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Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal surfactant accumulation in peripheral air spaces. Autoimmune PAP (APAP) results from macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and the presence of antibodies more than the cutoff value is specific for APAP. In contrast, secondary PAP (SPAP) does not require anti-GM-CSF autoantibodies and is complicated by other diseases, including myelodysplastic syndrome (MDS). A 73-year-old man with anemia and thrombocytopenia was diagnosed with APAP and MDS simultaneously. The measurement of serum anti-GM-CSF autoantibodies is important for the correct diagnosis and management of PAP, even with an established diagnosis of underlying SPAP-suggestive disease.

Background: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny., Case Presentation: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal., Conclusions: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind., (© 2024. The Author(s).)

Background: Pulmonary alveolar proteinosis is a very rare diffuse lung disease characterized by the accumulation of amorphous and periodic acid Schiff-positive lipoproteinaceous material in the alveolar spaces due to impaired surfactant clearance by alveolar macrophages. Three main types were identified: Autoimmune, secondary and congenital. Pulmonary alveolar proteinosis has been previously reported to be associated with several systemic auto-immune diseases. Accordingly, we present the first case report of pulmonary alveolar proteinosis associated with myasthenia gravis. Case: A 27-year-old female patient, ex-smoker, developed a dyspnea on exertion in 2020. The chest X-ray detected diffuse symmetric alveolar opacities. Pulmonary infection was ruled out, particularly COVID-19 infection. The chest scan revealed the "crazy paving" pattern. The bronchoalveolar lavage showed a rosy liquid with granular acellular eosinophilic material Periodic acid-Schiff positive. According to the lung biopsy results, she was diagnosed with pulmonary alveolar proteinosis. The granulocyte macrophage colony-stimulating factor autoantibodies were negative. Nine months later, she was diagnosed with bulbar seronegative myasthenia gravis, confirmed with the electroneuromyography with repetitive nerve stimulation showing significant amplitude decrement of the trapezius and spinal muscles. She was treated with pyridostigmine, oral corticosteroids and azathioprine. Given the worsening respiratory condition of the patient, a bilateral whole lung lavage was performed with a partial resolution of symptoms. Thus, this previously unreported association was treated successfully with rituximab, including improvement of dyspnea, diplopia and muscle fatigability at six months of follow-up. Conclusions: This case emphasizes on the possible association of auto-immune disease to PAP, which could worsen the disease course, as the specific treatment does not exist yet. Hence, further studies are needed to establish clear-cut guidelines for PAP management, particularly when associated to auto-immune diseases., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Mejri I et al.)

Background: To analyze the clinical data and next generation sequencing (NGS) results from a child with 22q11.2 deletion syndrome (22q11DS) complicated with pulmonary alveolar proteinosis (PAP) who was admitted to the Department of Pediatrics of Fuyang People's Hospital and to present a review of the literature., Case Presentation: A 9-year-old male child, whose face had a small mandible and high-arched palate, but lacked a cleft palate, had repeated respiratory tract infections and bronchiectasis. Clinical examination, computer tomography, and electronic bronchoscopy were performed. Genetic testing via NGS was undertaken. PAP was confirmed by Periodic Acid Schiff staining of milky white alveolar lavage fluid isolated by electronic bronchoscopy. A deletion of approximately 2.46 Mbp on chromosome 22q11.2 was confirmed by NGS. During hospitalization, anti-infection, nebulization, alveolar lavage, and regular application of thymosin were administered to the patient. The condition of the patient stabilized following treatment., Conclusions: 22q11DS and PAP are both rare diseases, and the manifestation of 22q11DS combined with PAP has not been previously reported. The diagnosis and treatment of this case will be a reference for future clinical work.

A 61-year-old patient with cystic bronchiectasis and bronchial artery hyperplasia in the left lung was diagnosed with polymyositis-related interstitial lung disease. After nine months of immunosuppressive therapy, he developed unilateral autoimmune pulmonary alveolar proteinosis (APAP) in the right lung with respiratory failure. After bronchial artery embolization to prevent massive hemoptysis, whole-lung lavage was performed using veno-venous extracorporeal membrane oxygenation. His respiratory condition improved, and he was discharged from the hospital with supplemental oxygen. Three reported cases of APAP with polymyositis-related interstitial lung disease, including the present case, were all positive for anti-glycyl tRNA synthetase antibody and were under immunosuppressive treatment.

Pulmonary Alveolar Proteinosis (PAP) is a rare, usually autoimmune, disease, where surfactant accumulates within alveoli due to decreased clearance, causing dyspnea and hypoxemia. The disease is even more rare in pregnancy; nevertheless, it has been reported in pregnant women and can even appear for the first time during pregnancy as an asthma-like illness. Therefore, awareness is important. Similarly to many autoimmune diseases, it can worsen during pregnancy and postpartum, causing maternal and fetal/neonatal complications. This paper offers a narrative literature review of PAP and pregnancy, while illustrating a case of a pregnant patient with known PAP who developed preeclampsia in the third trimester but had an overall fortunate maternal and neonatal outcome.

Background: Gastrointestinal lesions, which sometimes develop in Behçet's disease (BD), are referred to as intestinal BD. Although rare, intestinal BD can be accompanied by myelodysplastic syndrome (MDS) with abnormal karyotype trisomy 8, which is refractory to immunosuppressive therapy. Pulmonary alveolar proteinosis is a rare lung complication of BD and MDS. Herein, we present an extremely rare case of intestinal BD presenting with MDS and several chromosomal abnormalities, followed by secondary pulmonary proteinosis., Case Presentation: A 58-year-old Japanese woman with a 3-year history of genital ulcers and oral aphthae was admitted to our hospital. The patient developed abdominal pain and persistent diarrhea. Colonoscopy revealed multiple, round, punched-out ulcers from the terminal ileum to the descending colon. Intestinal BD was diagnosed and the patient was treated with colchicine, prednisolone, and adalimumab. However, her symptoms were unstable. Bone marrow examination to investigate the persistent macrocytic anemia revealed the presence of trisomy 8, trisomy 9, and X chromosome abnormalities (48, + 8, + 9, X, i(X) (q10) in 12 out of the examined 20 cells). Based on her hypoplastic bone marrow, the patient was diagnosed with low-risk MDS (refractory anemia). At the age of 61, the patient developed pneumonia with fever and diffuse ground-glass opacities on the lung computed tomography (CT). Chest high-resolution CT and histopathology via transbronchial lung biopsy revealed the presence of pulmonary alveolar proteinosis (PAP). These findings combined with the underlying disease led to the diagnosis of secondary PAP., Conclusions: Secondary pulmonary proteinosis may accompany intestinal BD with MDS and several chromosomal abnormalities. Physicians should pay attention to lung complications, such as PAP, in patients with intestinal BD complicated by MDS. Genetic abnormalities may be associated with the development of such diseases., (© 2021. The Author(s).)

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., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Autoantibodies to multiple cytokines have been identified and some, including antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), have been associated with increased susceptibility to infection. High levels of GM-CSF autoantibodies that neutralize signaling cause autoimmune pulmonary alveolar proteinosis (aPAP), an ultrarare autoimmune disease characterized by accumulation of excess surfactant in the alveoli, leading to pulmonary insufficiency. Defective GM-CSF signaling leads to functional deficits in multiple cell types, including macrophages and neutrophils, with impaired phagocytosis and host immune responses against pulmonary and systemic infections. In this article, we review the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis along with the increased incidence of infections (particularly opportunistic infections). Therefore, recombinant human GM-CSF products may have potential for treatment of aPAP and possibly other infectious and pulmonary diseases due to its pleotropic immunomodulatory actions., Competing Interests: AA serves on the Medical and Scientific Advisory Board of the PAP Foundation. VK received support for attending workshops, meetings, and education in leadership roles for Workshop in Primary Immunodeficiencies, College of American Pathologists, and Clinical Immunology Society, and served as President/Past President of the Association of Medical Laboratory Immunologists. BCC’s institution received an NIH-funded R01 grant related to the content of the manuscript. Outside of the current work, BC is a consultant to Partner Therapeutics, Inc. and serves on the Board of Directors and as Secretary/Treasurer of the PAP Foundation. EL’s institution received NIH-funded grants related to the content of the manuscript. EL has served as a consultant to Guidepoint Global and has received travel support from the PAP Foundation and the Rare Lung Disease Consortium. TW’s institution received a fellowship grant funded by Partner Therapeutics, Inc. TW received consultant fees from Partner Therapeutics for research outside of the current work; participated on an Advisory Board for IQVIA; and serves on the Board of Directors, Medical and Scientific Advisory Board, and as Vice President and Clinical Director of the PAP Foundation. The authors declare this study received funding from Partner Therapeutics, Inc. The funder had the following involvement with the study: Professional medical writing, graphic artist, and publication fees for this manuscript. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ataya, Knight, Carey, Lee, Tarling and Wang.)

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction due to anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. We experienced 2 cases of APAP complicated with sarcoidosis in a 42-year-old woman and a 51-year-old man (age at the sarcoidosis diagnosis). APAP preceded sarcoidosis in the woman, and both diseases were diagnosed simultaneously in the man. Sarcoidosis lesions were observed in the lung, skin, and eyes, and the pathological findings of APAP were not marked at the diagnosis of sarcoidosis in either case. Low-grade positive serum anti-GM-CSF autoantibody was suspected to be correlated with the occurrence of sarcoidosis and resolution of APAP.

Idiopathic hypoparathyroidism (IH) and autoimmune pulmonary alveolar proteinosis (PAP) are rare disorders. A patient with IH and optimal calcaemic control on calcium and alfacalcidol was detected to have PAP after 8 years of follow-up. Patient had no respiratory complaints. Routine abdominal imaging for renal calcification showed patchy ground glass opacities in the lower lung fields leading to incidental diagnosis of PAP. Pulmonary function tests showed impaired diffusion capacity of the lung. Anti-granulocyte macrophage-colony stimulating factor autoantibodies were positive. Patient regularly attended the pulmonary clinic and showed progressive improvement in diffusion capacity of the lung during 2 years of follow-up. The calcaemic control in IH remained stable despite its presence with PAP. The autoimmune PAP in the presented case suggests a possible autoimmune basis of IH., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Myelodysplastic syndrome (MDS) is frequently complicated by pulmonary disease. Here, we describe secondary pulmonary alveolar proteinosis (sPAP) that developed during corticosteroid therapy for organising pneumonia (OP) associated with MDS. A 75-year-old woman with MDS complained of cough for 2 weeks. Chest CT showed bilateral patchy consolidations with reversed halo sign. Bronchoalveolar lavage (BAL) examination showed remarkably increased cell density with an increased lymphocyte proportion. Abnormal radiological findings improved rapidly on administration of systemic corticosteroid under the diagnosis of OP; however, they relapsed a few weeks later. Transbronchial lung biopsy showed periodic acid-Schiff stain-positive amorphous materials. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum and BAL fluid (BALF) were both negative, while GM-CSF level in BALF was elevated. The patient was diagnosed with sPAP. When chest radiological findings show exacerbation during corticosteroid therapy for OP in a patient with MDS, physicians should consider sPAP complication as a differential diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The  methionyl-tRNA  synthetase  (MARS)  mutation is  a  very  rare  cause  of  congenital  pulmonary  alveolar proteinosis.We report a 6-month-old boy born with symmetrical intrauterine growth retardation presented with unexplained persistent tachypnea and hypoxemia associated with severe failure to thrive, anemia, hypoalbuminemia and hepatomegaly. Detailed pulmonary investigations including computed tomography chest scan, bronchoscopy and bronchoalveolar lavage revealed pulmonary alveolar proteinosis. Whole exome sequencing identified a homozygous novel variant in the MARS gene, c.854T>C p.(Ile285Thr).

A 65-year-old Japanese man was referred to our hospital for the further assessment of cough and dyspnea. He had a history of ulcerative colitis for which he was receiving treatment. Chest computed tomography showed a crazy-paving pattern. His bronchoalveolar lavage fluid had a milky appearance, and a transbronchial lung biopsy specimen revealed acellular periodic acid-Schiff stain-positive bodies. The serum anti-granulocyte macrophage-colony stimulating factor (GM-CSF) antibody titer was elevated. The diagnosis was autoimmune pulmonary alveolar proteinosis (PAP). There are few reports of autoimmune PAP in patients with ulcerative colitis. Some reports suggest that PAP and inflammatory bowel disease might have a common pathogenesis involving the anti-GM-CSF antibody.

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterised by the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies. A man with no history of infection developed cryptococcal meningitis and a right parahilar cryptococcal mass. Antifungal treatment led to infection control, although there was presence of neurological sequelae. After 3 years, thoracic CT revealed bilateral ground glass opacities and a crazy paving pattern. Transparietal needle biopsy showed proteinaceous alveolar deposits, confirming the diagnosis of PAP. A high titre of serum anti-GM-CSF autoantibodies was found. No specific treatment was started, and radiological lesions decreased progressively. Cryptococcal infection may occur in PAP and in patients with anti-GM-CSF antibodies without PAP. These antibodies dysregulate phagocytosis in monocytes and macrophages, possibly leading to opportunistic infections in previously healthy subjects., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2,'5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Aim: Precise clinical significance of antigranulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar proteinosis (aPAP) has not been well studied., Methods: We obtained sera from 50 healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP patients was assessed by scoring computed tomography images in 19 patients., Results: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and other diffuse lung diseases was 2.8 μg/ml with 100% sensitivity and 98% specificity. Antibody levels at baseline were significantly lower in the improved group than in the unimproved group (p = 0.008)., Conclusion: Our results indicate the existence of threshold levels of serum anti-GM-CSF IgG for the development and persistence of aPAP.

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stain-positive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynaud's phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.

We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Infection with multiple pathogens concurrently has become less common since the introduction of potent antiretroviral agent and effective prophylactic agents. We describe a patient with pulmonary alveolar proteinosis (PAP) admitted with pneumonia who was found to have AIDS and diagnosed with Pneumocystis jiroveci pneumonia, human herpesvirus type 1 (HHV-1), and a concomitant cytomegalovirus viremia. Polymerase chain reaction viral load was used for diagnosis of HHV-1 and follow-up. The patient was treated with trimethoprim-sulfamethoxazole and ganciclovir and had a resolution of pneumonia. Since patients with PAP who are diagnosed as having AIDS could be concomitantly infected with multiple pathogens, rapid accurate diagnosis and treatment may have a positive effect on outcome.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease where periodic acid Schiff (PAS)-positive eosinophilic material accumulates in the alveoli of the lungs. Here we describe two cases of young males who presented with dynpnoea and weight loss. The HRCT scan of the chest in both cases showed the typical "crazy-paving" pattern and lung biopsies confirmed the diagnosis of PAP. They showed remarkable symptomatic improvement with therapeutic whole lung lavage.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease in the pediatric population. There are currently few cases documenting hemophagocytic lymphohistiocytosis as a cause for secondary PAP. We describe an ex-preterm child with secondary hemophagocytic lymphohistiocytosis, complicated by PAP and hypoxemic respiratory failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 39-year-old man treated with dasatinib for chronic myelogenous leukaemia presented to our hospital with haemoptysis, coughing, and dyspnoea. Chest radiography and computed tomography revealed ground-glass opacities and a crazy-paving pattern. Bronchoalveolar lavage was not performed due to serious hypoxemia and bleeding. Significant bleeding from the peripheral bronchi led to a diagnosis of an alveolar haemorrhage. Dasatinib-induced alveolar haemorrhaging was suspected based on the clinical findings. His condition improved immediately after dasatinib withdrawal and initiation of steroid therapy. Reports of alveolar haemorrhaging induced by dasatinib are rare. As such, this is considered an important case.

Background: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease., Objectives: The aim of this study was to assess the efficacy of WLL in patients with PAP., Methods: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure., Results: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before., Conclusions: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed., (© 2017 S. Karger AG, Basel.)

Pulmonary alveolar proteinosis (PAP) is classified as autoimmune, secondary, or genetic. We herein describe a 69-year-old man with autoimmune PAP, simultaneously diagnosed with myeloproliferative neoplasm (MPN). Two years after the diagnosis, the MPN progressed to acute myeloid leukemia, and the patient died from an alveolar hemorrhage during remission induction chemotherapy. Throughout the clinical course, no progression of PAP was observed, despite the progression to leukemia. There are few reports of autoimmune PAP with hematological malignancy, and this case demonstrated that an evaluation for GM-CSF autoantibodies is important for distinguishing the autoimmune and secondary forms of PAP, even if the patient has hematological malignancy.

Introduction: Congenital surfactant deficiency is a condition infrequently diagnosed in newborns. A clinical case is presented of surfactant protein B deficiency. A review is performed on the study, treatment and differential diagnosis of surfactant protein deficiencies and infant chronic interstitial lung disease., Case Report: The case is presented of a term newborn that developed respiratory distress, recurrent pulmonary opacification, and a transient response to the administration of surfactant. Immunohistochemical and genetic studies confirmed the diagnosis of surfactant protein B deficiency., Conclusions: Pulmonary congenital anomalies require a high index of suspicion. Surfactant protein B deficiency is clinically progressive and fatal in the majority of the cases, similar to that of ATP binding cassette subfamily A member 3 (ABCA3) deficiency. Protein C deficiency is insidious and may present with a radiological pulmonary interstitial pattern. Due to the similarity in the histological pattern, genetic studies help to achieve greater certainty in the prognosis and the possibility of providing adequate genetic counselling., (Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The CT findings of pulmonary fibrosis in patients with pulmonary alveolar proteinosis (PAP) are not yet well defined. The objective of this study was to evaluate the CT findings of PAP with a focus on pulmonary fibrosis secondary to PAP., Materials and Methods: High-resolution CT (HRCT) scans of 44 patients with PAP were evaluated retrospectively with a focus on pulmonary fibrosis: 33 patients had autoimmune PAP, and 11 patients had secondary PAP. The intervals between the initial and last CT examinations ranged from 1 to 284 months (median, 60 months). The HRCT images were assessed by two chest radiologists independently; when the two radiologists disagreed, a final decision was made by consensus., Results: A crazy-paving pattern was a more common HRCT finding in patients with autoimmune PAP than in those with secondary PAP. Traction bronchiectasis was found in four patients (9%) on the initial scans and in 10 patients (23%) on the last scans. There was no honeycombing on the initial scans. Honeycombing developed in two patients (5%): It was detected on 2-year follow-up in one patient and on 6-year follow-up in the other patient. Among the patients with autoimmune PAP, those with fibrosis detected on HRCT during follow-up had a worse prognosis than those without fibrosis detected on HRCT (p = 0.041)., Conclusion: Fibrosis develops in approximately 20% of patients with PAP. The CT findings of parenchymal fibrosis suggest a poor outcome.

Alveolar proteinosis is a rare chronic lung disease, especially in children, characterized by abnormal accumulation of lipoproteins and derived surfactant in the intra-alveolar space that generates a severe reduction of gas exchange. Idiopathic presentation form constitutes over 90% of cases, a phenomenon associated with production of autoimmune antibodies directed at the receptor for granulocyte-macrophage colony-stimulating factor. A case of a girl of 5 years of age treated because of atypical pneumonia with unfavorable evolution due to persistent hypoxemia is presented. The diagnosis is obtained through pathologic examination of lung biopsy by thoracotomy, as treatment is carried out by 17bronchopulmonary bronchoscopy lavages and the patient evidences marked clinical improvement., (Sociedad Argentina de Pediatría.)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by alveolar accumulation of surfactant lipids and proteins. It is usually autoimmune and secondary to hematologic malignancy or infection. To date, only 5 case reports of PAP associated with lung cancers, including 2 cases of squamous cell carcinoma and 3 cases of adenocarcinoma, have been published. To the best of our knowledge, no case of PAP with small cell lung carcinoma has been reported thus far. We herein report the first case of PAP associated with small cell lung carcinoma., (© The Author(s) 2015.)

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies.

Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by dysfunctional alveolar macrophages, which ineffectively clear surfactant and typically cause mild hypoxemia. Characteristic Computed Tomography findings are septal reticulations superimposed on ground-glass opacities in a crazy paving pattern, with a clear juxtaposition between affected and unaffected parenchyma. While traditionally PAP was diagnosed via biopsy, bronchoalveolar lavage (BAL) is usually sufficient; the fluid appears milky, and on microscopic examination there are foamy macrophages with eosinophilic granules and extracellular hyaline material that is Periodic Acid-Schiff positive. Standard therapy is whole lung lavage (WLL), although novel treatments are under development. The case presented is a 55-year-old woman with six months of progressive dyspnea, who developed hypoxemic respiratory failure requiring mechanical ventilation; she had typical findings of PAP on imaging and BAL. WLL was ultimately successful in restoring adequate oxygenation. Respiratory failure of this magnitude is a rare finding in PAP.

Here, we describe a case of total anomalous pulmonary venous return with coarctation of the aorta that was diagnosed as pulmonary alveolar proteinosis at autopsy in a male infant. Surgical repair was performed at 1 day of age, but the infant died on postoperative day 51 due to respiratory insufficiency without any evidence of pulmonary venous obstruction. He had been unexpectedly diagnosed with pulmonary alveolar proteinosis and pulmonary hypoplasia on autopsy. Congenital pulmonary alveolar proteinosis is a serious condition with a high mortality rate, which should be considered in the differential diagnosis in patients with a clinical picture of pulmonary venous obstruction, because most patients are unable to survive without proper treatment. In this report, we address specific issues that should be discussed in such cases based on our recent experience., (© 2015 Japan Pediatric Society.)

Pediatric patients with pulmonary alveolar proteinosis require whole lung lavage to clear the accumulation of lipoproteinaceous material within the alveoli, to maintain respiratory function. Anesthesia for this presents a challenge due to preexisting respiratory failure, and the small diameter and length of the pediatric airway, which is often unable to accommodate existing one-lung isolation and ventilation equipment. Novel techniques to facilitate lung lavage on seven occasions are described and placed in the context of the existing literature to date., (© 2015 John Wiley & Sons Ltd.)

A 25-year-old woman, a never smoker with a history of heart-lung transplantation for World Health Organization group 1 pulmonary arterial hypertension performed 20 months prior to presentation, was evaluated for shortness of breath. Following transplantation, she was initiated on standard therapy of prednisone, tacrolimus, and azathioprine, along with routine antimicrobial prophylaxis. Her posttransplant course was complicated by persistent acute cellular rejection, as determined from a transbronchial biopsy specimen, without evidence of rejection in an endomyocardial biopsy specimen. The immunosuppressive medications were supplemented with pulse-dosed steroids, and the patient was transitioned from azathioprine to mycophenolate mofetil. Sirolimus was added 9 months prior to presentation. Three months prior to presentation, she was admitted for increasing oxygen requirements, shortness of breath, and bilateral infiltrates on the CT scans of the chest.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease caused by the autoantibody against granulocyte-macrophage colony stimulating factor (GM-CSF). The clinical course of aPAP is variable; in severe cases, patients develop lethal respiratory failure due to pulmonary fibrosis. However, the pathogenesis of pulmonary fibrosis in aPAP has never been delineated., Case Presentation: Here, we describe a rare case of aPAP that was subsequently complicated by microscopic polyangiitis-related pulmonary fibrosis. The patient was a 75-year-old Japanese man diagnosed with aPAP based on the crazy-paving appearance on high-resolution computed tomography (HRCT), "milky" appearance of broncho-alveolar lavage fluid (BALF), and elevated serum levels of the anti-GM-CSF antibody. The patient was followed-up without aPAP-specific treatment for 3 years. During this period, both hematuria and proteinuria appeared; in addition, serum myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) turned positive and increased markedly. The second BAL performed one year after the diagnosis, showed that the "milky" appearance had resolved. The HRCT showed that fibrotic changes had developed and that the crazy-paving appearance had disappeared. These data suggest an association between pulmonary fibrosis that developed during the natural course of aPAP and ANCA-related systemic vasculitis., Conclusion: This is the first case report that suggests the existence of a pathogenetic relationship between ANCA-associated systemic vasculitis and aPAP-related pulmonary fibrosis. The link between ANCA-associated systemic vasculitis and aPAP-related pulmonary fibrosis requires further investigation.