
  9. Gorski, Pawel, "Asthma Phenotypes," Power Point PPT Presentation, http://www.slideserve.com/liv/asthma-phenotypes