Morikawa Miki, Kanemitsu Yoshitomi, Tsukamoto Hiroki, Morikawa Akimasa, Tomioka Yoshihisa
Morikawa Pediatrics & Allergy Clinic.
Arerugi. 2016 May;65(3):200-5. doi: 10.15036/arerugi.65.200.
The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as β-lactoglobulin (β-LG) by Western blotting using specific monoclonal antibody and patient's sera. The β-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than β-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of β-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.
该患者为一名6岁女性,患有牛奶过敏和持续性哮喘。她在吸入用于治疗流感感染的依那韦(辛酸兰尼米韦水合物)后不久就出现了过敏反应。皮肤点刺试验显示依那韦吸入粉和用作辅料的乳糖呈阳性反应,但对兰尼米韦呈阴性反应。在药物刺激的嗜碱性粒细胞活化试验中也得到了相同的结果。依那韦吸入粉中的乳糖辅料被认为含有牛奶蛋白,从而引发了过敏反应。为了验证这种可能性,我们检测了乳糖辅料中过敏性牛奶蛋白的污染情况,并通过银染发现了涂片条带,使用特异性单克隆抗体和患者血清进行蛋白质印迹法鉴定该条带为β-乳球蛋白(β-LG)。依那韦中的β-LG被认为与乳糖发生了糖基化,因为其分子量在迁移率方面略高于β-LG标准参照物。事实上,在体外与乳糖孵育往往会增加分子量。基于这些结果,我们在此报告,依那韦乳糖辅料中污染的微量β-LG可能会引起即刻过敏反应。需要提醒的是,含乳糖的干粉吸入器对牛奶过敏患者有引起过敏反应的风险。特别是对于流感患者,由于这些患者气道高反应性增加,使用时应格外注意。