Anju Tripathi

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.

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.

Corticosteroid therapy in an additional 13 cases of Stevens-Johnson syndrome: a total series of 67 cases.

Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that can be a life-threatening emergency. Previously, we have reported our favorable experience in treating 54 patients with SJS with systemic corticosteroids. We continued our prospective analysis of consecutive patients with SJS treated with corticosteroids. Possible etiologic factors and clinical outcomes of the patients are described. All 13 patients improved with initiation of systemic corticosteroid therapy. There was no mortality or permanent sequelae attributable to SJS. Drugs were the offending agents in all 13 cases. There was one death unrelated to SJS. In conclusion, prompt treatment with systemic corticosteroids reduces morbidity and improves outcome of SJS patients. This analysis extends our series to 67 consecutive patients with SJS who were treated with corticosteroids and had a favorable outcome.

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-β 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-β 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-β 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-β 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-β expansion with the presence of corresponding toxin-specific IgE in the serum.

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.

Impact of allergic rhinitis treatment on quality of life

Allergic rhinitis is a chronic inflammatory disorder of the nasal passages. It affects approximately 20% of the population, is a significant health and economic burden, and severely impairs quality of life.Two main instruments, Medical Outcomes Study 36-Item Short Form health survey (SF-36) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) have been used to assess quality of life in patients with allergic rhinitis. Antihistamines, corticosteroids, anticholinergic agents, decongestants, cromoglycates, and immunotherapy are used to treat patients with allergic rhinitis.Of these, antihistamines and intranasal corticosteroids are the most efficacious and frequently utilised medications. Studies have demonstrated improvements in quality of life with both of these medications in patients with allergic rhinitis.

Superantigens and chronic rhinosinusitis: Skewing of T-cell receptor Vβ-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 (SAgs) have been identified, each of which bind the Vβ-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct Vβ-domains exist in the human repertoire, and distinct SAgs will bind only particular domains generating a pattern of Vβ-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of Vβ-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 Vβ-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 Vβ-expression >2 SD of that seen in normal blood. Results Seven of 20 subjects exhibited skewing in Vβ-domains with strong associations with S. aureus SAgs. The three antrochoanal polyps failed to show any significant Vβ-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 SAgs, additional study is necessary to establish the role of these toxins in disease pathogenesis.

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. (American Journal of Rhinology 18, 273–278, 2004)

Prevalence and onset of rhinitis and conjunctivitis in subjects with occupational asthma caused by trimellitic anhydride (TMA)

Individuals with occupational asthma may also report symptoms of rhinitis or conjunctivitis. The objective of this study was to investigate the prevalence of rhinitis and conjunctivitis in subjects with occupational asthma as a result of trimellitic anhydride (TMA). Additionally, we wanted to evaluate the onset of rhinitis and conjunctivitis symptoms as compared with the occupational asthma symptoms. In a case series design, we studied 25 consecutive employees with TMA-induced asthma; each of them had participated in an annual surveillance program in which they were queried about rhinitis, conjunctivitis, and other respiratory symptoms. Twenty-two of the 25 (88%) reported rhinitis symptoms whereas 17 of the 25 (68%) reported conjunctivitis symptoms. In 17 of the 22 (77%) individuals with rhinitis and asthma, the rhinitis symptoms preceded the asthma symptoms. In 14 of the 17 (82%) individuals with conjunctivitis, those symptoms preceded the asthma symptoms. In summary, symptoms of rhinitis and conjunctivitis are common in subjects with occupational asthma because of TMA and often precede the respiratory symptoms.

Superantigens and chronic rhinosinusitis II: Analysis of T-cell receptor Vβ 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 × 104 more lymphocytes than conventional antigens by binding specific Vβ-domains of the T-cell receptor (TCR). The net effect is skewing from the normal Vβ-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 Vβ-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 Vβ-domains. The average number of Vβ-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 Vβ-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.