The Link Between Cytokine Levels and Loss of Olfaction in Chronic Rhinosinusitis—Reply

In Reply We would like to thank Mr Chidambaram and Mr Goh for their interest in our recent article. They commend our study for using validated olfactory metrics, but raise a number of concerns regarding the labile nature of cytokines. Their first point is that the study was conducted on the grounds of ex vivo experiments and animal models and it is questionable that inflammatory cytokines display a consistent profile in chronic rhinosinusitis (CRS). While it is very likely that cytokine and biomarker levels vary throughout the dynamic course of CRS, our patients were sampled when they were most likely to demonstrate the most severe states of inflammation—off systemic steroids and presenting for treatment. Furthermore, our studies were actually based on numerous in vivo human studies that are pursuing local sampling of inflammatory cytokines as a means of classifying CRS. For example, recent work has shown that CRS patients can be clustered based on local tissue cytokine levels that may represent specific endotypes. While there are certainly going to be fluctuations from patient to patient or during various time points in the course of CRS, there are some consistent findings across studies, such as elevated T helper 2 cytokines in patients with nasal polyps, and these may allow prognostic and/or mechanistic insights. We have previously demonstrated that mucus cytokines typically correlate with tissue levels; thus, while mucus cytokines in CRS certainly vary, sampling them appears to be a reasonable approach to further understanding this inflammatory process.

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