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Clinical Trial
. 2017 Jul-Aug;5(4):998-1007.e2.
doi: 10.1016/j.jaip.2016.11.021. Epub 2017 Jan 31.

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

Elina Jerschow  1 , Matthew L Edin  2 , Teresa Pelletier  3 , Waleed M Abuzeid  4 , Nadeem A Akbar  4 , Marc Gibber  4 , Marvin Fried  4 , Fred B Lih  2 , Artiom Gruzdev  2 , J Alyce Bradbury  2 , Weiguo Han  3 , Golda Hudes  4 , Taha Keskin  4 , Victor L Schuster  4 , Simon Spivack  4 , Darryl C Zeldin  2 , David Rosenstreich  4
Affiliations
Free PMC article
Clinical Trial

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

Elina Jerschow et al. J Allergy Clin Immunol Pract. 2017 Jul-Aug.
Free PMC article

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.

Keywords: 15-hydroxyeicosatetraenoic acid; Aspirin desensitization; Aspirin-exacerbated respiratory disease; Eicosanoids; Eosinophils.

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Figures

Figure 1
Figure 1
A. Asthma Control Test (ACT) questionnaire scores before and after four weeks of aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Higher score corresponds to better asthma control, horizontal bars represent mean values. B. Rhinoconjunctivitis Quality Of Life Questionnaire (RQLQ) scores before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Lower score corresponds to better symptom control, horizontal bars represent median values. C. FEV1%-predicted before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent mean values. D. NPF before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent median values.
Figure 1
Figure 1
A. Asthma Control Test (ACT) questionnaire scores before and after four weeks of aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Higher score corresponds to better asthma control, horizontal bars represent mean values. B. Rhinoconjunctivitis Quality Of Life Questionnaire (RQLQ) scores before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Lower score corresponds to better symptom control, horizontal bars represent median values. C. FEV1%-predicted before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent mean values. D. NPF before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent median values.
Figure 1
Figure 1
A. Asthma Control Test (ACT) questionnaire scores before and after four weeks of aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Higher score corresponds to better asthma control, horizontal bars represent mean values. B. Rhinoconjunctivitis Quality Of Life Questionnaire (RQLQ) scores before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Lower score corresponds to better symptom control, horizontal bars represent median values. C. FEV1%-predicted before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent mean values. D. NPF before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent median values.
Figure 1
Figure 1
A. Asthma Control Test (ACT) questionnaire scores before and after four weeks of aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Higher score corresponds to better asthma control, horizontal bars represent mean values. B. Rhinoconjunctivitis Quality Of Life Questionnaire (RQLQ) scores before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Lower score corresponds to better symptom control, horizontal bars represent median values. C. FEV1%-predicted before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent mean values. D. NPF before and after aspirin treatment for four weeks in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent median values.
Figure 2
Figure 2
A. Differences in baseline plasma 15-HETE levels between patients with symptom improvement (left) and symptom worsening (right) after four weeks of aspirin therapy. Horizontal bars represent median values. B. Correlation between baseline plasma 15-HETE levels and ACT score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. C. Correlation between baseline plasma 15-HETE levels and FEV1 change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. D. Correlation between baseline plasma 15-HETE levels and RQLQ score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value.
Figure 2
Figure 2
A. Differences in baseline plasma 15-HETE levels between patients with symptom improvement (left) and symptom worsening (right) after four weeks of aspirin therapy. Horizontal bars represent median values. B. Correlation between baseline plasma 15-HETE levels and ACT score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. C. Correlation between baseline plasma 15-HETE levels and FEV1 change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. D. Correlation between baseline plasma 15-HETE levels and RQLQ score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value.
Figure 2
Figure 2
A. Differences in baseline plasma 15-HETE levels between patients with symptom improvement (left) and symptom worsening (right) after four weeks of aspirin therapy. Horizontal bars represent median values. B. Correlation between baseline plasma 15-HETE levels and ACT score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. C. Correlation between baseline plasma 15-HETE levels and FEV1 change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. D. Correlation between baseline plasma 15-HETE levels and RQLQ score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value.
Figure 2
Figure 2
A. Differences in baseline plasma 15-HETE levels between patients with symptom improvement (left) and symptom worsening (right) after four weeks of aspirin therapy. Horizontal bars represent median values. B. Correlation between baseline plasma 15-HETE levels and ACT score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. C. Correlation between baseline plasma 15-HETE levels and FEV1 change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value. D. Correlation between baseline plasma 15-HETE levels and RQLQ score change after four weeks of aspirin treatment. The effect size was determined by using Spearman correlation coefficient and denoted as an r-value.
Figure 3
Figure 3
Change in plasma 15-HETE levels after four weeks of aspirin therapy in patients with symptom improvement and symptom worsening. Horizontal bars represent median values.
Figure 4
Figure 4
Change in absolute eosinophil count after four weeks of aspirin treatment therapy in patients with symptom improvement (left panel) and symptom worsening (right panel). Horizontal bars represent mean values.
Figure 5
Figure 5
A. Eosinophil count after four weeks of aspirin treatment correlated with ACT score change. The effect size was determined by using Pearson correlation coefficient and denoted as an r-value. B. Eosinophil count after four weeks of aspirin treatment correlated with FEV1 change. The effect size was determined by using Pearson correlation coefficient and denoted as an r-value.
Figure 5
Figure 5
A. Eosinophil count after four weeks of aspirin treatment correlated with ACT score change. The effect size was determined by using Pearson correlation coefficient and denoted as an r-value. B. Eosinophil count after four weeks of aspirin treatment correlated with FEV1 change. The effect size was determined by using Pearson correlation coefficient and denoted as an r-value.
Figure 6
Figure 6
A. Correlation between eosinophil count after four weeks of aspirin treatment and plasma 15-HETE levels at baseline (closed circles) and at four weeks (open circles) in patients with symptom improvement. The effect size was determined by using Pearson correlation coefficient and denoted as an r-value. B. Correlation between eosinophil count after four weeks of aspirin treatment and plasma 15-HETE levels at baseline (closed circles) and at four weeks (open circles) in patients with symptom worsening.
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