Background

Pneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis.

Methods

We prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO₂, non-invasive ventilation, or MV.

Results

Of 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05).

Conclusions

Older age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

中文翻译：

---

免疫力低下成年人中吉氏肺孢子虫肺炎的结果和预后因素：一项前瞻性观察研究

背景

吉氏肺孢子虫肺炎（PJP）仍然是一种严重疾病，与有创机械通气（MV）的发生率高和死亡率高有关。这项研究的目的是评估严重PJP和90天死亡率的早期危险因素，包括诊断时的支气管肺泡灌洗液细胞学特征。

方法

我们前瞻性地收集了2012年1月至2017年1月在法国南特大学医院接受治疗且符合PJP预定诊断标准的所有患者。PJP的诊断标准为典型临床特征，可通过直接检查或阳性对微生物确诊为jirovecii囊肿。特异性定量实时聚合酶链反应（PCR）分析。严重的PJP被定义为低氧血症性急性呼吸衰竭，需要具有至少50％FiO _2的高流量鼻氧，无创通气或MV。

结果

在研究期间调查的2446份呼吸道样本中，有430例患者中的514例为吉氏疟原虫阳性。在这430例患者中，有107例符合PJP标准，并被纳入研究，其中53例（49.5％）患有严重PJP，包括30例需要MV。所有患者均免疫功能低下，血液恶性肿瘤排名第一（n  = 37，35％），其次是实体器官移植（n  = 27，25％），HIV感染（n = 21，20％），全身性疾病（n  = 13） ，12％），实体瘤（n  = 12、11％）和原发性免疫缺陷（n  = 6、8％）。通过多因素分析，与严重程度独立相关的因素是年龄较大（OR，3.36； 95％CI 1.4–8.5；p <0.05），一个P.卡氏肺囊虫从支气管肺泡灌洗（BAL显微镜阳性结果）（OR，1.3; 95％CI 1.54-9.3; p  <0.05）; 以及没有BAL液性肺泡炎的情况（OR，3.2； 95％CI 1.27–8.8；p  <0.04）。90天死亡率为27％，在严重的PJP组中增加到50％。与90天死亡率独立相关的因素在第1天的SOFA评分较差（OR，1.05； 95％CI 1.02–1.09；p  <0.001），而BAL的肺泡炎具有保护性（OR，0.79； 95％CI 0.65-0.96；p  <0.05）。在HIV阴性患者的亚组中，获得了相似的发现，然后病毒共感染与90天较高的死亡率独立相关（OR，1.25； 95％CI 1.02-1.55；p  <0.05）。

结论

在BAL的显微镜检查中，年龄较大的猪和罗氏疟原虫卵囊与严重的PJP独立相关。通过SOFA评分评估的初始PJP严重程度和病毒共感染都可预测90天死亡率。BAL检查中的肺泡炎与较轻的PJP相关。观察到的病理生理机制值得进一步研究。