Asthma Subgroups: Aspirin Exacerbated Respiratory Disease (AERD)

Last updated: September 2019

About 5% of asthmatics, including 5% of child asthmatics and 21% of adult asthmatics,1 are said to belong to a rare, but severe, subgroup of asthma called aspirin exacerbated respiratory disease (AERD). Here is all you need to know about this subgroup.


AERD is a combination of severe asthma, severe sinusitis, and nasal polyps. Exposure to aspirin (acetylsalicylic acid) and other non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil), and naproxen (Aleve) cause nasal congestion (stuffy and runny nose) and bronchospasm (chest tightness and shortness of breath) within 30 minutes to 3 hours.1,2,3,15


As you can see by the statistics above, it’s usually diagnosed in adults. It is also more common in females than males  In one study, about 57% of those with AERD were females. In another, females outnumbered males 2.3 to 1. It currently affects 30 million Americans, with global estimates at $6 billion annually.1,3,4


The ancient Egyptians used willow bark to relieve aches and pains and inflammation, although they had no idea how it worked. Hippocrates described how willow leaves were useful for pain and fever.

In the 18th century, Edward Stone discovered aspirin for the modern world and used powdered willow bark. In 1829, a French pharmacist named Henri Leroux isolated the active ingredient as acetylsalicylic acid. In 1899, Bayer introduced a powder for physicians to experiment with, and by 1915 it was sold as over the counter tablets.5

In 1902, the first report of aspirin being linked to asthma was made. In 1922, Fernand Widal and associates recognized a link between aspirin, asthma, and nasal polyps, and the triad became known as Widal’s syndrome.  In 1968, Max Samter and Beers described the triad of asthma, nasal polyps, and aspirin sensitivity, and the triad became known as Samter’s Triad or Samter’s Syndrome. Since then the syndrome has been referred to as by a variety of other names.2,3,6,7

Other names

Along with those listed above, you will also see it referred to as aspirin-sensitive respiratory disease (ASRD), aspirin-sensitive asthma (ASA), aspirin-induced asthma, aspirin hypersensitivity, aspirin intolerant asthma (AIA), aspirin intolerance, and non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD).8,9


The exact cause is unknown, although some researchers believe aspirin (acetylsalicylic acid) inhibits COX 1 and COX 2.2

COX 1 and COX 2

These are also called prostaglandin synthase or prostaglandin endoperoxide synthase (PTGS). They synthesize (make) from arachidonic acid an enzyme called prostaglandin E2 (PGE2).2,13


It’s an anti-inflammatory enzyme responsible for blocking the effects of pro-inflammatory enzymes, such as leukotriene.2


With the COX 1 and COX 2 inhibited by aspirin, arachidonic acid is broken down and the byproducts are used to make pro-inflammatory leukotrienes. They are known to cause both upper and lower airway inflammation. Some leave the airway and recruit eosinophils.2,16


When they come into contact with airways they release proteins that are toxic to cells and cause inflammation of both the upper and lower respiratory tract. They also release proteins that recruit T-helper 2 (Th2) cells that release more pro-inflammatory proteins. They also release proteins that tell other cells, such as mast cells lining airways, to release even more pro-inflammatory cytokines. They may also play a role in persistent airway inflammation.


Eosinophils are elevated in sputum, nasal drainage, and blood. Prolonged (day after day) exposure to NSAIDs leads to eosinophilia, which causes persistent underlying airway inflammation resulting in severe sinusitis, severe asthma, and nasal polyps. AERD is commonly combined with a diagnosis of eosinophilic asthma.

Leukotriene C4 Synthase (LTC4) gene

It contains the recipe for making leukotriene C4 Synthase (LTC4S), which synthesizes (makes) leukotrienes from arachidonic acid. A gene mutation here (perhaps caused by aspirin) causes an excess of LTC4S, resulting in an abundance of leukotrienes.1,10,11

Arachidonate 5-Lipoxygenase (ALOX) Gene

It contains the recipe for making a protein called 5-Lipoxygenase (5L), which also makes leukotrienes from arachidonic acid. A mutation here may also cause an abundance of leukotrienes.1,12

Airway inflammation

A common theory suggests that both leukotrienes and eosinophils cause both upper and lower airway inflammation. Corticosteroids suppress their effects, resulting in less airway inflammation and better asthma control. This inflammation does respond to inhaled corticosteroids, although the highest doses. It usually requires systemic steroids (like prednisone) to overcome acute asthma episodes. This should lead to a diagnosis of severe asthma. Persistent airway inflammation may also lead to eosinophilic sinusitis and eosinophilic nasal polyps.


It may occur along with allergies, most notably rhinitis and conjunctivitis. However, most often it’s non-allergic (intrinsic), meaning that it doesn’t involve IgE antibodies, such as what is described in “allergic asthma.” A sensitivity develops due to prolonged exposure to aspirin or other NSAIDs.2,3,4


Common triggers include air pollution (car exhaust), weather changes (thunderstorms), viral infections (colds), and exposure to NSAIDs.


The first symptoms to appear are runny nose and nasal congestion around the ages of 30-34. Asthma symptoms eventually develop, including coughing, chest tightness, wheezing, and shortness of breath. A diagnosis of sinusitis, asthma, and nasal polyps is made. A diagnosis of AERD is usually made between the ages of 30-50. It may also be associated with rhinitis, conjunctivitis and anosmia (loss of sense of smell). A sputum sample should show elevated leukotriene and eosinophil levels.1,3,4


Both sinusitis and asthma respond to corticosteroids, although the highest doses of inhaled corticosteroids are needed to control asthma. Systemic steroids may sometimes be needed. Leukotriene inhibitors like Singulair (montelukast) may also prove helpful. Surgery may be indicated to remove polyps, although they tend to grow back, and sometimes rapidly. NSAID avoidance is also indicated.3


When NSAIDs cannot be avoided (such as for fevers and heart disease), aspirin desensitization may be indicated. This usually begins by using Singulair, and then taking very low doses of aspirin daily. The dose is then gradually increased so your body gradually becomes less sensitive to it over time.2,3,4

The future

Researchers continue to work overtime to learn more about AERD in an effort to learn more about it and come up with better medicines. This should some day lead to asthma guidelines specifically tailored for AERD, which should help asthma doctors help those diagnosed with it obtain better asthma control.

By providing your email address, you are agreeing to our privacy policy.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

Join the conversation

or create an account to comment.

Community Poll

How does your asthma change with the seasons?