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Aspirin Exacerbated Respiratory Disease (AERD)



Aspirin Exacerbated Respiratory Disease (AERD)

Authors:
M. Julian Adame, MD
UTMB Allergy and Immunology Fellow
Julia W. Tripple, MD
Assistant Professor of Medicine
Division Director, ad interim
Division of Allergy & Immunology, Department of Internal Medicine
The University of Texas Medical Branch Galveston

 

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity reactions to cyclooxygenase (COX-1) inhibitors such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). AERD affects approximately 7.2 percent of asthmatics and up to 14.9 percent of severe asthmatics.1 Symptoms typically appear by middle age and there is a slight female predominance. The pathophysiology of AERD is an active area of research. However, dysregulation of lipid mediator production via the arachidonic acid pathway is a key component of the immunologic derangement.

AERD is primarily a clinical diagnosis. Classically, there is a history of upper and lower respiratory reactions (with or without urticaria and angioedema) upon ingestion of a COX-1 inhibitor in a patient with asthma and CRSwNP. Several clinical factors help predict the likelihood of AERD including: pansinusitis by imaging, complete anosmia, refractory sinus surgery and polypectomy, sinusitis incompletely resolved by antibiotics or steroids, severe persistent asthma, age of onset in third decade of life, and respiratory reactions with any NSAID or aspirin.2

The foundation of treatment for AERD consists of treating each of the individual components of the disease and avoidance of COX-1 inhibitors. Advanced therapies include aspirin desensitization and biologics.

For CRSwNP, high-dose intranasal steroid therapy should be implemented. Patients may also require short bursts of systemic corticosteroids to alleviate nasal congestion due to polyps. Surgery is reserved for refractory and severe sinusitis with multiple polyps and nasal obstruction.

Asthma therapy should reflect current guidelines and include a stepwise approach. Combination of inhaled corticosteroids and long-acting bronchodilators are the mainstay for moderate to severe asthma. For patients who have not been treated with a leukotriene modifying agent, a trial is reasonable.

Interestingly, aspirin desensitization is a unique option for management of AERD. Desensitization reduces both upper and lower airway symptoms, improves sense of smell, reduces sinus infections, decreases need for further surgery, and need for systemic steroids.3,4 Aspirin desensitization can be a first line therapy but is indicated particularly in patients who require daily aspirin or NSAID therapy for another comorbidity.

Under the guidance of an allergy specialist, a one- or two-day aspirin desensitization is performed by administering increasing doses of oral aspirin in a monitored setting. Doses are doubled until a dose of 325 mg is tolerated, at which point the patient is considered desensitized. Therapeutic doses are then gradually increased at home. Patients must continue to take aspirin to maintain tolerance and clinical benefit. Studies have shown that 325 mg is needed to maintain cross-desensitization to other NSAIDs, but target doses to achieve clinical benefit for AERD are in the range of 650–1300 mg daily.

Lastly, biologics can be considered. While none have approval yet for AERD, some are approved for asthma and/or CRSwNP, and can be helpful for patients with AERD. These include omalizumab, mepolizumab, and dupilumab.

In summary, AERD is a phenotype of severe asthma and should be considered in patients with a history of chronic rhinosinusitis with nasal polyps, asthma, and aspirin or NSAID hypersensitivity.

 

References:

  1. Rajan JP, Wineinger NE, Stevenson DD, White AA. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature. J Allergy Clin Immunol. Mar 2015;135(3):676-81.e1. doi:10.1016/j.jaci.2014.08.020
  2. Scott DR, White AA. Approach to desensitization in aspirin-exacerbated respiratory disease. Ann Allergy Asthma Immunol. Jan 2014;112(1):13-7. doi:10.1016/j.anai.2013.09.011
  3. Walters KM, Waldram JD, Woessner KM, White AA. Long-term Clinical Outcomes of Aspirin Desensitization With Continuous Daily Aspirin Therapy in Aspirin-exacerbated Respiratory Disease. Am J Rhinol Allergy. Jul 2018;32(4):280-286. doi:10.1177/1945892418770260
  4. Cho KS, Soudry E, Psaltis AJ, et al. Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease. Otolaryngol Head Neck Surg. Oct 2014;151(4):575-81. doi:10.1177/0194599814545750