Aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease
Other names	Aspirin-induced asthma, Samter's triad, Samter's syndrome, nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD/N-ERD)[1]
Coated aspirin tablets
Specialty	Rhinology, pulmonology, allergology
Symptoms	Adult-onset asthma, chronic rhinosinusitis with nasal polyps, NSAID hypersensitivity reactions
Usual onset	20s to 40s, average age 35-36[2]
Duration	Long term
Causes	Chronic immune dysregulation of unknown origin
Diagnostic method	Symptoms and medical history; aspirin challenge[2]
Differential diagnosis	Allergic rhinitis, nonallergic rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES)
Management	Inhaled and intranasal corticosteroids, aspirin desensitization and therapy, biologics, sinus surgery, diet, antileukotrienes
Frequency	0.3–0.9% (general population, US), ~7% of asthmatics[3]

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated respiratory disease (N-ERD) or historically aspirin-induced asthma and Samter's Triad, is a long-term disease defined by three simultaneous symptoms: asthma, chronic rhinosinusitis with nasal polyps, and intolerance of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).^[1][4] Compared to aspirin tolerant patients, AERD patients' asthma and nasal polyps are generally more severe. Reduction or loss of the ability to smell (hyposmia, anosmia) is extremely common, occurring in more than 90% of people with the disease.^[5] AERD most commonly begins in early- to mid-adulthood and has no known cure. While NSAID intolerance is a defining feature of AERD, avoidance of NSAIDs does not affect the onset, development or perennial nature of the disease.^[2]

The cause of the disease is a dysregulation of the arachidonic acid metabolic pathway and of various innate immune cells, though the initial cause of this dysregulation is currently unknown. This dysregulation leads to an imbalance of immune related molecules, including an overproduction of inflammatory compounds such as leukotriene E₄ and an underproduction of anti-inflammatory mediators such as prostaglandin E₂. This imbalance, among other factors, leads to chronic inflammation of the respiratory tract.^[2]

A history of respiratory reactions to aspirin or others NSAIDs is sufficient to diagnose AERD in a patient that has both asthma and nasal polyps. However, diagnosis can be challenging during disease onset, as symptoms do not usually begin all at once. As symptoms appear, AERD may be misdiagnosed as simple allergic or nonallergic rhinitis or adult-onset asthma alone. It is only once the triad of symptoms are present that the diagnosis of AERD can be made.^[5][2][6]

As there is no cure, treatment of AERD revolves around managing the symptoms of the disease. Corticosteroids, surgery, diet modifications and monoclonal antibody-based drugs are all commonly used, among other treatment options. Paradoxically, daily aspirin therapy after an initial desensitization can also help manage symptoms.

Reactions to aspirin and other NSAIDs range in severity but almost always have a respiratory component; severe reactions can be life threatening. The symptoms of NSAID-induced reactions are hypersensitivity reactions rather than allergic reactions that trigger other allergen-induced asthma, rhinitis, or hives. AERD is not considered an autoimmune disease, but rather a chronic immune dysregulation.^[2][7] EAACI/WHO classifies the syndrome as one of five types of NSAID hypersensitivity.