Mechanisms and Kinetics of Wound Healing in Chronic Rhinosinusitis Patients After Complete Sinus Surgery and Its Improvement by Doxycycline Therapy.

BACKGROUND

Chronic rhinosinusitis (CRS) may require endoscopic sinus surgery (ESS) as a complement to medical therapies. Type 2 dominant inflammation underlies nasal polyposis (CRSwNP), and is characterized by eosinophilic inflammation, poor therapeutic response, and high recurrence risk. Type 2 inflammation was defined as eosinophilic CRS (ECRS) based on clinical presentation and laboratory findings. Unfavorable wound healing, associated with elevated levels of matrix metalloproteinase 9 (MMP-9), can lead to failure of ESS. Doxycycline with its antibiotic, anti-inflammatory, and anti-protease (including MMP-9) properties may improve postoperative healing.

MATERIALS AND

METHODS

Thirty-three adult CRS patients scheduled for ESS were randomly assigned to receive either doxycycline or placebo for 56 days postoperative and were followed up until 48 weeks post-ESS. Postoperative wound healing was assessed endoscopically. Nasal secretions, serum, and patient-reported outcome measures were collected throughout the study. Nasal secretions were analyzed to monitor local myeloperoxidase (MPO), MMP-9, eosinophilic cationic protein (ECP), and IgE levels from baseline until 48 weeks post-ESS. Proteomics analysis, using LC-MS/MS, of nasal secretions was performed at baseline, 2- and 8-weeks post-ESS to investigate wound healing mechanisms.

RESULTS

Postoperative doxycycline significantly improved wound healing quality in patients with CRSwNP or ECRS. Increased local MMP-9, neutrophilic (MPO), and eosinophilic (ECP) inflammation post-ESS was dampened by doxycycline. Wound healing and extracellular matrix remodeling processes were upregulated by doxycycline treatment. In contrast, the placebo group showed increased neutrophilic inflammation and delayed healing.

CONCLUSIONS

Postoperative doxycycline therapy facilitated wound healing in CRSwNP and ECRS patients and suppressed local mucosal inflammation.