EXHANCE‐12: 1‐year study of the exhalation delivery system with fluticasone (EDS‐FLU) in chronic rhinosinusitis

Background

Inadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS.

Methods

This was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed.

Results

Of 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by ?21.5 and ?21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade.

Conclusion

Over 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition.

     

Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non‐eosinophilic chronic rhinosinusitis

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non‐eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.

Methods

Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis [IPA]) were used to interrogate the data sets.

Results

Hierarchical clustering and principal component analysis (PCA) collectively showed that ECRSwNP and NECRSwNP had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T‐helper 2 (Th2) and the eosinophilia–related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis–related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP.

Conclusion

These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.

     

Corticosteroid nasal irrigations are more effective than simple sprays in a randomized double‐blinded placebo‐controlled trial for chronic rhinosinusitis after sinus surgery

Background

Persistent mucosal inflammation in patients with chronic rhinosinusitis (CRS) often results in ongoing symptoms, recurrence of polypoid mucosa, infective exacerbations, and further systemic medication despite surgical intervention. Debate exists as to the most effective topical therapy in CRS.

Methods

The objective was to determine if corticosteroid delivered via a nasal irrigation or via a simple nasal spray would be more effective in controlling the symptoms and signs of CRS. A double‐blind placebo‐controlled randomized trial over 12 months was performed between 3 tertiary rhinologic clinics. After sinus surgery, all patients performed a nasal irrigation followed by a nasal spray once a day for 12 months. Groups were defined by corticosteroid (2 mg mometasone) delivered by either spray or irrigation. The primary outcomes were patient‐reported symptoms: visual analogue score (VAS) and 22‐item Sino‐Nasal Outcome Test (SNOT‐22), a global rating of sinonasal function. Secondary outcomes were also recorded from radiology (Lund‐Mackay score [LMS]) and endoscopic (Modified Lund‐Kennedy score [mLKS]) assessments.

Results

A total of 44 patients were randomized (age 50.3 ± 13.0 years; 40.9% female). Overall, patients improved significantly from either intervention. However, the corticosteroid nasal irrigation group had greater improvement in nasal blockage (?69.91 ± 29.37 vs ?36.12 ± 42.94; p = 0.029), a greater improvement on LMS (?12.07 ± 4.43 vs ?7.39 ± 6.94; p = 0.031) and less inflammation on mLKS at 12 months (7.33 ± 11.55 vs 21.78 ± 23.37; p = 0.018). One‐year posttreatment blockage, drainage, fever, and total VAS scores were all lower in the corticosteroid irrigation group.

Conclusion

In the setting of diffuse or patchy CRS disease, the use of corticosteroid delivered by nasal irrigation is superior to simple nasal spray in postsurgical patients.

     

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis

Background

IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS).