Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers

Not all stuffy noses are alike.  That’s the conclusion of a research study by Tomassen and colleagues published this month in the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol 2016; 137(5): 1449-1456).  Despite affecting one out of eight Americans, little is really known about chronic rhinosinusitis and treatment is often really frustrating.  To figure out more personalized approaches to tackling chronic rhinosinusitis, Tomassen’s group collected tissue samples from patients with chronic rhinosinusitis, as well as people who had no history of chronic rhinosinusitis.  They then analyzed 14 bio-markers to see if they could find groups of patients who had particular patterns of inflammation.

Ten distinct endotypes, or subgroups linked to biological pathways, that correlated to different features were identified.  The biggest differentiator was the level of IL-5.  Patients with higher levels were more likely to have polyps (outgrowths of the mucous membranes associated with more severe disease) and/or concomitant asthma.  Combined with the other markers, these findings can help identify people who would be expected to respond to different types of medications.  Since there are new medications that target individual inflammatory markers, such as IL-5, this information can provide valuable insight into personalizing an approach to reduce the frustration in treating chronic rhinosinusitis.

Toward precision medicine and health: Opportunities and challenges in allergic diseases

“Precision medicine” is a term that’s quickly gaining currency across all the different fields of medicine.  Specifically referring to the customization of healthcare in the context of each patient’s unique characteristics, including genetic and other biometric information, precision medicine seems to be on the cutting edge of healthcare.  But as Galli writes in this month’s issue, allergists have long prided themselves on a high degree of precision by testing for specific allergens and immunizing accordingly (J Allergy Clin Immunol 2016; 137(5): 1289-1300).  But now, with newer insights into genes and even the microbiome, we can take this precision medicine to another level.  Mining data from what is called the Information Commons – which includes the set of genetic and environmental factors predisposing to and/or exacerbating disease in individual patients – may help to devise approaches to more precisely and effectively diagnose and treat allergic disorders, or even to prevent these diseases.

The overarching goal is to move away from the “trial and failure” approach, where providers try therapeutics from the first-line down to the third- or fourth-line agents just to see if the approach works, towards a targeted selection of a treatment that is most likely to work.  Of course, all of this is easier said than done.  There is a lot of information about allergic disease that remains unknown and prevents us from applying precision medicine.  And even in diseases where a lot of data are available, we have yet to organize these data in a way that can move from the abstract towards a specific precise approach for a single patient.

Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among individuals with asthma

Asthma is a huge problem in the United States, and particularly among African-Americans.  Prior work has shown that African ancestry is associated with more asthma exacerbations, night-time symptoms, and worse lung function. What is it that makes African Americans so susceptible to poorly controlled asthma?  This is a question that Wells and colleagues investigate in this month’s issue of the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol 2016; 137(5): 1364-1369).  In particular, they seek to answer if African-American ancestry is linked to a poorer response to inhaled corticosteroids (ICS), one of the first-line agents in treating persistent asthma.

To measure the response to ICS, 399 participants completed six weeks of observed ICS treatment.  242 of these were African American, compared to 97 who were European in origin.  Adherence was monitored by a special device (DOSER-CT) to make sure that participants were taking their medication; asthma response was measured by simple lung function tests, and ancestry was confirmed by genetic analysis.  After six weeks, there did not appear to be a relationship between change in lung function in response to ICS and African ancestry.

That’s not to say that African Americans don’t have particular genes that make them more or less likely to respond to inhaled corticosteroids. Rather, genetic effects are spread in such a way that, all other things held equal, there’s a similar response among African Americans and European Americans.  It’s good to know that, in tackling the epidemic of asthma in African-Americans, ICS are useful and effective.