Saul Frenkiel

SεSμ and SεSγ Switch Circles in Human Nasal Mucosa Following Ex Vivo Allergen Challenge: Evidence for Direct as Well as Sequential Class Switch Recombination

B cells switch to IgE under the influence of IL-4, IL-13, and CD40 costimulation through a multistep process involving ε germline transcription and class switch recombination. Classically, switching has been considered an event restricted to lymphoid tissues; however, ε germline transcripts (I(initiator)ε RNA) have been observed within lung, sinus, and nasal tissue of individuals with asthma, sinusitis, and rhinitis. Furthermore, nasal mucosal tissue from allergic rhinitics produces ε germline transcripts following ex vivo allergen challenge. Collectively, these studies raised the possibility that switching to IgE may occur locally, at sites of allergic inflammation. Although ε germline transcripts are considered necessary to target the IgE locus, it is class switch recombination that ultimately leads to de novo IgE production. In this study, we demonstrate that SεSμ DNA switch circles (products of class switch recombination) as well as Iε and Cε RNA are produced within nasal tissue from allergic individuals following ex vivo allergen challenge. ε germline transcription was inhibited when tissue was cultured with a combination of allergen and neutralizing Abs against IL-4 and IL-13, indicating that de novo cytokine production mediated the isotype switch. We also show allergen-induced appearance of SεSγ DNA switch circles and up-regulation of Cγ4 mRNA, illustrating that sequential switching to IgE also occurred. This work strongly suggests that B cells residing within the nasal mucosa undergo switching to IgE in the context of a local immune response to allergen.

High prevalence of obstructive sleep apnea among patients with head and neck cancer.

OBJECTIVES To determine the prevalence of obstructive sleep apnea (OSA) in patients with cancer of the oral cavity and oropharynx scheduled for primary surgical resection. To correlate the presence of OSA and the occurrence of postoperative morbidities in this patient population. METHODS This was a prospective study involving 17 patients with malignancies of the oral cavity and oropharynx scheduled for primary surgical resection. Consecutive patients were approached to undergo overnight polysomnography to determine the apnea-hypopnea index (AHI). OSA was defined by an AHI value > or = 20 events per hour. Postoperative morbidities were evaluated in a blinded fashion for the patients completing surgery. RESULTS OSA was present in 13 of 17 patients, yielding a striking prevalence of 76% in this patient group. The mean AHI for patients with OSA was 44.7 +/- 3.5 (standard error) events per hour, with a mean nadir oxygen saturation of 88.2 +/- 1.8%, consistent with moderate to severe sleep-disordered breathing. The OSA and non-OSA patients were similar with respect to age and body mass index. The mean size of the primary tumour was 3.3 cm in patients with an AHI < 20 and 3.5 cm in those with an AHI > or = 20 (p = not significant). Overall, postoperative complications, defined as prolonged intensive care unit stay (> 24 hours), need for mechanical ventilation, and cardiopulmonary morbidities, were observed in 67% of OSA and 25% of non-OSA patients. CONCLUSIONS These findings point to a strong association between OSA and malignancies of the oral cavity and oropharynx. This relationship was independent of the size of the primary malignancy in this patient population with tumours ranging from 1 to 7 cm (p = not significant). When comparing the two groups (AHI < 20 and AHI > or = 20), there was a tendency for the group with OSA to have an increase in postoperative morbidities. Further research is warranted to further evaluate the postoperative morbidities and mortalities associated with OSA in this patient population and to determine the potential roles for preoperative treatment with continuous positive airway pressure and tracheotomy.

Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: Effect of topical corticosteroids

BACKGROUND Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions. OBJECTIVE To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis. METHODS Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6). Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa. In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells. Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined. RESULTS MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epithelium. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P <.001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils. CONCLUSION Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-4, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.

Spindle cell myoepithelioma of the nasal cavity.

Minor salivary gland neoplasms with mesenchymal-like features are uncommon in the sinonasal tract. We herein report a case of spindle cell myoepithelioma of the nasal cavity in a 69-year-old woman who presented with a rapidly expanding tumor accompanied by episodes of epistaxis. Although initially considered as a mesenchymal neoplasm, ultrastructural and immunophenotypical characterization demonstrated its myoepithelial nature. In the sinonasal setting, this unusual neoplasm may be confused with soft tissue tumors showing spindle cell or myxoid features. Staining for cytokeratin is found to be the most useful adjunct to diagnosis.

Inflammation and remodeling of the sinus mucosa in children and adults with chronic sinusitis.

Objectives/Hypothesis The sinus mucosal inflammatory response in adult patients with chronic sinusitis is well documented in the literature. In contrast, little is known about the pathogenesis of this condition in children. The objective of the study was to compare the inflammatory cell profile and the extent of tissue remodeling in the sinus mucosa of children and adults with chronic sinusitis.

Long-term outcome analysis of endoscopic sinus surgery for chronic sinusitis.

Background The purpose of this study was to determine long-term subjective outcome of endoscopic sinus surgery (ESS) for chronic sinusitis (CS) and to evaluate prognostic indicators for surgical treatment failure. Methods This is a prospective study of patients who underwent ESS for CS. Symptom assessment was performed using a visual analog scale at a pretreatment interview and then at regular intervals post-ESS for up to a 3-year period. The indicators for symptom scoring were nasal obstruction, facial pain, postnasal drip, anterior discharge, and anosmia/hyposmia. Results Data analysis indicates that ESS improves symptom scoring early on, but the effects begin to dissipate over time. Anosmia/ hyposmia is the most severe symptom overall for all patient subgroups and recurs to a greater degree 3 years postoperatively in Samters Triad sufferers (p = 0.006), asthmatic patients (p = 0.002), and those with a worse CT scan at presentation (p = 0.04). In addition, Triad sufferers who complain of nasal obstruction and anterior nasal discharge have a significant recurrence of their symptoms postoperatively (p = 0.04 and 0.001, respectively). Conclusion Individuals must be warned that ESS may not be a long-term solution for CS because of its chronic nature. Patients are relieved of their symptoms initially; however, these tend to recur over a 3-year period. Samters Triad is the strongest determinant of long-term treatment failure. Asthma also is a determinant of treatment failure, which lends credence to the notion of combined airway disease. Allergy was not a strong determinant of treatment failure in our study.

Intranasal corticosteroid use is associated with lower rates of bacterial recovery in chronic rhinosinusitis

Objective To determine whether use of a topical intranasal corticosteroid (INCS) preoperatively had an effect on the bacterial recovery rate and flora recovered at endoscopic sinus surgery (ESS). Study Design and Setting A prospective, multicenter, observational study from academic-based rhinology practices. Consecutive, unselected patients undergoing ESS had protected sinus cultures done at the time of ESS. Results 157 patients were assessed. Overall growth rate was 45.5%. INCS users had a positive culture rate of 35.4% vs 61.7% in nonusers (P = 0.0001). This effect was most pronounced in the subgroup undergoing revision surgeries (bacterial recovery rate INCS: 40.0%, no INCS: 82.6%, P = 0.001) and most marked for S. aureus (INCS: 12.5%, no INCS: 40.0%, P = 0.04) and CNS (INCS: 12.5%, no INCS: 30.4%, P = 0.05). While the rate of nasal polyposis was higher in both revision and the INCS-treated groups, rate of bacterial recovery was not influenced by a diagnosis of nasal polyposis. Conclusion INCS use preoperatively is associated with a lesser rate of bacterial recovery at the time of ESS, especially in individuals with previous ESS. Significance The results suggest a possible role of INCS in the management of post-ESS disease.

Laryngeal inflammation assessed using the reflux finding score in obstructive sleep apnea

OBJECTIVES: To evaluate the relationships between laryngeal inflammation assessed using the Reflux Finding Score (RFS), laryngeal sensory function, and apnea severity in patients with obstructive sleep apnea (OSA). METHODS: Endoscopic sensory testing (EST) was performed with subsequent blinded scoring from video of RFS. An RFS > 7 was indicative of increased inflammatory change. RESULTS: Of 34 patients evaluated, 29 had OSA (apneahypopnea index [AHI] ≥ 15 events/h) at polysomnography. Increased inflammation was present in 26/29 (90%), with changes suggestive of laryngopharyngeal reflux. There were significant correlations between: inflammation and OSA severity (eg, RFS vs AHI, r = 0.57, P < 0.001); inflammation and laryngeal sensory impairment (EST detection threshold and pressure required to elicit the laryngeal adductor reflex, LAR); and the degree of sensory impairment and OSA severity. CONCLUSIONS: Laryngeal inflammation is prevalent among OSA patients and correlates with laryngeal sensory dysfunction, attenuation of the LAR, and apnea severity. EBM rating: C-4

Effect of steroids on nasal inflammatory cells and cytokine profile.

Objectives: To assess the cellular and humoral effects of unilateral topical steroid application on the nasal mucosa of chronic sinusitis patients. Study Design: Cohort study with randomized grouping. Methods: Chronic sinusitis patients awaiting endonasal sinus surgery were randomly divided into a study group and a control group. All patients underwent allergy studies and categorized as allergic or nonallergic. Patients in the study group were exposed unilaterally to fluticasone propionate nasal spray, 100 μg/day for 4 to 6 weeks before the planned surgery. The control group was not exposed to steroids. At the time of surgery, anterior ethmoid mucosa specimens were obtained. The samples were immunostained for CD3, MBP, CD68, elastase, and tryptase. In situ hybridization was used for the detection of interleukin (IL)‐4, IL‐5, and interferon gamma (IFN‐γ) mRNA. The results were compared between the treated and untreated sides of exposed patients, as well as with non‐treated controls. Results: Twenty‐one patients consented to participate in the study. The number of CD3‐, MBP‐, and tryptase‐positive cells was significantly less in the treated and untreated sides of exposed patients, compared with unexposed controls. IL‐4 and IL‐5 mRNA were significantly downregulated in the treated side of allergic patients, as compared with nontreated patients. This effect could not be shown for IL‐4 in nonallergic patients. Conclusions: Topical steroid therapy had an anti‐inflammatory effect on both allergic and nonallergic chronic sinusitis patients. The unilateral application of the steroid spray affected the contralateral side as well.

Mycobacterial Infections of the Head and Neck

Despite the decline of pulmonary tuberculosis in the Western world, the incidence of cervical mycobacterial infections has remained relatively unaffected. A retrospective review was conducted of 20 patients treated for head and neck tuberculosis from 1984 to 1991. They were mostly an immigrant group coming from underdeveloped countries close to the equator. All cases were treated with antituberculous chemotherapy; 18 patients also underwent surgical excision of their lymphadenopathy. Sixteen patients showed complete response to combined treatment and one relapse was successfully retreated with antituberculous medication. Three patients died from unrelated causes–two from human immunodeficiency virus infection and one from nasopharyngeal carcinoma. The most reliable indicator of mycobacterial infection was the pathologic specimen, making the need for surgical intervention an important diagnostic consideration. As with other reports, most patients in our series had negative chest x-ray films, variable responses to skin testing, and negative cultures. The epidemiology, pathogenesis, and management of this disease are discussed. (OTOLARYNGOL HEAD NECK SURG 1993;109:427-33.)