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Plasma 15-Hydroxyeicosatetraenoic Acid Predicts Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease.

ABSTRACT: BACKGROUND:Aspirin desensitization followed by daily aspirin provides therapeutic benefits to patients with aspirin-exacerbated respiratory disease (AERD). It is not well understood how eicosanoid levels change during aspirin treatment. OBJECTIVE:To investigate associations between clinical outcomes of aspirin treatment and plasma eicosanoid levels in patients with AERD. METHODS:Thirty-nine patients with AERD were offered aspirin treatment (650 mg twice daily) for 4 weeks. Respiratory parameters and plasma levels of multiple eicosanoids were recorded at baseline and after 4 weeks of aspirin therapy using the Asthma Control Test and Rhinoconjunctivitis Quality of Life Questionnaire. Respiratory function was evaluated using the FEV1 and nasal inspiratory peak flow. RESULTS:After aspirin treatment, respiratory symptoms improved in 16 patients, worsened in 12 patients, and did not change in 4 patients. Seven patients were unable to complete the desensitization protocol. Patients with symptom improvement had higher baseline plasma 15-hydroxyeicosatetraenoic acid (15-HETE) levels than did patients with symptom worsening: 7006 pg/mL (interquartile range, 6056-8688 pg/mL) versus 4800 pg/mL (interquartile range, 4238-5575 pg/mL), P = .0005. Baseline 15-HETE plasma levels positively correlated with the change in Asthma Control Test score (r = 0.61; P = .001) and in FEV1 after 4 weeks of aspirin treatment (r = 0.49; P = .01). It inversely correlated with Rhinoconjunctivitis Quality of Life Questionnaire score (r = -0.58; P = .002). Black and Latino patients were more likely to have symptom worsening on aspirin or fail to complete the initial desensitization than white, non-Latino patients (P = .02). CONCLUSIONS:In patients with AERD, low baseline 15-HETE plasma levels and black or Latino ethnicity are associated with worsening of respiratory symptoms during aspirin treatment.

SUBMITTER: Jerschow E

PROVIDER: S-EPMC5491381 | biostudies-literature | 2017 Jul - Aug

REPOSITORIES: biostudies-literature

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Plasma 15-Hydroxyeicosatetraenoic Acid Predicts Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease.

Jerschow Elina E Edin Matthew L ML Pelletier Teresa T Abuzeid Waleed M WM Akbar Nadeem A NA Gibber Marc M Fried Marvin M Lih Fred B FB Gruzdev Artiom A Bradbury J Alyce JA Han Weiguo W Hudes Golda G Keskin Taha T Schuster Victor L VL Spivack Simon S Zeldin Darryl C DC Rosenstreich David D

The journal of allergy and clinical immunology. In practice 20170131 4

<h4>Background</h4>Aspirin desensitization followed by daily aspirin provides therapeutic benefits to patients with aspirin-exacerbated respiratory disease (AERD). It is not well understood how eicosanoid levels change during aspirin treatment.<h4>Objective</h4>To investigate associations between clinical outcomes of aspirin treatment and plasma eicosanoid levels in patients with AERD.<h4>Methods</h4>Thirty-nine patients with AERD were offered aspirin treatment (650 mg twice daily) for 4 weeks. ...[more]

PMID: 28159558

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Project description:BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.ObjectiveOur aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD.MethodsSingle-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence.ResultsThe gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO+ epithelium in NPs from patients with AERD.ConclusionsEpithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

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Plasma 15-Hydroxyeicosatetraenoic Acid Predicts Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease.

Publications

Plasma 15-Hydroxyeicosatetraenoic Acid Predicts Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease.

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