Emerging Biomarkers Beyond Leukotrienes for the Management of Nonsteroidal Anti-inflammatory Drug (NSAID)-Exacerbated Respiratory Disease

Kim

Clin Experimental Allergy

et al. 2023

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BackgroundAspirin‐exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin‐tolerant asthma (ATA).ObjectivesThis study aimed to investigate the long‐term clinical outcomes between AERD and ATA.MethodsAERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real‐world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD.ResultsAmong asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10‐year follow‐up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group.Conclusion and Clinical RelevanceWe demonstrated that AERD patients presented poorer long‐term clinical outcomes than ATA patients in real‐world data analyses.

Section: Discussionmentioning

confidence: 99%

Long‐term clinical outcomes of aspirin‐exacerbated respiratory disease: Real‐world data from an adult asthma cohort

Kim

Clin Experimental Allergy

et al. 2023

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“…Especially, an increased level of urinary leukotriene E4 (which is a stable and final product of CysLTs) is considered a useful biomarker for the diagnosis of AERD ( 44 ). In addition, this mediator could induce mast cell and ILC2 activation as well as eosinophils recruitment into the upper and lower airway mucosa, enhancing persistent type2/eosinophilic inflammation in the upper and lower airways of patients with AERD and resulting in poor clinical outcomes of AERD ( 45 46 ).…”

Section: Asthma and Immune Cellsmentioning

confidence: 99%

Immunologic Basis of Type 2 Biologics for Severe Asthma

2022

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Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

Clinical & Translational All

“…AERD represents a distinct endotype with dysregulation of arachidonic acid metabolism and upregulated T H 2 inflammation. 14 Overproduction of cysteinyl leukotrienes which potentially induce eosinophilic inflammation is the hallmark of AERD in pathogenic mechanism. It has been reported that asthmatics with AERD are most likely to have severe disease, which has a higher risk of UA, SA, and AE.…”

Section: Introductionmentioning

confidence: 99%

“…Aspirin‐exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyp, and hypersensitivity to nonsteroidal anti‐inflammatory drugs (NSAIDs)/aspirin. AERD represents a distinct endotype with dysregulation of arachidonic acid metabolism and upregulated T H 2 inflammation 14 . Overproduction of cysteinyl leukotrienes which potentially induce eosinophilic inflammation is the hallmark of AERD in pathogenic mechanism.…”

Section: Introductionmentioning

confidence: 99%

Association of eosinophil‐derived neurotoxin levels with asthma control status in patients with aspirin‐exacerbated respiratory disease

Ban

Yang

et al. 2023

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Background The long‐term goals of asthma treatment are to achieve well control of symptoms and to minimize the future risk of asthma exacerbation. Identifying biomarkers for uncontrolled asthma is important for improving the asthma outcome. This study aimed to investigate the association of the levels of eosinophil‐derived neurotoxin (EDN) with asthma control status in specific asthma phenotype, aspirin‐exacerbated respiratory disease (AERD), and aspirin‐tolerant asthma (ATA). Methods A total of 136 adult asthmatics, including 47 asthmatics with AERD and 89 asthmatics with ATA, were enrolled. Plasma, sputum, and urine were collected at enrollment and the levels of EDN were measured by the K‐EDN ELISA kit. Urinary leukotriene E4 (LTE 4 ) level was measured using liquid chromatography–mass spectrometry (LC‐MS)/MS methods. Asthma control status was evaluated according to the GINA guideline, asthma control test and asthma control questionnaire scores. Results In the total study subjects, sputum levels of EDN as well as of urine and plasma EDN showed significantly higher levels in patients with uncontrolled asthma than in those with well‐controlled or partly‐controlled asthma (ANOVA, p < 0.001); in patients with AERD, the sputum EDN levels showed significant correlations with ACT, ACQ, and AQLQ scores ( p = 0.010, r = −0.536, p = 0.001, r = 0.665, and p < 0.001, r = −0.691, respectively), while no differences were noted in patients with ATA. Sputum EDN level was the only significant factor for ACT, ACQ, and AQLQ scores in patients with AERD ( p = 0.001, p < 0.001, and p < 0.001, respectively) in the multivariate analysis adjusting for age, sex, peripheral eosinophil count, and urine LTE 4 . The ROC curve analysis demonstrated that sputum EDN can predict uncontrolled asthma with 80% sensitivity and 88.2% specificity for ACT ≤ 19 (area under the ROC curve [AUC] = 0.824, p = 0.019); 71.4% sensitivity and 86.7% specificity for ACQ ≥ 1.5 (AUC = 0.752, p = 0.049) only in AERD patients. Conclusion The level of sputum EDN may be a potential biomarker for identifying the asthma control status in patients with AERD.