Key Points
- Patients with olfactory dysfunction are at an increased risk of trigeminal nerve dysfunction.
- This association is stronger in patients with parosmia.
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.
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.
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.
Postoperative doxycycline therapy facilitated wound healing in CRSwNP and ECRS patients and suppressed local mucosal inflammation.
Elevated immunoglobulin (Ig) E has been frequently observed in eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP). However, the relationship between IgE levels and immune microenvironment remains poorly understood. This study aimed to characterize the transcriptomic and immunologic profiles associated with different IgE levels in eCRSwNP, and to explore their potential clinical and biological significance.
We enrolled 30 patients with eCRSwNP and stratified them into IgE-high (tissue total IgE ≥ 34.55 kU/L and serum total IgE ≥ 100 kU/L, n = 18) and IgE-low (below both thresholds, n = 12) groups. Healthy nasal mucosa from 10 control subjects was included. Bulk RNA sequencing, gene ontology (GO), KEGG pathway analysis, and immunohistochemistry were performed to characterize IgE-associated transcriptional and protein expression profiles in nasal polyp tissues.
Compared with controls, IgE-high patients exhibited higher tissue-specific IgE levels against aeroallergens, more severe clinical manifestations, and greater asthma comorbidity. Transcriptomic profiling revealed distinct gene expression patterns between eCRSwNP and healthy mucosa, with enrichment of T2 inflammation markers (CCL13, POSTN, IL5, IGHG4, and IGHE). IgE-high polyps demonstrated mucus hypersecretion and increased antimicrobial peptide expression (ITLN1, LTF, LYZ), alongside downregulated ciliary function–related genes. Immunohistochemistry validated increased IgE, IgG4, CD79a⁺ B cells and reduced FOXJ1⁺ ciliated cells in IgE-high tissues, consistent with the transcriptomic findings.
Tissue IgE levels delineate clinically and transcriptionally distinct eCRSwNP endotypes. IgE-high nasal polyps demonstrated epithelial barrier dysfunction, mucus overproduction, and antimicrobial peptide activation, highlighting the potential of IgE-based stratification to guide personalized treatment strategies in eCRSwNP.
Botulinum toxin type A is a potent neurotoxin and was first approved for use in 1989; since there has been a surge in its uses. The latest international trend is the unapproved use of botulinum toxin for allergic and nonallergic rhinitis, being advertised as “Haytox.”
A single-group open-label non-randomized Phase 1 clinical trial was completed. Rhinitis and nonallergic rhinitis were confirmed via formalized examination and testing with total IgE and radioallergosorbent test (RAST). Participants received 40 units of botulinum toxin type A, administered topically intranasally, 20 units per nostril, using the LMA MAD Nasal Intranasal Mucosal Atomization Device. Safety of the intervention was assessed with adverse event tracking logs. Symptom scores were used to assess symptom reduction, including total nasal symptom score (TNSS), visual analog scale (VAS) measurements at Weeks 0, 2, 4, and 12. In addition, peak nasal inspiratory flow (PNIF) was measured at Weeks 0 and 4, with the minimum clinically important difference (MCID) being used to demonstrate any clinically significant change in the TNSS score.
15 participants enrolled, of which 14 participants received treatment, with no serious adverse or related adverse events reported. There was a statistically and clinically significant reduction in TNSS and a statistically significant reduction in VAS from Weeks 0 to 12.
In this Phase 1 trial, topical application of botulinum toxin via spray was shown to be safe, without any significant adverse events. It reduced the TNSS and VAS across the cohort. However, the treatment efficacy should be taken in context as there was no blinding, alternative dosing, or comparison against placebo or recognized active treatment options. This safety data should embolden future research trials.
TGA number: CT-2024-CTN-02905-1; ANZCTR number: ACTRN12624000772549
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