Aspirin-exacerbated Respiratory Disease: Causes, Symptoms, Treatment, Prognosis, Pathophysiology, Complications

Respiratory diseases are very common these days. Respiratory disease could be triggered by pollen grains, pollution, dust and also drugs. Aspirin-exacerbated respiratory diseases occurs due to sensitivity to the drug Aspirin. It is also referred to as Samterd’s triad, Aspirin sensitive asthma, Aspirin exacerbated asthma, aspirin intolerant asthma or aspirin-exacerbated asthma.

What is Aspirin-exacerbated respiratory disease (AERD)?

What is Aspirin-exacerbated respiratory disease (AERD)?

Aspirin-exacerbated respiratory disease is defined as a respiratory disease and one of the worst conditions of asthma which occurs following ingestion of aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) such as COX-1 inhibitors. This chronic medical condition is characterized by co-occurrence of:

  • Asthma
  • Chronic sinus inflammation with nasal polyps
  • Sensitivity (Acute allergic reaction) to aspirin and NSAIDs.

These 3 main symptoms are life threatening and called as ‘Samterd traid’. The three components of aspirin-exacerbated respiratory disease develop serially over a period of years. However, some patients may have a rapid progression of this syndrome. The disorder typically starts with rhinitis and progress to asthma, followed by nasal polyposis and finally shows sensitivity to aspirin.

Symptoms of Aspirin-exacerbated Respiratory Disease

The reactions to aspirin and other NSAIDs which induce symptoms of nasal congestion and bronchoconstriction typically begin 20 minutes to 3 hours after ingestion. The symptoms induced in this respiratory syndrome are hypersensitivity reactions to NSAIDs and are not true allergic reactions.

  • Nasal and Ocular Symptoms of Aspirin-Exacerbated Respiratory Disease:
    • Rhinitis (inflammation or irritation of the nasal mucosa) which causes sneezing, runny nose and nasal congestion.
    • Some patients even lose the sensation of smell (anosmia)
    • Eye watering and redness
  • Bronchospasm Symptoms of Aspirin-Exacerbated Respiratory Disease:
  • Additional Symptoms of Aspirin-Exacerbated Respiratory Disease:
    • Facial pain
    • Flushing
    • Nausea
    • Abdominal cramps
    • Sleep disturbances
    • Malaise accompanied by dizziness.

About 10% of patients with aspirin-exacerbated respiratory disease manifest skin symptoms like urticaria and/or gastrointestinal symptoms such as abdominal pain or vomiting due to aspirin intake.

Prevalence of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated Respiratory Disease affects 0.3-0.9% of the general population. Aspirin-exacerbated respiratory disease is seen to be prevalent in 7% of all asthmatics and in 15% of patients with severe asthma. Aspirin-exacerbated Respiratory Disease is more prevalent in women. It is acquired between teenage to adulthood years. Aspirin-exacerbated respiratory disease is prevalent in some children as well. It is not ethnically linked and has rare familial associations.

Prognosis of Aspirin-Exacerbated Respiratory Disease

In case of advanced aspirin-exacerbated respiratory disease stages or for aspirin-exacerbated respiratory disease with complications, treatment may not be very effective and may have poor prognosis.

While in case of early aspirin-exacerbated respiratory disease stages, treatment such as aspirin desensitization, will lead to better prognosis.

Causes of Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease is caused due to the inhibition of COX-1 enzymes which leads to subsequent attacks in the form of reactions on the upper and lower respiratory tract which is manifested as rhinitis and bronchospasm. The exact cause is not known and is speculative due to overproduction of and sensitivity to chemicals known as leukotrienes.

Pathophysiology of Aspirin-Exacerbated Respiratory Disease

The pathophysiology of aspirin-exacerbated respiratory disease is only partially understood. It is mediated by defective Eicosanoid metabolism and is not due to an IgE mediated reaction.

A disturbance in the Arachidonic acid (AA) metabolism is also noticed. Aspirin and NSAIDs inhibits COX-1 enzyme which in turn leads to reduction in the levels of anti-inflammatory mediators such as prostaglandin (PG2). This increases production of pro-inflammatory chemicals Cysteinyl-Leukotrienes (Cys-LT), which leads to the upper airway inflammation. This is mediated by the mast cells, leading to the annoying symptoms of aspirin-exacerbated respiratory disease.

Risk Factors of Aspirin-exacerbated Respiratory Disease

  • If a person is unaware that he/she has Aspirin-exacerbated respiratory disease and ingests aspirin and/or NSAIDs/or other Cox-1 inhibitors/pain killers, it will aggravate the aspirin-exacerbated respiratory disease symptoms.
  • Young women with moderate to severe asthma.

Complications of Aspirin-exacerbated Respiratory Disease

Since the clinicians fail to recognize this syndrome, hence the patients remain undiagnosed and do not get appropriate treatment in time. This allows the diseases to progress and become severe leading to complications.

Complications arise in the following conditions:

  • Aspirin-exacerbated respiratory disease patients show poor response to the traditional treatment strategies.
  • Aspirin-exacerbated respiratory disease symptoms occur more frequently and maybe severe enough to hospitalize the person.
  • Asthma patients with aspirin-exacerbated respiratory disease have compromised lung function and lead a poor quality of life as compared to the asthma patients without non-Aspirin-exacerbated respiratory disease. Most patients require corticosteroids; however these do not relieve obstruction and can have adverse effects on life.
  • Formation of nasal polyps is aggressive. It may fill the nasal cavity and protrude into the face. This causes deformation and may protrude into the nasopharynx bone as well.

Diagnosis of Aspirin-exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease is much better diagnosed when all the three main symptoms namely, rhinitis, nasal polyps and asthma are present together.

While clinical diagnosis becomes difficult in patients with isolated cases of asthma or rhinitis. In such cases, the patient’s entire clinical history of symptoms is noted, followed with history of ingestion of NSAIDs. This may be further followed with diagnostic aspirin challenge (also called as aspirin desensitization).

Diagnostic aspirin challenge is a gold standard in Aspirin-exacerbated respiratory disease diagnosis. It is performed under close observation of an allergist or a pulmonary specialist to handle any potential side effects. The patient is advised to take a very small dose of aspirin and is carefully observed for any signs of allergic reactions. The dose is increased every 2 hours and the patient is monitored till the patient responds to the dose. This allows diagnosing Aspirin-exacerbated respiratory disease.

Treatment of Aspirin-exacerbated Respiratory Disease

Asthma desensitization allows patients to tolerate aspirin and can be continued as long as they can tolerate the dose daily to maintain the desensitized state. Clinical studies have shown that aspirin desensitization followed by daily aspirin intake reduces symptoms of aspirin-exacerbated respiratory disease and also decreases intake of other medicines.

Many aspirin-exacerbated respiratory disease patients are advised to take medications to control their asthma symptoms. They are prescribed daily corticosteroids for inhalation by intranasal sprays or nasal/sinus irrigation. This practice also helps to control rhinitis and nasal polyps.

Medications that block the production of leukotrienes or stop their action are known to provide some benefit in treating aspirin-exacerbated respiratory diseases symptoms.

Nasal polyps can be treated with intra-polyp steroid injections. Further, surgical removal of nasal polyps is common. Surgery reduces the recurrence of these polyps when an additional Montelukast medicine is given.

Prevention of Aspirin-exacerbated Respiratory Disease

Till date there is no proper cure for aspirin-exacerbated respiratory disease. The treatment aims to reduce inflammation of nasal and respiratory tract mucosa, prevent formation of nasal polyps, control of sinusitis, infections and asthma.

In order to prevent occurrence of the symptoms, aspirin-exacerbated respiratory disease patients must avoid ingestion of aspirin and other NSAIDs containing medicines unless aspirin desensitization treatment is done. One must be selective in taking the analgesics (pain killers).


Aspirin-exacerbated respiratory disease is a complicated disorder and there is proper treatment for it. Further research is required to understand the mechanism underlying its pathogenesis which will help in developing effective treatment strategy.

Also Read:

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:May 24, 2018

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