Background Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance. Objective We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ( CysLT 2 ) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, n = 23 ) as compared to patients with aspirin tolerant asthma (ATA, n = 17 ) and a control group with nasal polyps, but without asthma (NPwA, n = 15 ). Methods Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and CysLT 2 in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing. Results We observed a stronger expression of 5-LOX and CysLT 2 in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and CysLT 2 between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups. Conclusions The AA-metabolizing enzymes and the CysLT 2 were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.

中文翻译：

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阿司匹林加重气道疾病患者鼻息肉和支气管组织中COX-1、COX-2、5-LOX和CysLT 2的表达。

背景 阿司匹林加重呼吸系统疾病 (AERD) 是一种上呼吸道和下呼吸道疾病。它的特点是严重哮喘、慢性鼻窦炎伴鼻息肉 (CRSwNP) 和对非甾体镇痛药 (NSAR) 的不耐受。花生四烯酸（AA）代谢物在AERD的发病机制中起重要作用。尚不清楚上呼吸道和下呼吸道之间以及患有和不患有 NSAR 不耐受的患者之间的 AA 代谢是否具有可比性。目的我们试图分析1型和2型环氧合酶（COX-1、COX-2）、花生四烯酸5-脂氧合酶（5-LOX）和2型半胱氨酰白三烯受体（CysLT 2）在鼻息肉和支气管中的表达差异。阿司匹林不耐受哮喘患者（AIA，n = 23）与阿司匹林耐受哮喘患者（ATA，n = 17) 和有鼻息肉但没有哮喘的对照组 (NPwA, n = 15)。方法在全麻插管患者鼻息肉手术治疗鼻息肉的过程中，采集鼻息肉和支气管黏膜组织活检标本。免疫组化分析COX-1、COX-2、5-LOX和CysLT 2在鼻、支气管黏膜中的表达。根据患者病史、临床和实验室数据、肺功能和激发试验以及过敏试验，将患者分类为不同的患者组。结果 与上皮表达相比，我们观察到 5-LOX 和 CysLT 2 在鼻和支气管组织的粘膜下腺中的表达更强。与黏膜下腺体相比，上皮细胞中 COX-1 和 COX-2 的表达更强。在所有患者组中，上呼吸道和下呼吸道之间的酶和 CysLT 2 表达相似。我们没有发现患者组之间有任何显着差异。结论 AA 代谢酶和 CysLT 2 在个体患者上、下气道样品的不同显微结构中以非常相似的方式表达。我们没有检测到患者组之间的差异，表明 AA 代谢在这些疾病中的致病作用与 NSAR 不耐受的存在无关。结论 AA 代谢酶和 CysLT 2 在个体患者上、下气道样品的不同显微结构中以非常相似的方式表达。我们没有检测到患者组之间的差异，表明 AA 代谢在这些疾病中的致病作用与 NSAR 不耐受的存在无关。结论 AA 代谢酶和 CysLT 2 在个体患者上、下气道样品的不同显微结构中以非常相似的方式表达。我们没有检测到患者组之间的差异，表明 AA 代谢在这些疾病中的致病作用与 NSAR 不耐受的存在无关。