Long‐term results of disodium etidronate treatment in pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease with alveolar microliths mainly composed of calcium phosphate. The gene responsible for the disease is SLC34A2, which encodes a type‐IIb sodium phosphate cotransporter, has been described recently. Treatment of this disease is not clearly defined. Disodium etidronate is a member of bisphonates and it has been administered in these patients due to its inhibitory effect on the precipitation of hydroxyapatite microcrystals. Here, clinical and radiological improvement of two patients with PAM who were treated with disodium etidronate for 9 and 11 years, respectively, are presented. The pathogenetic mechanism of this treatment on the genetic basis of disease is discussed. Pediatr Pulmonol. 2010; 45:514–517. © 2010 Wiley‐Liss, Inc.     

肺泡微石症3例并文献复习

目的加强对肺泡微石症的认识,提高其诊断率。方法通过中国生物医学文献光盘数据库(CBM-Disk)检索1994年1月至2010年5月有关报道肺泡微石症的文献,剔除重复累计报道病例,结合本院收治的3例,回顾性分析中国人肺泡微石症的临床资料。结果共报道了120例肺泡微石症,男70例(58.3％),女50例(41.7％)。有临床症状者65例,主要表现为咳嗽51例(42.5％)、气促49例(40.8％)、咯痰26例(21.7％)、胸痛18例(15.0％)、胸闷17例(14.2％)、心悸4例(3.3％)、咯血3例(2.5％)。无症状者55例。肺功能检查22例,7例正常,12例呈限制性通气功能障碍,弥散功能下降。120例均行胸部X线检查,显示双肺粟粒影106例,其中92例中下肺粟粒影增加,病灶聚集融合41例,肺门正常104例,心膈模糊55例,线状钙化48例,肺尖气肿1例。结论我国肺泡微石症较为少见,临床症状无特异性,易漏诊、误诊。对可疑患者应及早行胸部高分辨率CT及纤维支气管镜肺活检以确诊。     

Pulmonary alveolar microlithiasis in childhood: Diagnosis by transbronchial biopsy

A 7-year-old girl of Arabic origin by consanguineous parents presented with a miliary pattern on chest x-ray. Transbronchial lung biopsy revealed a histological diagnosis of pulmonary alveolar microlithiasis, a condition rarely described in childhood. This report highlights the clinical and radiological features, documents the transbronchial lung biopsy as a useful diagnostic procedure, and suggests a possible genetic etiology with autosomal recessive inheritance. Pediatr Pulmonol. 1996; 21:62–64. © 1996 Wiley-Liss, Inc.     

Update on diagnosis and treatment of pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis(PAM)(MIM265100)is a rare disease characterized by the diffuse deposit of microlithiasis in alveolar spaces.PAM could occur worldwide with high prevalence in Asia and Europe.Familial occurrence indicates its autosomal recessive trait and the SLC34A2 gene was identified as the responsible gene for the disease.In spite of the versatile mutation sites in patients from other countries,exon 7and exon 8 might be the most liable gene in Chinese and Japanese patients.Most mutations caused the premature termination of proteins and produced truncated proteins,leading to the blocking of the recycling and degrading of outdated surfactant which is full of phospholipids.The most outstanding clinical feature of PAM is the discrepancy between the paucity of symptoms and the degree of pulmonary involvement.Diagnosis is easy to establish based on typical chest radiograph image and nuclear medicine improves its early diagnosis and active evaluation.Pathology of the unique intra-alveolar lamellar microliths gives strong support for diagnosis.No effective treatment is considered valid currently.However,lung transplantation is effective for advanced-stage patients,and long term treatment of disodium etidronate seems promising.     

Pulmonary fibrolysis in a patient with idiopathic pulmonary fibrosis: improvement of clinical and radiological pattern after treatment with pirfenidone

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high‐resolution computed tomography pattern of “definite UIP” is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex‐heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.     

肺泡微石症1例并文献复习

目的总结1例诊断和治疗肺泡微石症的临床过程,提高对该疾病的认识。方法分析我院1例肺泡微石症的临床资料,并文献复习。结果患者以咳嗽及气喘起病,并逐渐加重,入院时已出现肺动脉高压及右心功能不全表现,肺部CT表现为双肺弥漫性密度增高的间质性改变,以中下肺野和近胸膜下较为密集,呈典型的"火焰征",通过外送基因检测发现SLC34A2基因中第8个外显子有纯合子突变(c.A910T),因此临床诊断为肺泡微石症。入院后予吸氧、抗感染、平喘、利尿及降低肺动脉压等对症治疗,患者症状可减轻。结论肺泡微石症临床表现无特异性,影像学表现较典型,若发展至晚期,可通过SLC34A2基因检测协助临床诊断。     

Pulmonary alveolar microlithiasis with cor pulmonale: An autopsy case demonstrating a marked decrease in pulmonary vascular beds

Pulmonary alveolar microlithiasis (PAM) is a very rare autosomal recessive disorder in which microliths are formed in the alveolar space. PAM is infrequently complicated by pulmonary hypertension, the cause of which is unclear. The author in this paper found that the pulmonary hypertension was caused by a marked decrease in pulmonary bascular beds. Here, an autopsy case of PAM with a marked cor pulmonale is reported. A 14-year-old woman was found to have an abnormal pulmonary shadow, but the cause was unclear. At 24 years, she was diagnosed with a diffuse pulmonary abnormal shadow. At 42 years, she was diagnosed with PAM by imaging techniques. Her condition gradually worsened and she had to be treated with oxygen. She died of respiratory failure at 54 years. An autopsy revealed severe PAM and marked cor pulmonale. The heart weighed 360 g and right ventricular thickness was 10 mm (normal, 2–3 mm). Microscopically, the alveolar space was diffusely filled with microliths, and heart failure cells were recognized. Bone formations were scattered. The alveolar walls showed fibrous thickening, and pulmonary arteries showed atherosclerosis. The right ventricle showed marked cardiac hypertrophy. Chronic severe liver congestion was noted. A morphometric analysis using CD34-stained specimens showed a marked decrease (one tenth) in pulmonary capillary beds (capillary number: 8.6 ± 3.1 per image), compared with normal lungs obtained from two other autopsies (85.3 ± 9.4 and 96.2 ± 10,3). It was concluded that the cor pulmonale and pulmonary hypertension in the present case were caused by the marked decrease of the pulmonary arterial vascular beds. More research is required regarding the etiology and treatment of PAM.     

SLC34A2基因与肺泡微结石症

肺泡微结石症是一种很早就被认识、病程进展缓慢的罕见疾病,以肺泡内广泛的磷酸钙盐沉积为特征.其病因长期未能得到明确,新近发现该病为SCL34A2基因突变所引起的常染色体隐性遗传疾病.现就SLC34A2基因与肺泡微结石症进行综述,为该领域的深入研究提供参考.     

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2例报告并文献回顾

目的总结肺泡蛋白沉积症（PAP）的临床特征、诊断及治疗。方法对2例患者的临床资料进行分析,并回顾复习有关文献。结果 PAP临床无特征性,以咳嗽、咳痰、气促多见,但体征较少。胸部CT可见＂地图样＂改变或＂铺路石＂征。结论 PAP发病率低,起病隐匿,误诊或漏诊率较高,支气管肺泡灌洗液及肺组织的病理检查可用于PAP的早期诊断,全肺灌洗是安全有效的治疗方法 。     

肺泡状棘球蚴病的CT表现

目的探讨肺泡状棘球蚴病的CT表现特征。方法回顾性分析经手术病理或临床证实的16例肺泡状棘球蚴病的临床资料和CT表现。结果16例均属血行转移,其中2例合并肺底直接侵犯。弥漫分布4例,多发肿块结节10例,单发肿块2例。9例病灶有小囊泡征,13例病灶出现钙化灶,6例肿块病灶内不规则偏心形空洞,其中1例见液气平;6例病灶邻近胸膜局限性增厚,2例胸腔少量积液。16例患者均有肝脏泡状棘球蚴病。结论肺泡状棘球蚴病CT表现有一定的特征性,结合流行病史和肝脏CT表现综合分析有利于提高其诊断。     

肺泡微石症患者磷酸钠协同转运蛋白基因的检测及其变异

目的 检测3例肺泡微石症患者的磷酸钠协同转运蛋白基因(SLC34A2)基因变异情况,探讨该基因对人肺泡上皮细胞A549系(简称A549细胞)中钙、磷转运的影响.方法 采用分段PCR和基因测序的方法对3例肺泡微石症患者的SLC34A2基因进行检测,用Trizol法从新鲜肺组织中获得RNA,逆转录-PCR调取目的 基因,构建该基因真核表达载体,质脂体方法转染A549细胞,逆转录-PCR检测SLC34A2 mRNA的表达,检测细胞上清液中钙、磷含量.细胞实验分为转染组(5×105/孔,4孔)、对照组(5×105/孔,1孔)和空白组(5×105/孔,1孔),实验重复6次.计量资料采用单因素方差分析,多组问两两比较采用SNK-q检验.结果 3例肺泡微石症患者中未发现变异的外显子.获得完整的SLC34A2 cDNA,成功构建peDNA3.1(+)-SLC34A2真核表达载体,并转染A549细胞.转染组SLC34A2 mRNA的吸光度值(2.48.±0.45)明显高于对照组(0.55±0.07)和空白组(0.60±0.06),差异均有统计学意义(q值分别为16.25和15.78,均P＜0.01);转染组细胞上清液中钙、磷含量[(0.110±0.016)mmol/L和(3.8±0.4)mmol/L]明显低于对照组[(0.254±0.047)mmol/L和(7.3±0.8)mmol/L]和空白组[(0.262±0.041)mmoL/L和(7.1±0.4)mmol/L],差异均有统计学意义(q值为8.657～13.892,均P＜0.01).结论 随着SLC34A2基因的表达量增加,细胞外液钙、磷含量随之下降.SLC34A2的变异可能未发生在基因组水平.     

肺泡蛋白沉着症10例临床分析

目的通过临床病例分析,了解肺泡蛋白沉着症（PAP）的临床和影像学表现,提高诊断水平。方法回顾分析确诊的10例PAP患者的临床资料。结果男8例,女2例,平均年龄46．7岁。病程慢性迁延,主要症状活动后气促,咳嗽等,体征较少。胸部影像表现呈多样化,可归纳为：地图样表现、碎石路样表现、肺实变样表现、肺水肿样表现及肺间质纤维化样表现等。10例经支气管镜肺活检（TBLB）和支气管肺泡灌洗（BALF）明确。结论肺部影像可以充分显示肺泡蛋白沉积症的特点,尽早作TBLB、BALF确诊。     

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%.     

Elevated serum surfactant protein A and D in pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by widespread localization of calcispherites in the alveolar spaces. The authors report two cases of PAM, with markedly elevated sera concentrations of surfactant protein-A and surfactant protein-D, which showed a tendency to increase as the disease progressed. Therefore, surfactant protein-A and surfactant protein-D may function as serum markers to monitor the disease activity and progression of PAM.     

SARS: radiological features

Air-space disease is typical in severe acute respiratory syndrome (SARS) and may be indistinguishable from pneumonia of other causes. In the majority of patients, ground glass opacities on chest radiographs progress rapidly to focal, multifocal or diffuse consolidation. Unilateral involvement is common in the early acute phase, becoming bilateral at maximal lung involvement. Generally, radiographic opacities peak between 8 and 10 days after onset of illness, with radiographic scores reflecting temporal changes in clinical and laboratory parameters such as oxygen saturation (SaO₂) and liver transaminases. Pleural effusions, cavitating consolidation and mediastinal lymphadenopathy are not typical radiographic features. Pneumomediastinum and pneumothoraces are complications that are associated with extensive disease, with or without assisted ventilation.
The utility of high resolution computed tomography (HRCT) and CT scans lies in the confirmation of airspace opacities in cases with normal initial chest radiographs that have strong contact history and signs and symptoms highly suspicious of SARS during the outbreak, allowing early treatment and prompt isolation. The characteristic HRCT feature in the acute phase is ground-glass opacities with smooth interlobular septal thickening, sometimes with consolidation in a subpleural location, which progress rapidly to involve other areas of the lungs. Temporal lung changes documented on HRCT suggest that some residual opacities found may not be reversible.     

Bronchiolitis obliterans in children: clinical profile and diagnosis

OBJECTIVE: The aim of the study was to determine the clinical profile, aetiology and radiological categories in children diagnosed with bronchiolitis obliterans (BO). METHODOLOGY: We undertook a review of the medical records and radiological studies of 14 children with BO. RESULTS: Unresolving cough and wheeze after a short respiratory illness was the commonest presentation. A viral pneumonitis was identified as the initial respiratory event prior to the development of BO in six children and Mycoplasma pneumoniae was the cause in another three children. Chest X-ray findings could be divided into four distinct patterns that were hyperinflation (n=5), mixed pattern of atelectasis, hyperlucency and bronchial thickening (n=4), unilateral small hyperlucent lung (n=3) and unilateral collapse of one lung (n=2). High resolution computed tomogram (HRCT) chest showing areas of hyperaeration and mosaic ground glass patterns with bronchial thickening were commonly found in patients whose chest X-ray showed bilateral changes. Patients with bilateral lung changes were more likely to have failure to thrive and persistent respiratory symptoms on follow up. CONCLUSION: A diagnosis of BO can be made from typical clinical features combined with an understanding of the different chest X-ray categories and HRCT of the chest. A viral aetiology was the commonest cause for BO in our series.