Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and Management

Abstract

The correlation between aspirin sensitivity, asthma, and nasal polyposis was recognized in the early 20th century. Today, this classic triad of symptoms, eponymously named Samter's Triad, is known as aspirin exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease affects approximately 0.3⁻0.9% of the general population in the USA and approximately 7% of asthmatic patients. The management of AERD is challenging as no single modality has proven to have high rates of symptom control. Consequently, disease management typically involves a multimodality approach across both medical and surgical disciplines. This review describes the epidemiology of AERD and the current state-of-the-art as it relates to the underlying pathophysiologic mechanisms of this disease process. A significant proportion of the review is focused on the appropriate diagnostic workup for AERD patients including the utility of aspirin provocation testing. The spectrum of medical treatments, including aspirin desensitization and recently introduced immunotherapies, are discussed in detail. Furthermore, surgical approaches to disease control, including advanced endoscopic techniques, are reviewed and treatment outcomes presented.

Keywords: AERD; Samter’s Triad; aspirin desensitization; aspirin exacerbated respiratory disease; chronic rhinosinusitis; endoscopic sinus surgery; nasal polyposis.

Figure 1

Arachidonic acid pathway (left panel) with associated impact of aspirin/non-steroidal anti-inflammatory disease (NSAID) therapy and inhibition (right panel). COX-1/2—cyclooxygenase 1/2; PGD2—prostaglandin D2; PGE2—prostaglandin E2; PGF2—prostaglandin F2; PGG2—prostaglandin G2; PGH2—prostaglandin H2; PGI2—prostaglandin I2; TXA2—thromboxane A2; 5-HPETE—5-hydroxyeicosatetranoic acid; LTA4—leukotriene A4; LTB4—leukotriene B4; LTC4—leukotriene C4; LTD4—leukotriene D4; LTE4—leukotriene E4; ASA—acetylsalicylic acid.

Figure 2

Schematic diagram depicting the role of Cys-LT1 activation and mast cell activation in pathogenesis of aspirin exacerbated respiratory disease (AERD) symptoms. INF-γ—interferon-gamma; IL-4—interleukin-4; Cys-LT—cysteinyl-leukotriene; Cys-LT1—cysteinyl-leukotriene 1; LTC4—leukotriene C4; LTD4—leukotriene D4; LTE4—leukotriene E4; IL-33—interleukin-33; PGD2—prostaglandin D2. This figure incorporates free publicly available images [41,42,43,44].