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Increased expression of serine palmitoyl transferase and ORMDL3 polymorphism are associated with eosinophilic inflammation and airflow limitation in aspirin-exacerbated respiratory disease.

ABSTRACT: BACKGROUND:Patients with aspirin-exacerbated respiratory disease (AERD) are known to have poor clinical outcomes. The pathogenic mechanisms have not yet been completely understood. OBJECTIVE:We aimed to assess the involvement of the de-novo synthetic pathway of sphingolipid metabolism in patients with AERD compared to those with aspirin tolerant asthma (ATA). METHODS:A total of 63 patients with AERD and 79 patients with ATA were enrolled in this study. Analysis of mRNA expression of serine palmitoyl transferase, long-chain base subunit 2 (SPTLC2) and genotyping of ORMDL3 SNP (rs7216389) was performed. RESULTS:Significantly higher levels of SPTLC2 mRNA expression were noted in patients with AERD, which showed significant positive correlations with peripheral/sputum eosinophil counts and urine LTE4 (all P<0.05). The levels of SPTLC2 mRNA expression showed significant negative correlations with the level of FEV1 and FEV1/FVC (P = 0.033, r = -0.274; P = 0.019, r = -0.299, respectively). Genotype frequencies of ORMDL3 SNP (rs7216389) showed no significant differences between the AERD and ATA groups. Patients with AERD carrying the TT genotype of ORMDL3 had significantly lower levels of FVC (%) and PC20 methacholine than those carrying the CT or CC genotype (P = 0.026 and P = 0.030). CONCLUSION & CLINICAL RELEVANCE:This is the first study that shows the dysregulated de novo synthetic pathway of sphingolipids may be involved in the eosinophilic inflammation and airflow limitation in AERD.

SUBMITTER: Ban GY

PROVIDER: S-EPMC7544079 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased expression of serine palmitoyl transferase and ORMDL3 polymorphism are associated with eosinophilic inflammation and airflow limitation in aspirin-exacerbated respiratory disease.

Ban Ga-Young GY Youn Dong-Ye DY Ye Young-Min YM Park Hae-Sim HS

PloS one 20201008 10

<h4>Background</h4>Patients with aspirin-exacerbated respiratory disease (AERD) are known to have poor clinical outcomes. The pathogenic mechanisms have not yet been completely understood.<h4>Objective</h4>We aimed to assess the involvement of the de-novo synthetic pathway of sphingolipid metabolism in patients with AERD compared to those with aspirin tolerant asthma (ATA).<h4>Methods</h4>A total of 63 patients with AERD and 79 patients with ATA were enrolled in this study. Analysis of mRNA expr ...[more]

PMID: 33031402

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Project description:Study objectivesThe presence of flow limitation during sleep is associated with adverse health consequences independent of obstructive sleep apnea (OSA) severity (apnea-hypopnea index, AHI), but remains extremely challenging to quantify. Here we present a unique library and an accompanying automated method that we apply to investigate flow limitation during sleep.MethodsA library of 117,871 breaths (N = 40 participants) were visually classified (certain flow limitation, possible flow limitation, normal) using airflow shape and physiological signals (ventilatory drive per intra-esophageal diaphragm EMG). An ordinal regression model was developed to quantify flow limitation certainty using flow-shape features (e.g. flattening, scooping); breath-by-breath agreement (Cohen's ƙ); and overnight flow limitation frequency (R2, %breaths in certain or possible categories during sleep) were compared against visual scoring. Subsequent application examined flow limitation frequency during arousals and stable breathing, and associations with ventilatory drive.ResultsThe model (23 features) assessed flow limitation with good agreement (breath-by-breath ƙ = 0.572, p < 0.001) and minimal error (overnight flow limitation frequency R2 = 0.86, error = 7.2%). Flow limitation frequency was largely independent of AHI (R2 = 0.16) and varied widely within individuals with OSA (74[32-95]%breaths, mean[range], AHI > 15/h, N = 22). Flow limitation was unexpectedly frequent but variable during arousals (40[5-85]%breaths) and stable breathing (58[12-91]%breaths), and was associated with elevated ventilatory drive (R2 = 0.26-0.29; R2 < 0.01 AHI v. drive).ConclusionsOur method enables quantification of flow limitation frequency, a key aspect of obstructive sleep-disordered breathing that is independent of the AHI and often unavailable. Flow limitation frequency varies widely between individuals, is prevalent during arousals and stable breathing, and reveals elevated ventilatory drive. Clinical trial registration: The current observational physiology study does not qualify as a clinical trial.

Dataset Information

Increased expression of serine palmitoyl transferase and ORMDL3 polymorphism are associated with eosinophilic inflammation and airflow limitation in aspirin-exacerbated respiratory disease.

Publications

Increased expression of serine palmitoyl transferase and ORMDL3 polymorphism are associated with eosinophilic inflammation and airflow limitation in aspirin-exacerbated respiratory disease.

Similar Datasets

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