Scoring tool for systemic symptoms during aspirin challenge detects mediator production in aspirin-exacerbated respiratory disease.
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ABSTRACT:
SUBMITTER: Staso PJ
PROVIDER: S-EPMC8222107 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Oral aspirin challenge may induce different global CpG methylation patterns between aspirin-exacerbated respiratory disease (AERD) and aspirin-tolerant asthma (ATA), which may affect gene expression several hours later. Therefore, in the present study, we compared global CpG methylation profiles before and after an oral aspirin challenge in patients with asthma. In addition, we compared differences in methylation profiles between AERD and ATA using an Illumina 860K Infinium Methylation EPIC BeadChip array platform, which had greater coverage than in the previous study (26,485 CpGs) to discover new methylated CpGs in PBLs associated with aspirin-induced bronchospasm.
2023-06-27 | GSE235569 | GEO
Project description:BackgroundA large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true prevalence of respiratory reactions caused by alcoholic beverages in these patients was not known.ObjectiveWe sought to evaluate the incidence and characteristics of alcohol-induced respiratory reactions in patients with AERD.MethodsA questionnaire designed to assess alcohol-induced respiratory symptoms was administered to patients at Brigham and Women's Hospital and Scripps Clinic. At least 50 patients were recruited into each of 4 clinical groups: (1) patients with aspirin challenge-confirmed AERD, (2) patients with aspirin-tolerant asthma (ATA), (3) patients with aspirin tolerance and with chronic rhinosinusitis, and (4) healthy controls. Two-tailed Fisher exact tests with Bonferroni corrections were used to compare the prevalence of respiratory symptoms among AERD and other groups, with P ≤ .017 considered significant.ResultsThe prevalence of alcohol-induced upper (rhinorrhea and/or nasal congestion) respiratory reactions in patients with AERD was 75% compared with 33% with aspirin-tolerant asthma, 30% with chronic rhinosinusitis, and 14% with healthy controls (P < .001 for all comparisons). The prevalence of alcohol-induced lower (wheezing and/or dyspnea) respiratory reactions in AERD was 51% compared with 20% in aspirin-tolerant asthma and with 0% in both chronic rhinosinusitis and healthy controls (P < .001 for all comparisons). These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol.ConclusionAlcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant.
| S-EPMC4018190 | biostudies-literature
Project description: Not available
| S-EPMC8810664 | biostudies-literature
Project description:BackgroundAspirin-exacerbated respiratory disease (AERD) is a condition of the upper and lower respiratory tract characterized by reactions to nonsteroidal anti-inflammatory drugs. The Severe Asthma Research Program reported a strong association between perimenstrual asthma (PMA) and aspirin-sensitive asthma.ObjectiveTo evaluate the prevalence and characteristics of PMA among a cohort of patients with AERD.MethodsWomen 18 years and older enrolled in the Brigham and Women's AERD registry were surveyed about their reproductive, asthma, and sinus history. Subjects reporting the development of asthma before menopause were included. Continuous and categorical variables were compared between those reporting menstruation as a trigger for asthma symptoms and those who did not. Covariates expected a priori to have a positive effect on the odds of PMA were included in a multivariate logistic regression model to test associations between PMA and clinical factors.ResultsAmong females of childbearing potential, 369 of 695 responded to the survey and 322 met inclusion criteria. Twenty-four percent of subjects (n = 74) reported PMA. Earlier age of AERD onset, concurrent worsening of sinus symptoms the week before or during menstruation, increased emergency department visits for asthma, and a change in the severity of respiratory symptoms at menopause were more common in PMA. Earlier age at first nonsteroidal anti-inflammatory drug-induced respiratory reaction and emergency department visits increased the odds of reporting PMA.ConclusionsPMA and increased sinus symptoms with menstruation are common in females with AERD. Females with AERD should be counseled about upper and lower respiratory symptom deterioration with menstruation.
| S-EPMC7012664 | biostudies-literature
Project description:Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.
| S-EPMC3151506 | biostudies-literature
Project description:Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights.
| S-EPMC4790533 | biostudies-other
Project description:Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease characterized clinically by the triad of asthma, nasal polyposis, and pathognomonic respiratory reactions after ingestion of aspirin. It is a distinct syndrome associated with eosinophilic infiltration of respiratory tissues and excessive production of cysteinyl leukotrienes. Despite the consistent clinical phenotype of the respiratory disease, the underlying pathogenesis of the disease remains unclear. In addition to their role in hemostasis, platelets have the capacity to influence the activation state and function of other immune cells during inflammation and to facilitate granulocyte recruitment into the tissues. Platelets also possess a repertoire of potent preformed mediators of inflammation that are released on activation and are a rich source of newly synthesized lipid mediators that alter vascular permeability and smooth muscle tone. Accordingly, platelet activity has been linked to diverse inflammatory diseases, including asthma. Both human and animal studies strongly suggest that platelet activity is uniquely associated with the pathophysiology of AERD. This article summarizes the evidence supporting an effector role for platelets in asthmatic patients in general and in patients with AERD in particular and considers the potential therapeutic implications.
| S-EPMC4559084 | biostudies-literature
Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD
2014-09-05 | GSE61129 | GEO
Project description:Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often in the form of a severe and sudden attack. Due to time consuming and laborious oral aspirin challenge (OAC) for diagnosis of AERD, non-invasive biomarkers have been searched. Therefore, we scrutinize AERD-associated exonic SNPs and examine the diagnostic potential of combination of these candidate SNPs to predict AERD DNA obtained from 164 AERD subjects, 397 subjects with aspirin-tolerant asthma (ATA), 398 normal controls and 10 null samples were subjected to Exome Chip assay of 240K SNPs. 1023 model (210-1) were generated from combination of the top 10 SNPs selected by p-values. The area under the curve (AUC) value of receiver operating characteristic (ROC) curves was calculated for each model. SNP functional Portal and PolyPhen-2 was used to validate the functional significance of the candidate SNPs
2014-09-05 | E-GEOD-61129 | biostudies-arrayexpress
Project description:BackgroundAspirin desensitization followed by daily aspirin use is an effective treatment for aspirin-exacerbated respiratory disease (AERD).ObjectiveTo 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.MethodsWe 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.ResultsThere 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 relevanceFemale 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.
| S-EPMC9292205 | biostudies-literature