A PILOT STUDY TO INVESTIGATE THE MECHANISMS UNDERLYING STEROID REDUCTION IN SEV

这是一项开放标签的试点研究，正在评估 IVIG通过体外激素反应性测定，改善了肺 严重类固醇依赖患者的功能和口服类固醇减量 哮喘患者。我们招募了12名激素依赖型哮喘患者。 到目前为止。在12名登记的患者中，有11名患者成功地完成了 研究，1名患者完成了研究，但由于 在她入选后被诊断为中性粒细胞缺陷 走进书房。这种中性粒细胞缺陷导致了她的发育 复发性肺炎合并假单胞菌和葡萄球菌。经常性的 肺部感染使得很难确定静脉注射免疫球蛋白对HER的影响 肺功能。所有入选的患者都是青少年或年轻人。 年龄14至21岁(15.5+/-0.8岁)。有5只雄性 女性6例。4名患者是非洲裔美国人，1名患者是西班牙裔， 6人是高加索人。六个月的IVIG治疗导致&gt；70% 口服GC剂量减少(IVIG治疗前34+/-8 mg/d对9+/-3 mg/d；p=0.01)， 减少强的松爆发次数(2.6+/-0.5对1.1+/-0.4； 和住院率(3.0+/-.3vs.0.6+/-0.3；p=0.001)相比 6入境前几个月。PEFR和FEV1值保持不变 在研究期间，尽管口服GC减少。IVIG导致 改进的GCR结合亲和力(基线KD 38+/-5、3mo KD 22+/-3、6mo KD 21+/-3 NM)。静脉注射丙种球蛋白也引起剂量依赖性抑制。 静脉注射丙种球蛋白和GC联合刺激淋巴细胞 比单独的任何一种都更大的压制。我们有两个严重的不良事件 与静脉注射免疫球蛋白有关，导致住院-严重头痛 还有过敏反应。科目(WR)于1996年10月入学，按 方案，静脉注射丙种球蛋白(IVIG)，剂量2 克/公斤体重。他平安无事地忍受了输液，但 输液后2天出现严重头痛、恶心和嗜睡。他 住进儿科特别护理(PSC)病房进行观察和 到了第二天，他的症状已经缓解。与 研究药物(IVIG)被认为是可能的。由于上述反应，WR 接受氢化可的松、苯海拉明和他的前处理 输液分两天进行。有了上述变化，WR 可以忍受随后的输液，没有问题。主体(JV)是 1997年6月登记，按照方案，接受了静脉注射 球蛋白(IVIG)，剂量为2克/公斤体重。JV已经容忍了 在1997年10月13日之前没有困难的输液(5号输液) 他出现了过敏反应。他收到了大约70克的现金 当他出现面部刺痛感时，总共服用了90克Gamimune-N，总计 全身潮红，以及泛发性荨麻疹。他还感到“头晕目眩”， 恶心。输液立即停止，他的血压 被测量和注意到从输液前的135/72下降到91/44。 他服用了50毫克的苯那君和100毫克的氢化可的松 静脉注射。当我到达的时候，JV看起来面红耳赤。 在他的上半身和脸部。他也有眼皮浮肿，但没有 苦恼。没有听到刺耳的响声或喘息声，他的空气进入得很好。氧 在下午3点给药，他被转到儿科特别病房 在护理病房接受0.3cc肾上腺素皮下注射，正常 生理盐水以200毫升/小时的速度静脉注射。在接下来的几个小时里，JV的血液 压力改善了，荨麻疹消失了，他出院了 门诊部。第二天，他接受了第二次输液 静脉注射丙种球蛋白(90克)超过6小时无意外。与 研究药物(IVIG)被认为是可能的。由于上述反应，合资公司 接受氢化可的松和苯海拉明的预治疗， 他的输液速度变慢了。有了上述变化，合资公司容忍了 他随后的输液没有发生任何意外。

This is an open-label pilot study which is evaluating the effectiveness of IVIG as measured by in vitro steroid responsiveness, improved pulmonary function, and oral steroid reduction in severe steroid dependent asthmatics. We have enrolled 12 patients with steroid dependent asthma thus far. Of the 12 enrolled, 11 patients have successfully completed the study, 1 patient completed the study but her data will not be analyzed due to the diagnosis of a neutrophil defect being made after she was enrolled into the study. This neutrophil defect resulted in her developing recurrent pneumonias with pseudomonas and staph species. The recurrent lung infections made it difficult to determine the effect of IVIG on her lung function. All patients enrolled been were adolescents or young adults with an age range of 14 to 21 years (15.5+/-0.8 yrs). There were 5 males and 6 females. Four patients were African American, 1 patient Hispanic, and 6 were Caucasian. Six months of IVIG therapy resulted in >70% reduction in oral GC dose (34+/-8 pre- vs. 9+/-3 mg/d post-IVIG; p=0.01), decreased the number of prednisone bursts (2.6+/-0.5 vs. 1.1+/-0.4; p=0.04) and hospitalizations (3.0+/-.3 vs. 0.6+/-0.3; p=0.001) compared to 6 the months prior to entry. PEFR and FEV1values remained unchanged during the study despite the reductions in oral GC. IVIG resulted in improved GCR binding affinity (baseline Kd 38+/-5, 3 mo Kd 22+/-3, 6 mo Kd 21+/-3 nM). IVIG also caused a dose dependent suppression of lymphocyte stimulation with the combination of IVIG and GC resulting in greater suppression than either alone. We had two serious adverse events associated with IVIG which resulted in hospitalization- severe headache and anaphylaxis. Subject (WR) was enrolled in October 1996, and per protocol, received intravenous gamma globulin (IVIG) at a dose of 2 grams/kg of body weight. He tolerated the infusion without incident, but developed severe headache, nausea and lethargy 2 days post infusion. He was admitted to the Pediatric Special Care (PSC) Unit for observation and by the second day, his symptoms had resolved. The association to the study drug (IVIG) was considered likely. Due to the above reaction, WR received pre-treatment with hydrocortisone and diphenhydramine and his infusions were divided over two days. With the above changes, WR tolerated subsequent infusions without problems. Subject (JV) was enrolled in June 1997, and per protocol, received intravenous gamma globulin (IVIG) at a dose of 2 grams/kg of body weight. JV had tolerated the infusions without difficulty until October 13, 1997 (infusion #5) when he developed anaphylaxis. He had received approximately 70 gm out of a total of 90 gm of Gamimune-N when he developed facial "tingling", total body flushing, and generalized urticaria. He also felt "light headed" and nauseated. The infusion was immediately discontinued, his blood pressure was measured and noted to have fallen from 135/72 pre-infusion to 91/44. He was given 50 mg of Benadryl, and 100 mg of hydrocortisone intravenously. Upon my arrival, JV appeared "flushed" with urticaria over his upper body and face. He also had eyelid edema but was in no distress. No stridor or wheezing heard and he had good air entry. Oxygen was administered at 3 LPM and he was transferred to the Pediatric Special Care Unit where he received 0.3 cc epinephrine subcutaneously, and normal saline at 200 cc/hr intravenously. Over the next couple hours, JV's blood pressure improved, the urticaria resolved, and he was discharged to the outpatient department. The following day, he received his second infusion of IVIG (90 gm) over 6 hours without incident. The association to the study drug (IVIG) was considered likely. Due to the above reaction, JV received pre-treatment with hydrocortisone and diphenhydramine and the rate of his infusions were slowed. With the above changes, JV tolerated his subsequent infusions without incident.