Nyall R. London

Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice

&NA; Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all‐cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 &mgr;m) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 &mgr;m/m3, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin‐1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL‐13, eotaxin‐1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.

Nuclear erythroid 2-related factor 2 activation inhibits house dust mite-induced sinonasal epithelial cell barrier dysfunction.

Dysregulated sinonasal epithelial cell (SNEC) barrier function has been proposed to contribute to the pathogenesis of sinonasal inflammatory conditions such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Allergens such as house dust mite (HDM) have been reported to disrupt SNEC barrier integrity. We have recently identified nuclear erythroid 2‐related factor 2 (Nrf2) activation via sulforaphane (SFN) stimulation to stabilize SNEC barrier function. The purpose of this study was to explore whether Nrf2 activation could ameliorate HDM‐induced SNEC barrier dysfunction.

Bactericidal antibiotics promote oxidative damage and programmed cell death in sinonasal epithelial cells

Antibiotics are widely and heavily used in the treatment of chronic sinusitis. Bactericidal antibiotics can stimulate reactive oxygen species (ROS) formation, a proinflammatory response, and cell death in cultured human sinonasal epithelial cells (SNECs). Sulforaphane (SFN) is a potent stimulator of the antioxidant nuclear factor erythroid 2‐related factor 2 (Nrf‐2) system and a suppressor of inflammation. In this study we utilized SFN to further explore the relationship between levofloxacin treatment, ROS formation, and the cell death response.

Characterization of a novel, papain-inducible murine model of eosinophilic rhinosinusitis: Papain-induced murine rhinosinusitis

Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. Current animal models fail to recapitulate many of the innate and adaptive immunologic hallmarks of the disease, thus hindering the development of effective therapeutics. In the present study, mice were exposed intranasally to the cysteine protease papain, which shares functional similarities with parasitic proteases and aeroallergens, to generate a rapidly inducible murine model of eosinophilic rhinosinusitis.

The Role of the Sinonasal Epithelium in Allergic Rhinitis

The sinonasal epithelial barrier is comprised of tight and adherens junction proteins. Disruption of epithelial barrier function has been hypothesized to contribute to allergic disease such as allergic rhinitis through increased passage of antigens and exposure of underlying tissue to these stimuli. Several mechanisms of sinonasal epithelial barrier disruption include antigen proteolytic activity, inflammatory cytokine-mediated tight junction breakdown, or exacerbation from environmental stimuli. Mechanisms of sinonasal epithelial barrier stabilization include corticosteroids and nuclear erythroid 2-related factor 2 (Nrf2) cytoprotective pathway activation. Additional studies will aid in determining the contribution of epithelial barrier function in allergic rhinitis pathophysiology and treatment.

Frontoethmoidal Sinus Schwannoma Eroding Through the Nasal Bone: Case Report and Literature Review

The sinonasal cavity is an extremely rare location for schwannomas to arise. In this location, a sinonasal schwannoma is thought to either arise from Schwann cells of sensory nerve fibers in the sinonasal mucosa or from the autonomic nervous system. We report a case of sinonasal schwannoma presumed to be metastatic papillary thyroid carcinoma based on the patient’s medical history as well as the presence of adjacent bony destruction on CT imaging. We discuss the clinical presentation and treatment of this patient as well as review the literature.