Aspirin Exacerbated Respiratory Disease | Samter’s Triad

What is AERD/Samter’s Triad?

Aspirin Exacerbated Respiratory Disease (AERD), also known as Samter’s Triad or Aspirin Sensitive Asthma, is a chronic medical condition that consists of asthma, recurrent sinus disease with nasal polyps, and a sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Approximately 10% of all adults with asthma and 40% of patients with asthma and nasal polyps are sensitive to aspirin and NSAIDs.

What are the symptoms?

Patient with AERD/Samter's TriadPatients with AERD/Samter's Triad usually have asthma, nasal congestion, and nasal polyps, and often do not respond to conventional treatments. Many have experienced chronic sinus infections and can lose their sense of smell. The characteristic feature of AERD/Samter's Triad is that patients develop reactions triggered by aspirin or other NSAIDs.

These reactions can include:

  • Increased nasal congestion or stuffiness
  • Eye watering or redness
  • Cough, wheezing, or chest tightness
  • Frontal headache or sensation of sinus pain
  • Flushing and/or a rash
  • Nausea and/or abdominal cramping
  • General feeling of malaise, sometimes accompanied by dizziness

What is aspirin desensitization therapy?


Latest News & Information

Patients with AERD who develop a skin rash and gastrointestinal symptoms with aspirin desensitization produce large amounts of prostaglandin D2.

Prostaglandin D2: A dominant mediator of aspirin-exacerbated respiratory disease.

The AERD Center at Brigham and Women’s Hospital in Boston, MA collected clinical characteristics and biologic specimens from 29 patients with AERD undergoing an aspirin desensitization procedure. In addition to the classical respiratory symptoms triggered by aspirin challenge in AERD, 6 of these 29 patients developed a red, flat, itchy rash that started on their hands and feet during aspirin exposure. 5 of the 6 also reported gastrointestinal symptoms including nausea, abdominal pain, vomiting or diarrhea. These patients were harder to desensitize and 5 of 6 failed to go on to tolerate high-dose aspirin. The presence of rash and gastrointestinal symptoms was associated not only with a rise in leukotrienes but also a dramatic increase in PGD2 when compared with the 23 patients with AERD who developed only the classical respiratory symptoms. Patients with AERD who did go on to be treated with high-dose aspirin therapy demonstrated a significant fall in PGD2 levels. These findings provide novel insight into the role PGD2 has in symptom generation during aspirin-induced reactions. Additionally, they offer a clue about the mechanism by which aspirin therapy provides clinical benefit in AERD. This study provides the foundation for the use of novel therapeutics, currently under development, which target PGD2 in AERD.

Patients who tolerate daily low-dose aspirin may still have Aspirin-Exacerbated Respiratory Disease/Samter’s Triad.

Tolerance of daily low-dose aspirin does not preclude aspirin-exacerbated respiratory disease.

The AERD Center at Brigham and Women’s Hospital in Boston, MA identified a group of 7 AERD/Samter’s Triad patients with recurrent nasal polyps who, at the time of AERD diagnosis, had taken 81mg of aspirin daily for months to years. Although none of them recalled having a respiratory reaction to aspirin, all of them developed reactions on diagnostic aspirin challenge after stopping their daily aspirin for at least 10 days. Four of these patients pursued treatment with high-dose aspirin (at least 325mg twice daily), all of whom experienced improvement in their AERD sinus and asthma symptoms and none of whom required repeat polyp surgery over an average follow-up period of 26 months. This study highlights the need to consider the possibility of AERD in patients with recurrent polyps, even those who appear to tolerate low-dose aspirin.

Patients with AERD/ Samter’s Triad may have high IgE levels but without any true allergies

Elevated total IgE in nonatopic patients with Aspirin-Exacerbated Respiratory Disease.

AERD/Samter’s Triad is characterized by allergic-like reactions to aspirin and other nonsteroidal anti-inflammatory drugs, although it is not a true immunoglobulin E (IgE)–mediated allergy. Allergies to other substances, including pollens, animals, and other environmental agents can exist in patients with AERD, but are not characteristic of the disease. Interestingly, we have found a subgroup of patients with AERD who do not have any true allergies, yet have abnormally elevated serum total IgE, an antibody usually related to allergic diseases. Of 82 patients with AERD who were included in this analysis, 22 did not have any allergies identified to either foods or environmental substances, and of those, six had abnormally elevated levels of serum total IgE. This subgroup did not differ from the overall population of patients with AERD in terms of blood eosinophil count. While further research is necessary to uncover both the cause and the mechanism behind this phenomenon, its existence may be helpful in diagnosing AERD.

Four subclasses (subphenotypes) of AERD: All AERD patients are not the same

Certain subphenotypes of aspirin-exacerbated respiratory disease distinguished by latent class analysis.

AERD/Samter’s Triad is recognized as a distinct asthma phenotype, but the recent work of Dr. Ewa Nizankowska-Mogilnicka and the late Dr. Andrzej Szczeklik, now sheds new insights on the disease, and shows that individual patients with AERD are not homogeneous. They identified four classes or subphenotypes of AERD: Class 1, moderate asthma, intensive upper airway symptoms, and blood eosinophilia (18.9% of patients); Class 2, mild and relatively well-controlled asthma with low health care use (34.8% of patients); Class 3, severe and poorly controlled asthma with severe exacerbations and airway obstruction (41.3% of patients); and Class 4, poorly controlled asthma with frequent and severe exacerbations in female subjects (5.0% of patients). Atopic/allergic status did not affect class membership. Patients with particularly intensive upper airway symptoms had the highest levels of blood eosinophilia and the highest concentrations of urinary LTE4. Understanding what leads to such discrimination might facilitate more individualized treatment in difficult-to-treat patients. Further work is underway to learn more about whether class membership affects the severity of aspirin-induced reactions, or predicts the therapeutic response to treatment with high-dose aspirin.

A mouse model of AERD: Prostaglandin E2 (PGE2) deficiency results in AERD-like phenotype

Prostaglandin E2 (PGE2) deficiency results in AERD-like phenotype.

AERD/Samter’s Triad is characterized by mast cell activation with overproduction of cysteinyl leukotrienes following inhibition of COX-1 by medications like aspirin or NSAIDs. The cause of the mast cell activation that occurs following COX-1 inhibition is unknown.
Recent work in the Boyce Lab by Liu et al revealed that in a mouse model of dust mite-induced asthma, impairment in PGE2 production following challenge with aspirin in an inflamed lung resulted in an AERD-like phenotype that was dependent upon platelets and thromboxane receptors. Aspirin challenge in these mice resulted in overproduction of cysteinyl leukotrienes that led to mast cell activation, thereby showing that the scientists had for the first time created a mouse model of AERD. This is a leap forward in the field, as some of the authors’ findings suggest potential new targets for therapy, and the future applications of a mouse model as a research tool are endless.

Entire course at AAAAI 2013 dedicated to Samter’s Triad!


On February 22, 2013, at the annual meeting of the American Academy of Allergy, Asthma & Immunology in San Antonio TX, there was an entire day-long course dedicated to teaching and learning about AERD/Samter’s Triad! This is the first such extensive gathering of AERD/Samter’s Triad experts from around the world. The morning session was dedicated to Clinical/Pathological Observations and included speakers from Scripps Clinic in CA, Northwestern University in IL, Poland, and the UK. The afternoon session was titled Basic Mechanisms of AERD: From Mouse to Man to Novel Treatment and included speakers from Brigham and Women’s Hospital in MA, Korea, and Sweden.
The team of researchers and doctors reviewed what is understood about the disease thus far, and highlighted how much we have yet to learn. The audience consisted largely of practicing allergists and other physicians who treat patients with AERD/Samter’s Triad, and overall the day conveyed a mood of enthusiasm and renewed interest in improving our diagnoses and treatments for this disease. Ongoing clinical trials around the world for patients with AERD/Samter’s Triad were also reviewed.

Could eating chocolate reduce leukotrienes?

Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells.

One study suggests that eating the right kind of chocolate can decrease leukotriene production. Leukotrienes are signaling molecules that are responsible for many allergic and inflammatory reactions. Their overproduction is attributed to the nasal polyps, asthma, and aspirin sensitivity experienced by individuals with Samter’s Triad/AERD.
The study examined leukotriene synthesis as affected by the consumption of cocoa, which contains an anti-inflammatory organic compound known as procyanidin. To test procyanidin’s effect on leukotriene production, ten healthy individuals were asked to consume 37 grams of either low-procyanidin or high- procyanidin chocolate. The study was done a week a part so that all ten individuals would have a chance to consume both chocolates. The results showed that high-procyanidin chocolate decreased leukotriene levels to a greater extent than low-procyanidin chocolate.

Tobacco smoke and AERD / Samter’s Triad

Smoking, environmental tobacco smoke, and aspirin-exacerbated respiratory disease.

A study published in 2012 by a group of researchers at the Scripps Clinic in California found that childhood exposure to environmental tobacco smoke was associated with increased odds of developing AERD, and the effect was even greater if there was also exposure to tobacco smoke during adulthood. This study, of 260 patients with AERD and matched controls, suggests that environmental tobacco smoke is at least one contributor to the development of AERD/Samter’s Triad.

Low fat diet with fish oils can reduce LTB4 levels

A low-fat diet supplemented with dietary fish oil (Max-EPA) results in improvement of psoriasis and in formation of leukotriene B5

An older study, published in 1989, indicated that eating a low fat diet can reduce the body’s leukotriene B4 levels. Leukotrienes are signaling molecules that cause inflammatory and vascular reactions. Individuals suffering from Samter’s Triad/AERD generally have higher systemic levels of leukotrienes. A low fat diet may be able to reduce the effects of LTB4 by replacing arachidonic acid with eicosapentaenoic acid. Unlike arachidonic acid eicosapentaenoic acid is not metabolized to LTB4, but rather to LTB5. The original study was done to help individuals suffering from an autoimmune skin condition called psoriasis. Patients were placed on a low fat diet with fish oil for four months. Fifty eight percent of the patients who completed the study saw improvement in their psoriasis suggesting that a low fat diet with fish oil could improve the condition of individuals with psoriasis. It is possible that this diet may also be beneficial for other individuals suffering from leukotriene-related disorders, such as Samter’s Triad/AERD.

PGE2 Deficiency Uncovers Role for TXA2

Prostaglandin E2 deficiency uncovers a dominant role for thromboxane A2 in house dust mite-induced allergic pulmonary inflammation.

In this study, published in the July 2012 issue of the Proceedings of the National Academy of Sciences, Liu and colleagues showed that in mice that lacked the ability to make prostaglandin E2 (which is a deficiency that some have suggested is similar in patients with Samter’s Triad/AERD), the lung inflammation that developed was dependent on the presence of another chemical called thromboxane A2 (TXA2). As TXA2 is predominantly made by platelets, this research suggests that anti-thromboxane or anti-platelets medications could be helpful in decreasing lung inflammation.