Pulmonary alveolar proteinosis

PAP is an ultra‐rare disease in which surfactant components, that impair gas exchange, accumulate in the alveolae. There are three types of PAP. The most frequent form, primary PAP, includes autoimmune PAP which accounts for over 90% of all PAP, defined by the presence of circulating anti‐GM‐CSF antibodies. Secondary PAP is mainly due to haematological disease, infections or inhaling toxic substances, while genetic PAP affects almost exclusively children. PAP is suspected if investigation for ILD reveals a crazy‐paving pattern on chest CT scan, and is confirmed by a milky looking BAL that gives a positive PAS reaction indicating extracellular proteinaceous material. PAP is now rarely confirmed by surgical lung biopsy. WLL is still the first‐line treatment, with an inhaled GM‐CSF as second‐line treatment. Inhalation has been found to be better than subcutaneous injections. Other treatments, such as rituximab or plasmapheresis, seem to be less efficient or ineffective. The main complications of PAP are due to infections by standard pathogens (Streptococcus, Haemophilus and Enterobacteria) or opportunistic pathogens such as mycobacteria, Nocardia, Actinomyces, Aspergillus or Cryptococcus. The clinical course of PAP is unpredictable and spontaneous improvement can occur. The 5‐year actuarial survival rate is 95%.     

自身免疫性肺泡蛋白沉积症治疗进展

自身免疫性肺泡蛋白沉积症是一种发病率低、临床表现多样的疾病,全肺灌洗是目前治疗的标准方法,但并不是所有的患者治疗有效.本文将对最近出现的针对其发病机制的治疗方法进行综述.     

胸部高分辨CT在肺泡蛋白沉积症分级诊断中的应用价值

目的从胸部影像学角度探讨肺泡蛋白沉积症(PAP)的诊断分级,以指导治疗。方法对上海市肺科医院2000年1月至2010年12月收治的31例确诊PAP患者胸部高分辨CT(HRCT)进行分级,选择4个代表层面(主动脉弓、隆突、左或右下肺静脉汇合层面和膈上层面),病灶在这些层面的所占范围进行5级评分,结合临床症状、肺功能指标,建立一套PAP胸部HRCT诊断分级标准,根据诊断分级提出相应的治疗决策。结果 (1)按胸部HRCT病灶范围将PAP患者分为4级:1级(≤8分)3例;2级(>8～16分)12例;3级(>16～24分)6例;4级(>24分)10例。(2)PAP患者胸部HRCT评分与呼吸困难评分、症状总评分呈正相关(r=0.748、0.578,P均<0.01)。(3)PAP患者胸部HRCT评分与用力肺活量(FVC)占预计值%、第一秒用力呼气容积(FEV1)占预计值%、一氧化碳弥散量占预计值%及动脉血氧分压(PaO2)均呈负相关(r=-0.486、-0.376、-0.596、-0.444,P<0.01或0.05)。(4)结合胸部HRCT分级和PaO2将PAP患者分为4期:1期:HRCT分级1级伴PaO2≥8.0 kPa;2期:HRCT分级2级伴PaO2≥8.0 kPa;3期:HRCT分级3级伴PaO2≥8.0 kPa;4期:HRCT分级4级,或HRCT分级2～3级伴PaO2<8.0 kPa。(5)不同PAP患者胸部HRCT诊断分级建议:1、2期建议对症治疗及长期随访胸部HRCT;3期患者建议序贯肺泡灌洗或GM-CSF治疗;4期患者建议全肺灌洗。结论胸部HRCT诊断分级可以作为评估PAP患者病情严重程度的基础,并在此基础上选择合适的治疗方法,对临床上诊断和治疗PAP具有一定指导意义。     

肺泡蛋白沉积症研究进展

肺泡蛋白沉积症(PAP)是一种肺部少见病,以肺泡腔和细支气管腔沉积PAS染色阳性的不可溶性富磷脂蛋白质物质为特征.可分为因表面活性蛋白或GM-CSF受体基因突变导致的先天性PAP、因GM-CSF抗体阻断了肺泡巨嗟细胞的激活导致的自身免疫性PAP和继发于血液系统疾病或吸入有毒气体导致的继发性PAP.临床表现主要为进行性气促、低氧血症,胸部高分辨率CT主要表现为毛玻璃样高密度影和“疯狂堆砌”改变,支气管肺泡灌洗液PAS染色阳性可确诊.肺泡灌洗治疗有效,GM-CSF替代疗法和针对GM-CSF抗体的治疗是正在研究的治疗方法.     

粒细胞巨噬细胞刺激因子联合全肺灌洗对特发性肺泡蛋白沉积症的疗效和安全性

目的 观察粒细胞巨噬细胞刺激因子（GM-CSF）联合全肺灌洗治疗特发性肺泡蛋白沉积症（IPAP）的疗效和安全性。方法 选取2015年8月至2017年3月在第二军医大学附属长海医院就诊的2例IPAP患者,经全肺灌洗后,分别予皮下注射和雾化吸入GM-CSF治疗,观察其疗效和安全性。结果 2例患者经GM-CSF联合全肺灌洗治疗,病情缓解。结论 GM-CSF联合全肺灌洗治疗对IPAP患者治疗有效、用药安全。     

Diagnostic yield and safety of bronchofiberscopy for pulmonary alveolar proteinosis

BackgroundPulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the abnormal accumulation of surfactant-like material within the alveolar spaces and distal bronchioles. If high-resolution computed tomography (HRCT) indicates the presence of PAP, a definitive diagnosis of PAP is established when consistent pathological findings are obtained. Herein, we retrospectively studied the yield and safety of bronchofiberscopy in the diagnosis of PAP.MethodsOne hundred and fifty consecutive patients with PAP were prospectively registered in the PAP cohort database of the National Hospital Organization Kinki-Chuo Chest Medical Center between January 1991 and December 2018. We examined 86 patients who underwent bronchofiberscopy with bronchoalveolar lavage (BAL) and transbronchial lung forceps biopsy (TBLB).ResultsThe patients included 56 men and 30 women, with a median age of 57 years. All patients had autoimmune PAP, and the median level of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies was 42.8 μg/mL. The diagnostic yield was 90.7% (78/86) with BAL and 81.4% (70/86) with TBLB. The combination of BAL and TBLB increased the yield to 98.8%. Age, disease severity score, and frequency of traction bronchiectasis on HRCT were significantly different between the TBLB-positive and TBLB-negative groups. No patient developed serious complications due to bronchofiberscopy; TBLB-related complications included pneumothorax (3.5%) and minimal bleeding (7.0%).ConclusionsBronchofiberscopy, in combination with BAL and TBLB, is an effective and safe method for the diagnosis of PAP, with a yield of 98.8%.     

体外循环膜氧合支持下全肺灌洗治疗肺泡蛋白沉积症一例并文献复习

目的提高对肺泡蛋白沉积症(PAP)患者肺灌洗治疗过程中低氧血症危险性的认识。方法介绍1例经病理证实的PAP患者体外循环膜氧合下的全肺灌洗治疗过程，并复习相关文献。结果57岁男性患者，因咳嗽和进行性呼吸困难12个月入院，动脉血氧分压(PaO2)为46mmHg(1mmHg=0．133kPa)，脉搏容积血氧饱和度(SpO2)85％～88％。胸部CT、经纤维支气管镜支气管肺泡灌洗和肺活检病理检查符合PAP。在手术室常规静脉全麻后，经口腔插入双腔管，分隔为通气肺和灌洗肺。两肺机械通气SpO2为80％～90％；当右侧单侧肺机械通气SpO2为68％～80％。于右股动脉和右股静脉插管，建立体外循环通道，开始静脉-动脉体外循环膜氧合(ECMO)支持，右侧单侧肺机械通气SpO2为89％～97％。左侧肺用总计20800ml生理盐水灌洗，灌洗期间SpO2为80％～94％；灌洗后，患者无呼吸困难。28d后未用ECMO完成右肺灌洗。1个月后复查CT示双肺浸润影基本消失。结论当PAP患者全肺灌洗操作前出现顽固的低氧血症，应考虑使用ECMO支持，以避免患者在全肺灌洗治疗中的危险低氧血症。     

9例肺泡蛋白沉积症病人大容量全肺灌洗术的护理

[目的]总结9例肺泡蛋白沉积症病人进行双肺同期大容量全肺灌洗术前、术后的护理措施。[方法]采用同期大容量双侧全肺灌洗术,并电话随访。[结果]灌洗治疗有效率100%;治疗前与治疗后血氧分压和指脉血氧饱和度比较差异有统计学意义(P<0.05);电话随访结果:9例全部脱离原来的工作场所,经全肺灌洗治疗后,7例咳嗽、咳痰和气促症状痊愈,2例再次住院灌洗,死亡率0,再次住院率(2例)22.2%。[结论]灌洗术前做好术前准备、心理护理以及教会病人有效咳嗽和缩唇腹式呼吸;灌洗术后严密观察病人的病情变化,清醒前做好气道管理,清醒后进行有效的呼吸功能锻炼,预防并发症是确保病人灌洗治疗成功的关键。出院后定期门诊复查,优化工作环境,做好防护,预防吸入粉尘、有害气体可减少相关疾病的发生。