Who is at risk for a hypersensitivity reaction to NSAIDs?
A severe asthmatic with nasal polyps is at most risk for a hypersensitivity reaction to NSAIDs; up to 78% may react to ASA ( Samter’s triad = asthma, nasal polyps, ASA sensitivity). Patients with isolated asthma (10%–20% ASA sensitivity overall), nasal polyps, or chronic urticaria are also mildly at risk to react to NSAIDs, usually with acute bronchospasm and shortness of breath. It is important to note that this is a sensitivity and not an allergy, because it is not IgE-mediated.
Two theories have been proposed to explain ASA/NSAID-sensitive asthma. One suggests that asthma is caused by COX inhibition resulting in decreased production of PGE 2 , an important bronchodilator. A second theory proposes that this type of asthma is a consequence of the five-fold increased bronchial expression of leukotriene C4 synthetase. When ASA or NSAIDs block COX, the arachidonic acid precursors can shunt down the leukotriene pathway resulting in excessive production of leukotrienes C, D, and E (slow reacting substance of anaphylaxis). These theories are supported by: (1) salsalate does not inhibit COX to a large degree and has not been found to cause asthma attacks (it is the NSAID of choice for ASA-sensitive asthma patients), (2) leukotriene inhibitors block bronchospasm provoked by NSAIDs in ASA-sensitive patients, and (3) NSAID-induced asthma attacks are acute in onset, severe and prolonged, and can be resistant to glucocorticoids.
Small studies of patients with ASA-sensitive asthma given celecoxib did not demonstrate an increased risk of hypersensitivity reaction, but there are no long-term studies documenting its safety in this population. As such, the selective COX-2 inhibitors have the same warning as nonselective NSAIDs in their package inserts.