Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic mechanisms in aspirin-exacerbated respiratory disease.

ABSTRACT: 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.

SUBMITTER: Shrestha Palikhe N

PROVIDER: S-EPMC3151506 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genetic mechanisms in aspirin-exacerbated respiratory disease.

Shrestha Palikhe Nami N Kim Seung-Hyun SH Jin Hyun Jung HJ Hwang Eui-Kyung EK Nam Young Hee YH Park Hae-Sim HS

Journal of allergy 20110807

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 respons ...[more]

PMID: 21837245

Similar Datasets

Genetic and Epigenetic Components of Aspirin-Exacerbated Respiratory Disease.

Project description:Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment.

| S-EPMC5720138 | biostudies-literature

Perimenstrual Asthma in Aspirin-Exacerbated Respiratory Disease.

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

Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances.

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

Platelets in patients with aspirin-exacerbated respiratory disease.

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

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

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

Plasma tryptase elevation during aspirin-induced reactions in aspirin-exacerbated respiratory disease.

Project description: Not available

| S-EPMC6519056 | biostudies-literature

Appropriate extent of surgery for aspirin-exacerbated respiratory disease.

Project description:The current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease (AERD), who present with the clinical triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), bronchial asthma, and aspirin/nonsteroidal anti-inflammatory drug intolerance. To further define the effectiveness of sinus surgery in treating AERD patients, this review article discusses current evidence regarding outcomes associated with more extensive surgery, the benefits of frontal sinus surgery on polyposis, and the role of Draf III intervention. Numerous studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical therapies. Future studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.

| S-EPMC7729211 | biostudies-literature

Update on the Management of Aspirin-Exacerbated Respiratory Disease.

Project description:Aspirin-exacerbated respiratory disease (AERD) is an adult-onset upper and lower airway disease consisting of eosinophilic nasal polyps, asthma, and respiratory reactions to cyclooxygenase 1 (COX-1) inhibitors. Management includes guideline-based treatment of asthma and sinus disease, avoidance of COX-1 inhibitors, and for some patients aspirin desensitization followed by high-dose aspirin therapy. Despite this, many patients have inadequately controlled symptoms and require multiple sinus surgeries. In this review, we discuss the current standard approaches to the management of AERD, and we introduce several therapeutics under development that may hold promise for the treatment of AERD.

| S-EPMC4853506 | biostudies-literature

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease.

Project description:BackgroundNonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD.MethodsIn this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6 months. Clinical parameters (e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6 months after starting dupilumab therapy.ResultsOf the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6 months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: -2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6.ConclusionIn this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

| S-EPMC10017890 | biostudies-literature

Automated identification of an aspirin-exacerbated respiratory disease cohort.

Project description:BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by 3 clinical features: asthma, nasal polyposis, and respiratory reactions to cyclooxygenase-1 inhibitors (nonsteroidal anti-inflammatory drugs). Electronic health records (EHRs) contain information on each feature of this triad.ObjectiveWe sought to determine whether an informatics algorithm applied to the EHR could electronically identify patients with AERD.MethodsWe developed an informatics algorithm to search the EHRs of patients aged 18 years and older from the Partners Healthcare system over a 10-year period (2004-2014). Charts with search terms for asthma, nasal polyps, and record of respiratory (cohort A) or unspecified (cohort B) reactions to nonsteroidal anti-inflammatory drugs were identified as "possible AERD." Two clinical experts reviewed all charts to confirm a diagnosis of "clinical AERD" and classify cases as "diagnosed AERD" or "undiagnosed AERD" on the basis of physician-documented AERD-specific terms in patient notes.ResultsOur algorithm identified 731 "possible AERD" cases, of which 638 were not in our AERD patient registry. Chart review of cohorts A (n = 511) and B (n = 127) demonstrated a positive predictive value of 78.4% for "clinical AERD," which rose to 88.7% when unspecified reactions were excluded. Of those with clinical AERD, 12.4% had no mention of AERD by any treating caregiver and were classified as "undiagnosed AERD." "Undiagnosed AERD" cases were less likely than "diagnosed AERD" cases to have been seen by an allergist/immunologist (38.7% vs 93.2%; P < .0001).ConclusionsAn informatics algorithm can successfully identify both known and previously undiagnosed cases of AERD with a high positive predictive value. Involvement of an allergist/immunologist significantly increases the likelihood of an AERD diagnosis.

| S-EPMC5266739 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data