TOLERANCE TO ASPIRIN IN ASPIRIN-SENSITIVE ASTHMATICS - METHODS OF INDUCING THE TOLERANCE STATE AND ITS INFLUENCE ON THE COURSE OF ASTHMA AND RHINOSINUSITIS

Aspirin-sensitive asthma is a serious clinical problem, frequently inv olving dramatic exacerbation and sometimes even death after the accide ntal ingestion of aspirin or other nonsteroidal anti-inflammatory drug s (NSAIDs). The majority of such asthmatics usually suffer from chroni c rhinosinusitis and nasal polyps as well, and almost haff of them fro m headaches. Widal et al. in 1922, and later, Zeiss and Lockey were ab le to elicit tolerance to aspirin (ASA). In all the studies performed so far, tolerance to ASA was achieved by giving double threshold ASA d oses every day or every few hours. This method elicited severe dyspnea and sometimes pronounced extrabronchial sensitivity symptoms. From ou r previous studies, it appeared that the smaller the aspirin dose, the weaker the sensitivity symptoms, and that it is possible to induce to lerance after eliciting only very slight sensitivity reactions. Based on this observation, we elaborated a new method of eliciting aspirin t olerance by the daily administration of gradually increasing doses of aspirin starting with subthreshold doses. Applying this method, we ach ieved tolerance to aspirin without any adverse reactions. The patients in a tolerance state to ASA also tolerated well other NSAIDs, i.e. in domethacin and diclofenac. It is possible to maintain a tolerance stat e for a long time by the administration of ASA at proper intervals. It was shown that such a procedure may have a beneficial influence on th e course of asthma and rhinitis. In our opinion, inducing and maintain ing aspirin tolerance in aspirin-sensitive asthmatics is indicated in the following situations: 1) the need to treat coexisting rheumatic di seases; 2) the need to treat coexisting intraCtable headaches; and 3) the need for symptomatic treatment of ASA-sensitive asthma and rhiniti s. A new alternative method for inducing tolerance to ASA in the nose to prevent polyp relapse is the intranasal administration of lysine-ac etylsalicylate, reported recently by Patriarca. The possible mechanism s of inducing the tolerance state are discussed.