Biomarkers for predicting response to aspirin therapy in aspirin‐exacerbated respiratory disease

Abstract

Background Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin‐exacerbated respiratory disease (AERD). Objective To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high‐dose aspirin therapy in AERD. Methods We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52‐week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high‐dose aspirin were defined as patients with improvement in 5‐item Asthma Control Questionnaire score, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score and forced expiratory volume in 1 second at 52 weeks. Results There were 28 responders (82%). Positive baseline predictors of response included female sex (p = .002), higher SNOT‐22 score (p = .03), higher blood eosinophil count (p = .01), lower neutrophil percentage in induced sputum (p = .003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p = .004) and lower expression of the proteoglycan 2 gene, PRG2 (p = .01). The best prediction model included Asthma Control Test and SNOT‐22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and Clinical Relevance Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long‐term high‐dose aspirin therapy in patients with AERD.

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

“…1,2 Aspirin desensitization followed by daily high-dose aspirin therapy can be offered as a therapeutic option to most patients with AERD. 3,4,5,6,7,8,9 This is supported by studies reporting that 82% to 87% of these patients experience improvement on long-term aspirin treatment. 3,4 However, there is still a percentage of individuals who do not derive benefits from such therapy, while predictive factors of response to aspirin remain poorly understood.…”

“…3,4,5,6,7,8,9 This is supported by studies reporting that 82% to 87% of these patients experience improvement on long-term aspirin treatment. 3,4 However, there is still a percentage of individuals who do not derive benefits from such therapy, while predictive factors of response to aspirin remain poorly understood. Therefore, the assessment of eligibility for and prediction of response to aspirin therapy continue to be clinically relevant issues.…”

“…In one study female sex was proposed to be positive prognostic factor, as only one woman (4% of females) did not benefit from treatment. 4 There is also a study showing no difference in treatment outcomes by gender. 10 Responders to aspirin were also characterized by severe nasal symptoms based on 22-item Sino-Nasal Outcome Test (SNOT-22) and a longer period from sinus surgery to aspirin desensitization than non-responders.…”

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease

“…To differentiate potential responders from non-responders to aspirin treatment, many researchers have tried to identify biomarkers able to predict a positive response to ATAD. Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high hydroxyprostaglandin dehydrogenate, and low proteoglycan 2 gene expression have recently been shown to be good predictors for a positive response to oral ATAD (650 mg/day) [32]. Patients with an inflammatory neutrophilic phenotype are unlikely to respond to aspirin treatment [32] and a recent study found that the use of antileukotrienes reduces the response to LAS nasal challenge [33].…”

“…Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high hydroxyprostaglandin dehydrogenate, and low proteoglycan 2 gene expression have recently been shown to be good predictors for a positive response to oral ATAD (650 mg/day) [32]. Patients with an inflammatory neutrophilic phenotype are unlikely to respond to aspirin treatment [32] and a recent study found that the use of antileukotrienes reduces the response to LAS nasal challenge [33]. However, we were not able to find any correlation between the variables studied and intranasal LAS treatment response failing to confirm our previous findings of higher PNIF and smell scores in allergic patients and those with later N-ERD onset [9].…”