Chest：非HIV相关耶氏肺孢子菌肺炎中辅助性糖皮质激素的使用与临床结局

Abstract

Background: Adjunctive corticosteroids improve outcomes in HIV-associated Pneumocystis jirovecii pneumonia (PCP), but their role in non-HIV patients is uncertain. Prior evidence has largely been limited to binary treatment groups and has rarely accounted for daily or cumulative dose effects.

背景：辅助性糖皮质激素可改善 HIV 相关性耶氏肺孢子菌肺炎（PCP）的预后，但其在非 HIV 患者中的作用尚不明确。既往证据多局限于二元治疗分组，且很少考虑每日剂量或累积剂量的影响。

Research question: What is the dose-response relationship between adjunctive corticosteroids and outcomes in non-HIV immunocompromised adults with PCP requiring supplemental oxygen?

研究问题：在非 HIV 免疫缺陷成人 PCP 患者中，需要吸氧治疗时，辅助性糖皮质激素与临床结局之间是否存在剂量–反应关系？

Methods: We conducted a multicenter retrospective cohort analysis of 375 non-HIV immunocompromised adults with proven or probable PCP hospitalized between 2019-2025. All patients were hypoxemic at treatment initiation. Corticosteroid exposure was modeled as a continuous, cumulative time-varying dose over 21 days using marginal structural models with inverse probability of treatment weighting to adjust for baseline covariates and time-varying illness severity.

方法：我们对 2019–2025 年间住院的 375 例经确诊或拟诊的非 HIV 免疫缺陷成人 PCP 患者进行了一项多中心回顾性队列分析。所有患者在治疗开始时均存在低氧血症。使用边际结构模型并采用逆概率治疗加权法，将糖皮质激素暴露建模为 21 天内的连续、累积、随时间变化的剂量，以校正基线协变量和随时间变化的疾病严重程度。

Results: Of 375 patients, 351 (93.6%) received corticosteroids. The most common etiologies of immunosuppression were hematologic malignancy (30%), solid tumors on chemotherapy (30%), autoimmune disease (17%), and solid organ transplantation (14%); 56% required ICU admission and 44% died within 90 days. Greater cumulative steroid dose was associated with increased risk of 90-day mortality (weighted HR 1.01 per 100 mg prednisone-equivalent, 95% CI 1.00-1.02, p=0.006). Steroid exposure was not associated with risk of intubation (HR 0.99, 95% CI 0.97-1.02) or faster liberation from advanced respiratory support (HR 1.00, 95% CI 0.98-1.02).

结果：在 375 例患者中，351 例（93.6%）接受了糖皮质激素治疗。免疫抑制的最常见病因依次为血液系统恶性肿瘤（30%）、化疗中的实体瘤（30%）、自身免疫性疾病（17%）以及实体器官移植（14%）；56% 需入住 ICU，44% 在 90 天内死亡。更高的累积激素剂量与 90 天死亡风险增加相关（加权风险比 [HR] 每 100 mg 泼尼松当量 1.01，95% 置信区间 1.00–1.02，p=0.006）。激素暴露与气管插管风险（HR 0.99，95% CI 0.97–1.02）或无创/有创高级呼吸支持撤机速度加快无关（HR 1.00，95% CI 0.98–1.02）。

Interpretation: In non-HIV PCP with hypoxemia, higher cumulative corticosteroid exposure was not associated with improved respiratory outcomes and was linked to increased mortality. Use of doses exceeding trial-tested regimens should be approached with caution. 

解读：在低氧血症的非 HIV PCP 患者中，较高的累积糖皮质激素暴露并未带来呼吸预后的改善，反而与死亡率升高相关。对于超出临床试验验证方案的剂量应谨慎使用。