Bozzette S A, Sattler F R, Chiu J, Wu A W, Gluckstein D, Kemper C, Bartok A, Niosi J, Abramson I, Coffman J
Department of Medicine, University of California, San Diego 92103.
N Engl J Med. 1990 Nov 22;323(21):1451-7. doi: 10.1056/NEJM199011223232104.
Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial.
A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy.
Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms.
Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.
卡氏肺孢子虫肺炎仍是获得性免疫缺陷综合征（艾滋病）患者严重发病和死亡的常见原因。与肺孢子虫相关的呼吸衰竭所伴随的广泛肺损伤以及辅助使用皮质类固醇带来临床获益的报道为这项前瞻性多中心试验提供了理论依据。
333例患有艾滋病和肺孢子虫肺炎的患者接受了标准治疗，并被随机分配接受皮质类固醇治疗（开始时相当于每日两次服用40毫克泼尼松）或不接受额外治疗。在这项非盲试验中，主要终点是呼吸衰竭（低氧血症比值[动脉血氧分压除以吸入氧分数]小于75、插管或死亡）、死亡以及初始标准治疗的剂量限制性毒性的发生情况。
在确诊或疑似肺孢子虫肺炎的患者中（分别为225例和26例），接受皮质类固醇治疗的患者在31天时呼吸衰竭的累积风险较低（0.14对0.30，P = 0.004）以及死亡风险较低（0.11对0.23，P = 0.009），并且在84天内死亡风险也较低（0.16对0.26，P = 0.026）。两个治疗组中标准治疗的剂量限制性毒性频率相似。对整个队列的意向性分析证实了这些发现。然而，对于轻度疾病（低氧血症比值大于350）的患者，即相当于在室内空气中氧分压大于75托的患者，未显示出临床获益。接受皮质类固醇治疗的患者局部疱疹病变过多（26%对15%，P = 0.04），但其他感染或肿瘤并非如此。
早期辅助使用皮质类固醇可降低艾滋病合并中重度肺孢子虫肺炎患者呼吸衰竭和死亡的风险。由于不良反应较少，皮质类固醇应作为艾滋病合并中重度肺孢子虫肺炎患者初始治疗的一部分。
