肺泡蛋白沉着症患者的肺功能与胸部分辨率CT的相关性

目的 探讨PAP患者的肺功能与高分辨率CT定量测量指标之间的相关性.方法 对2004至2007年在广州医学院第一附属医院呼吸疾病研究所住院的17例PAP患者(男10例,女7例,年龄15～51岁)进行肺通气及弥散功能检查和高分辨率CT检查,分析肺功能指标与高分辨率CT定量指标之间的相关性.比较其中6例行全肺肺泡灌洗治疗前、后的肺功能和高分辨率CT定量指标的变化.采用SPSS 13.0软件进行数据处理,结果 以x±s表示.结果 PAP患者的肺功能检查结果 以限制性通气功能障碍和弥散功能下降为主,弥散功能下降更为显著,DLCO占预计值%为(46±22)%,异常率为94.1%.肺功能检查结果 与高分辨率CT定量检查结果 之间存在一定的相关性,其中平均肺密度与FVC、肺重量与FEV1、肺含气容积比与呼气峰流量、DL.CO、DLCO与肺泡通气量比值(DLCO/VA)等指标的改变差异有统计学意义,(r值分别为-0.469、-0.482、0.511、0.659、0.692,均P<0.05),在所有指标中以肺含气容积比与DLCO/VA关系最为密切.6例肺泡灌洗术治疗的患者术后肺功能和高分辨率CT定量测量指标有所改善.结论 PAP的肺功能和胸部高分辨率CT改变之间存在相关性.2项检查同时进行可作为PAP患者随访的重要参考指标.     

肺泡蛋白沉积症患者及合并严重感染的病例临床分析

目的 通过分析肺泡蛋白沉积症(PAP)及合并严重感染的PAP患者误诊、误治情况及其原因,以提高PAP的临床诊治水平.方法 回顾性分析确诊的PAP患者84例及其中6例合并严重感染的PAP患者的临床表现,入院前的误诊、误治情况及后果.结果 84例PAP患者中66.7%(56/84)存在误诊,其中32.1%(27/84)误诊为特发性问质性肺炎(IIP),14.3%(12/84)误诊为肺结核.88.1%(74/84)患者曾接受抗感染治疗,33.3%(28/84)患者曾接受糖皮质激素治疗,19.0%(16/84)曾接受抗痨治疗.患者在院外行支气管镜检查率仅为53.6%(45/84).84例患者中86.9%(73/84)通过支气管镜、支气管肺泡灌洗(BAL)及经支气管镜肺活检(TBLB)确诊.确诊PAP时有6例患者合并严重感染,全部曾误诊为IIP并接受糖皮质激素治疗,2例死亡.结论 PAP患者误诊、误治仍很普遍,误用糖皮质激素治疗导致部分患者出现严重感染.应重视PAP的影像学特征,积极行支气管镜、BAL、TBLB检查,避免误诊.诊断不明确时务必慎用糖皮质激素.     

类脂质蛋白沉积症两家系调查及ECM1基因突变检测

目的:检测类脂质蛋白沉积症二家系中细胞外基质蛋白(ECM1)基因突变位点。方法:提取1号家系先证者及其母亲,2号家系先证者、父母、配偶及儿子外周血DNA。PCR技术扩增ECM1基因编码序列,采用一代Sanger法对PCR扩增产物进行测序。结果:1号家系先证者在7号外显子发现已知突变(纯合突变c.960GA),其母亲为杂合携带者;2号家系先证者为遗传复合体,是上述突变位点的杂合携带者,此外在3号外显子上存在1个插入突变c.142insC。结论:类脂质蛋白沉积症存在遗传异质性。     

Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is an under‐reported and under‐diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti‐granulocyte‐macrophage colony‐stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non‐specific interstitial pneumonitis preceding the development of PAP.     

Pulmonary alveolar proteinosis associated with psoriasis and complicated by mycobacterial infection: successful treatment with granulocyte-macrophage colony stimulating factor after a partial response to whole lung lavage

Pulmonary alveolar proteinosis (PAP) is a rare lung disease. Although whole lung lavage is considered the most effective treatment, not every patient shows a complete response. The case ofa young man with PAP in association with psoriasis who underwent frequent whole lung lavage but only achieved remission following treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) is reported. His lung problem was complicated by atypical mycobacterial infection,which resolved with treatment. The role of GM-CSF is discussed.     

Serum neutralizing capacity of GM-CSF reflects disease severity in a patient with pulmonary alveolar proteinosis successfully treated with inhaled GM-CSF

Existence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody and treatment with recombinant GM-CSF are new topics in idiopathic pulmonary alveolar proteinosis (PAP). We have hypothesized inhaled GM-CSF is effective and neutralizing capacity of GM-CSF, not concentration of anti-GM-CSF antibody in serum reflect disease severity. A 57-year-old female smoker with idiopathic PAP was treated with inhaled GM-CSF. The response to the treatment was evaluated by diffusing capacity for carbon monoxide (DLCO), alveolar-arterial oxygen gradient ([A-a]DO2). Conventional serum markers, including KL-6, surfactant apoprotein (SP)-A, SP-D, carcino-embryonic antigen and cytokeratin fragment 19 (CYFRA), and concentration of anti-GM-CSF antibody were examined. The neutralizing capacity of GM-CSF in serum was evaluated using a GM-CSF dependent cell line, TF-1. Ground glass opacity disappeared at the end of the treatment. Her DLCO, [A-a]DO2 remarkably improved after treatment. The neutralizing capacity of GM-CSF declined in line with disease remission and it correlated significantly with DLCO (P = 0.0137). The concentration of anti-GM-CSF antibody had no significant relation with disease severity and serum markers including neutralizing capacity. Conventional serum markers other than CYFRA showed no significant correlation with Inhaled GM-CSF was effective for idiopathic PAR Serial measurement of neutralizing capacity of GM-CSF was useful to evaluate disease severity and the anti-GM-CSF antibody was proved to be a causative factor for PAR In the future, inhaled GM-CSF may replace whole lung lavage and response to GM-CSF and its optimal amount may be decided by the capacity.     

Extra-pulmonary aspects of acquired pulmonary alveolar proteinosis as predicted by granulocyte-macrophage colony-stimulating factor-deficient mice

Abstract:   Granulocyte-macrophage colony-stimulating factor (GM-CSF)^–/– mice are an invaluable model for exploring the effects of systemic GM-CSF deficiency. Their lung phenotype exactly reproduces the abnormalities seen in human pulmonary alveolar proteinosis (PAP). However, GM-CSF^–/– mice also have significant systemic functional abnormalities. These include immune defects which result in a reduced susceptibility to a range of experimentally induced autoimmune disorders. These immunological defects are also functionally manifest as an impaired ability to resolve a range of infections under certain conditions, usually implicating cellular effectors, including Listeria , Group B streptococcus, adenovirus, Pneumocystis carinii , and malaria. These observations are consistent with the known propensity for patients with PAP to develop a range of opportunistic infections. Conversely, the diminished immunological response to inflammatory stimuli may be beneficial in some settings by limiting inflammatory cell recruitment and pro-inflammatory mediator-release. GM-CSF^–/– mice also have distinct fertility defects, manifest as reduced litter size and an increased rate of early fetal loss. These observations may be clinically relevant for women affected by PAP and further support the evaluation of the role of GM-CSF in human reproduction. These observations reinforce the importance of clinicians viewing PAP as a state of systemic functional GM-CSF deficiency, albeit with prominent pulmonary manifestations, rather than purely a 'lung disease'. These systemic manifestations of GM-CSF deficiency should also be considered when deciding on the choice between pulmonary or systemic delivery of GM-CSF as therapy for PAP, as only systemic drug delivery has the potential capcity to correct the systemic manifestations of GM-CSF deficiency in these patients.     

肺泡蛋白沉着症肺功能检查特点:附27例分析

目的 肺泡蛋白沉着症(PAP)在临床上极为罕见,其肺功能检查特点的报道也极少,本研究目的在于探讨肺功能检查在PAP诊断和治疗中的价值.方法 回顾性分析本院呼吸疾病研究所经肺组织病理(过碘酸雪夫反应阳性)确诊的27例PAP患者的临床资料.全部病例均给予肺通气和弥散功能测试,其中12例进行了肺容积测试.比较了10例行支气管肺泡灌洗(BAL)治疗的患者在灌洗前、后肺功能的改变情况.结果 27例患者入院后的基础通气肺功能情况:用力肺活量(FVC):(79.67±16.21)%;第1秒用力呼气容积(FEV1):(83.94±16.07)%,一秒率(FEV1/FVC):(89.20±5.50)%;最大呼气流量(PEF):(107.64±17.73)%;肺一氧化碳弥散量(DLCO):(49.27±21.83)%;DLCO与肺泡通气量比值(DLCO/VA):(69.92±20.11)%.肺总量(TLC):(80.60±19.56)%;残气容积(RV):(86.03±38.10)%;残总比(RV/TLC):(32.73±9.48)%;功能残气量(FRC):(84.91±28.08)%.27例患者基础肺功能下降的异常率:FVC:55.6%(15例);FEV1:44.4%(12例);FEV1/FVC:0%(0例);PEF:3.7 %(1例);DLCO:88.9%(24例);DLCO/VA:70.4%(19例).12例患者肺容积的异常率:TLC下降者占50%(6例);RV下降者占41.7%(5例),升高者占16.7%(2例);RV/TLC升高者占50%(6例);FRC下降者占33.3%(4例).10例进行BAL治疗的患者术后肺功能改善率:FVC:5.47%;FEV1:5.50%;DLCO:31.07%;DLCO/VA:20.35%.灌洗前后DLCO及DLCO/VA差异有统计学意义(t=-3.551,-3.159;P=0.006,0.012).结论 PAP的肺功能检查以肺限制性通气功能障碍及肺弥散功能障碍为常见,尤其为弥散功能障碍.PAP经BAL治疗后肺弥散功能有显著性改善.     

Autoimmune pulmonary alveolar proteinosis: Treatment options in year 2013

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of a periodic acid Schiff (PAS)‐positive eosinophilic material in the distal airways. For decades, the standard treatment of PAP has been whole lung lavage (WLL), where large quantities of saline are instilled into the lungs to remove the proteinaceous material. However, not all patients respond to this treatment. Thus, new treatment modalities, such as subcutaneous or inhaled granulocyte macrophage colony‐stimulating factor (GM‐CSF), and the CD20 antibody rituximab and plasmapheresis, have been investigated. Based on the current literature, a stepwise treatment plan is suggested starting with WLL, continuing to inhaled GM‐CSF, and then to rituximab if the former treatment regimes are unsuccessful.     

Hyperoxygenated solution for improved oxygen supply in patients undergoing lung lavage for pulmonary alveolar proteinosis

Background At present, the most effective treatment for pulmonary alveolar proteinosis （PAP） remains whole-lung lavage in spite of the usually accompanying severe hypoxemia, which is expected to be prevented by hyperoxygenated solution improving oxygen supply during lavage. In this study, the efficacy and safety of the effect of hyperoxygenated solution were evaluated. Methods Five patients underwent whole-lung lavage over a 28-month period. Each lung was lavaged with hyperoxygenated （HO） and normal saline solution （plain lactated Ringer＇s solution, NO） randomly and alternatively until the reclaimed fluid was clear. Random number was generated by computer before every cycle of lavage. If the number was odd, the patient was assigned to receive a lavage cycle with hyperoxygenated solution （HO group, n=-109）; if the number was even, normal saline solution was used （NO group, n=-115）. Data of saturation of peripheral oxygen （SPO2）, mean arterial pressure （MAP）, central venous pressure （CVP）, heart rate （HR） and end-tidal carbon dioxide tension （PETCO2） were taken down at 0, 30, 60, 90, 120, 150, 180, 210 and 240 seconds from the beginning of the instillation of solution, and frequency and volume of unilateral lung lavage were also recorded. Time interval between the leR and the right lung lavage was 1 week. Results No patient was withdrawn from the study due to low SPO2 or leakage. Oxygen pressure was （730.21±7.43） mmHg in the hyperoxygenated solution against （175.73±5.92） mmHg in the normal saline solution （P 〈0.01）. Compared with baseline, 8PO2 increased significantly as the instillation of solution began （P〈0.01）, leveled for about 30 seconds （P 〉0.05）, and then decreased significantly to the lowest at the time of drainage （compared with 120 seconds or peak, P 〈0.01）. SPO2 was higher in HO group than in NO group （P 〈0.01）. There were no significant differences in MAP, HR, CVP and PETCO2 between HO group and NO group （P 〉0.05） and also among different time points （P 〉0.05）. Conclusion During the lung lavage for pulmonary alveolar proteinosis, hyperoxygenated solution could significantly improve oxygen supply in comparison with normal saline solution without obvious side effects.