Cahill Katherine N, Bensko Jillian C, Boyce Joshua A, Laidlaw Tanya M
Department of Medicine, Harvard Medical School, Boston, Mass; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Mass; Jeff and Penny Vinik Center for Allergic Disease Research, Brigham and Women's Hospital, Boston, Mass.
Department of Medicine, Harvard Medical School, Boston, Mass; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Mass.
J Allergy Clin Immunol. 2015 Jan;135(1):245-52. doi: 10.1016/j.jaci.2014.07.031. Epub 2014 Sep 11.
Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin-exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy.
We investigated differences in urinary eicosanoid metabolite levels and blood eosinophil counts in patients with AERD who tolerate and those who fail aspirin desensitization and also in patients with AERD who were successfully treated with high-dose aspirin therapy.
Twenty-nine patients with AERD were stratified into those who tolerated aspirin desensitization (group I) and those who did not (group II). Urine was analyzed for eicosanoid metabolites at baseline, during aspirin reactions, and during high-dose aspirin therapy. Blood was analyzed for cell differentials at baseline and during aspirin therapy.
Basal prostaglandin D2 metabolite (PGD-M; 13.6 ± 2.7 vs 7.0 ± 0.8 pmol/mg creatinine [Cr], P < .05) and thromboxane metabolite (TX-M; 1.4 ± 0.3 vs 0.9 ± 0.1 pmol/mg Cr, P < .01) levels were higher in group II than in group I. During aspirin reactions, PGD-M levels remained unchanged, whereas TX-M levels (0.7 ± 0.1 pmol/mg Cr, P = .07) tended to decrease in group I. In contrast, PGD-M levels increased dramatically in group II (61.3 ± 19.9 pmol/mg Cr, P < .05), whereas TX-M levels did not change. The decrease in FEV1 inversely correlated with basal urinary levels of both leukotriene E4 and PGD-M. Blood eosinophil and basophil levels increased and urinary PGD-M levels (2.2 ± 0.8 pmol/mg Cr, P < .001) decreased on 2 months of high-dose aspirin therapy in group I.
Failure to tolerate aspirin desensitization in a subset of patients with AERD is associated with prostaglandin D2 overproduction. The increase in blood eosinophil and basophil counts during high-dose aspirin therapy might reflect the functional consequences of decreased prostaglandin D2 release and the therapeutic benefit of aspirin.
对于阿司匹林加重性呼吸系统疾病（AERD）患者，常规进行阿司匹林脱敏后给予高剂量阿司匹林治疗。除半胱氨酰白三烯外，其他介质对阿司匹林反应及高剂量阿司匹林治疗疗效的作用知之甚少。
我们研究了耐受阿司匹林脱敏和未耐受阿司匹林脱敏的AERD患者以及接受高剂量阿司匹林治疗成功的AERD患者尿类花生酸代谢物水平和血液嗜酸性粒细胞计数的差异。
29例AERD患者被分为耐受阿司匹林脱敏者（I组）和未耐受者（II组）。在基线、阿司匹林反应期间和高剂量阿司匹林治疗期间分析尿液中的类花生酸代谢物。在基线和阿司匹林治疗期间分析血液中的细胞分类。
II组的基础前列腺素D2代谢物（PGD-M；13.6±2.7对7.0±0.8 pmol/mg肌酐[Cr]，P<.05）和血栓素代谢物（TX-M；1.4±0.3对0.9±0.1 pmol/mg Cr，P<.01）水平高于I组。在阿司匹林反应期间，I组PGD-M水平保持不变，而TX-M水平（0.7±0.1 pmol/mg Cr，P=.07）趋于下降。相比之下，II组PGD-M水平显著升高（61.3±19.9 pmol/mg Cr，P<.05），而TX-M水平未改变。FEV1的下降与白三烯E4和PGD-M的基础尿水平呈负相关。I组在高剂量阿司匹林治疗2个月时血液嗜酸性粒细胞和嗜碱性粒细胞水平升高，尿PGD-M水平下降（2.2±0.8 pmol/mg Cr，P<.001）。
一部分AERD患者不能耐受阿司匹林脱敏与前列腺素D2产生过多有关。高剂量阿司匹林治疗期间血液嗜酸性粒细胞和嗜碱性粒细胞计数增加可能反映了前列腺素D2释放减少的功能后果以及阿司匹林的治疗益处。
