Parikh, AA; (2007) Effectiveness of intranasal lysine-aspirin in patients with aspirin-sensitive, and aspirin tolerant nasal polyposis: controlled trials. Doctoral thesis , UCL (University College London).

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Abstract

Therapeutic options for patients with aspirin-sensitive, and aspirin tolerant nasal polyps include corticosteroids (topical and systemic), surgery to relieve nasal obstruction, or a combination of the two. Medical therapy i.e. corticosteroids aims to reduce the underlying inflammation and alleviates all nasal symptoms. The aim of surgery is to provide an adequate nasal airway for breathing. Intranasal lysine-aspirin has been used as an option in these patients, and trials have shown its beneficial effects. However, their design and interpretation have been open to scientific criticism. Therefore, we planned to study the effectiveness of intranasal lysine-aspirin in the two groups of polyp patients by conducting trials in a randomised, double blind, and placebo controlled manner. Diagnosis of aspirin-sensitivity or tolerance was confirmed by intranasal lysine-aspirin challenge prior to enrolment in the appropriate trials. Nasal biopsy and polyp tissue were collected from the patients for laboratory-based experiments. Analysis of their results was aimed at improving our understanding of aspirin-sensitivity, and to generate a hypothesis on its pathogenesis. Intranasal lysine-aspirin did not reduce polyp growth, or improve nasal symptoms in aspirin-sensitive or aspirin tolerant patients when compared to placebo. However, intranasal lysine-aspirin (16 mgs) did not have any deleterious effects in both groups. Immunohistochemistry revealed a significant increase in expression of CysLTj receptor on inflammatory cells in nasal biopsies from aspirin-sensitive compared to tolerant patients. This expression reduced following treatment with intranasal lysine-aspirin, which suggested a possible mechanism of desensitization. We also found significantly higher levels of iNOS activity in polyp tissue from aspirin-sensitive compared to tolerant patients. Enhanced expression of CysLTi receptor provides further evidence of the central role played by leukotrienes in aspirin-sensitivity. Also, we suggest that high iNOS activity in polyp tissue is secondary to increased leukotriene production, and that the latter is most likely to be confined to the respiratory mucosa of patients with aspirin-sensitive asthma and/or polyposis.

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