The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Periostin is a recently discovered biomarker for eosinophilic inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease. Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory cascade. The effect on nasal and serum periostin levels is however yet unknown. We aimed to evaluate the effect of omalizumab, mepolizumab, methylprednisolone and doxycycline on nasal and systemic periostin expression. METHODS: This study is based on 3 previously published trials. Nasal and systemic periostin were assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14), methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a control group for each treatment scheme. Doxycycline (200 mg on the first day, followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were administered during 20 days; mepolizumab was injected at baseline and at 4 weeks. Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet. RESULTS: Methylprednisolone and omalizumab significantly reduced serum periostin levels at 4 and 8 weeks, respectively, after the start of the treatment. The effect of methylprednisolone was transient. Nasal periostin levels decreased significantly after 8 weeks of treatment with mepolizumab. The periostin expression is in accordance with the previously reported effect on the eosinophilic inflammation and clinical outcome. CONCLUSION: All treatment options distinctly influence periostin expression, reflecting the interference with the local or systemic eosinophilic inflammatory cascade.

The response to nasal allergen provocation with grass pollen is reduced in patients with chronic rhinosinusitis with nasal polyposis and grass sensitization.

BACKGROUND: The majority of grass pollen-sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens. OBJECTIVE: We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen-sensitized CRSwNP patients. METHODS: Twelve grass pollen-sensitized CRSwNP patients underwent NAPT with grass pollen and were compared with 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen-specific IgE and tryptase were measured in serum and nasal secretions. RESULTS: NAPT was positive in 6 of 12 of the grass pollen-sensitized CRSwNP patients, and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test. CONCLUSION AND CLINICAL RELEVANCE: These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared with grass pollen allergic rhinitis patients.

Middle ear damages.

Middle ear damages. The eardrum and middle ear are often exposed to blunt and penetrating trauma, blasts, thermal or caustic injuries. These injuries may result in tympanic membrane perforation, middle ear haemorrhage, dislocation and fracture of the ossicular chain, perilymphatic fistula and damage to the chorda tympani and/or facial nerve. In case of life-threatening injuries and/or mass casualty incidents, middle ear trauma obviously does not take highest priority. However, middle ear lesions should be suspected and recognized as early as possible. After meticulous history taking, physical examination consists of cranial nerve evaluation, thorough inspection of the outer ear, otoscopy and assessment of hearing and vestibular function. In the majority of cases, traumatic tympanic membrane perforations by penetrating and blunt injuries have a good prognosis with spontaneous resolution. Tympanic membrane perforations from blast trauma, thermal or caustic injuries are less likely to heal spontaneously. Perforations lasting six months after injury warrant surgery. A high resolution CT scan of the temporal bone is required in case of immediate complete facial nerve paralysis and when oval window pathology or perilymphatic fistula is suspected. Early surgical intervention is needed in case of early onset facial nerve paralysis, when there is suspicion of a perilymphatic fistula with persisting or increasing vestibular symptoms or neurosensory hearing loss and in case of vestibular dislocation of the stapes footplate. When ossicular chain damage is suspected, elective tympanoplasty is indicated. As any traumatic tympanic membrane perforation runs the risk of cholesteatoma formation, biannual follow-up during a minimum of two years is recommended.

Local free light chain expression is increased in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Free light chain (FLC) concentrations are demonstrated to be increased in different inflammatory disorders and are proposed to mediate mast cell-dependent immune responses. A role for mast cells is suggested in chronic rhinosinusitis with nasal polyposis (CRSwNP), which is characterized by a local Th2 inflammatory response. However, clear mast cell-activating factors are not always apparent. In this study, the presence of FLCs in CRS patients with or without nasal polyps (CRSw/sNP) was investigated and the effect of different treatments on FLC expression was analyzed. METHODS: Nasal tissue, nasal secretion, and serum of control patients, patients with CRSwNP, and CRSsNP were analyzed for the presence of kappa and lambda FLC. The expression of FLCs in nasal polyp tissue was investigated using immunohistochemistry. In addition, FLC was measured in serum and nasal secretion of nasal polyp patients treated with methylprednisolone, doxycycline, anti-IL-5, or placebo. RESULTS: Free light chain concentrations were increased in nasal secretion and mucosal tissue homogenates in patients with chronic rhinosinusitis, and this effect was most prominent in CRSwNP patients. Immunohistochemical analysis confirmed the increased FLC concentrations in nasal polyp tissue. In CRSwNP patients, treatment with methylprednisolone or anti-IL-5 resulted in the reduction in systemic or local FLC concentrations, respectively. CONCLUSION: The presence of FLC in CRSwNP and CRSsNP suggests a possible role in mediating the local immune reaction in the paranasal cavities. Furthermore, the decrease in local FLCs after treatment with anti-IL-5 presumes that IL-5 creates an environment that favors FLC production.