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Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous materials accumulate in the alveolar compartments. A 72-year-old man was diagnosed with autoimmune PAP with severe respiratory failure. We decided to perform segmental lung lavage (SLL) with fiberoptic bronchoscopy under general anesthesia. If improvement was not significant, whole-lung lavage (WLL) would be done. SLL improved the respiratory failure and computed tomography findings. This case showed improvement in not only the area where lavage was done but also the non-lavaged area. SLL with fiberoptic bronchoscopy under general anesthesia might be an appropriate treatment option for patients with severe PAP.

Pulmonary alveolar proteinosis is a rare disease characterized by progressive accumulation of lipoprotein material in the alveoli as a result of a dysfunction in surfactant clearance. The whole-lung lavage procedure is considered the current standard of care and consists of the sequential lavage of both lungs for mechanical removal of residual material in the alveoli. However, a lack of standardization has resulted in different procedural techniques among institutions. Even though whole-lung lavage is considered to be a safe procedure, unforeseen complications might occur, and proper knowledge of physiologic implications may allow clinicians to establish the appropriate therapy. This review provides an insight into the underlying physiology of the disease, the technical details of the procedure from an anesthesiologist's perspective, and discussion of potential intraoperative complications.

Background Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient’s condition. Methods APAP patients numbering 151 were enrolled in this study. All patients’ severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1–2 and 3–5 through receiving operating characteristics (ROC) curve. Results Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1–2 and 3–5) showed an optimal cutoff of LDH of over 203 U/L ( 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748–0.882], sensitivity: 0.606, specificity: 0.877). Conclusion Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Introduction Pulmonary alveolar proteinosis (PAP) is defined by increased accumulation of surfactant in the alveolar space. PAP has been reported to be associated with a large number of clinical conditions and diseases. Whole lung lavages can be helpful to stabilize the clinical course of PAP until the underlying condition is identified, which may enable more specific treatment. Recently, heterozygous OAS1 gain-of-function variants were described as cause in a patient with infantile-onset PAP combined with hypogammaglobulinemia. Case presentation At age 4 months, a female infant born to term was diagnosed with hypogammaglobulinemia and treated with monthly immunoglobulin injections. At age 15 months, the girl needed supplemental oxygen at night, and at age 18 months, also during the day. At age 2 years, pulmonary alveolar proteinosis of unknown etiology was diagnosed by computed tomography scan and open lung biopsy. Subsequently, monthly whole lung lavages (WLLs) were started, which stabilized the clinical course for over 2 years until a disease-causing OAS1 variant was diagnosed and the patient was successfully treated by hematopoietic stem cell transplantation. Conclusion Here, we describe the successful management of a female patient with severe PAP caused by a heterozygous OAS1 gain-of-function variant until a definitive diagnosis was made and cured by hematopoietic stem cell transplantation. This article is protected by copyright. All rights reserved.

Congenital interstitial lung diseases can affect both adults and children. Pediatric congenital interstitial lung diseases generally carry high risk for morbidly and mortality and include congenital alveolar capillary dysplasia with misalignment of pulmonary veins, congenital alveolar dysplasia, acinar dysplasia, congenital pulmonary lymphangiectasis, diffuse pulmonary lymphangiomatosis, neuroendocrine cell hyperplasia of infancy, pulmonary hemosiderosis, pulmonary alveolar proteinosis, and pulmonary interstitial glycogenosis. Given their usual non-specific clinical presentation, they are frequently misdiagnosed and recognized late, particularly in children who have been apparently healthy for several years (eg, diffuse pulmonary lymphangiomatosis). Some diseases have a very poor prognosis, whereas others have a benign course with appropriate treatment. The current manuscript reviews congenital interstitial lung diseases that typically affect neonates and young children and may be encountered by the pediatric anesthesiologist.

Pulmonary alveolar proteinosis (PAP) is an uncommon disease characterized by progressive accumulation of lipoprotein material in the lungs due to impaired surfactant clearance. Whole-lung lavage (WLL) is the current standard treatment and consists of sequential lavage of each lung to mechanically remove the residual material from the alveoli. Although WLL is considered safe, unexpected complications can occur. Moreover, due to the rarity of the disease itself, this procedure is unknown to many physicians, and management of intraoperative complications can be challenging for anesthesiologists. Lung ultrasound (LUS) provides reliable and valuable information for detecting perioperative pulmonary complications and, in particular, quantitation of lung water content. There have been reports on monitoring the different stages of controlled deaeration of the non-ventilated lung during WLL using LUS. However, it has been limited to non-ventilated lungs. Therefore, we report the use of LUS in WLL to proactively detect pulmonary edema in the ventilated lung and implement a safe and effective anesthesia strategy. Given the limited diagnostic tools available to anesthesiologists in the operating room, LUS is a reliable, fast, and noninvasive method for identifying perioperative pulmonary complications in patients with PAP undergoing WLL.

Case Presentation A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.

The article presents a modern understanding of the components of the surfactant, the functions of non-serum proteins SP-A, SP-B, SP-C and SP-D. The history of the discovery of protein deficiencies SP-B, SP-C and ABCA3 is described. The authors had analyzed modern epidemiology, clinical and histological features of various deficiencies of surfactant proteins. Va­rious variants of SFTPC, SFTPB and ABCA3 mutations and their influence on the course, clinical manifestations and outcome of interstitial lung disease in children are demonstrated.

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94–3.73, p

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary surfactant homeostasis disorder resulting in buildup of lipo-proteinaceous material within the alveoli. PAP is classified as primary (autoimmune and hereditary), secondary, congenital and unclassifiable type based on the underlying pathogenesis. PAP has an insidious onset and can, in some cases, progress to severe respiratory failure. Diagnosis is often secured with bronchoalveolar lavage in the setting of classic imaging findings. Recent insights into genetic alterations and autoimmune mechanisms have provided newer diagnostics and treatment options. In this review, we discuss the etiopathogenesis, diagnosis and treatment options available and emerging for PAP.

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.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome. The current standard treatment is whole lung lavage (WLL). We reviewed PAP cases treated with WLL during a 243-month period. The primary objective was to describe the efficacy of WLL. We compared chest imaging resolution and pulmonary function tests (PaO(2) and DLCO) before the first and after the last WLL. The secondary objectives were to compare mMRC dyspnea scores, other lung function parameters, and complications of WLL. METHODS: We retrospectively reviewed PAP patients from 1 January 2000 to 31 March 2020. Demographic data, pulmonary function tests, and the efficacy of WLL were collected from the electronic medical database and analyzed by descriptive analysis. Differences in data used the student t-test to compare parameters pre- and post-WLL. RESULTS: A total of 19 PAP patients and 50 WLL procedures were included. Eleven patients (57.9%) were females and the mean age was 51.5±11.7 years. Dyspnea (100%) and cough (94.7%) were the two leading symptoms. The most common indication for WLL was progressive dyspnea. There were significant improvements in SpO(2) from 86% to 94% (P

Lung transplantation is an established treatment for a variety of end-stage lung diseases; however, chest wall deformities such as an asymmetric pectus excavatum are often considered a contraindication for lung transplantation. Consequently, the published experience of lung transplants and simultaneous chest wall reconstruction is limited to a few case reports. This article aims to provide a detailed description of surgical steps as well as technical challenges and pitfalls of lung transplantation with a simultaneous modified Ravitch procedure. Exemplary technical aspects will be discussed for a pediatric patient in whom such a combined procedure resulted in an excellent outcome.

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 colony-stimulating factor antibody-positive) complicated with nocardiosis (periodic acid-Schiff-positive). After a 6 mo course of anti-infective treatment (sul-famethoxazole), the lesion was completely absorbed, such that only fibrous foci remained, and the patient exhibited significant symptom improvement. Follow-up 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, the potential for nocardiosis should be considered.

The subpleural sparing pattern is a common finding on computed tomography (CT) of the lungs. It comprises of pulmonary opacities sparing the lung peripheries, typically 1cm and less from the pleural surface. This finding has a variety of causes, including idiopathic, inflammatory, infectious, inhalational, cardiac, traumatic, and bleeding disorders. Specific disorders that can cause subpleural sparing patterns include nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), pulmonary alveolar proteinosis (PAP), diffuse alveolar hemorrhage (DAH), vaping-associated lung injury (VALI), cracked lung, pulmonary edema, pneumocystis jirovecii pneumonia (PJP), pulmonary contusion, and more recently, Coronavirus disease 2019 (COVID-19) pneumonia. Knowledge of the many etiologies of this pattern can be useful in preventing diagnostic errors. In addition, although the etiology of subpleural sparing pattern is frequently indistinguishable during an initial radiologic evaluation, the differences in location of opacities in the lungs, as well as the presence of additional radiologic findings, patient history, and clinical presentation, can often be useful to suggest the appropriate diagnosis. We did a comprehensive search on Pubmed and Google Scholar database using keywords of "subpleural sparing," "peripheral sparing," "sparing of peripheries," "CT chest," "chest imaging," and "pulmonary disease." This review aims to describe the primary differential diagnosis of subpleural sparing pattern seen on chest imaging with a strong emphasis on clinical and radiographic findings. We also discuss the pathogenesis and essential clues that are crucial to narrow the differential diagnosis.

Pulmonary alveolar proteinoisis (PAP) is a rare disease characterized by accumulation of proteinaceous material in the alveolar spaces. Here, we report a case of mild dyspnea with incidental ‘crazy-paving’ pattern on chest computed tomography (CT). Further evaluation and bronchoscopy found to have PAP.

Systemic onset juvenile arthritis is the complex autoinflammatory disease with multigenic type of inheritance. It is characterized by significant systemic manifestations and unfavourable adverse events, among which macrophage activation syndrome and pulmonary involvement are playing crucial role. This article presents data on the frequency and features of the disease course, possible development predictors and clinical-radiological picture of pulmonary involvement in systemic onset juvenile arthritis. Possible factors (including hereditary) affecting the process of pulmonary involvement development and the role of genetically engineered biologic therapy are considered.

Background Autoimmune pulmonary alveolar proteinosis (APAP) results from the suppression of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling by a neutralizing autoantibody against GM-CSF. B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in immunoglobulin G production and are overproduced in various autoimmune disorders. We hypothesized that BAFF and/or APRIL levels would be elevated in serum and bronchoalveolar lavage fluid (BALF) and serum and BALF levels of BAFF and APRIL respond to the treatments (whole lung lavage (WLL) or inhalation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF)) in patients with APAP. Subjects and methods BAFF and APRIL levels in serum and BALF from 110 patients with APAP were measured at baseline and during and after treatment, using an enzyme-linked immunosorbent assay kit. We enrolled 34 healthy volunteers as serum cytokine controls, and 13 disease controls for BALF. Associations of BAFF and APRIL levels with clinical measures were assessed to clarify their clinical roles. Results In patients with APAP, serum BAFF and APRIL levels were significantly increased relative to healthy volunteers (p Conclusions BAFF and APRIL levels of sera and BALF in APAP were significantly increased compared with healthy volunteer and disease control, and the BAFF and APRIL pathway might have important specific roles in pathogenesis of APAP. Our data suggest a new perspective of future treatment for APAP.

Pulmonary alveolar proteinosis (PAP) describes the accumulation of surfactant in the alveolar space. Secondary PAP has been reported in a variety of diseases, and in rare cases has been associated with hematologic malignancy. Treatment for PAP is based on the underlying disease process, and may include whole lung lavage, inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor, or statins. PAP secondary to hematologic malignancy has been reported to demonstrate poor response to whole lung lavage. We report a case of successful treatment of a pediatric patient with acute myeloid leukemia and secondary PAP using whole lung lavage.

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.

Occupational exposures are associated with a wide array of respiratory disorders that include asbestosis, coal workers’ pneumoconiosis and silicosis, asthma, COPD, bronchiolitis, hypersensitivity pneumonitis, pulmonary fibrosis, sarcoidosis, and certain infections. Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages. Autoimmunity is the most common etiology for PAP and involves autoantibodies targeting GM-CSF signaling. However, certain occupational and environmental inhalational exposures have been considered causative for PAP, although this constitutes a relative minority of the patients. The review article sheds light on the current knowledge of occupational/environmental respiratory exposures that can cause PAP. There is increased recognition of occupational respiratory exposures implicated in PAP. The role of silica exposure in causing PAP is well recognized and constitutes the most common etiology for occupational PAP. However, since its original description, several other agents have been identified that can trigger PAP in those exposed. Most recently, PAP has been described in a cohort of indium workers who produce indium-tin oxide (ITO), used to manufacture transparent conductive coating for flat panel displays such as liquid crystal displays (LCDs), touch screens, and solar cells. Some exposed workers with PAP have been found to have autoantibodies to GM-CSF. Besides silica, PAP is associated with a wide variety of vapors, gases, dusts, and fumes. In some patients with occupational exposure, it is possible that the offending agent may trigger autoimmunity against GM-CSF that can induce PAP. Patients with occupational PAP may have concomitant emphysema and/or pulmonary fibrosis. Depending on the degree of manifestations, treatment approach ranges from watchful monitoring to invasive modalities like whole lung lavage. Recognition of an occupational etiology for PAP has implication both for the patient and for co-workers, who may also be at risk. Physician reporting to regulatory and public health authorities can ensure that existing exposure limits and medical surveillance requirements, such as are in place for silica, are enforced and that novel or unregulated exposures are characterized.

Interstitial lung disease in children (chILD) is rare and encompasses more than 200 entities, with new especially genetic causes being discovered. Several classifications have been proposed, and there is considerable overlap with entities which present in adult life. Presentation may be shortly after birth with acute respiratory distress and in infancy and childhood either with a primary respiratory presentation or with systemic symptoms such as poor feeding and failure to thrive. Newborn acute presentations are usually due either to a mutation in one of the surfactant protein (Sp) genes or the alveolar capillary dysplasia (ACD)-congenital alveolar dysplasia (CAD) spectrum. The latter usually progress rapidly to extracorporeal membrane oxygenation, and early lung biopsy is advisable to prevent prolonged futile treatment being offered. Outside the newborn period, a staged protocol for investigation is proposed. This starts with a computed tomography scan, which confirms or otherwise the presence of chILD, and occasionally can lead to a specific diagnosis. In particular in settings where there is a high burden of infection, infective mimics of chILD need to be excluded. The next investigations aim to try to move from pattern recognition to specific diagnoses, both genetic and environmental. The speed of progression to lung biopsy will depend on the clinical state of the child, and the biopsy itself may suggest a hunt for a new underlying cause, such as immunodeficiency. Specific genetic causing chILD includes mutations in SpB and SpC and processing genes (thyroid transcription factor-1 [TTF-1] and adenosine triphosphate-binding cassette subfamily A) (the last three can present at any time in the life course); genes involved in Sp catabolism (granulocyte-macrophage colony factor receptor A and B genes), an increasing number implicated in the ACD-CAD spectrum, and other non-Sp related genes such as Filamin-A and integrin genes. Environmental causes are also important and vary across the world. Vaping has been implicated as causing a large number of chILDs, and a vaping history is essential in any young person with an unusual respiratory illness. Medications, both prescribed and over-the-counter such as oily laxatives, are also causes of chILD. There are important conditions of unknown cause presenting in early childhood. Neuroendocrine cell hyperplasia of infancy (NEHI) and pulmonary interstitial glycogenosis generally have a good prognosis, and are probably best considered as part of a spectrum of pulmonary dysmaturity syndromes, in some of which underlying gene mutations have been detected, for example, TTF-1 for NEHI. Pulmonary alveolar proteinosis is an example of an umbrella description, which may present at any age, and has a number of underlying causes with different specific treatments, underscoring the need to move from pattern recognition to specific diagnoses. chILDs have important implications for adult physicians; there may be late as yet poorly described sequelae of the disease or its treatment in adult life; there may be genetic implications for the wider family; and there may be late chILD relapses. Smooth transition to adult services is essential for all chILD survivors, with pediatric and adult chest physicians working closely together.

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that appears after the accumulation of lipoproteinaceous material in the alveoli. We aimed to compare the effects of using chest physiotherapy during a whole-lung lavage (WLL) to those without its use in a PAP case. A 33-year-old male patient with complaints of difficulty breathing, coughing, and dyspnea was admitted to the hospital. After the patient underwent a chest screening and diagnostic tests, WLLs were planned for his left and right lungs on separate days. Manual chest physiotherapy, including tapotement and vibration, was performed during the right WLL at the physician's request. Much more lipoproteinaceous material was visually detected in the saline collection bottles after the WLL using manual tapotement and vibration when compared to the WLL without tapotement and vibration. The improvement in the patient's clinical status was supported by chest X-ray and auscultation results.

The hereditary form of pulmonary alveolar proteinosis (PAP) is an uncommon entity. We report a case of PAP due to colony-stimulating factor 2 receptor alpha (CSF2RA) gene mutation. The standard of care includes whole lung lavage (WLL). We faced two challenges: Firstly, a severely hypoxemic patient, and secondly, the nonavailability of appropriate size of double-lumen endotracheal tube for pediatric patients for a WLL while permitting single-lung ventilation. Hence, we performed WLL using venovenous extracorporeal membrane oxygenation (VV ECMO) with a successful outcome. The patient has been discharged and is off oxygen support since more than a year. There are only a few case reports of children having hereditary PAP treated with WLL using ECMO in Indian and Western literature. How to cite this article Prabhudesai P, Khosla I, Kulkarni S, Arya MK, Pandey A, Yadav N. Bilateral Whole Lung Lavage in Hereditary Pulmonary Alveolar Proteinosis in a 4-year-old Child Using Extra corporeal Membrane Oxygenation. Indian J Crit Care Med 2021;25(9):1069–1072.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome, characterized by ground-glass opacities associated with reticulations giving a characteristic crazy paving appearance which is diagnostic but not pathognomonic in imaging. A 47-year-old male presented with breathlessness and dry cough. Arterial blood gas (ABG) showed hypoxemia and respiratory alkalosis with Alveolar- arterial (A-a) O2 gradient of 82. HRCT thorax suggestive of crazy paving pattern along with solitary nodules of low density in right upper and lower lobes giving suspicion of malignancy with secondary PAP. The clinical probability of malignancy was moderate hence surgical lung biopsy was performed which suggested PAP. Granulocytemacrophage colony-stimulating factor (GM-CSF) autoantibody concentration was 118.7mcg/ml suggestive of autoimmune PAP. Patient was treated with inhalational GM-CSF with significant clinical response ((A-a) O2 gradient improved to 24). Though crazy paving is characteristic for PAP, speculated low density atypical multi nodular appearance may also be possible which mandates biopsy for confirmation. Keywords: Fiber optic Bronchoscopy (FOB), Hypoxemia, Pulmonary alveolar proteinosis (PAP).

Introduction Pulmonary alveolar proteinosis (PAP) is a rare lung disease, characterized by abnormal alveolar accumulation of enlarged foamy macrophages and periodic acid-Schiff (PAS)-positive materials. Knowledge of the disease characteristics is still lacking. Objective To help clinicians gain a better understanding of this rare disease. Methods We undertook a retrospective analysis of 14 adult patients with PAP, treated in Zhongshan Hospital, Fudan University. Results Serum lactate dehydrogenase (LDH) was correlated with the arterial partial pressure of oxygen (PaO2) and diffusion capacity for carbon monoxide (DLCO). Transbronchial lung biopsy (TBLB) established a definitive diagnosis for a positive rate of 100%. The patients underwent whole lung lavage (WLL) and exhibited varying degrees of remission. The patients with mild symptoms received only supportive care and observation, and remained stable during follow-up. Conclusion LDH may correlate with disease severity. Bronchoscopy is sufficiently sensitive for a definite diagnosis. Conventional bilateral whole lung lavage proved a reliable treatment for indicated patients, but selective unilateral lung lavage or observation may be a rational choice in certain patients.

Background: Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited. Methods: The clinical course of two brothers with pathogenic variants in the methionyl-tRNA synthetase (MARS)1 gene was compared to previously published patients. Functional studies in patient-derived fibroblasts were performed and therapeutic options evaluated. Results: The younger brother was diagnosed with PAP at the age of 1 year. Exome sequencing revealed the homozygous MARS1 variant p.(Arg598Cys), leading to interstitial lung and liver disease (ILLD). At 2 years of age, following surgery hypoglycemia was detected, the pulmonary condition deteriorated, and the patient developed multiorgan failure. Six therapeutic whole lung lavages (WLL) were necessary to improve respiratory insufficiency. Methionine supplementation was started and a high protein diet ensured, leading to complete respiratory recovery. The older brother, homozygous for the same MARS1 variant, had a long-known distinct eating preference of methionine-rich food and showed a less severe clinical phenotype. Decreased aminoacylation activity confirmed the pathogenicity of p.(Arg598Cys) in vitro. In agreement with our review of currently published ILLD patients, the presence of hepatopathy, developmental delay, muscular hypotonia, and anemia support the multisystemic character of the disease. Conclusions: Catabolic events can provoke a severe deterioration of the pulmonary situation in ILLD with a need for repetitive WLL. Although the precise role of oral methionine supplementation and high protein intake are unknown, we observed an apparent treatment benefit, which needs to be evaluated systematically in controlled trials.