ESS for CRS Does Not Reduce CST1 Expression in Asthmatics

Introduction: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by simultaneous presence of Type 2 and non-Type 2 inflammation. When medical therapy fails, endoscopic sinus surgery (ESS) may be performed, however, resolution of disease following ESS does not always occur, particularly in patients with comorbid asthma. We wished to assess differences in response to surgery between asthmatic and non-asthmatic patients undergoing surgery for CRSwNP.

Methods: This is a secondary analysis of a prospective cohort study of patients with CRSwNP undergoing ESS, that was undertaken between November 2014 and December 2016. Pattern of recovery following ESS was assessed using transcriptomic analysis performed on sinus mucosal brushings collected on the day of surgery and 4 months post-op and was compared for asthmatic and non-asthmatic patients.

Results: Of 116 patients enrolled in the study, 65% were asthmatic. Greatest differences in pattern of recovery were for CST1 gene expression. While high preoperative CST1 levels were present in both groups, these resolved following surgery only in non-asthmatics. In contrast, asthmatics completely failed to resolve CST1, yielding higher postoperative levels (FC=41.4; adj. pval= 0.036). Other differences identified were increased cell dysfunction and higher T1 inflammation in asthmatics after ESS.

Conclusions: A major difference in response to ESS between asthmatics and non-asthmatics is the inability of asthmatics to resolve expression of cysteine antiproteases, leading to persistently high level of CST1 expression. This finding extends upon previous reports describing cysteine antiproteases as markers of failure of response to surgery (Blier, 2021) and offer a mechanistic link between CST1 and asthma.