In the future, we will be able to subdivide patient groups more precisely, and that will lead to rolling out precision, personalized medicine in which we can really predict from mucus or a blood sample how to treat patients. —Robert Kern, MD
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July 2019
Clinical Patterns and Subtypes
Although the presence or absence of nasal polyps is the cornerstone on which the current treatment of CRS is based, additional information on the clinical patterns of CRS is emerging that provides more direction for clinicians. These data point toward clinical indicators such as age, geography, ethnicity, and others associated with different underlying pathogenic mechanisms of CRS and, therefore, support the use of endotyping.
One area of research suggests the importance of age in distinguishing the type of inflammation and its potential impact on treatment outcomes. Dr. Turner and his colleagues recently published a study in which they found that older people with CRS had elevated tissue and mucus levels of pro-inflammatory cytokines associated with innate immune system dysfunction, were more likely to harbor colonizing bacteria in the sinonasal tract, and had more neutrophilic inflammation regardless of polyp status or other clinical variables when compared with younger patients (J Allergy Clin Immunol. 2019;143:990–1002). “Older CRS patients may appear similar to younger patients on physical exam but differ in many other ways,” said Dr. Turner. “Given the unique inflammatory signature that we have identified in older patients, we feel that it is essential that age be taken into account when planning treatment approaches.”
Specifically, when examining tissue and mucus specimens of 147 patients ranging in age from 18 to 78 years who underwent sinus surgery for CRS, the investigators found that the inflammatory signature of a subgroup of patients older than age 60 was very different from that found in patients younger than 60. Whereas the inflammatory signature in the younger patients was characterized by a group of cytokines (Th2-associated) found in most CRS in North America, these cytokines were not significantly elevated in older patients. Rather, the inflammatory signature in the older patients was associated with a neutrophilic proinflammatory response characterized by an elevation in cytokines linked to the body’s innate immune function and acute and chronic inflammatory response. “You don’t see an elevation in those cytokines until around age 60, and then from that age on, there’s a progressive increase in the levels of those cytokines seen in the mucus and tissue of those patients,” said Dr. Turner.
One important implication of this finding is that current treatment approaches for CRS may be less effective in older patients. “Neutrophilic inflammation is typically less responsive to topical and systematic corticosteroids,” said Dr. Turner. “This would suggest that great care should be taken when prescribing repeated courses of oral steroids in older patients, and strongly suggests the need for alternative therapies to more effectively target this vulnerable population.”
Another area of research shows that people with CRS living in Asian countries are likely to have more neutrophilic inflammation than people living in Europe/North American countries. For example, a 2017 study found that most people with CRS in Europe/North America (80%) have nasal polyps characterized by increases in eosinophilic cytokines (type 2 inflammation), compared to 20% in China and 60% in Korea or Thailand (J Allergy Clin Immunol. 2017;140:1230–1239).
According to Amber Luong, MD, PhD, associate professor in the department of otorhinolaryngology–head and neck surgery at McGovern Medical School of The University of Texas Health Science Center at Houston, the differences in the types of inflammation found in nasal polyps in these geographical populations highlights the fact that while people with CRS can look clinically similar (i.e., have the presence of nasal polyps), they are very different molecularly.