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Aspirin in tablets
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Aspirin-induced asthma is also termed Samter's triad, Samter's syndrome, aspirin-exacerbated respiratory disease (AERD), and recently by an appointed task force of the European Academy of Allergy and Clinical Immunology/World Allergy Organization (EAACI/WAO) Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD). The syndrome, which EAACI/WHO classifies as one of 5 types of non-steroidal anti-inflammatory drug hypersensitivity or NSAID hypersensitivity reactions, is a medical condition initially defined as consisting of three key features viz., asthma, symptom evocation by aspirin, and nasal/ethmoidal polyposis; however, the syndrome's symptoms are evoked by a large variety of other NSAID besides aspirin and rhinitis is an important accompaniment to, and often the earliest manifestation of, AERD. The asthma and rhinitis components of this syndrome are hypersensitivity reactions to NSAID rather than true allergic reactions that trigger common allergen-induced asthmatic and rhinitis responses; the syndrome does not appear to involve, for example, the common mediators of allergen-induced disease, immunoglobulin E or T cells. Rather, aspirin-induced asthma is a subtype of NSAID-induced non-allergic syndromes that include NSAID-induced urticaria/angioedema associated with underlying chronic urticaria, NSAID-induced urticaria/angioedema not associated chronic urticarial, and various other types of typically delayed (i.e. more than 1 day post-exposure) pathological responses to NSAID such as bullous or maculopapular skin eruptions, contact dermatitis, photocontact dermatitis, pneumonitis, and aseptic meningitis. It should be noted, however, that about 10% of patients with AERD manifest urticaria and/or angioedema reactions to NSAID.
Signs and symptoms
The various non-allergic NSAID hypersensitivity syndromes affect 0.5-1.9% of the general population, with aspirin-intolerant asthma affecting up to 0.3 percent of the general population and, when tested by aspirin provocation, up to 21% of asthmatics without nasal polyps and 25.6% of asthmatics with nasal polyps. AERD, which is more prevalent in women, usually begins in young adulthood (twenties and thirties are the most common onset times although children are afflicted with it and present a diagnostic problem in pediatrics) and may not include any other allergies. Most commonly the first symptom is rhinitis (inflammation or irritation of the nasal mucosa), which can manifest as sneezing, runny nose, or congestion. The disorder typically progresses to asthma, then nasal polyposis, with aspirin sensitivity coming last. Anosmia (lack of smell) is also common, as inflammation within the nose and sinuses likely reaches the olfactory receptors.
The reactions to aspirin vary in severity, ranging from mild nasal congestion and eye watering to lower respiratory symptoms including wheezing, coughing, an asthma attack, anaphylaxis, and in rare cases urticaria. In addition to aspirin, patients usually also react to other NSAIDs such as ibuprofen, and to any medication that inhibits the cyclooxygenase-1 (COX-1) enzyme, although paracetamol (acetaminophen) in low doses is generally considered safe. NSAID that are highly selective in blocking COX-2 and do not block its closely related paralog, COX-1, such as the COX-2 inhibitors celecoxib and rofecoxib, are also regarded as safe. Nonetheless, recent studies do find that these types of drugs, e.g. acetaminophen and celecoxib, may trigger adverse reactions in these patients; caution is recommended in using any COX inhibitors. In addition to aspirin and NSAIDs, consumption of even small amounts of alcohol also produces uncomfortable respiratory reactions in many patients.
The disorder is thought to be caused by an anomaly in the arachidonic acid metabolizing cascade which leads to increased production of pro-inflammatory cysteinyl leukotrienes, a series of chemicals involved in the body's inflammatory response. When medications like NSAIDs or aspirin block the COX-1 enzyme, production of thromboxane and some anti-inflammatory prostaglandins is decreased, and in patients with aspirin-induced asthma this results in the overproduction of pro-inflammatory leukotrienes to causes severe exacerbations of asthma and allergy-like symptoms. The underlying cause of the disorder is not fully understood, but there have been several important findings:
- Abnormally low levels of prostaglandin E2 (PGE2), which is protective for the lungs, has been found in patients with aspirin-induced asthma and may worsen their lung inflammation.
- In addition to the overproduction of cystinyl leukotrienes, overproduction of 15-lipoxygenase-derived arachidonic acid metabolites viz., 15-hydroxyicosatetraenoic acid and eoxins by the eosinophils isolated from the blood of individuals with AERD; certain of these products may help promote the inflammatory response.
- Overexpression of both the cysteinyl leukotriene receptor 1 and the leukotriene C4 synthase enzyme has been shown in respiratory tissue from patients with aspirin-induced asthma, which likely relates to the increased response to leukotrienes and increased production of leukotrienes seen in the disorder.
- The attachment of platelets to certain leukocytes in the blood of patients with aspirin-sensitive asthma has also been shown to contribute to the overproduction of leukotrienes.
- There may be a relationship between aspirin-induced asthma and TBX21, PTGER2, and LTC4S.
- Eosinophils isolated from the blood of aspirin-induced asthma subjects (as well as severe asthmatic patients) greatly overproduce 15-hydroxyicosatetraenoic acid and eoxin C4 when challenged with arachidonic acid or calcium ionophore A23187, compared to the eosinophils taken from normal or mildly asthmatic subjects; aspirin treatment of eosinophils from aspirin intolerant subjects causes the cells to mount a further increase in eoxin production. These results suggest that 15-lipoxygenase and certain of its metabolites, perhaps eoxin C4, as contributing to aspirin-induced asthma in a fashion similar to 5-lipoxygenase and its leukotriene metabolites.
Urinary cystyl-leukotriene or urinary LTE4 can be used after a supervised challenge with aspirin. In aspirin sensitivity, no change in N-methylhistamine is observed; while LTE4 levels are increased. This test however lacks sensitivity and has a 25 percent false negative rate among affected persons.
The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. In the United States, the Scripps Clinic in San Diego, CA, the Massachusetts General Hospital in Boston, MA, the Brigham and Women's Hospital in Boston, MA, National Jewish Hospital in Denver  and Stanford University Adult ENT Clinic have allergists who routinely perform aspirin desensitization procedures for patients with aspirin-induced asthma. Patients who are desensitized then take a maintenance dose of aspirin daily and while on daily aspirin they often have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and many have an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence, and can slow the regrowth of nasal polyps. Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists.
Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) are often helpful in treating the symptoms of aspirin-induced asthma. Some patients require oral steroids to alleviate asthma and congestion, and most patients will have recurring or chronic sinusitis due to the nasal inflammation.
Often surgery is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization is not undertaken.
Some people have reported relief of symptoms by following a low-salicylate diet such as the Feingold diet. Aspirin is quickly converted in the body to salicylic acid, also known as 2-Hydroxybenzoic acid. However, there is little evidence that a low-salicylate diet is beneficial for patients with AERD,. Only tiny amounts of salicylic acid (2-Hydroxybenzoic acid) are present in the diet. The foods with the highest concentrations of salicylic acid are beer with 0.2 mg per 100 ml and red wine with 0.04 mg per 100 ml. It would thus require 2.5 liters of beer or 12.5 liters of red wine to achieve the 5 mg dose of salicylic acid or aspirin considered to a minimum reactive dose to trigger aspirin-induced asthma. Other foods however do contain related hydroxybenzoic acids. Wintergreen flavoring Methyl 2-hydroxybenzoate is found in toothpaste and candies, and 4-Hydroxybenzoic acid is found in coconuts, strawberries, cherries and carrots and other foods. The average intake of hydroxy benzoates in the French diet has been estimated to be 41 mg per day with most of that (25 mg) from tea. Relief during exclusion diets may arise from non-aspirin co-morbid food intolerances. Current clinical trials are underway to determine whether or not the difficult dietary changes truly provide worthwhile therapeutic improvement for these patients.
A diet low in omega-6 oils (precursors of arachidonic acid), and high in omega-3 oils, may also help. In a small study, aspirin-sensitive asthma patients taking 10 grams of fish oil daily reported relief of most symptoms after six weeks, however symptoms returned if the supplement was stopped.
- Aspirin-induced asthma is also referred to as leukotriene associated hypersensitivity 
Samter's triad goes by several other names:
- Acetylsalicylic acid triad 
- Widal's triad
- Francis' triad
- Aspirin triad
- Aspirin-exacerbated respiratory disease (AERD).
- Aspirin-induced asthma and rhinitis (AIAR)
A sufferer who has not yet experienced asthma or aspirin sensitivity might be diagnosed as having:
- Non-allergic rhinitis
- Non-allergic rhinitis with eosinophilia syndrome (NARES)
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