Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial

Cahill, Katherine N.; Cui, Jing; Kothari, Parul H.; Murphy, Katherine; Raby, Benjamin A.; Singer, Joseph; Israel, Elliot; Boyce, Joshua A.; Laidlaw, Tanya M.

doi:10.1164/rccm.201809-1755oc

Cited by 44 publications

(67 citation statements)

References 25 publications

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“…28,29 In a presumably majority Caucasian AERD population from Poland, higher IgE levels were associated with more emergency department visits and hospitalizations for asthma exacerbations and poorer asthma control as measured through the ACT, further supporting the concept of IgE being a significant biomarker of worse disease in AERD. 30 Although serum IgE levels did not change over the course of treatment in aspirin responders in this study, as well as in another recent report, 20 IgE levels increased significantly in nonresponders during aspirin treatment. This is consistent with the recent observation that high-dose aspirin therapy increases markers of type 2 inflammation in AERD patients 20 and may make patients with higher baseline levels of IgE more prone to treatment failure.…”

Section: Discussionsupporting

confidence: 62%

“…3,7 Aspirin therapy has been shown to impart a long-term benefit of polyp regrowth reduction, improved sense of smell, and need for revision sinus surgery in prospective clinical trials. 6,[18][19][20] In addition to aspirin therapy, ESS has been shown to improve the disease process in both physician-reported (nasal endoscopy and Lund-Mackay [LM] computed tomography scores) and patient-reported (SNOT-22 score) measures. 21 Although aspirin therapy may be beneficial, its impact does not appear to be universal.…”

Section: Discussionmentioning

confidence: 99%

“…1). [17][18][19][20][21][22], p = 0.1) (Fig. 2), or in percent FEV 1 (78% [IQR, 65-102%] vs 81% [IQR, 70-99%], p = 0.8) (Fig.…”

Section: Study Cohort and Response To Aspirin Treatmentmentioning

confidence: 97%

“…Treatment outcomes after aspirin treatment in responders and nonresponders are summarized in Figure 1. Nineteen patients classified as "responders" had a significant increase in the ACT score after 4 weeks of treatment compared with baseline (23 [IQR, [21][22][23][24][25] vs 20.5 [IQR, [17][18][19][20][21][22], p < 0.01) and a significant decline in RQLQ score compared with baseline (2.5 [IQR, 1.5-3.0] vs 1.2 [IQR, 0.5-2.0], p < 0.05). Twenty-one patients classified as "nonresponders" had a decline in ACT score at 4 weeks compared with baseline (15 [IQR, [12][13][14][15][16][17][18] , p = 0.05), although this outcome was of borderline significance.…”

Section: Study Cohort and Response To Aspirin Treatmentmentioning

confidence: 99%

“…vs 19 [IQR,[15][16][17][18][19][20][21][22], p < 0.05), but no significant change in RQLQ score at 4 weeks compared with baseline (2.9 [IQR, 2.2-3.7] vs 2.6 [IQR, 2.0-3.8], p = 0.6).The baseline characteristics for responders (n = 19) and nonresponders (n = 21) are presented inTable 1. Compared with responders, nonresponders were more likely to be African American than Caucasian (71% vs 26%, p < 0.01), with a lower baseline NPF (94 ± 8.7 L/min vs 125 ± 12.2 L/min, p < 0.05), fewer sinus surgeries before aspirin desensitization(1 [IQR, 0-1] vs 1 [IQR, 1-2], p < 0.01), and higher total serum IgE levels (252 [IQR, 96-479] kU/L vs 87 [IQR, 53-193] kU/L, p < 0.01).…”

mentioning

confidence: 99%

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Endoscopic sinus surgery improves aspirin treatment response in aspirin‐exacerbated respiratory disease patients

Shah

Abuzeid

Ponduri

et al. 2019

Int Forum Allergy Rhinol

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Background Aspirin desensitization and treatment benefits most patients with aspirin‐exacerbated respiratory disease (AERD), although some patients fail therapy. Our objective was to assess whether recent endoscopic sinus surgery (ESS) improved aspirin treatment outcomes in AERD patients who initially failed aspirin therapy. Methods Outcomes of aspirin desensitization and treatment in AERD patients prospectively enrolled were assessed preoperatively and at 4, 12, and 24 weeks after ESS by determining changes in Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and respiratory function. Biomarkers, including fractional excretion of nitric oxide (FeNO), spirometry, nasal inspiratory peak flow (NPF), immunoglobulin E (IgE), and eosinophil count, were measured. Results Nineteen patients who benefited (responders) and 21 patients who failed (nonresponders) preoperative aspirin treatment with a distant history of ESS (mean, 48 months) were identified. Nonresponders were more likely to be African American (71%, p < 0.01) and have higher baseline IgE levels (252 kU/L vs 87 kU/L in responders, p < 0.01). 24 of the 40 patients (nine responders and 15 non‐responders) required subsequent ESS and underwent another aspirin desensitization 3‐4 weeks after ESS. All 24 patients tolerated a second round of aspirin desensitization and treatment. The primary aspirin therapy was associated with a significant increase in IgE in nonresponders, but there was no significant increase in IgE after the second aspirin desensitization and treatment. Conclusion Antecedent ESS enhances aspirin treatment responses in AERD patients and may convert patients who failed aspirin treatment before surgery to a more responsive phenotype after ESS. Patients with higher baseline serum IgE levels may benefit from ESS performed shortly before aspirin desensitization and therapy.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

“…1). [17][18][19][20][21][22], p = 0.1) (Fig. 2), or in percent FEV 1 (78% [IQR, 65-102%] vs 81% [IQR, 70-99%], p = 0.8) (Fig.…”

Section: Study Cohort and Response To Aspirin Treatmentmentioning

confidence: 97%

Section: Study Cohort and Response To Aspirin Treatmentmentioning

confidence: 99%

mentioning

confidence: 99%

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Endoscopic sinus surgery improves aspirin treatment response in aspirin‐exacerbated respiratory disease patients

Shah

Abuzeid

Ponduri

et al. 2019

Int Forum Allergy Rhinol

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Biomarkers for predicting response to long‐term high dose aspirin therapy in aspirin‐exacerbated respiratory disease

Mastalerz

Tyrak

2021

Clinical & Translational All

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Introduction Aspirin‐exacerbated respiratory disease (AERD) is a phenotype of asthma characterized by eosinophilic inflammation in the airways, mast cell activation, cysteinyl leukotriene overproduction, and acute respiratory reactions on exposure to cyclooxygenase‐1 inhibitors. Aspirin desensitization followed by daily high‐dose aspirin therapy is a safe and effective treatment option for the majority of patients with AERD. However, there is still some percentage of the population who do not derive benefits from daily aspirin use. Methods Based on the current literature, the biomarkers, which might predict aspirin treatment outcomes in AERD patients, were evaluated. Results and conclusions Patients with severe symptoms of chronic rhinosinusitis, type 2 asthma based on blood eosinophilia, non‐neutrophilic inflammatory phenotype based on sputum cells, as well as high plasma level of 15‐hydroxyeicosatetraenoic acid (15‐HETE) are potentially good responders to long term high‐dose aspirin therapy. Additionally, high expression of the hydroxyprostaglandin dehydrogenase gene, HPGD encoding prostaglandin‐degrading enzyme 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) and low expression of the proteoglycan 2 gene, PRG2 encoding constituent of the eosinophil granule in sputum cells might serve as a predictor of good response to aspirin therapy. Variations in the expression of cysteinyl leukotriene receptor 1 in the airways could additionally influence the response to long‐term aspirin therapy. Arachidonic acid metabolites levels via the 5‐lipoxygenase as well as via the cyclooxygenase pathways in induced sputum supernatant do not change during high dose long‐term aspirin therapy and do not influence outcomes of aspirin treatment.

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Aspirin‐exacerbated respiratory disease: A review

Dominas

Gadkaree

Maxfield

et al. 2020

Laryngoscope Investig Oto

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ObjectivesAspirin‐exacerbated respiratory disease (AERD) is a chronic respiratory condition characterized by a triad of symptoms: asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory reaction to aspirin and other cyclooxygenase‐1 inhibitors, also known as nonsteroidal anti‐inflammatory drugs. The objective of this review is to provide otolaryngologists with an overview of the pathophysiology, diagnosis, and treatment of this under‐recognized condition.Data sources and methodsFoundational papers on AERD were reviewed, focusing on the clinical otolaryngology and allergy/immunology literature and other high impact journals or trials.ResultsAERD results from increased production of pro‐inflammatory leukotrienes and a decrease in production of anti‐inflammatory prostaglandins associated with the dysregulation of multiple enzymes influencing eicosanoid metabolism. Diagnosis hinges on a high index of suspicion, careful history, and confirmatory testing for all three elements. Treatments include endoscopic sinus surgery; topical, inhaled, or oral corticosteroids; aspirin desensitization; leukotriene modifying drugs; and the new class of biologics such as dupilumab.ConclusionAERD is an under‐recognized disease associated with substantial patient‐reported morbidity. We expect rapid progress in the pathophysiological understanding of this disease and available treatments in the coming decades.Level of evidence5

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Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial

Cited by 44 publications

References 25 publications

Endoscopic sinus surgery improves aspirin treatment response in aspirin‐exacerbated respiratory disease patients

Endoscopic sinus surgery improves aspirin treatment response in aspirin‐exacerbated respiratory disease patients

Biomarkers for predicting response to long‐term high dose aspirin therapy in aspirin‐exacerbated respiratory disease

Aspirin‐exacerbated respiratory disease: A review

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