Inhibition of capsaicin-driven nasal hyper-reactivity by SB-705498, a TRPV1 antagonist.

AIMS: To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal SB-705498, a selective TRPV1 antagonist. METHODS: Two randomized, double-blind, placebo-controlled, clinical studies were performed: (i) an intranasal SB-705498 first time in human study to examine the safety and PK of five single escalating doses from 0.5 to 12 mg and of repeat dosing with 6 mg and 12 mg twice daily for 14 days and (ii) a PD efficacy study in subjects with non-allergic rhinitis (NAR) to evaluate the effect of 12 mg intranasal SB-705498 against nasal capsaicin challenge. RESULTS: Single and repeat dosing with intranasal SB-705498 was safe and well tolerated. The overall frequency of adverse events was similar for SB-705498 and placebo and no dose-dependent increase was observed. Administration of SB-705498 resulted in less than dose proportional AUC(0,12 h) and Cmax , while repeat dosing from day 1 to day 14 led to its accumulation. SB-705498 receptor occupancy in nasal tissue was estimated to be high (>80%). Administration of 12 mg SB-705498 to patients with NAR induced a marked reduction in total symptom scores triggered by nasal capsaicin challenge. Inhibition of rhinorrhoea, nasal congestion and burning sensation was associated with 2- to 4-fold shift in capsaicin potency. CONCLUSIONS: Intranasal SB-705498 has an appropriate safety and PK profile for development in humans and achieves clinically relevant attenuation of capsaicin-provoked rhinitis symptoms in patients with NAR. The potential impact intranasal SB-705498 may have in rhinitis treatment deserves further evaluation.

Evidence-based surgery for chronic rhinosinusitis with and without nasal polyps.

Meta-analysis of both large outcome studies as well as cohort studies support the safety and efficacy of Endoscopic Sinus Surgery for Chronic Rhinosinusitis. The efficacy of endoscopic sinus surgery is demonstrated in the improvement of both disease-specific and generic QOL as well as objective measures. However, this must be interpreted together with a well-recognized long-term 15-20 % revision rate, seen more often in patients with ASA trias and cystic fibrosis as well as osteitis and previous surgery. The effect of surgery is higher in managing nasal obstruction (effect size 1.7) and less so hyposmia (effect size 0.8). Allergy has an additive role on the symptomatology of CRS; however, its role if any on the outcome of ESS for CRS is unclear. The concurrent presence of aspiring sensitivity and asthma is associated with increased disease burden and more revision surgeries. Improved phenotyping of CRS may lead in the future to better tailoring of surgical treatments.

Clinical Approach After Complicated Ear Mold Fitting: A Case Series of Six Patients and Evaluation of Literature.

OBJECTIVES: Insertion of mold material into the middle ear is a complication of molding procedure for ear impression. These cases are referred to an ENT specialist. There is no standardized approach to this problem. Literature shows different clinical strategies. The aim of this study is to share our experience and to analyze the adverse outcome of different clinical approaches. METHODS: A case series of six patients with molding material inside the middle ear after complicated molding procedure for swimming earplugs are described. Additionally, available literature was reviewed to analyze results of the clinical approach after iatrogenic molding procedures. Forty-nine ears were included. RESULTS: In-office removal of the material is associated with a significant risk of adverse outcome if the eardrum cannot be examined. This also accounts for ossicular involvement. CONCLUSIONS: Temporal bone CT is advised in patients after complicated ear mold fitting if the tympanic membrane cannot be examined completely or the middle ear is involved. Blind removal should be avoided. Retroauricular transcanal tympanotomy or transmastoidal tympanotomy with facial recess approach is best practice in case the mold material has entered the middle ear. A clinical treatment algorithm is presented.