Management Of Pulmonary Alveolar Proteinosis Research Articles

European Respiratory Society guidelines for the diagnosis and management of pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP. A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations. The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy. The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.

One-session bilateral sequential whole lung lavage (OSBSWLL) for the management of pulmonary alveolar proteinosis

BackgroundWhole Lung Lavage (WLL) has been an important part in the management of Pulmonary Alveolar Proteinosis (PAP) since it improves radiologic and clinical parameters. Bilateral WLL is usually performed in two sessions on different days. Few case reports have described one-session bilateral sequential lung lavage (OSBSWLL), and none have described ambulatory management (same-day discharge).MethodsDemographic characteristics, physiologic parameters, procedure details and outcomes were retrospectively collected on consecutive patients who underwent OSBSWLL for PAP following an ambulatory protocol stablished in our institution.ResultsA total of 13 patients underwent 30 OSBSWLL (61.5% male; mean age 40). The mean SpO2 was 90% (IQR 9) and 94% (IQR 6), before and after OSBSWLL respectively. In 63.3% of cases, patients were discharged home the same day of procedure. Only in two cases (6.6%), patients required post-procedure prolonged mechanical ventilation (> 4 h) due to persistent hypoxia.ConclusionsOSBSWLL can be performed with same-day discharge.

How to do whole lung lavage for treatment of pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis is a rare condition characterized by progressive accumulation of surfactant lipoproteins in the alveolar space, leading to poor gas exchange. We describe our technique of whole lung lavage for management of pulmonary alveolar proteinosis.

The Clinical Clues of Pulmonary Alveolar Proteinosis: A Report of 11 Cases and Literature Review.

Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterized by the abnormal alveolar accumulation of surfactant components. The diagnosis of PAP can be easily missed since it is rare and lacks specific clinical symptoms. It is of great importance to have a better understanding of the crucial clue to clinically diagnose PAP and take PAP into consideration in the differential diagnosis of interstitial pulmonary diseases or other diseases with similar manifestations. Here, we analyze the clinical characteristics of 11 cases of PAP patients in local hospital and review the relevant literature in order to provide more information in diagnosis and management of PAP. In our observation, cyfra21-1 and neuron-specific enolase (NSE) known as tumor markers probably can be useful serum markers for diagnosis of PAP. As for the method of pathologic diagnosis, open-lung biopsy was the gold standard but now it is less required because findings on examination of bronchoalveolar lavage fluid (BALF) can help to make the diagnosis. We also have deep experience about when and how to carry out lung lavage.

Therapeutic Whole-Lung Lavage for Pulmonary Alveolar Proteinosis: A Procedural Update.

Pulmonary alveolar proteinosis is a disease caused by increased accumulation and impaired clearance of surfactant by alveolar macrophages. This narrative review summarizes the role of therapeutic whole-lung lavage in the management of pulmonary alveolar proteinosis. We describe the preprocedural evaluation, indications, and anesthetic considerations, along with step-by step technical aspects of the procedure, postoperative recovery, potential complications, and long-term outcomes.

Assessment and management of pulmonary alveolar proteinosis in a reference center

Pulmonary alveolar proteinosis (PAP) is a term defining an ultra-rare group of disorders characterised by a perturbation in surfactant homeostasis, resulting in its accumulation within airspaces and impaired gas transfer. In this report we provide data from a cohort of PAP patients (n = 81) followed for more than two decades at the San Matteo University Hospital of Pavia, Italy. In agreement with other large series in PAP individuals, 90% of the study subjects were affected by autoimmune/idiopathic PAP, while the remaining subjects were divided as follow: congenital 1%, secondary 4% and PAP-like 5%. The disease affected males and females with a ratio of 2:1 and approximately one third of PAP patients were lifelong nonsmokers. Occupational exposure was reported in 35% of subjects in this series. With reference to the PAP clinical course, in 29 patients (7% with spontaneous remission) disease severity did not necessitate whole lung lavage (WLL) in the long-term follow up. On the other hand, 44 PAP patients underwent therapeutic WLL: in 31 subjects a single WLL was sufficient to provide long term, durable benefit, whereas 13 patients required multiple WLLs. The intra-patient mean interval between two consecutive WLLs was 15.7 ± 13.6 months. When baseline data among never lavaged and PAP patients lavaged at least once were compared, the need for lavage was significantly associated with serum biomarkers (CEA, Cyfra, LDH), lung function parameters forced vital capacity (FVC), and lung diffusing capacity (Dlco). We conclude that patient cohorts with an ultra-rare disease, such as PAP, referred to a single reference center, can provide useful information on the natural history and clinical course of the disease.

Anaesthetic, Procedure and Complications Management of Serial Whole-Lung Lavage in an Obese Patient with Pulmonary Alveolar Proteinosis: Case Report

The first case of Pulmonary Alveolar Proteinosis (PAP) was described by Rose in 1958, but it is still a rare disorder. PAP is characterized by deposition of lipoproteinaceous material secondary to abnormal processing of surfactant by macrophages. Patients may suffer from progressive dyspnea and cough that at times is accompanied by worsening hypoxia and its course can vary from progressive deterioration to spontaneous improvement. Many therapies have been used to treat PAP including antibiotics, postural drainage, and intermittent positive pressure breathing with aerosolized Acetylcysteine, heparin and saline. At present, the mainstay of treatment is whole lung lavage (WLL). Although generally well tolerated, WLL can be associated with some complications. We report a case of severe PAP through the anaesthetic, procedure and complications management of pulmonary alveolar proteinosis in one patient who has undergone multiple, alternating, single-lung lavages over the past seven years, the last three in our hospital, with improvements in her symptoms following each therapy.

Pulmonary Alveolar Proteinosis

Abstract: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant phospholipids and proteins in the alveoli (Trapnell et al, N Engl J Med. 2003;349:2527–2539). Less than 500 separate cases of PAP have been reported in the literature from the time of first description in 1958. These reports suggest an annual incidence of 0.36 and prevalence of 3.7 cases per million population (Seymour et al, Am J Respir Crit Care Med. 2002;166:215–235). The clinical course of PAP ranges from spontaneous resolution to death because of superimposed infection or respiratory failure. A number of important milestones mark the key advances in the study of this disease, which have led to an improved classification based on pathogenesis. In the last decade, the serendipitous finding of a lung disease reminiscent of PAP in transgenic granulocyte-macrophage colony-stimulating factor knockout mice (GM-CSF−/−) led to the link between GM-CSF and PAP (Dranoff et al. Science. 1994;264:713–716; Stanley et al. Proc Natl Acad Sci USA. 1994;91:5592–5596). The finding of neutralizing antibodies to GM-CSF suggest an autoimmune basis to idiopathic PAP (Kitamura et al. J Exp Med. 1999;190:875–880). These findings have resulted in innovative treatment approaches to enhance the current standard of care. This review summarizes some of these landmark studies and provides a rationale and plan for investigations that lead to the diagnosis, classification, and management of PAP.

Management of Pulmonary Alveolar Proteinosis by Repeated Bronchoalveolar Lavage

Pulmonary alveolar proteinosis is a rare disease of the lung in which excessive thick granular phospholipoproteinaceous material accumulates within the air spaces. Many patients with this disease suffer from progressive dyspnea and cough that at times is accompanied by worsening hypoxia. At present, the only effective treatment is bronchoalveolar lavage, first described by Ramirez in 1963 (1). Presumably, this therapy is effective because it washes the proteinaceous debris from the airways and alveolar spaces. This case report describes the management of pulmonary alveolar proteinosis in 1 patient, who has undergone multiple, alternating, single-lung lavages over the past 10 years, with dramatic improvements in her symptoms following each therapy. We believe this to be the longest reported treatment of pulmonary alveolar proteinosis with repetitive bronchoalveolar lavage.