Aspirin asthma

All antiplatelet drugs increase the risk of bleeding. Even at the low ASA doses used to inhibit platelet function (100 mg/d), ulcerogenic and bronchocon-strictor (aspirin asthma) effects may occur. Ticlopidine frequently causes diarrhea and, more rarely, leukopenia, necessitating cessation of treatment Clopidogrel reportedly does not cause hematological problems. 

Aspirin sensitive asthma, affecting about 10% of all asthmatics, is a nonallergic response to aspirin and other agents that inhibit cyclooxygenase-1. Mechanistically, the most likely reasons are lack of bronchoprotective prostaglandin E2 and shunting of arachidonic acid into the leukotriene pathway. 

There are few definitive data to substantiate the efficacy of LTRA therapy in refractory asthma, except for patients with aspirin-sensitive asthma. This is a fairly uncommon form of asthma that occurs generally in adults who often have no prior (i.e., childhood) history of asthma or atopy, may have nasal polyposis, and who often are dependent upon oral corticosteroids for control of their asthma. This syndrome is not specific to aspirin but is provoked by any inhibitors of the cycloxygenase-1 (COX-1) pathway. These patients have been shown to have a genetic defect that causes... 

Montelukast—Take once daily in the evening, even when free of symptoms. Contact physician if the asthma is not well controlled. This drug is not for the treatment of an acute attack. Avoid taking aspirin and the NSAIDs while taking montelukast. 

Three years after introduction of aspirin into therapy, Hirschberg in Poznan, now in Poland, described the first case of a transient, acute angioedema/urticaria, occurring shortly after ingestion of aspirin. Reports of anaphylactic reactions to aspirin soon followed. The other major type of adverse reaction, acute bronchospasm, was described in the second decade of the 20th century. In 1920, Van der Veer reported the first death due to aspirin. The association of aspirin sensitivity, asthma and nasal polyps was first recorded by Widal in 1922. This clinical entity, later named the aspirin triad was popularized in 1968 by Samter and Beers [3], who presented a... 

The term refers to a distinct clinical syndrome characterized by aggressive and continuous inflammatory disease of the airways with chronic eosinophilic rhinosinus-itis, asthma and often nasal polyposis [6-8]. Aspirin and other NSAIDs that inhibit COX-1 exacerbate the condition, precipitating violent asthmatics attacks. This is a hallmark of the syndrome. The prevalence of aspirin hypersensitivity in the general population ranges from 0.6 to 2.5%, but is much more frequent in adult asthmatic subjects where it reaches 10-15%, although it is often underdiagnosed. 

AIA runs a characteristic clinical course [9]. It is more frequent in women than men, and is unusual in children, beginning in adulthood, on average at the age of 30 years. Rhinorrhea and nasal congestion are usually the first symptoms, subsequently complicated by polyposis. Asthma and aspirin hypersensitivity develop 2-15 years later. Once developed, aspirin intolerance remains through life, although sporadic disappearance of intolerance has been reported. Asthma, characterized by blood and nasal eosinophilia, rims a protracted course despite avoidance of analgesics. In about half the patients, the course of asthma is severe, necessitating use of systemic corticosteroids. 

A non-allergic mechanism imderlying precipitation of asthmatic attacks by aspirin in hypersensitive patients was proposed over 30 years ago [4]. It was founded on pharmacological inhibition of COX of arachidonic acid and explained a cross-reactivity between different NSAIDs varying in chemical structure. This COX theory was confirmed by several studies [11] and was further refined following discovery of the second COX isoenzyme - COX-2. At least two COX isoenzymes, COX-1 and COX-2, are coded by separate genes. Their role in inflammation, asthma and anaphylaxis has been reviewed previously [12]. 

Once diagnosed, patients with AlA should avoid aspirin and any other NSAIDs strongly inhibiting COX-1 their education is of utmost importance. They should receive a list of contraindicated and well-tolerated analgesics (table 2). Even topical administration (intravascular or by iontophoresis) of a NSAID may cause an asthma attack and should be avoided. 

In general, treatment of the asthma underlying NSAlDs sensitivity should follow standard asthma guidelines. This type of asthma is often severe and frequently high doses of inhaled corticosteroids and daily doses of oral corticosteroids are necessary. A special treatment option is a chronic desensitization to aspirin [8]. Desensitization and aspirin maintenance is routinely used in some centers for treatment of chronic rhinusinusitis with nasal polyposis. It is the only available procedure which allows AIA patients with ischemic heart disease to use aspirin. During the state of desensitization to aspirin, not only aspirin but almost all strong NSAIDs are tolerated, so desensitization and NSAID maintenance could be used for treatment of rheumatic disease or chronic pain syndromes. 

Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. Br Med J 1975 1 67-69. 

Jenkins C, Costello J, Hodge L Systematic review of prevalence of aspirin-induced asthma and its implications for clinical practice. BMJ 2004 328 434-437. Baldassarre S, Schandene L, Choufani G, Michils A Asthma attacks induced by low doses of celecoxib, aspirin and acetaminophen. J Allergy Clin Immunol 2006 117 215-217. 

Zembowicz A, Mastalerz L, Setkowicz M, Radzis-zewski W, Szczeklik A Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria. J Cutan Pathol 2004 31 323-329. Mastalerz L, Setkowicz M, Sanak M, Szczeklik A Hypersensitivity to aspirin common eicosanoid alterations in urticaria and asthma. J Allergy Clin Immunol 2004 113 771-775. 

Genetic factors cannot explain the recent rapid rise in asthma prevalence. Asthma appears to require both genetic predisposition and environmental exposure. Many patients with occupational asthma develop the disease late in life upon exposure to specific allergens in the workplace. Environmental influences in utero or in infancy may contribute to the development of asthma. Maternal smoking during pregnancy or exposure to secondhand smoke after birth increases the risk of childhood asthma.3 Adult-onset asthma is not uncommon and may be related to atopy, nasal polyps, aspirin sensitivity, occupational exposure, or a recurrence of childhood asthma. 

Acute and chronic sinusitis can also aggravate asthma, and antibiotic therapy of sinusitis may improve asthma symptoms.3 Nasal polyps are associated with aspirin-sensitive asthma, and adult patients with nasal polyps should be counseled against using non-steroidal anti-inflammatory medications.1,3... 

COX-2 inhibitors such as celecoxib are associated with adverse effects such as nephrotoxicity and a potential increased risk of myocardial infarction (see Chaps. 55 and 15 for additional information). Combination of COX-2 inhibitors with alcohol may increase GI adverse effects. All NSAIDs should be used with caution in patients with aspirin-induced asthma.31... 

Application of topical salicylates can lead to systemic effects, especially if the product is applied liberally. Repeated application and occlusion with a wrap or bandage also can increase systemic concentrations.41 Salicylate-containing counterirritants should be used with caution in patients in whom systemic salicylates are contraindicated, such as patients with severe asthma or aspirin allergy.42 Topical salicylates have been reported to increase prothrombin time in patients on warfarin and should be used with caution in patients on oral anticoagulants.43... 

Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A. Enhanced expression of the leukotriene C(4) synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma. Am J Respir Cell Mol Biol 2000 23 290-296. 

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