Non-steroidal anti-inflammatory drugs (NSAIDs) – exacerbated respiratory disease: epidemiology, pathogenesis, clinical findings and management

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Non­-steroidal anti­-inflammatory drugs (NSAIDs) ­– exacerbated respiratory disease (N­-ERD) are characterized by non­-allergic hypersensitivity (intolerance) to NSAIDs and aspirin in patients with asthma and/or eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP). Asthma in N­-ERD patients is usually characterized by eosinophilic inflammation, tends to become severe and intractable, and needs chronic oral corticosteroid therapy. For some patients recurrent CSwNP is more significant problem due to nasal congestion, anosmia, and multiple repeated surgeries. Intolerance to aspirin and other NSAIDs limits the choice of pain relievers and antipyretics. Accidental use of these medications can lead to dangerous consequences, including anaphylaxis. This review presents the current understanding of the N­-ERD pathogenesis and perspective trends in therapy.

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About the authors

Ksenia S. Pavlova

NRC Institute of Immunology FMBA of Russia

Author for correspondence.
ORCID iD: 0000-0002-4164-4094

Senior Research Assistant of Bronchial Asthma, NRC Institute of Immunology FMBA of Russia, MD, PhD

Russian Federation, Moscow

Miramgul E. Dyneva

NRC Institute of Immunology FMBA of Russia

ORCID iD: 0000-0003-1965-8446

post-graduate student, NRC Institute of Immunology FMBA of Russia

Russian Federation, Moscow

Oksana M. Kurbacheva

NRC Institute of Immunology FMBA of Russia

ORCID iD: 0000-0003-3250-0694

Head of the Asthma department, NRC Institute of Immunology FMBA of Russia, PhD, professor

Russian Federation, Moscow


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Supplementary files

Supplementary Files
1. Fig. 1. Metabolism of arachidonic acid in NSAID-induced RD. 5-LOG - 5-lipoxygenase; BLT1, BLT2 - receptors for leukotriene B4; LTA4, LTV4, LTS4, LTD4, LTE4 - leukotrienes; CysLTR1, CysLTR2, CysLTR3 - leukotriene receptors; PGE2, PGF2á, PGG2, PGH2 - prostaglandins; COX-1 - cyclooxygenesis 1; COX-2 - cyclooxygenase 2

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2. Fig. 2. Signaling cascades involved in the relationship between platelets and eosinophils. Adapted from [1]. PG - prostaglandins; LT - leukotrienes; 5-LOG - 5-lipoxygenase; MAC-1 - macrophage-1 antigen (membrane protein, heterodimeric integrin); CysLTR1, CysLTR2 - cysteinyl leukotriene receptors; P2Y12 is a chemoreceptor for adenosine diphosphate, which belongs to the GI class of the group of G protein-coupled purinergic receptors; GPIIb / IIIa - platelet integrin receptor; FLAP - 5-lipoxygenase activating protein

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3. Fig. 3. Possible mechanisms of pathogenesis of NSAID-induced RH. IgE - immunoglobulin E; DC - dendritic cell; IL - interleukin; ILC2 - type 2 congenital lymphoid cells; MHCII - major histocompatibility complex II; PGD2 - prostaglandin D2; PGE2 - prostaglandin E2; GATA, erythroid transcription factor; RORá - retinoid-linked orphan alpha receptor; TCR, T-cell receptor; Th2 - T-helper type 2; TSLP, thymic stromal lymphopoietin; CysLTR - cysteinyl leukotriene receptors; 5-LOG - 5-lipoigenase; LTA4, LTV4, LTS4, LTD4, LTE4 - leukotrienes; PGE2, PGF2á, PGG2, PGH2 - prostaglandins

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4. Fig. 4. The central role of ILC2 in the fibrotic process. TSLP, thymic stromal lymphopoietin; TGF-â - transforming growth factor-â; Th2 - T-helper type 2; IL - interleukin; ILC2 - congenital type 2 lymphoid cells

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5. Fig. 5. Algorithm for the diagnosis of NSAID-induced RD. * - provocative tests with aspirin are not certified in Russia

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