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Role of aspirin desensitization in the management of
chronic rhinosinusitis
Habib Rizk
Introduction
The triad of sinusitis, bronchial asthma, and aspirin
intolerance is known as Widal’s syndrome, Samter’s triad,
and aspirin-exacerbated respiratory disease (AERD).
The most recent consensus nomenclature describing
acetylsalicylic acid (ASA)-induced respiratory reactions
is nonallergic hypersensitivity reaction. Patients with
chronic rhinosinusitis (CRS) with nasal polyps are more
likely to have aspirin hypersensitivity or asthma than the
general population. Nasal polyps are reported in up to
70% of aspirin intolerant patients with asthma, whereas
their prevalence is only 4% in the general population. In
sensitive individuals, even a very small single dose of
aspirin or other cyclooxygenase-1 (COX-1) inhibitor can
cause rhinorrhea, bronchospasm, and shock [1
].
These patients usually have a more aggressive sinonasal
disease with need for multiple endoscopic sinus surgery
over the years.
Aspirin desensitization, although unpopular because of
the fear of severe reactions, has proven to be a valuable
therapeutic tool in these severe recalcitrant cases. This
paper sums up the pathogenesis of AERD, explores the
diagnostic methods that can be used, and finally reviews
the role of aspirin desensitization specifically in the
treatment of upper airway disease with focus on the
mechanism of action of this underutilized treatment
modality.
Pathogenesis: nonallergic hypersensitivity
reaction
In 1971, Vane discovered the effects of ASA and NSAIDs
on inhibition of COX enzymes in the metabolic cascade
of arachidonic acid metabolism. The COX enzymes exist
in at least two isoforms, COX-1 and COX- 2. COX-1 is
expressed in most mammalian cells. COX-2 is induced
during inflammation. COX 3 is expressed in the brain and
heart. In 1980, the first report of a second metabolic
pathway for arachidonic acid metabolism also involved
in inflammation was published. This pathway involves
5-lipoxygenase enzyme induction of leukotriene syn-
thesis. Leukotrienes C, D, and E4 [(LTC, LTD,
and LTE4)] are potent mediators of chemotaxis of
Department of Otolaryngology/Head and Neck
Surgery, Hotel-Dieu de France Hospital, Faculty of
Medicine, Saint-Joseph University, Beirut, Lebanon
Correspondence to Habib Rizk, MD, Department of
Otolaryngology/Head and Neck Surgery, Hotel-Dieu
de France Hospital, Alfred Naccache Street, Beirut,
Lebanon
Tel: +961 1 615300x3030; fax: +961 1 325382;
e-mail: habib.rizk@usj.edu.lb, habibrizk84@hotmail.com
Current Opinion in Otolaryngology & Head and
Neck Surgery 2011, 19:000–000
Purpose of review
This review is set to revisit the pathogenesis of aspirin-exacerbated respiratory disease
(AERD), the diagnostic method used, and finally the real impact of aspirin
desensitization on chronic sinusitis with nasal polyposis (CRSwNP) in aspirin intolerant
patients.
Recent findings
In AERD, increased baseline production of cysteinyl-leukotriene (Cys-LT) is associated
with upregulation of Cys-LT receptors on nasal inflammatory cells. This is further
aggravated by inhibition of cyclooxygenase-1 by aspirin and other NSAIDs. New-found
genetic markers need further study. Oral aspirin challenge is still the gold standard of
diagnosis and can be safely conducted in a specialized outpatient clinic. Oral and
endonasal aspirin desensitization show positive impact on CRSwNP course with
decreased polyp recurrence, decreased number of hospitalizations, and decreased
need for corticosteroids. Modulation of arachidonic acid metabolism and inhibition of
intracellular biochemical pathways in key inflammatory cells involving anti-inflammatory
cytokines interleukin (IL)-4 and IL-13 explain the clinical outcomes.
Summary
Future studies should focus on establishing the lowest possible dose to maintain
disease under check, allowing more widespread use of this underutilized and
underrecognized treatment modality.
Keywords
aspirin desensitization, aspirin-exacerbated respiratory disease, chronic rhinosinusitis
with nasal polyposis, cysteinyl-leukotrienes
Curr Opin Otolaryngol Head Neck Surg 19:000–000
ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
1068-9508
1068-9508 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MOO.0b013e3283450102