What Is Aspirin-Exacerbated Respiratory Disease (AERD)?

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Aspirin-exacerbated respiratory disease (AERD), also known as Sampter's triad or aspirin-induced asthma, is a chronic disorder characterized by three co-occuring conditions: asthma, chronic rhinosinusitis with nasal polyps, and hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms include those typical of respiratory problems (shortness of breath, wheezing, coughing, nasal congestion, fever, and so forth) and in some cases hives or gastrointestinal issues. The condition is diagnosed based on the presence of the three respiratory issues and treated by avoiding aspirin and NSAIDS. When symptoms of AERD are severe or persistent, treatment to desensitive a patient to aspirin may be needed.

AERD affects between 0.3% and 0.9% of the general population, between 10% to 20% of people with asthma, and between 30% and 40% of people with asthma and nasal polyps.

Symptoms

Asthma and rhinosinusitis with nasal polyps are characteristic features of AERD, particularly when symptoms do not respond to standard treatment.

Common symptoms of AERD include:

  • Shortness of breath
  • Wheezing
  • Mouth breathing
  • Rapid breathing
  • Chest pressure
  • Cough, either dry or productive
  • Nasal congestion
  • Nasal discharge
  • Nasal drainage in the back of the throat
  • Headache
  • Low-grade fever
  • Watery eyes
  • Bad breath
  • Daytime fatigue
  • Reduced sense of smell
  • Reduced sense of taste
  • Pain in the upper teeth
  • Snoring
  • Frequent nosebleeds

In around 10% of cases, urticaria (hives) may develop, while 26% of cases may be accompanied by gastrointestinal symptoms such as vomiting and stomach ache.

Drinking alcohol can increase the risk of AERD symptoms. In fact, 51% of people with AERD will experience lower respiratory symptoms after a few sips of alcohol, which does not occur in the general population.

Complications

As a persistent or frequently recurring chronic disorder, AERD can progress and worsen even without exposure to aspirin.

In some cases, polyps can form aggressively even after they've been surgically removed. The ongoing obstruction of breathing can lead to other potentially severe complications, including middle ear infections, ear effusion (the build-up of fluid in the middle ear), chronic ear drainage, and permanent hearing loss.

There is even the risk of permanent asmonia (the loss of the sense of smell) in people with severe or uncontrolled AERD. As many as 39% of people with AERD report that loss of smell is the symptom that most affects their quality of life. Without smell, the ability to taste is also invariably impaired.

Causes

AERD is caused by a hypersensitive reaction to aspirin and other COX-1 inhibitors, which is not the same as an allergic reaction: With a hypersensitive reaction, there is no evidence of immunoglobulins or mast cell activation. Instead, the immune system overreacts in distinctive yet idiosyncratic ways to certain substances.

As per its name, AERD is inextricably linked to aspirin but can also occur in response to other COX-1 inhibitors, including:

  • Advil (ibuprofen)
  • Aleve (naproxen)
  • Voltaren (diclofenac)
  • Tivorbex (indomethacin)

Reactions may also occur with drugs that exhibit dual COX-1/COX-2 action, such as Tylenol (ibuprofen) and Felden (piroxicam), although the symptoms tend to be far less severe.

Asthma and sinusitis symptoms are believed to be triggered by the release of inflammatory compounds known as leukotrienes, which the body produces in excess in people with aspirin hypersensitivity.

The underlying cause of aspirin hypersensitivity is not well understood. It does not appear to be inherited and tends to affect all ethnicities equally.

Men are generally affected by AERD more than women, with symptoms appearing around age 35. It is not unusual for AERD to co-occur with allergic rhinosinusitis, gastroesophageal reflux disease (GERD), or exercise-induced asthma, suggesting that each has shared triggers and disease mechanisms.

Diagnosis

AERD is diagnosed when the triad of conditions (asthma, rhinosinusitis with polyps, and aspirin hypersensitivity) are met. If in doubt about a diagnosis, a doctor may recommend an aspirin challenge, in which a small dose of aspirin is given over several days under medical supervision to see if upper and lower respiratory symptoms develop.

If a reaction occurs, a doctor may perform a pulmonary function test (PFT) to measure the volume of air exhaled, how well the oxygen inhaled moves into the bloodstream, and how much air is left in the lungs after an exhale. These values can help direct the appropriate treatment.

Blood tests may be used to measure leukotrienes in the body, along with white blood cells, called eosinophils, that both occur with nasal polyps and potentiate their growth.

Computed tomography (CT) scans or nasal endoscopy are used to detect nasal polyps and visualize the sinus and nasal passages.

Treatment

The obvious way to prevent AERD symptoms is to avoid aspirin and other COX-1 inhibitors. In some cases, low-dose Tylenol may be used. Stronger COX-2 inhibitors like Celebrex (celecoxib) can sometimes be substituted for COX-1 drugs in people with acute pain, osteoarthritis, rheumatoid arthritis, or migraine.

That said, COX-2 inhibitors may not be appropriate for all people, especially those with certain cardiovascular or renal diseases.

Nasal Polyps

Even if you are able to avoid aspirin, this doesn't mean that the other symptoms will suddenly disappear. This is especially true with regard to nasal polyps.

Nasal polyps are typically treated with medications such as corticosteroids (nasal, oral, or injectable) or the biologic drug Dupixent (dupilumab), all of which can decrease the size of a polyp. If necessary, a nasal polyp can be surgically removed with a polypectomy.

The chronic nature of AERD—most especially the low-level inflammation that persists even when symptoms are controlled—means that polyps are likely to recur even if they have been surgically removed.

Asthma and Sinusitis

One way to reduce the risk of polyp recurrence is to keep the upper and lower respiratory symptoms under control.

In addition to not taking aspirin, an oral asthma medication such as Singulair (montelukast) or Accolate (zafirlukast) may reduce the frequency or severity of asthma attacks. Daily inhaled corticosteroids may also be prescribed.

The immunosuppressant drug prednisone may be used if other options fail to provide relief, although side effects can be significant and sometimes severe.

Rhinosinusitis may be treated with oral and/or intranasal antihistamines. In people prone to seasonal allergies, a daily dose may be needed to help manage symptoms. Intranasal corticosteroids may be used for 14 to 20 days to treat severe acute outbreaks.

Aspirin Desensitization

As the gold standard for AERD treatment, aspirin desensitization removes the trigger for the disease and provides sustained control of AERD symptoms. It is conducted under medical supervision, can take anywhere from a few days to a week, and involves being challenged with graded doses of aspirin, starting with the smallest dose and increasing day by day.

Aspirin desensitization must be supervised to monitor for any reactions that may occur. If symptoms occur at a specific dose, that dose is continued until it can be tolerated without a reaction.

Studies have shown that people who have successfully completed aspirin desensitization are less likely to experience polyp recurrence and have greater sustained control over respiratory symptoms.

After aspirin desensitization, it is necessary to continue taking a daily maintenance dose to remain desensitized. The dose may be as high as 1,300 milligrams (mg) per day to start, but it can be gradually decreased to as low as 81 mg per day.

Side effects of daily aspirin use include gastric bleeding, stomach ulcer, and an increased risk of hemorrhagic stroke.

Not all people with AERD are eligible for aspirin desensitization. You should not undergo treatment if you are pregnant or have stomach ulcers, bleeding disorders, or unstable asthma.

A Word From Verywell

If you have been diagnosed with aspirin-exacerbated respiratory disease, don't assume you can skip aspirin. This is especially true if your doctor has prescribed a daily, low-dose aspirin to reduce your risk of a heart attack or stroke. Aspirin cannot be substituted with any other NSAIDs for this purpose. You would need to speak with your doctor to weigh the benefits and risks before even thinking about stopping treatment.

By working closely with your doctor and taking things one step at a time, you should be able to find the right combination of treatments to prevent AERD from undermining your quality of life.

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