Aspirin and Asthma

K. Suresh Babu, MD, DNB; and Sundeep S. Salvi, MD, DNB, PhD, From the Department of Respiratory Cell and Molecular Biology, University of Southampton, Southampton General Hospital, Southampton, UK.

Disclosures

CHEST. 2000;118(5) 

In This Article

Aspirin Desensitization

In aspirin-sensitive patients, there are strategies available to administer aspirin. These subjects could be made to tolerate aspirin. This is particularly important in AIA patients with coexistent arthritis or arterial thromboembolic diseases, or after AIA patients experience myocardial infarctions. The availability of alternate drugs for cardiovascular and thromboembolic diseases has lead to the utilization of aspirin desensitization in the management of aspirin-sensitive patients with rhinosinusitis and nasal polyps. All aspirin-sensitive patients can be successfully desensitized. [44] Oral administration is used for aspirin desensitization, but alternative approaches, such as intrabronchial and inhalational administration, have been tried.

Small incremental doses of aspirin are ingested over the course of 2 to 3 days until 400 to 650 mg aspirin is tolerated. Aspirin then can be administered daily, with doses of 100 to 300 mg used for desensitization. After each dose of aspirin, there is a refractory period of 2 to 5 days during which aspirin and other COX inhibitors can be taken with impunity. It is possible to maintain the tolerance state for a long time by the administration of aspirin at proper intervals. [45] Patients maintained on aspirin desensitization do respond to an aspirin challenge. This manifests as a rise in the level of urinary LTE4 excretion, however, the responses appear blunted. [46] Problems that are encountered during desensitization of an AIA patient include gastritis, which is seen in about 20% of aspirin-treated patients. [47] Cutaneous reactions to aspirin also have been observed. Patients can be successfully desensitized but need to take the treatment regularly to maintain the refractory state. If patients discontinue ASA for some days, their sensitivity to ASA can revert to their predesensitization levels, and this could precipitate an acute asthma attack on exposure to NSAIDs.

Endonasal administration of lysine-ASA has been used in some studies for ASA desensitization. [48] Endonasal desensitization with lysine-ASA has been found to be effective in nasal polyposis induced by aspirin. The relapse rates of nasal polyps were significantly lower (lysine-ASA group, 57.5%; group treated without lysine-ASA, 88%) on a 5-year follow-up. [49] Aspirin desensitization by the endonasal route may represent a valid alternative to classical surgical approaches in patients with nasal polyposis.

Desensitization by the inhalational route also has been tried and was based on the premise that AIA becomes refractory by repeated provocation with lysine-ASA inhalation. This is termed as adaptive deactivation. [50]

Aspirin desensitization plays an important role in the management of post-myocardial infarction patients with AIA. [51] Symptoms of nasal inflammatory disease seem to respond well to aspirin desensitization, which has been shown to delay the recurrence of nasal polyp formation by an average of 6 years. [48] Although the precise mechanism of aspirin desensitization is still unclear, studies have shown a substantial decline in the peripheral monocyte synthesis of LTB4 in AIA patients after aspirin desensitization. [52] In addition, the cysteinyl LT receptors were down-regulated, thereby reducing the effectiveness of the same load of LTs. [53] It was observed that in aspirin-induced urticaria, mast cell degranulation did not occur after aspirin desensitization. [54] The increase in the level of urinary LTE4 during aspirin challenge and its reduction after desensitization is inversely proportional to that of thromboxane B2 and suggests a shunting of the arachidonic acid metabolites of the target cells. [55] These findings suggest a change in the balance between inflammatory mediators after desensitization, leading to aspirin tolerance in the AIA population.

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