In patients with chronic rhinosinusitis following endoscopic sinus surgery, azithromycin restores epithelial function through upregulation of DNA repair and cycle pathways. Azithromycin also decreases type 1 (T1) inflammation through interferon (IFN) and tumor necrosis factor (TNF) pathways in these patients. These were among study findings presented at the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) 2022 Annual Meeting and OTO Experience, held in Philadelphia, Pennsylvania, September 10 to 14, 2022.
Previous in vitro studies have shown azithromycin reduces T1 inflammation and restores epithelial barrier function. Researchers for the current study sought to add confirmation to these in vitro results.
The researchers conducted transcriptional profiling within a clinical trial of azithromycin that included 31 patients who failed endoscopic sinus surgery (ESS) and budesonide nasal irrigation. These patients were randomized to receive placebo (n=18) or azithromycin (n=13) for 16 weeks. The researchers’ analysis included gene expression profiling and gene set enrichment analysis (GSEA).
Researchers found that after 16 weeks, azithromycin was linked to a greater down-regulation of pathways associated with T1 inflammation than placebo. These pathways included IFN response (P =.001), hallmark TNF–α signaling through the nuclear factor kappa B (NFkB) pathway (P =.001), and inflammatory response (P =.001). The researchers also found an increase in epithelial progenitors with upregulation of key pathways, including E2F targets (P =.001), G2M checkpoint (P =.001), hallmark DNA repair (P =.001), and MYC targets V1 (P =.001), and concomitant restoration of the cell cycle.
Trial limitations include the underpowered sample size.
Researchers concluded that “This study demonstrates for the first time that azithromycin successfully decreases T1 inflammation through the IFN and TNF pathways along with restoration of epithelial function through upregulation of DNA repair and cycle pathways.” They added that these findings suggest “azithromycin may be employed as a T1 modulating agent in refractory T1 chronic rhinosinusitis.”
Renteria AE, Maniakas A, Filai-Mouhim A, Cardoso FV, Brochiero E, Desrosiers MY. Azithromycin reduces type 1 inflammation and induces epithelial restoration after endoscopic sinus surgery. Otolaryngol Head Neck Surg. 2022;167(1 suppl):P141.