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.