Heterogenous Inflammation in Chronic Rhinosinusitis without Nasal Polyps

Rationale: Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation, the type of inflammation in non-polypoid CRS (CRSsNP) is controversial. In European studies, CRSsNP showed distinct type 1 inflammation in ethmoid tissue (ET), but not in studies of CRSsNP uncinate tissue (UT) in the US. We have found regional differences in the expression of innate host defense molecules in the sinuses leading us to hypothesize that inflammatory patterns may have similar regional variability.

Methods: We collected inferior turbinate (IT), UT, and ET from controls, CRSsNP and CRSwNP and nasal polyp tissue (NP). Tissue mRNA expression for type 1 (IFN-γ), 2 (CLC, IL-13) and 3 (IL-17A) inflammatory markers was examined.

Results: Inflammatory signals in ET were stronger than in IT and UT, thus we focused on ET. The pattern of inflammation in CRSsNP ET (n=59) was heterogenous, and there were no significant differences, except in levels of CLC mRNA, compared to controls (n=20) and CRSwNP (n=36). When thresholds using the 90^th percentile of expression in controls were defined, 24%, 51% and 22% of CRSsNP ET showed type 1, 2 and 3 inflammation, respectively. In contrast, 81% and 83% of CRSwNP ET and NP had type 2 inflammation. Interestingly, several CRSsNP donors had mixed inflammation, and 10% showed all three types. Among CRSsNP patients, Lund-Mackay scores significantly correlated with type 2, but not type 1 or 3, inflammation.

Conclusions: CRSsNP is a heterogenous disease in the US, and therefore distinct therapeutic strategies may need to be determined based on the type of inflammation.