Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

Clinical approach for pulmonary alveolar proteinosis in children

In this editorial,we discuss the clinical implications of the article by Zhang et al.Pulmonary alveolar proteinosis(PAP)is a rare lung disease characterized by excessive surfactant accumulation in the alveoli.It is classified into four categories:Primary,secondary,congenital,and unclassified forms.Primary PAP is caused by the disruption of granulocyte-macrophage colony-stimulating factor(GM-CSF)receptor signaling,which is necessary for the clearance of surfactant by alveolar macrophages.It is further divided into autoimmune PAP,caused by anti-GM-CSF antibodies blocking alveolar macrophage activation,and hereditary PAP,resulting from mutations in genes encoding GM-CSF receptors.Secondary PAP develops due to conditions affecting the number or function of alveolar macrophages,such as infections,immunodeficiency,hematological disorders,or exposure to inhaled toxins.Congenital PAP is linked to mutations in genes involved in surfactant protein production.Notably,the causes of PAP differ between children and adults.Diagnostic features include a characteristic"crazypaving"pattern on high-resolution computed tomography,accompanied by diffuse ground-glass opacities and interlobular septal thickening.The presence of PAP can be identified by the milky appearance of bronchoalveolar lavage fluid and histological evaluation.However,these methods cannot definitively determine the cause of PAP.Whole lung lavage remains the standard treatment,often combined with specific therapies based on the underlying cause.

Unexpected diffuse lung lesions in a patient with pulmonary alveolar proteinosis:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)often presents nonspecifically and can be easily confused with:(1)Idiopathic interstitial lung fibrosis;(2)alveolar carcinoma;(3)pulmonary tuberculosis;and(4)other lung diseases such as viral pneumonia,mycoplasma pneumonia,and chlamydial pneumonia.CASE SUMMARY Diagnosis:In this case,a patient was diagnosed with PAP through transbronchial cryobiopsy(TBCB)and quantitative metagenomic next-generation sequencing,which confirmed the impairment of surfactant turnover as the underlying cause of PAP.Interventions:High-volume total lung lavage was performed for this patient.Outcomes:The patient's clinical condition had improved significantly by the 6-month follow-up,with a 92%finger oxygen saturation.A repeat chest computed tomography scan revealed scattered patchy ground-glass shadows in both lungs,which was consistent with alveolar protein deposition but with a lower density than in the radiograph from October 23,2022.CONCLUSION TBCB has unique advantages in diagnosing atypical alveolar protein deposition,particularly for enabling the early detection of PAP.This information can help patients take preventive measures to prevent or halt PAP development by avoiding dusty environments and seeking treatment with total lung lavage and inhaled granulocyte macrophage colony-stimulating factor.

Pulmonary alveolar proteinosis complicated with tuberculosis:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)is a rare lung disease characterized by the accumulation of phospholipoproteinaceous material in the alveoli.Cases of PAP complicated with tuberculosis are much more complex and have rarely been well recorded.CASE SUMMARY We describe a 21-year-old Han Chinese patient with suspicious lung infection associated with mild restrictive ventilatory dysfunction and diffusion reduction.High resolution computed tomography revealed a“crazy-paving”appearance and multiple pulmonary miliary nodules around the bronchi.Bronchoalveolar lavage demonstrated a small amount of periodic acid-Schiff positive proteinaceous materials.A serological test for the presence of a Mycobacterium tuberculosis antibody and an interferon-gamma release assay were both positive.The patient received a standard course of first-line anti-tuberculosis treatment after diagnostic bronchoalveolar lavage.To date,clinical remission has been achieved and maintained for five years.CONCLUSION In summary,the diagnosis of PAP complicated with tuberculosis was supported by a combination of clinical manifestations,imaging,pulmonary function,laboratory examinations,bronchoalveolar lavage,etc.This case highlighted that diagnostic bronchoalveolar lavage in combination with anti-tuberculosis treatment is a safe and effective option for mild PAP patients with tuberculosis.

Pulmonary alveolar proteinosis complicated with nocardiosis: A case report and review of the literature

BACKGROUND Pulmonary alveolar proteinosis(PAP)is a pulmonary syndrome wherein large volumes of phospholipid and protein-rich surfactants accumulate within the alveoli.PAP forms include primary(auto-immune PAP),secondary,and congenital.Nocardiosis is a form of suppurative disease induced upon infection with bacteria of the Nocardia genus.Clinically,cases of PAP complicated with Nocardia infections are rare,regardless of form.Unfortunately,as such,they are easily overlooked or misdiagnosed.We describe,here,the case of a patient suffering from simultaneous primary PAP and nocardiosis.CASE SUMMARY A 45-year-old Chinese man,without history of relevant disease,was admitted to our hospital on August 8,2018 to address complaints of activity-related respiratory exertion and cough lasting over 6 mo.Lung computed tomography(CT)revealed diffuse bilateral lung infiltration with local consolidation in the middle right lung lobe.Subsequent transbronchial lung biopsy and CT-guided lung biopsy led to a diagnosis of primary PAP(granulocyte-macrophage colonystimulating factor antibody-positive)complicated with nocardiosis(periodic acid-Schiff-positive).After a 6 mo course of anti-infective treatment(sulfamethoxazole),the lesion was completely absorbed,such that only fibrous foci remained,and the patient exhibited significant symptom improvement.Followup also showed improvement in pulmonary function and the CT imaging findings of PAP.No whole-lung lavage has been conducted to date.This case highlights that active anti-nocardia treatment may effectively improve the symptoms and alleviate PAP in patients with PAP and nocardia,possibly reducing the need for whole-lung lavage.CONCLUSION When evaluating patients presenting with PAP and pulmonary infections, thepotential for nocardiosis should be considered.

Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis:A case report and review of literature

BACKGROUND Pulmonary alveolar proteinosis(PAP)is a rare condition that can cause progressive symptoms including dyspnea,cough and respiratory insufficiency.Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia(CMML).To the best of our knowledge,this is the first reported case of PAP occurring secondary to CMML.CASE SUMMARY We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever.Based upon clinical symptoms,computed tomography findings,bone marrow aspiration,flow cytometry studies and cytogenetic analyses,the patient was diagnosed with PAP secondary to CMML.He underwent whole lung lavage in March 2016 to alleviate his dyspnea,after which he began combined chemotherapeutic treatment with decitabine and cytarabine.The patient died in January 2020 as a consequence of severe pulmonary infection.CONCLUSION This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

CT MANIFESTATIONS IN PULMONARY ALVEOLAR PROTEINOSIS AND COMPARED WITH CHEST RADIOGRAPHY(REPORT OF SIX CASES)

The CT including HRCT appearances of six patients with histopathologically confirmed pulmonary alveolar proteinosis(PAP) were evaluated and compared with those of chest radiographs In all patients the CT manifestations were quite similar: bilateral and diffuse airspace consolidation was usually patchy or confluent with sharply defined margins, intermingled with normal lung tissue The configuration of lung lesions was “geographical” in outline with angulate, strait and curved margins There were white branching linear opacities within the ground glass background Although various pulmonary diseases may mimic PAP in some way, a full awareness of the characteristic CT appearances of PAP is helpful in achieving a correct diagnosis CT may provide more accurate evidence than chest radiograph for the evaluation of the extent and delineation of PAP

A Case Report of Pulmonary Alveolar Proteinosis with Associated Opportunistic Infection of Pneumocystis jirovecii and Molluscum Contagiosum

Pulmonary alveolar proteinosis(PAP)is an idiopathic rare diffuse pulmonary disease,first described in 1958 by Rosen et al.Its estimated prevalence is about 1 in 3.7-6.9×10^(6) with a male:female ratio of 1:1-2:1.Majority of the patient’s age ranges between 20 and 50 years.PAP on microscopy is characterized by the presence of massive insoluble,amorphous,phospholipid-rich protein deposits in the bronchial and alveolar cavities.Most patients with acquired PAP present with cough and exertional dyspnea.It has been studied that there is increased risk of superinfection in PAP with opportunistic organisms like pneumocystis and vice versa.Definitive diagnosis of Pneumocystis jirovecii pneumonia rests on the demonstration of the organism within the alveoli by special stains like Grocott Methenamine Silver stain.Molluscum contagiosum(MC)is a common superficial skin infection caused by the poxvirus.MC is characterized by painless papules commonly seen in children and immunocompromised individuals.Here,we present a 34-year-old female who had complaints of severe difficulty in breathing and was brought dead to our hospital.On external examination,she had multiple warts over chest,abdomen,and over genitalia.Internal examination was unremarkable.Specimens of kidney,lung,and skin biopsy of genital warts sent for histopathological examination revealed acute tubular necrosis,P.jirovecii with PAP,and MC respectively.

《欧洲呼吸学会肺泡蛋白沉积症诊断和管理指南》解读

肺泡蛋白沉积症(PAP)是一种呼吸系统罕见病,为进一步提高临床医生对PAP的认识和诊疗水平,欧洲呼吸学会发布了第一版诊断和管理指南,包括对文献的系统回顾和应用建议、评估、发展和评估分级(GRADE)方法来评估证据的确定性和建议的强度,制定了5个患者、干预、比较、结果(PICO)问题和2个叙述性问题,并给出了相应的建议和循证证据,包括PAP的管理与全肺灌洗,粒细胞-巨噬细胞集落刺激因子(GM-CSF)替代治疗,利妥昔单抗,血浆置换和肺移植。此外,还就GM-CSF抗体检测、支气管肺泡灌洗和肺活检的使用提出了建议。该文就指南的主要建议内容进行综述解读。

单核细胞减少与分枝杆菌感染综合征患儿的护理

总结1例单核细胞减少与分枝杆菌感染综合征患儿的护理体会。针对患儿疾病罕见、移植高风险、预后未知等特点,采取降低有创诊疗风险等级,协助诊断、明确移植需求;居家肺部治疗联合远程康复,寻找最佳移植时机;双学科协同长程随访,优化患者预后等措施。患儿多次住院经反复穿刺活检及病理会诊,提示鸟分枝杆菌感染,PAS(+),DPAS(+),GATA2基因2号外显子插入突变,确诊为单核细胞减少与分枝杆菌感染综合征合并肺泡蛋白沉积症。于2022年10月行造血干细胞移植术,术后继续抗感染治疗。随访至今,间质性病变较移植前明显改善,继续抗排异治疗,现居家学习中。

肺泡蛋白沉积症患者全肺灌洗术中的风险管理

总结12例肺泡蛋白沉积症患者行全肺灌洗术中应用霍尔三维模型进行风险管理的护理经验。针对疾病特殊性及全肺灌洗术的多重风险,对患者风险分级管控,提前预警;引入霍尔三维模型,以全肺灌洗术围手术期为线轴,以专科知识及思辨逻辑能力系统排查及处理风险隐患,提升安全护理效能。该组患者住院治疗护理4~29 d,症状好转出院。

CT影像组学特征在肺泡蛋白沉积症中的诊断价值

目的探讨CT影像组学特征在肺泡蛋白沉积症(PAP)中的诊断价值。方法回顾性分析2008年11月-2022年8月在解放军总医院就诊的24例PAP患者的一般资料及临床特征;另选取同期该院就诊的53例非PAP弥漫性肺疾病患者作为对照组;比较两组间10个常规胸部CT征象(语义特征)和107个CT影像组学特征的差异。将所有患者再按7:3随机分为训练组53例及验证组24例,采用训练组构建PAP诊断的CT语义特征模型、影像组学模型及联合模型,并在验证组利用受试者工作特征(ROC)曲线进行诊断效能比较。采用临床决策分析法检验各模型的临床PAP诊断应用价值。对PAP诊断效能最高的模型,计算影像学特征评分。结果共纳入PAP患者24例,男女比例3:1,年龄(44.6±15.2)岁,主要临床症状为气促、咳嗽、咳痰及胸闷等。与对照组比较,PAP组胸腔积液发生率明显降低(P<0.05),其余CT特征差异无统计学意义(P>0.05)。CT语义特征模型在训练组和验证组诊断PAP的曲线下面积(AUC)分别为0.590和0.594,在验证组诊断PAP的准确度、敏感度、特异度分别为0.188、1.000、0.188。影像组学模型在训练组和验证组诊断PAP的AUC分别为0.845和0.867,其在验证组诊断PAP的准确度、敏感度、特异度分别为0.641、0.938、0.703。联合模型在训练组和验证组诊断PAP的AUC分别为0.850和0.883,其在训练组诊断PAP的准确度、敏感度、特异度分别为0.688、0.750、0.938。联合模型或影像组学模型诊断PAP的AUC均明显大于CT语义特征模型(P<0.05),但联合模型与影像组学模型诊断PAP的AUC差异无统计学意义(P>0.05)。临床决策曲线分析结果显示,使用联合模型或影像组学模型预测PAP的临床应用价值均较高。结论与传统CT特征比较,CT影像组学在PAP诊断中有较高的临床应用价值。

肺泡蛋白沉积症的CT诊断分析

目的探讨肺泡蛋白沉积症(PAP)的CT表现,以提高对该病的CT诊断水平。方法收集并整理16例穿刺活检或/和肺泡灌洗确诊的PAP患者病例,将其CT表现进行分析总结,并文献复习。结果PAP肺部阴影重而临床症状轻微,CT表现多样化,可表现为双肺广泛不呈叶段分布的斑片状磨玻璃密度影、铺路石征、地图征、蝶翼征、支气管充气征、肺实变及肺间质纤维化等;“铺路石征”、“地图征”同时出现,临床症状、体征与CT表现不一致时,强烈提示本病。结论PAPCT表现具特征性,结合临床可与肺炎、肺水肿、肺炎型肺癌、弥漫性肺泡出血及特发性肺间质纤维化等其他肺部病变相鉴别。

Analysis of the GM-CSF and GM-CSF/IL-3/IL-5 receptor common beta chain in a patient with pulmonary alveolar proteinosis

Objective To investigate the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and GM-CSF/IL-3/IL-5 receptor common beta chain (βc receptor) in an adult patient with idiopathic pulmonary alveolar proteinosis (PAP), so as to demonstrate the possible association of the GM-CSF and βc receptor with the pathogenesis of human PAP.Methods The GM-CSF levels were measured with a commercial ELISA kit (sensitivity 5?pg/ml) and the βc receptor expression on the cell surface was detected by flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was employed to detect the expression of the GM-CSF mRNA and the βc receptor mRNA in peripheral blood mononuclear cells and alveolar macrophages. The entire coding regions of the GM-CSF cDNA and the βc receptor cDNA were sequenced by the Sanger dideoxy-mediated chain termination method to detect possible mutations.Results The patient with PAP failed to release the GM-CSF protein either from circulating mononuclear cells or from alveolar macrophages. The expression of the GM-CSF mRNA was normal after the stimulation of lipopolysaccharide, whereas a point mutation at position 382 of the GM-CSF cDNA from 'T' to 'C' was revealed by cDNA sequencing, which caused a change in amino acid 117 of the protein from isoleucine to threonine. The βc receptor expression on the cell surface was normal, and the βc receptor mRNA expression and the sequence of the entire coding region of the βc receptor were also normal.Conclusions The decreased GM-CSF production is associated with the pathogenesis of human PAP. A point mutation of the GM-CSF cDNA may contribute to the decreased GM-CSF production in our adult PAP patient. The mutation of the βc receptor in some of paediatric patients with PAP may not be a common problem in adult patients.

Pulmonary alveolar proteinosis in an indium-processing worker

With the increasing number of workers engaged in liquid-crystal displays （LCD） manufacturer, lung diseases related to this occupational exposure are attracting more attention. Herein we report a case of interstitial lung disease in a LCD processing worker, which was pathologically confirmed as pulmonary alveolar proteinosis （PAP）.

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.

Pulmonary alveolar proteinosis associated with tuberculosis and aspergilloma formation

Pulmonary alveolar proteinosis （PAP） is a rare diffuse lung disease, characterized by accumulation of surfactant-associated phosphor lipoproteinaceous material in the alvoli. Finding the periodic acid-Schiff （PAS） positive substance in the alveolar lavage can help to make the diagnosis.

Whole Lung Lavage Treatment of Chinese Patients with Autoimmune Pulmonary Alveolar Proteinosis： A Retrospective Long-term Follow-up Study

Background： Pulmonary alveolar proteinosis （PAP） is a rare lung disease, the most common type of which is autoimmune PAP. The gold standard therapy for PAP is whole lung lavage （WLL）. Few studies have reported the optimal technique with which to evaluate the response to WLL. In this study, we aimed to identify parameters with which to assess the need for repeat WLL during a long-term 8-year follow-up. Methods： We conducted a retrospective analysis of 120 patients with autoimmune PAP with 80 of whom underwent WLL. Physiologic, serologic, and radiologic features of the patients were analyzed during an 8-year follow-up after the first WLL treatment. Results： Of the 40 patients without any intervention, 39 patients either achieved remission or remained stable and only one died of pulmonary infection. Of the 56 patients who underwent WLL for 1 time, 55 remained free from a second WLL and 1 patient died of cancer. Twenty-four required additional treatments after their first WLL. The baseline PaO2, （P = 0.000）, PA-aO2 （P = 0.000）, shunt fraction rate （P = 0.001）, percent of predicted normal diffusing capacity of the lung for carbon monoxide （DLCO%Pred） （P = 0.016）, 6-rain walk test （P = 0.013）, carcinoembryonic antigen （CEA） （P = 0.007）, and neuron-specific enolase （NSE） （P = 0.003） showed significant differences among the three groups. The need for a second WLL was significantly associated with PaO2 （P = 0.000）, CEA （P= 0.050）, the 6-minute walk test （P= 0.026）, and DLCO%Pred （P = 0.041 ）. The DLCO%Pred on admission with a cut-off value of42.1% （P = 0.001） may help to distinguish whether patients with PAP require a second WLL. Conclusions： WLL is the optimal treatment method for PAP and provides remarkable improvements for affected patients. The DLCO%Pred on admission with a cut-offvalue of 42.1% may distinguish whether patients with PAP require a second WLL.

Isolated cerebral aspergillus abscess as a complication of pulmonary alveolar proteinosis in a child

Pulmonary alveolar proteinosis (PAP) poses a risk of opportunistic infections with a variety of organisms with Nocardia being the most common pathogen followed by mycobacteria and fungi. Case presentation: A 7-year-old female child, presented with headache and multiple episodes of vomiting. There was no fever or altered sensorium. On examination, there were no focal deficits or cranial nerve palsies. An MRI brain showed a small T2 hyperintense lesion in the left superior parietal lobe suggestive of an abscess. She was diagnosed as PAP based on CT chest and bronchioloalveolar lavage 7 months earlier and treated with corticosteroids. A left parieto-occipital craniotomy was done with drainage of abscess and abscess wall excision. Histopathology revealed a suppurative lesion with slender septate acute angle branching hyphae which were positive on fungal stains. Culture done on the pus was positive for Aspergil us fumigatus. The patient was treated with voriconazole and stable at 1 year follow-up. Conclusion: Opportunistic infections are common in patients diagnosed with PAP. High index of clinical suspicion and early diagnosis are important for favorable outcome.