Aspirin hypersensitivity diagnostic index (AHDI): In vitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTE4 excretion.

BACKGROUND: 15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. METHODS: The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. RESULTS: Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. CONCLUSIONS: We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.

Unsuccessful linguistic validation of the Symptom Questionnaire for assessing quality of life in Polish patients with pelvic vein disorders.

Pelvic venous disorder (PeVD) is a prevalent chronic condition characterized by the presence of varicose veins in the pelvis, leading to the development of chronic pelvic pain. Despite the growing interest in assessing quality of life in PeVD, well-designed and validated disease-specific questionnaires are missing. The objective of this study was a linguistic and clinical validation of the Symptom Questionnaire (SQ) in a cohort of Polish females with pelvic vein incompetence. The Polish version of SQ was developed using a standardized validation process that involved a back-and- forth translation protocol. A total of 58 female patients diagnosed with pelvic varicose veins, representing diverse educational back- grounds, participated in the study. Multiple issues were observed during linguistic validation, primarily originating from disparities between the Polish and British healthcare systems, as well as differing levels of sexual health education of those two populations. Cronbach α was calculated separately for each part of the questionnaire with results exceeded 0.6 for each section. Test-retest analysis indicated most Pearson correlation coefficients surpassing 0.70. The absolute agreement consistency between pretest and post-test measures, evaluated using the Intra Class Correlation (ICC), exceeded 0.8 in three sections and 0.7 in the remaining three sections. However, the clinical validation failed due to the lack of standardized score calculation proposed by the authors of the questionnaire and inaccurately assigned values in the answer key for five questions. Consequently, the practical utility of SQ in daily clinical settings remains uncertain, highlighting the urgent need for the development of a new, user-friendly questionnaire specifically tailored to assess the quality of life in individuals with PeVD.

Biomarkers for predicting response to aspirin therapy in aspirin-exacerbated respiratory disease.

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.

Artificial neural network identifies nonsteroidal anti-inflammatory drugs exacerbated respiratory disease (N-ERD) cohort.

BACKGROUND: To date, there has been no reliable in vitro test to either diagnose or differentiate nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD). The aim of the present study was to develop and validate an artificial neural network (ANN) for the prediction of N-ERD in patients with asthma. METHODS: This study used a prospective database of patients with N-ERD (n = 121) and aspirin-tolerant (n = 82) who underwent aspirin challenge from May 2014 to May 2018. Eighteen parameters, including clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant (ISS) and urine were extracted for the ANN. RESULTS: The validation sensitivity of ANN was 94.12% (80.32%-99.28%), specificity was 73.08% (52.21%-88.43%), and accuracy was 85.00% (77.43%-92.90%) for the prediction of N-ERD. The area under the receiver operating curve was 0.83 (0.71-0.90). CONCLUSIONS: The designed ANN model seems to have powerful prediction capabilities to provide diagnosis of N-ERD. Although it cannot replace the gold-standard aspirin challenge test, the implementation of the ANN might provide an added value for identification of patients with N-ERD. External validation in a large cohort is needed to confirm our results.

Local and Systemic Production of Pro-Inflammatory Eicosanoids Is Inversely Related to Sensitization to Aeroallergens in Patients with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by overproduction of the pro-inflammatory eicosanoids. Although immunoglobulin E-mediated sensitization to aeroallergens is common among AERD patients, it does not belong to the defining disease characteristics. In this study of 133 AERD patients, we sought to find a relationship between sensitization to aeroallergens and local (leukotriene E4, prostaglandin E2 and prostaglandin D2) and/or systemic (leukotriene E4) production of arachidonic acid metabolites. Interestingly, a negative association between pro-inflammatory eicosanoid levels in induced sputum supernatant or urine and sensitization to aeroallergens was observed. This inverse relationship might suggest the presence of a protective effect of atopic sensitization to aeroallergens against stronger local airway inflammation and higher systemic AERD-related inflammatory activity.