Dataset Information

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

ABSTRACT:

Purpose

Data on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes.

Methods

The clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were characterized based on the clinical history and drug provocation. The uLTE4 levels were measured at baseline, after aspirin provocation and after desensitization.

Results

More than half of the patients (56.5%) presented with cutaneous symptoms (NSAID-exacerbated cutaneous disease), while one-third (33.7%) developed symptoms in at least 2 systems (NSAID-induced blended reactions; NIBR). Fifty-two patients underwent drug provocation and 59.6% of them yielded positive results. After drug provocation, a significant number of patients with confirmed NSAID cross-reactivity experienced clinical symptoms in more than one organ system. The uLTE4 levels at baseline were comparable between the NSAID-tolerant and NSAID-sensitive groups, but were substantially increased after aspirin provocation predominantly in NERD (983.4 pg/mg creatinine) and NIBR (501.0 pg/mg creatinine) compared to NSAID-tolerant subjects (122.1 pg/mg creatinine, P < 0.01 and 0.05, respectively). The uLTE4 levels were elevated after aspirin desensitization, although nasal polyposis and asthma were under control in 3 NERD and 3 NIBR subjects.

Conclusions

NIBR is not uncommon among NSAID-sensitive patients in Thailand. The diagnostic value of basal uLTE4 levels was limited, but increased uLTE4 levels upon aspirin provocation suggest NSAID cross-reactivity with respiratory components. This study indicates that aspirin desensitization, if necessary, might be effective in both NERD and NIBR.

Trial registration

ClinicalTrials.gov Identifier: NCT03849625.

SUBMITTER: Klaewsongkram J

PROVIDER: S-EPMC7840864 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

Klaewsongkram Jettanong J Buranapraditkun Supranee S Mongkolpathumrat Pungjai P Palapinyo Sirinoot S Chantaphakul Hiroshi H

Allergy, asthma & immunology research 20210301 2

<h4>Purpose</h4>Data on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes.<h4>Methods</h4>The clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were cha ...[more]

PMID: 33474858

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Project description:Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA). Objectives: To characterize the transcriptomic and metabolomic profiles of NIUA patients undergoing aspirin desensitization. Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were separated from the blood of NIUA patients undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to mRNA- and lncRNA-seq. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semi-targeted metabolomics panel. Results: Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of pre- versus post-desensitization and healthy control versus post-desensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from pre-aspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, post-dose and pre-dose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in pre-aspirin desensitization samples. Interleukin (IL)-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in pre-aspirin desensitization patients compared to controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of pre-aspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in pre-aspirin desensitization patients compared to healthy controls. Conclusion: This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way towards a molecular diagnosis of NSAID hypersensitivity.

Project description:Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a clinical syndrome characterized by nasal polyposis, asthma, and intolerance to aspirin/NSAID. It affects approximately 15% cases of severe asthma, 10% of nasal polyps and 9% of rhinosinusitis. N-ERD results in associated asthma exacerbations, oral corticosteroids bursts, corticosteroid-dependent disease, and multiple endoscopic sinus surgeries. Unknown influences cause polyp epithelium to release alarmins, such as IL-33 and TSLP. These cytokines activate lymphoid cells, both Th2 and ILC2, to release cytokines such as IL5, IL4 and IL13, resulting in complex type 2 inflammation involving mast cells, eosinophils and platelets. Arachidonic acid released from such cells is metabolized into mediators. N-ERD is characterized by an imbalance in eicosanoid levels, especially CysLTs, PDG and PGE2. Patients with N-ERD present nasal symptoms (congestion, hyposmia/anosmia, nasal discharge) and lower airways symptoms (cough, sneezing, shortness of breath, chest tightness), anosmia, severe hyposmia as well as severe asthma which impacts the quality of life in this disease and leads to safety concerns in patients daily lives. Despite the variety of treatment strategies, the likelihood of recurrence of symptoms is high in patients with N-ERD. The most important strategies for treating N-ERD are listed as following: drug therapies, aspirin desensitization, monoclonal antibodies and other therapies associated. N-ERD treatment remains a major challenge in the current situation. Selecting the appropriate patient for aspirin desensitization, monoclonal antibodies or both is essential. This review provides an overview on aspirin desensitization and biologics in N-ERD and might help in decision making from both the perspective of the physician and patient. Patient characteristics, safety, efficacy, health care costs, but also patient preferences are all factors to take into account when it comes to a choice between biologics or aspirin desensitization.

Dataset Information

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

Purpose

Methods

Results

Conclusions

Trial registration

Publications

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

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