Aspirin-sensitive asthma: The effect of aspirin on the release of prostaglandins from nasal polyps

Szczeklik, Andrzej; Gryglewski, Ryszard J.; Olszewski, E; Dembińska-Kieć, A.; Czerniawska-Mysik, G

doi:10.1016/s0031-6989(77)80027-1

Cited by 41 publications

(16 citation statements)

References 10 publications

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“…The impaired expression of COX-2 in nasal polyps from subjects with AERD, combined with hypermethylation of the PTGES gene (33), predict that subjects with AERD may not sustain PGE 2 in the respiratory tissue when COX-1 is inhibited. This prediction was supported by early ex vivo studies of excised, aspirin-treated nasal polyps (43). However, no study had directly addressed whether these lesions are causative, and which functional perturbations were essential to manifest the response to COX-1 inhibitors.…”

Section: Deletion Of Hematopoietic Ep 2 Receptors Partially Reproducementioning

confidence: 99%

Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Liu

Laidlaw

Katz

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

105

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Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, tissue eosinophilia, overproduction of cysteinyl leukotrienes (cysLTs), and respiratory reactions to nonselective cyclooxygenase (COX) inhibitors. Ex vivo studies suggest that functional abnormalities of the COX-2/microsomal prostaglandin (PG)E 2 synthase-1 system may underlie AERD. We demonstrate that microsomal PGE 2 synthase-1 null mice develop a remarkably AERD-like phenotype in a model of eosinophilic pulmonary inflammation. Lysine aspirin (Lys-ASA)-challenged PGE 2 synthase-1 null mice exhibit sustained increases in airway resistance, along with lung mast cell (MC) activation and cysLT overproduction. A stable PGE 2 analog and a selective E prostanoid (EP) 2 receptor agonist blocked the responses to Lys-ASA by ∼90%; EP 3 and EP 4 agonists were also active. The increases in airway resistance and MC products were blocked by antagonists of the type 1 cysLT receptor or 5-lipoxygenase, implying that bronchoconstriction and MC activation were both cysLT dependent. Lys-ASA-induced cysLT generation and MC activation depended on platelet-adherent granulocytes and T-prostanoid (TP) receptors. Thus, lesions that impair the inducible generation of PGE 2 remove control of platelet/granulocyte interactions and TP-receptor-dependent cysLT production, permitting MC activation in response to COX-1 inhibition. The findings suggest applications of antiplatelet drugs or TP receptor antagonists for the treatment of AERD.A spirin-exacerbated respiratory disease (AERD) affects 5-10% of all adults with asthma (1-3), ∼30% with severe asthma (4), and ∼40% with refractory chronic hyperplastic sinusitis (5). It involves severe eosinophilic respiratory tract inflammation and is defined by bronchoconstriction following the ingestion of nonselective COX inhibitors (6). Cysteinyl leukotrienes (cysLTs) (LTC 4 , LTD 4 , and LTE 4 ) drive these reactions, as well as some of the chronic features of AERD (7,8). CysLTs derive from arachidonic acid metabolized by 5-lipoxygenase (5-LO) to LTA 4 , conjugated to reduced glutathione by leukotriene C 4 synthase (LTC 4 S) to LTC 4 in mast cells (MCs), eosinophils, basophils, macrophages, and granulocyte-platelet complexes (9). After export, LTC 4 is converted sequentially to LTD 4 and LTE 4 . CysLTs induce bronchoconstriction (10, 11), tissue eosinophilia (12), and remodeling (13) through G-protein-coupled receptors (GPCRs) expressed by structural and hematopoietic cells (14-16). Individuals with AERD display higher urinary levels of LTE 4 than do aspirin-tolerant asthmatic (ATA) control subjects (17). Reactions to aspirin or other nonselective COX inhibitors are accompanied by marked further increases in urinary levels of LTE 4 and can be blocked by pretreatment with the 5-LO inhibitor zileuton or with antagonists of the type 1 receptor for cysLTs (CysLT 1 R) (18,19). The dependency on COX products to maintain homeostasis over 5-LO activity is a unique feature of AERD. Remarkably, subjects with AERD can tolerate selective ant...

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Section: Deletion Of Hematopoietic Ep 2 Receptors Partially Reproducementioning

confidence: 99%

Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Liu

Laidlaw

Katz

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

106

105

View full text Add to dashboard Cite

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“…Inhibitory action of aspirin on prostaglandin generation is far more pronounced in slices of nasal polyps obtained from aspirin-sensi tive asthmatics than from asthmatic patients without this sensitivity [6]. It might well be that this phenomenon is not restricted to nasal mucosa, but occurs also in further seg ments of respiratory tract, namely in bron chi.…”

Section: Discussionmentioning

confidence: 97%

Bronchial Reactivity to Prostaglandins F<sub>2α</sub>, E<sub>2</sub>, and Histamine in Different Types of Asthma

Szczeklik¹,

Nizankowska²,

Niżankowski³

1977

Respiration

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Bronchial reactivity to prostaglandins F_2α (PGF_2α), E₂ (PGE2) and histamine has been studied in 27 patients with aspirin-sensitive asthma and in 28 asthmatics without this sensitivity. Of the latter group, 13 patients had atopic, 9 infectious, and 6 mixed type of asthma. Atopic patients were characterized by vivid reactivity to low doses of both PGF_2α and histamine. In patients with infectious asthma significantly higher doses of both PGF_2α and histamine were necessary to induce bronchoconstriction as compared to atopies. Aspirin-sensitive patients responded quickly with bronchial spasm to similar doses of histamine as atopies, but tolerated significantly higher doses of PGF_2α. There was no difference in reactivity to PGF_2α between patients with aspirin sensitivity and those with infectious asthma. 5 and 10 min after administration of 60 μg PGE₂ significantly better improvement in ventilation occurred in aspirin-sensitive patients than in those of either atopic or infectious groups. The results obtained point to differences in bronchial reactivity to prostaglandins and histamine depending on type of asthma and severity of its symptoms.

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“…As early as 1976, Szczeklik et al [66] reported an increased susceptibility in nasal polyp cells from ASA-sensitive patients to inhibitory action of aspirin, prompting others to study arachidonic acid metabolism and its possible abnormalities in this subpopulation of patients.…”

Section: Arachidonic Acid Metabolitesmentioning

confidence: 99%

Pathogenesis of nasal polyps: An update

Pawliczak

Lewandowska–Polak

Kowalski

2005

Curr Allergy Asthma Rep

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The cause of nasal polyp formation is still unknown. Genetic predisposition has been suggested, but there are scanty data to support such theories. Activated epithelial cells may be the major source of mediators inducing influx of inflammatory cells (mostly eosinophils) and proliferation and activation of fibroblasts leading to nasal polyp formation. Infectious agents (including viruses, bacteria, or fungi) may be potential primary factors activating nasal epithelial cells. Proinflammatory cytokines and growth factors play important roles in the persistence of mucosal inflammation associated with nasal polyps. Arachidonic acid metabolites seem to be particularly important in the pathogenesis of nasal polyps in patients with aspirin hypersensitivity rhinosinusitis/asthma syndrome.

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Aspirin-sensitive asthma: The effect of aspirin on the release of prostaglandins from nasal polyps

Cited by 41 publications

References 10 publications

Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Bronchial Reactivity to Prostaglandins F<sub>2α</sub>, E<sub>2</sub>, and Histamine in Different Types of Asthma

Pathogenesis of nasal polyps: An update

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Aspirin-sensitive asthma: The effect of aspirin on the release of prostaglandins from nasal polyps

Cited by 41 publications

References 10 publications

Prostaglandin E2deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Prostaglandin E2deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Bronchial Reactivity to Prostaglandins F<sub>2α</sub>, E<sub>2</sub>, and Histamine in Different Types of Asthma

Pathogenesis of nasal polyps: An update

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Product

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Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

Prostaglandin E₂deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes