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Biomedical subjects

David B Conley

Publications and source records attributed to David B Conley.

17 recordsLinked to original sources

Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps.

OBJECTIVE/HYPOTHESIS: The role of infectious agents in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unclear. Recent studies have provided indirect evidence of exposure to staphylococcal exotoxins in the blood and polyp tissue of patients with CRSwNP. These exotoxins have the capacity to act as superantigens, bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of the study was to analyze mucus and polyp tissue samples from patients with CRSwNP for the presence of staphylococcal exotoxins. STUDY DESIGN: Prospective study. METHODS: Tissue and mucus samples were obtained from 42 patients undergoing endoscopic sinus surgery for chronic rhinosinusitis and 11 normal control patients. Twenty-nine of 42 patients had chronic rhinosinusitis with bilateral nasal polyposis, 2 had antrochoanal polyps, and 11 had chronic rhinosinusitis without nasal polyps. Eleven patients without chronic rhinosinusitis or polyps served as normal control patients. Specimens were analyzed for the presence of five staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin type 1 [TSST-1]) using enzyme-linked immunosorbent assay (ELISA). Histological analysis of specimens and mean eosinophil counts were correlated with the presence of toxin. RESULTS: At least one toxin was detected in 14 of 29 patients with bilateral nasal polyposis. Nine of the 14 patients also had positive findings for additional toxins. The dominant histological pattern in the CRSwNP patient group was polypoid mucosa with edema, which was found in both ELISA-positive and ELISA-negative patients. Mean eosinophil counts tended to be higher in ELISA-positive patients with polyps compared with patients without toxin detection. No toxin was detected in the 11 specimens taken from normal control patients. Only 1 of the 13 patients with CRS without polyps had positive ELISA results for toxin. CONCLUSION: The current study demonstrates the presence of superantigen toxins in 14 of 29 patients with CRSwNP, with SEB and TSST-1 being the most common. Further studies are necessary to correlate the presence of toxin with the pathological changes present in polyp tissue.

Adult↗

Aging and olfactory and taste function.

This article focuses on the change in olfaction and taste with aging. It discusses histopathology with an emphasis on age-related changes, causes of chemosensory dysfunction in the elderly, how to evaluate a patient with dysfunction, useful tests and imaging, clinical consequences of chemosensory impairments, and available treatment options.

Aged↗

Medicolegal analysis of injury during endoscopic sinus surgery.

OBJECTIVES: To survey the causes, characteristics, and outcomes of malpractice litigation resulting from injuries sustained during endoscopic sinus surgery (ESS). STUDY DESIGN: A retrospective analysis of United States state and federal civil litigation involving injuries resulting from ESS. METHODS: Sources were state and federal court decisions and jury verdict reports accessed through a computerized legal database. The 41 cases were decided or settled between 1990 and 2003. The cases and reports were analyzed for pertinent data regarding plaintiffs, defendants, allegations of wrongdoing, resulting injury, expert witnesses, and resulting verdict or settlement. Correlation between severity of injury and case outcome was analyzed. RESULTS: All suits reviewed involved ESS. Many cases included multiple causes of action, or types of malpractice, including negligent technique, 31 (76%); lack of informed consent, 15 (37%); and wrongful death, 2 (5%). The defendant-physician specialty was overwhelmingly otolaryngology, 40 (98%). The most common presenting complaint, or indication for surgery, was chronic sinusitis, 30 (73%). The injuries caused by surgery were frequently multiple, including cerebrospinal fluid (CSF) leak, 10 (24%); brain damage, 6 (15%); diplopia, 7 (17%); and death, 2 (5%). The majority of cases reviewed (83%) resulted in a verdict rather than settlement. The result of the verdict or settlement was 17 (41%) in favor of the plaintiff, 23 (56%) in favor of the defendant, and 1 (2%) unknown. The average award was 751,275 dollars, with a median of 410,239 dollars and a range of 61,000 dollars to 2,870,000 dollars. CONCLUSIONS: This is the first study to review malpractice litigation resulting from injuries sustained during ESS and shows a hitherto unexpected pattern between severity of injury and case outcome.

Endoscopy↗

Immunoglobulin E to staphylococcal and streptococcal toxins in patients with chronic sinusitis/nasal polyposis.

BACKGROUND: The role of infectious agents and their contribution to the inflammation in chronic sinusitis/nasal polyposis (CS/NP) is not clear. Staphylococcal and streptococcal toxins have superantigen activity and have been implicated in inflammatory conditions such as atopic dermatitis, psoriasis, and asthma. OBJECTIVE: We investigated the presence of immunoglobulin (Ig)E antibodies to staphylococcal and streptococcal toxins in the serum of individuals with CS/NP. METHOD: IgE antibodies to staphylococcal exotoxins, A, B, and toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, B, and C were measured in 23 individuals with CS/NP before functional endoscopic sinus surgery and in controls (7 atopic and 6 nonatopic) individuals without chronic sinusitis. Presence of IgE to the toxins was also correlated with disease severity on sinus computed tomography (CT) scans. RESULTS: Staphylococcal and streptococcal toxin specific IgE antibodies were detected in 18 of 23 (78%) and 7 of 21 (33.3%) patients, respectively. None of the controls had IgE to the staphylococcal or streptococcal toxins (P <.0001). There was no association between radiographic severity of sinus disease and the presence of IgE antibody to the toxins. CONCLUSION: A significantly greater proportion of CS/NP patients had IgE to staphylococcal or streptococcal toxins. Evidence of IgE antibodies directed against staphylococcal and streptococcal toxins in the sera of patients with CS/NP suggests a potential role of these toxins with established superantigen effects in the pathogenesis of CS/NP.

Adult↗

Improved repair of cervical esophageal fistula complicating anterior spinal fusion: free omental flap compared with pectoralis major flap. Report of four cases.

Esophageal injury is a serious complication of anterior cervical fusion. A team approach to the management of these cases is described. The authors performed spinal assessment, control of the fistula, and interposition of a vascularized flap between the spine and the esophagus. They compared the overall efficacy of the pectoralis major flap (pedicled; two cases) and omental flap (free; two cases).

Adolescent↗

Olfactory neurons in bax knockout mice are protected from bulbectomy-induced apoptosis.

Surgical ablation of the olfactory bulb (bulbectomy) triggers a massive wave of apoptosis in mature olfactory sensory neurons within the olfactory epithelium. The aim of the current study was to determine if this process is dependent on expression of the pro-apoptotic protein Bax. Immunohistochemical detection of caspase-3 activation and olfactory epithelial thickness was used to demonstrate and quantify neuronal apoptosis in bax knockout and wild type mice, following bulbectomy. Caspase-3 activation and epithelial thinning were both reduced in the bax knockout mouse compared to the wild type mouse, at least up to 9 days post-bulbectomy, indicating that apoptosis was inhibited not just delayed. This study demonstrates that Bax plays a major role in olfactory neuron apoptosis following surgical deafferentation.

Animals↗

Laser-assisted uvulopalatoplasty and tonsillectomy for the management of obstructive sleep apnea syndrome.

OBJECTIVES/HYPOTHESIS: Laser-assisted uvulopalatoplasty (LAUP) is a widely accepted procedure for the management of snoring, but its role in the treatment of obstructive sleep apnea syndrome is currently unclear. The objective of the study was to evaluate the role of LAUP in treating moderate and severe obstructive sleep apnea syndrome. STUDY DESIGN: Retrospective review of a surgical treatment protocol for obstructive sleep apnea syndrome. METHODS: Between October 1993 and January 1999, 80 patients with moderate or severe obstructive sleep apnea syndrome and a significant component of retropalatal obstruction were treated with surgery at the Department of Otolaryngology at Northwestern University Medical School (Chicago, IL). Surgery consisted of LAUP with tonsillectomy (if tonsils were present) with the patient under general anesthesia or LAUP alone with local anesthesia (if the tonsils were absent). No patients received traditional uvulopalatopharyngoplasty. Sixty-four of the 80 patients underwent both preoperative and postoperative polysomnograms. Surgical "response" was defined as a 50% decrease in the apnea-hypopnea index (AHI) (the total number of apneic and hypopneic events per hour of sleep); surgical "cure" was defined as a 50% decrease in AHI and a final AHI of less than 20. RESULTS: The surgical response rate was 59% (38 of 64 patients), and the surgical cure rate was 39% (25 of 64 patients). Twelve patients (18.8%) had a higher AHI after surgery. The AHI (mean +/- SD) changed significantly from 51.4 +/- 30.9 preoperatively to 26.3 +/- 20.8 on postoperative polysomnogram (P = 7.0 x 10-9). Laser-assisted uvulopalatoplasty alone was performed in 33 patients with a response rate of 61% and a cure rate of 42%. Laser-assisted uvulopalatoplasty with tonsillectomy was performed in 31 patients with a response rate of 58% and a cure rate of 35%. The overall incidence of nasopharyngeal insufficiency was 0%. CONCLUSION: The results of the study suggested that LAUP with adjunctive tonsillectomy is an effective treatment for patients with obstructive sleep apnea syndrome and retropalatal obstruction with a lower complication rate than standard surgical therapy (uvulopalatopharyngoplasty).

Adult↗

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma.

OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid-dependent asthma. STUDY DESIGN: Retrospective chart review. METHODS: The study included 17 patients who underwent ESS with nasal polyps, steroid-dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow-up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. RESULTS: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund-Mackay scores were statistically lower for the 17 patients (P <.0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P <.014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P <.048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P >.08) and sinonasal symptoms (P >.16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. CONCLUSION: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin-tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin-sensitive patients.

Adult↗

Superantigens and chronic rhinosinusitis II: analysis of T-cell receptor V beta domains in nasal polyps.

BACKGROUND: The superantigen (SAg) hypothesis of chronic rhinosinusitis (CRS) suggests that toxins within the nose stimulate massive oligoclonal expansion of T-cell populations with subsequent eosinophil recruitment and tissue inflammation. SAgs are capable of activating 1 x 10(4) more lymphocytes than conventional antigens by binding specific Vbeta-domains of the T-cell receptor (TCR). The net effect is skewing from the normal Vbeta-profile by oligoclonal expansion of specific domains. This study will assess polyp tissue for evidence of an SAg response in CRS with nasal polyps (CRSwNP). METHODS: This study consists of a prospective analysis of 18 CRSwNP subjects undergoing sinus surgery. Flow cytometry was used to analyze the distribution of 24 specific TCR V beta-domains in lymphocytes from polyp tissue and blood. Evidence of oligoclonal expansion was tabulated for each specimen and defined as mean normative percentage + 2 SD. RESULTS: Eighteen of 18 CRSwNP subjects showed expansion of polyp lymphocytes expressing TCRs with specific V beta-domains. The average number of V beta-clones per CRSwNP subject was seven in polyp lymphocytes but only two in blood lymphocytes. CONCLUSION: The current results indicate that polyp lymphocytes exhibit significant oligoclonal expansion of specific V beta-domains. These data are considered diagnostic of a SAg effect. The corresponding blood profile is much less, suggesting that the nose is the primary source of stimulus. Although the trigger(s) for this expansion are unknown, these data are consistent with the hypothesis that staphylococcal toxins are central to the development of CRSwNP.

Chronic Disease↗

Superantigens and chronic rhinosinusitis: skewing of T-cell receptor V beta-distributions in polyp-derived CD4+ and CD8+ T cells.

BACKGROUND: Recent studies have suggested that Staphylococcus aureus secrete superantigenic toxins that play a role in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP). Twenty S. aureus superantigens (SAg's) have been identified, each of which bind the V beta-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct V beta-domains exist in the human repertoire, and distinct SAg's will bind only particular domains generating a pattern of V beta-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of V beta-expression in polyp-derived lymphocytes from CRSwNP patients. METHODS: Polyps were harvested from 20 patients with CRSwNP and 3 patients with antrochoanal polyps. Flow cytometry was used to analyze the V beta-repertoire of polyp-derived CD4+ and CD8+ lymphocytes. Data were analyzed in light of the known skewing associated with SAg exposure in vivo and in vitro. Skewing was defined as a percentage of V beta-expression >2 SD of that seen in normal blood. RESULTS: Seven of 20 subjects exhibited skewing in V beta-domains with strong associations with S. aureus SAg's. The three antrochoanal polyps failed to show any significant V beta-skewing. CONCLUSION: This study establishes evidence of S. aureus SAg-T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAg's, additional study is necessary to establish the role of these toxins in disease pathogenesis.

CD4-Positive T-Lymphocytes↗

The effect of FloSeal on mucosal healing after endoscopic sinus surgery: a comparison with thrombin-soaked gelatin foam.

BACKGROUND: The optimal form of nasal packing after endoscopic sinus surgery (ESS) still has not been established Although wide variations exist among sinus surgeons, the goals are adequate hemostasis, rapid healing, and patient comfort. Preliminary studies indicated that FloSeal (FS), a novel absorbable hemostatic paste used as a nasal pack, was associated with minimal postoperative discomfort and effective hemostasis. This study was designed to evaluate the effects of this agent on mucosal healing in ESS. METHODS: Twenty consecutive patients underwent bilateral ESS. For each patient, one ethmoid cavity was randomized to receive FS and the other received thrombin-soaked gelatin foam. The extent of granulation tissue and adhesion formation was evaluated at 6-8 weeks after surgery. RESULTS: No significant differences were observed between the FS and the thrombin-soaked gelatin foam groups with respect to the preoperative Lund-Mackay score, extent of surgery performed, or need for additional nasal packing. However, the FS group showed clear trends toward increased granulation tissue (p = 0.007) and adhesion (p = 0.006) formation. CONCLUSION: Absorbable hemostatic agents are associated with a high degree of patient comfort and provide hemostasis comparable with traditional techniques. Different materials may induce differential patterns of mucosal healing, potentially affecting the ultimate result of ESS.

Endoscopy↗

Age-related olfactory dysfunction: cellular and molecular characterization in the rat.

BACKGROUND: Olfactory receptor neurons (ORNs) undergo apoptosis at a baseline rate even in the absence of obvious disease. Although the precise triggers of the apoptotic cascade are unclear, ORNs are exposed directly to the external environment, making them susceptible to injury. As an adaptive mechanism, mammals have the ability to replace lost ORNs throughout adult life from neuronal precursors within the olfactory epithelium (OE). In humans, this process fails with age as the surface area of the OE and the number of ORNs decline, coupled with a loss of clinical olfactory function. The question addressed in this study is whether this age-related failure of olfactory sensation is a result of a decrease in neuronal proliferation or an increase in ORN cell death. METHODS: To begin to address this question the ribonuclease protection assay was used to assess expression of apoptosis-related genes in rat OE as a function of age. Second, the terminal deoxynucleotide transferase end labeling assay was used to assess the percentage of ORNs undergoing apoptosis (apoptotic index) in three groups of animals: young (12 weeks), old (32 months), and bulbectomized rats. Bulbectomy is a standard model for ORN injury associated with a massive increase in ORN apoptosis and serves as a positive control. RESULTS: Ribonuclease protection assay data indicate an age-related increase in Bax, Bcl-xL, and procaspase-3 messenger RNA expression in aged compared with young rats. A similar but more pronounced increase in expression of these apoptotic-related genes is seen after bulbectomy. The terminal deoxynucleotide transferase end labeling assay also showed a statistically significant increase in the apoptotic index with both age and bulbectomy. CONCLUSION: Taken together, the current results indicate that aging and injury induce parallel changes in OE. Furthermore, these findings support the hypothesis that age-related olfactory dysfunction is, at least in part, related to an increase in ORN cell death.

Aging↗

Specific inflammatory cell types and disease severity as predictors of postsurgical outcomes in patients with chronic sinusitis.

Chronic sinusitis is a common condition that is frequently refractory to medical and surgical intervention. It has not been well defined as to which patient subgroups benefit from surgical intervention and which do not. Our purpose is to determine whether the presence of certain inflammatory cell types is predictive of postoperative outcome in sinus surgery for chronic sinusitis. We performed a retrospective chart review of 75 patients who underwent endoscopic sinus surgery or polypectomy between 1994 and 1996. Of these patients, 15 met inclusion criteria for chronic sinusitis, asthma requiring inhaled steroids, and 1 year preoperative and postoperative management by the allergist or otolaryngologist at Northwestern Medical Faculty Foundation. Ten of these 15 patients had a complete set of data allowing immunohistochemical analysis. Sections of sinus tissue obtained at surgery were hematoxylin and eosin stained and evaluated for the presence of lymphocytes, plasma cells, eosinophils, and macrophages. Immunostains for T lymphocytes, B lymphocytes, and macrophages were performed also. The total number of antibiotic courses patients received were enumerated into 6-month blocks for 1 year preoperatively and 1 year postoperatively as markers of disease activity. Postoperatively, four patients improved, three patients worsened, and three patients remained unchanged, as defined by the number of antibiotic courses required 1 year postoperatively compared with 1 year preoperatively. We found no difference in the magnitude or specific type of inflammatory cells present at the time of surgery between the groups. However, when the difference between the preoperative versus postoperative antibiotic courses was compared between patients who improved versus patients who did not improve, the improved group required markedly fewer courses relative to the nonimproved group (p < 0.009). Neither total magnitude of inflammation nor specific inflammatory cell types correlated with surgical outcome in this group. The patients who did not improve postoperatively had a statistically significantly lower number of preoperative antibiotics than the patients who improved. These findings suggest that patients with less severe disease may be less likely to benefit from sinus surgery.

Adult↗

Chronic sinusitis with nasal polyps: staphylococcal exotoxin immunoglobulin E and cellular inflammation.

BACKGROUND: The etiology of chronic sinusitis with nasal polyposis (CS/NP) remains enigmatic. Frequently, Staphylococcus aureus is present in the nose of CS/NP patients, although the significance is unclear. Recent reports have suggested the hypothesis that these bacteria may secrete exotoxins triggering the inflammatory mucosal changes seen in CS/NP. This mechanism of immunopathology has been established in other diseases associated with Staphylococcus colonization and exotoxin secretion such as atopic dermatitis. In atopic dermatitis, the exotoxins incite a local superantigen response in which clonal T-cell activation and massive cytokine release occur in the affected skin. Second, these exotoxins can act as traditional allergens, stimulating a typical immunoglobulin E (IgE) response in the serum, which has been correlated with disease severity. This study is designed to begin the assessment of the hypothesis that a similar mechanism takes place in CS/NP. METHODS: Serum was drawn from patients with CS/NP undergoing endoscopic sinus surgery as well as 13 atopic and nonatopic control subjects without sinusitis. IgE levels to S. aureus exotoxins A (SEA), SE exotoxins B (SEB), and toxic shock syndrome toxin 1 were measured using enzyme-linked immunosorbent assay. Tissue eosinophilia and the presence of lymphocytes on hemotoxylin and eosin-stained sections of polyps were scored by a blinded pathologist and correlated to presence of toxin IgE in the serum. RESULTS: Staphylococcal exotoxin (SE)-specific IgE was found in the serum of 5/10 (50%) of the patients with CS/NP. In contrast, 0/13 control patients had IgE to the exotoxins (p = 0.031). Polyp eosinophil, lymphocyte, and mononuclear cell counts were compared in IgE exotoxin-positive and -negative subjects. A trend toward increased eosinophil counts in patients with SE IgE (SE IgE+) was present, but not statistically significant. CONCLUSION: These results indicate that a high percentage of CS/NP patients show a systemic IgE response to S. aureus exotoxins in comparison with controls without CS/NP. Although these results are consistent with the actions of Staphylococcus toxins in other diseases, additional work is necessary to establish a local superantigen response in the nasal mucosa of CS/NP patients.

Adult↗

Aeroallergen hypersensitivity: comparing patients with nasal polyps to those with allergic rhinitis.

Immunoglobulin E-mediated allergy generally has not been considered to be important in the pathogenesis of nasal polyps, despite elevated immunoglobulin E in polyp exudates, tissue eosinophilia, and degranulated mast cells. In previous reports, patients with nasal polyps were more likely to have positive skin tests to perennial than to seasonal allergens. It is postulated that nasal polyps result from the constant nature of perennial allergen exposure. The objective of this report is to compare the prevalence of sensitization to six aeroallergens in a group of nasal polyp (NP) patients, a group of allergic rhinitis (AR) patients, and those subjects with positive skin tests in the National Health and Nutrition Examination Survey (NHANES) II. Twenty-five consecutive NP patients evaluated over a 3-month period of time at Northwestern Allergy and Immunology Outpatient Center, in addition to 50 of the allergic rhinitis patients evaluated over the same time, were chosen randomly. All were skin tested with the following antigens: dog, cat, dust mite, grass, tree, and ragweed. Published skin test data from the NHANES II study of 14,367 individuals was obtained also. The percent of NP patients, AR patients, and NHANES II subjects with sensitization to perennial allergens was 72, 96, and 7.6%, respectively. The difference between the AR and NP patients was statistically significant (p = 0.006). The percent of NP, AR, and NHANES II subjects sensitized to seasonal allergens was 84, 86, and 17.7%, respectively. No statistical significance existed between the AR and NP patients, regarding seasonal allergens. Although the AR and NP had similar levels of reactivity to perennial and seasonal allergens, the NHANES II group was more than twice as likely to be sensitized to a seasonal allergen. The NP and AR groups were similar in prevalence of reactivity to seasonal allergens, but the NP patients in our population actually were less likely to be sensitized to perennial allergens than individuals with AR.

Air Pollution↗

Long-term effects of FloSeal packing after endoscopic sinus surgery.

BACKGROUND: A previous study by our group showed increased adhesions and granulation tissue in ethmoid cavities packed with FloSeal (FS) compared with those packed with thrombin-soaked gelatin foam after endoscopic sinus surgery (ESS). That study included 20 patients whose cavities were graded 6-8 weeks postoperatively. The goal of this study was to report long-term follow-up on this cohort. METHODS: At least 1 year follow-up was available in 18/20 patients. The number of office procedures required to lyse adhesions during the follow-up period was tabulated also. Pathology was available from one patient who underwent lysis of adhesions on an FS side. The histopathological findings are presented. RESULTS: The mean follow-up period was 21.4 (+/- 2.3) months, and none of the 18 patients required revision ESS during this interval. The overall incidence of adhesions (p = 0.013) and the number requiring lysis of adhesions (p = 0.046) were both greater in the FS group. During the interval between previous study evaluation (6-8 weeks postop) and last follow-up, five FS sides required a total of seven procedures to lyse adhesions. Silent adhesions were observed in an additional five FS sides. Although asymptomatic adhesions were observed in two thrombin-soaked gelatin sides at last examination, none underwent lysis. Biopsy of an adhesion from a patient packed with FS 25 months earlier revealed incorporated foreign material. CONCLUSION: FS appears to be associated with scar tissue formation and may be incorporated into recovering mucosa. Use of FS may increase the degree of postoperative care required after ESS.

Cohort Studies↗

Staphylococcal exotoxins and nasal polyposis: analysis of systemic and local responses.

BACKGROUND: Staphylococcal exotoxins have been implicated in the pathogenesis of several chronic inflammatory diseases including atopic dermatitis (AD), asthma, and, most recently, chronic rhinosinusitis with nasal polyposis (CRS/NP). In severe AD, these toxins act both as superantigens (SAg), triggering massive T-cell activation, and as conventional allergens, triggering toxin-specific immunoglobulin E (IgE) in the serum. In CRS/NP, evidence for both processes has been reported but it is unclear whether these processes are linked. The aim of this study was to correlate SAg activity as inferred by staphylococcal-specific T-cell receptor (TCR) V-beta expansion in the polyp and blood of CRS/NP patients with staphylococcal-specific anti-IgE antibodies in the serum. METHODS: IgE antibodies to staphylococcal exotoxin A (SEA), staphylococcal exotoxin B (SEB), and toxic shock syndrome toxin (TSST) 1 were measured in the serum of 12 individuals with CRS/NP before functional endoscopic sinus surgery. Flow cytometry was used to analyze the SEA, SEB, and TSST-1-specific TCR V-beta domains on the T cells from the polyp and blood of these patients. RESULTS: Serum SEA-, SEB-, and TSST-1-specific IgE antibodies were detected in 0/12 (0%), 6/12 (50.0%), and 9/12 (75%) of CRS/NP patients, respectively. Evidence of SAg effect in the polyp lymphocytes (TCR V-beta expansion in both CD4+ and CD8+ subsets) was noted in 7/12 (58.3%) patients. Five of 6 CRS/NP patients had overlapping evidence of a systemic IgE response and TCR V-beta expansion, suggestive of exposure to the same exotoxin. No patients had evidence a SAg effect in blood lymphocytes. Nine of 12 subjects also had coexistent asthma. CONCLUSION: These results provide evidence for a local SAg effect in 7/12 (58.3%) polyp patients and establish a positive correlation of V-beta expansion with the presence of corresponding toxin-specific IgE in the serum.

Adult↗