Relating endotypes to phenotypes and clinical findings of disease
Several groups have examined the association between endotypes and clinical phenotypes in CRS. In general, T2 inflammation is associated with NP (in the West) and asthma 43,102. The type 2 eosinophilic inflammation is also associated with disease recurrence and severity in CRSsNP and CRSwNP 70,103,104. A study of the association between endotypes and phenotypes was conducted by Stevens et al., who examined inflammatory endotypes using markers including IFN-γ (T1), eosinophilic cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3) in the ethmoid and NP tissue and related them to clinical parameters from medical and surgical records58. The T2 endotype was associated with the presence of NP, asthma comorbidity, smell loss, and allergic mucin in all CRS patients. The presence of pus was associated with the T3 endotype, and headache/migraine was negatively associated with the T1 endotype. When assessing patients with CRSsNP alone, smell loss and headache/migraine were associated with a T2 endotype, and the presence of pus was more common in T1 and T3 endotypes. Similarly, the T3 endotype was also associated with pus in patients with CRSwNP, and the T2 endotype tended to be associated with smell loss in patients with mixed endotypes. In contrast to the CRSsNP subgroup, headache/migraine was lower in the presence of T2 endotype in patients with CRSwNP 58.Figure 4 summarizes the relationship between phenotype and endotype based on these findings.
A study using cluster analysis showed that older adults with CRS were more likely to have neutrophilic inflammation in the sinus tissue and elevated proinflammatory cytokines, IL-1β, IL-9, TNF-α, and IL-6 in the mucus compared to younger individuals with CRS 105. The neutrophilic inflammatory pattern observed in older individuals was clinically associated with purulent drainage and a higher likelihood of bacteria. Potentially, these patients with predominantly neutrophilic inflammation are less likely to respond to corticosteroids or biologics and may respond to macrolides. Finally, elevated local IgE in NP tissue compared to control sinonasal tissue has been observed in patients with CRSwNP. Bachert and others have reported elevated levels of specific IgE (sIgE) against Staphylococcus aureus enterotoxins (SAE) in the NP tissue and systemic circulation 106,107. The presence of sIgE to SAE has been associated with comorbid asthma and more severe sinonasal disease 108,109.