Nonsteroidal/Aspirin exacerbated asthma: A new understanding and more questions to answer

Published Online: November 14, 2014

Asthma is the result of a complex group of disease mechanisms, also called endotypes, with a variety of clinical manifestations, also called phenotypes. Aspirin or Other Nonsteroidal Inflammatory Agent-Exacerbated Asthma is a classic asthma phenotype. Research in NSAID/ASA-exacerbated asthma has provided many answers but has also raised additional questions. The answers to these questions may advance our understanding of asthma in general.

In a paper recently published in The Journal of Allergy and Clinical Immunology: In Practice, Ledford and colleagues provide an overview of the current understanding of NSAID or ASA-exacerbated respiratory disease (AERD). The authors combine their clinical experience and an extensive review of the literature to provide a perspective of the beginnings and current state of the art with respect to AERD.

This article provides an overview of the pathogenetic mechanisms associated with NSAID/AERD. These include an overproduction of leukotrienes and a further increase following NSAID/ASA ingestion. Identification of affected subjects relies upon a history of increased upper and lower airway symptoms with NSAID/ASA ingestion, but double-blind challenges are necessary to prove AERD for research purposes. Clinical features which permit an operational, clinical identification of AERD are provided in the paper.
The increased production of proinflammatory leukotrienes and an intense eosinophilic mucosal inflammation in AERD are established by multiple studies, but the identification of the specific mechanism by which leukotriene production is increased remains an unanswered question. A variety of biologic markers and pathophysiologic mechanisms are described, suggesting there may be multiple pathways leading to this subtype of asthma. This possibility is supported by the research summarized in the paper showing that multiple genes with single nucleotide polymorphisms are associated with AERD. This genetic variability may reflect differences among various ethnicities or result from multiple pathways resulting in the same outcome.

Despite the unanswered questions, the fact remains that the severe phenotype of AERD asthma is modified by regular aspirin ingestion following desensitization. Paradoxically, the same medications that, when taken intermittently, result in exacerbations of the respiratory disease, will result in improvement of the respiratory disease when taken regularly. Further understanding ASA/NSAID will help in the understanding of all types of asthma.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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