SummaryThis guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.

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Patients with infectious mononucleosis (IM) undergoing primary EBV infection show large expansions of EBV-specific CD8+ T cells in the blood. While latent infection of the B cell pool is quickly controlled, virus shedding from lytically infected cells in the oropharynx remains high for several months. We therefore studied how responses localize to the tonsil, a major target site for EBV, during primary infection and persistence. In acute IM, EBV-specific effectors were poorly represented among CD8+ T cells in tonsil compared with blood, coincident with absence of the CCR7 lymphoid homing marker on these highly activated cells. In patients who had recently recovered from IM, latent epitope reactivities were quicker than lytic reactivities both to acquire CCR7 and to accumulate in the tonsil, with some of these cells now expressing the CD103 integrin, which mediates retention at mucosal sites. By contrast, in long-term virus carriers in whom both lytic and latent infections had been controlled, there was 2- to 5-fold enrichment of lytic epitope reactivities and 10- to 20-fold enrichment of latent epitope reactivities in tonsil compared with blood; up to 20% of tonsillar CD8+ T cells were EBV specific, and many now expressed CD103. We suggest that efficient control of EBV infection requires appropriate CD8+ T cell homing to oropharyngeal sites.

Following our previous description of the serotonin transporter (SERT) acting as a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell malignancy, while exploring additional SERT substrates for potential therapeutic activity. SERT was readily detected in derived B cell lines with origins as diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse kinetics for the antiproliferative and proapoptotic activities of the amphetamine derivatives fenfluramine (an appetite suppressant) and 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being similar to the endogenous indoleamine. A tricyclic antidepressant, clomipramine, instead mirrored the behavior of the selective serotonin reuptake inhibitor fluoxetine, both being effective in the low micromolar range. A majority of neoplastic clones were sensitive to one or more of the serotonergic compounds. Dysregulated bcl-2 expression, either by t(14;18)(q32;q21) translocation or its introduction as a constitutively active transgene, provided protection from proapoptotic but not antiproliferative outcomes. These data indicate a potential for SERT as a novel anti-tumor target for amphetamine analogs, while evidence is presented that the seemingly more promising antidepressants are likely impacting malignant B cells independently of the transporter itself.

Allergic rhinitis represents a global health issue affecting between 10% to 25% of the world population, with increasing prevalence over the last decade. Although often trivialized by patients and doctors, allergic rhinitis is a significant cause of morbidity, in addition to its substantial economic impact. While allergic rhinitis is an inflammatory disorder of the upper airways, inflammation alone is insufficient to explain the chronic nature of the disease. An exciting concept which has recently emerged in asthma concerns the role of the bronchial epithelium as a key regulator of airway inflammatory and remodelling responses in asthma. It has been shown by our group that the disruption and alteration in the function of the lower airway epithelium in asthma leads to the generation of a variety of stimuli that lead to the restructuring of the airway wall. This raises interesting questions regarding a similar role for the upper airway epithelium in allergic rhinitis. This review aims to interpret past and current research into allergic rhinitis, and to address specific areas where future research is warranted, particularly in relation to the possibility of an altered upper airway epithelial phenotype in allergic rhinitis.

Using a photometric method of measuring ciliary beat frequency, the effect of temperature on ciliary activity was investigated. A linear increase in ciliary beat frequency between 19 degrees and 32 degrees C was found. Between 32 degrees and 40 degrees a plateau was reached in which temperature did not significantly affect frequency and above 40 degrees C the frequency began to decline. It is concluded that nasal cilia are not critically dependent upon temperature in the range 32 degrees and 40 degrees C, the temperature range in which this tissue normally operates.

Wegener's granulomatosis initially affects upper respiratory tract organs including the nasal mucosa in more than 90% of patients. The inflammation is typically granulomatous with associated vasculitis. T lymphocytes are usually a prominent component of the leucocyte infiltrate. Previous studies using peripheral blood T cells have implicated IFN‐γ rich Th1‐type responses. This study addressed the cytokine milieu in nasal mucosa from 10 patients with active Wegener's granulomatosis using immunohistochemistry. Increased levels of CD3+ T cells and eosinophils were present compared with normal and disease controls. There was increased expression of IL‐4, down‐regulation of IL‐2 and no detectable IFN‐γ. There was increased expression of the chemokine receptor CCR3 by infiltrating cells, consistent with an IL‐4 dominant, Th2‐biased response. In contrast, renal biopsy tissue from 10 patients with active Wegener's granulomatosis showed expression of IL‐2 and IL‐4. The Th2‐type environment within nasal mucosa, often the initial site of disease activity in Wegener's, is consistent with a local allergic response in these patients.

Nasal polypectomy is a common operation. There is debate about whether all nasal polyps removed at operation should be sent for histopathological examination. To investigate this, a prospective study was performed to check the correlation of clinical and histopathological examination. Three hundred and forty-four nasal polypectomy specimens during the period from September 1997 to September 1999 were sent for histopathological diagnosis, with the clinical diagnosis documented on the pathology form. The clinical diagnosis was then correlated with the histological diagnosis. Three hundred and twenty-eight specimens were diagnosed as inflammatory polyps and 16 as tumours, of which seven were malignant. There was a good correlation between the clinical and histological findings in 340 cases. There was disagreement between the forms and reports in four cases. When the notes were consulted, three cases had forms that were incorrectly filled in. There was only one unsuspected case of inverted papilloma in a polyp specimen, which looked like a benign inflammatory polyp. This study indicates there is a 99.7% correlation between clinical and histopathological diagnosis.