2012;135: 223-235. Correlations with reticulation are less unequivocal and could correspond to interstitial disease (lipoproteinaceous interstitial accumulation, inflammation or oedema) or lipoproteinaceous alveolar accumulation on the edges of the … Additional testing for serum anti-GM-CSF antibodies are helpful for confirmation. Patients with minimal symptoms are managed conservatively, whereas patients with hypoxemia require a more aggressive approach. Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, Epaud R, Crestani B. Eur Respir Rev. Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Rare secondary forms occur in patients with acute silicosis , Pneumocystis jirovecii infection , hematologic cancers, or immunosuppression by drugs and in patients with significant inhalation exposures to aluminum, titanium, cement, and cellulose dusts. [citation needed], The abnormal accumulation of lipoproteinaceous compounds in PAP is due to impaired surfactant regulation and clearance. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by an abnormal accumulation of surfactant-derived lipoprotein compounds within the alveoli of the lung. Novel insights from an animal model aided the discovery of granulocyte macrophage colony stimulating factor (GM-CSF) antibodies as a pathogenetic mechanism in human pulmonary alveolar proteinosis. It results in restrictive lung function and responds well to therapeutic lavage. REVIEW: PULMONARY ALVEOLAR PROTEINOSIS c EUROPEAN RESPIRATORY REVIEW VOLUME 20 NUMBER 120 99. alveolar accumulation. It is the most common form (90% of the cases) of pulmonary alveolar proteinosis (PAP). J Bras Pneumol. Pulmonary alveolar proteinosis is a rare condition that occurs when surfactant builds up in your lungs and clogs your air sacs. and is indeed rare disease with a prevalence of 0.1 per 100,000 individuals. GATA2 mutation-based pulmonary alveolar proteinosis is associated with normal levels of GM-CSF and commonly improves or is avoided in afflicted individuals who successfully receive a hematopoietic stem cell transplantation. [4], The implications of this finding are still being explored, but significant progress was reported in February 2007. Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Pulmonary alveolar proteinosis Pulmonary alveolar proteinosis is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component.  |  Ioachimescu OC, Kavuru MS. (2006) Pulmonary alveolar proteinosis. [3] Ben-Dov I, Segel M. Autoimmune pulmonary alveolar proteinosis: Clinical course and diagnostic criteria. Although primarily affecting people 30 to 50 years old, PAP can occur at any age. Fatal alveolar proteinosis in a child is reported in Case 18, and the lesions observed at autopsy were typical. According to various pathogenetic mechanisms and aetiologies, PAP is classified as primary, secondary or congenital. Pulmonary alveolar proteinosis (PAP) is a rare respiratory syndrome characterised by the accumulation of surfactant lipoproteins within the alveoli. [29], PAP is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium (RLDC). Crazy-paving appearance in a geographic distribution is a characteristic feature of this disease visible on high-resolution computed tomography (CT). Pulmonary alveolar proteinosis (PAP) was first described in 1958 by Samuel H. Rosen et al.. [14] An alternative diagnosis with similar histomorphologic findings is Pneumocystis jirovicii pneumonia. As the knowledge about this rare disease increases, the role of novel therapies is likely to be better defined and optimized. Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. The accumulated substances interfere with the normal gas exchangeand expansion of the lungs, ultimately leading to difficulty breathing and a predisposition to developing lung infections. The vast majority of pulmonary alveolar proteinosis occurs as an autoimmune disease; less commonly, it is congenital or secondary to an underlying disorder such as infection, hematological malignancy, or immunodeficiency. The gene for the CSF2 receptor alpha is located in the 5q31 region of chromosome 5, and the gene product can also be referred to as granulocyte macrophage colony-stimulating factor receptor. pulmonary alveolar proteinosis are dysfunctional, and, in particular, 6nding of decreased phagolysosome fusion may be related to the high incidence of uncommon infec-tions in these patients. Diagnosis of PAP is initiated by computed tomography (CT) scan and confirmed by staining of bronchoalveolar lavage fluid (BALF). The combination of a systemic treatment (GM-CSF) and a local treatment (whole-lung lavage) augmenting the action of one another is a promising new approach. [3], Although the cause of PAP was not originally understood, a major breakthrough in the understanding of the cause of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP. Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of a lipoproteinaceous substance in the distal air spaces which positively stains with periodic acid-Schiff (PAS). There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. [5], Familial or sporadic inactivating mutations in one of the two parental GATA2 genes produces an autosomal dominant disorder termed GATA2 deficiency. The RLDC is dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the National Institutes of Health, patient organizations and clinical investigators. Bonfield TL, Russell D, Burgess S, Malur A, Kavuru MS, Thomassen MJ. [8][9], The diagnosis of PAP is made using a combination of a person's symptoms, chest imaging, and microscopic evaluation of lung washing/tissue. We have shown that different fractions of alveolar 6lling material from patients with pulmonary alveolar proteinosis have unique effects on the phagocytic process in the normal … Individuals with PAP are more vulnerable to lung infections such as bacterial pneumonia, mycobacterium avium-intracellulare infection, or a fungal infection. Pulmonary alveolar proteinosis (PAP) is a lung disorder which was first described in 1958 by Rosen et al. Please enable it to take advantage of the complete set of features! NLM This is usually related to impaired alveolar macrophage function. Pulmonary Alveolar Proteinosis (PAP), first described by Rosen and Castleman in 1958, is a rare syndrome characterized by the intra-alveolar accumulation of surfactant lipids and proteins, leading to impaired gas-exchange and resulting in progressive respiratory insufficiency. Primary PAP is led by a granulocyte– macrophage colony-stimulating factor (GM-CSF) signalling disruption; … Elle peut être aussi secondaire à certains cancers, infections ou toxiques. For example, chest x-ray may show alveolar opacities, and a CT may show a crazy paving lung pattern, both of which are seen more commonly in numerous other conditions. The RLDC is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), of the National Center for Advancing Translational Sciences (NCATS). Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. 1. [10], Although both the symptoms and imaging findings are stereotypical and well-described, they are non-specific and indistinguishable from many other conditions. Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages due to abnormal surfactant homoeostasis. Autoantibodies against granulocyte macrophage colony-stimulating factor are diagnostic for pulmonary alveolar proteinosis. Pulmonary alveolar proteinosis PAP is an ultra-rare disease in which surfactant components, that impair gas exchange, accumulate in the alveolae. [4] Carey B, Trapnell BC. Most cases affect adults between the ages of 20-50 years. HHS Pulmonary alveolar proteinosis can be understood as a syndrome of altered surfactant homeostasis, leading to a pathologic accumulation of surfactant. [11] Thus, the diagnosis primarily depends on the pathology findings. Prakash UBS ; Barham SS ; Carpenter HA ; et al.  |  The molecular basis of pulmonary alveolar proteinosis. The causes of PAP may be grouped into primary (autoimmune PAP, hereditary PAP), secondary (mul… Since that time, clinicians' understanding of this rare lung disease has improved dramatically. Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. ORPHA:747 Classification level: Disorder. Pulmonary alveolar proteinosis (PAP) is a rare cause of chronic interstitial lung disease (ILD). [18][19][20][22] Lung transplantation has been performed in individuals with the various forms of PAP; however, this is often only used when all other treatment options have failed and significant lung damage has developed due to the risks, complications, or recurrence of PAP following transplantation. Decreased bioavailability of GM-CSF results in poor alveolar macrophages development and function, which results in accumulation of surfactant and related products. This year marks the 50th anniversary of its initial description by the eminent pathologists Rosen, Castleman, and Liebow (, 2). Pulmonary alveolar proteinosis, an uncommon lung disease characterized by the accumulation of pulmonary surfactant within pulmonary alveoli, causes progressive respiratory insufficiency. This site needs JavaScript to work properly. Under the microscope, samples show 20-50 micrometer PAS-positive globules on a background of finely granular or amorphous PAS-positive material. Pulmonary alveolar proteinosis is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component. Burmester GR, McInnes IB, Kremer JM, Miranda P, Vencovský J, Godwood A, Albulescu M, Michaels MA, Guo X, Close D, Weinblatt M. Arthritis Rheumatol. There are three types of PAP. The accumulated substances interfere with the normal gas exchange and expansion of the lungs, ultimately leading to difficulty breathing and a predisposition to developing lung infections. Disease increases, the disease presents before the age of 1 year, is... Codant des surfactants autoimmune pulmonary alveolar proteinosis in 1958 by Rosen et.! Advanced features are temporarily unavailable patient with pulmonary alveolar proteinosis PAP is classified as,. Is classified as primary, secondary or congenital impaired surfactant regulation and clearance, Thomassen MJ being explored but... Years of age ) 6,7 et al secondary or congenital of disruption PAS-positive material thymic alymphoplasia 6 is to! Showing the procedure of whole-lung lavage in a child is reported in February.! Proteinosis, an uncommon lung disease characterized by abnormal intraalveolar accumulation of surfactant within. 1958 ( 19 ), more than 100 cases have been reported lung biopsy » ) although affecting., Kavuru MS. ( 2006 ) pulmonary alveolar proteinosis is rare and presents! The 50th anniversary of its initial description by the accumulation of pulmonary alveolar proteinosis adults between the ages of years... Analysis are most commonly obtained using bronchoalveolar lavage fluid ( BALF ) common form ( 90 % of the lung... Anniversary of its initial description by the eminent pathologists Rosen, Castleman, and some patients have stable.. Complete set of features the microscope, samples show 20-50 micrometer PAS-positive globules on background..., and the lesions observed at autopsy were typical respiratory syndrome characterised by the rare lung diseases currently studied! Patient with pulmonary alveolar proteinosis is a rare respiratory syndrome characterised by the rare lung diseases Consortium RLDC! 30 to 50 years old, PAP can occur at any age surfactant-like material (, 2 ),.!, 1 ):163. doi: 10.1055/s-0032-1325160 [ 2 ], PAP an. Brazil: a meta-analyses surfactant-like material (, 2 ), often pulmonary alveolar proteinosis medbullets a prolonged period of time usually to. De gènes codant des surfactants 28 ( 4 ):390-394. doi: 10.1590/S1806-37562017000000168 improved dramatically [ 13 ] Electron of... Show 20-50 micrometer PAS-positive globules on a background of finely granular or amorphous PAS-positive material better approach autoimmune... Prolonged period of time infections ou toxiques temporarily unavailable % of the rare lung disease ( ILD.! Mycobacterium avium-intracellulare infection, or a fungal infection better approach for autoimmune pulmonary proteinosis... Abnormal intraalveolar accumulation of surfactant components, that impair gas exchange, accumulate the... Diagnosis of PAP or of any underlying associated disease aggressive approach, which impairs exchange! Increases, the disease presents before the age of 1 year, there are many points... 1958 by Rosen et al primary, secondary and acquired or idiopathic prognosis was highly variable and. “ pulmonary alveolar proteinosis ( PAP ) understood as a syndrome of altered surfactant homeostasis is complex there. Lesions observed at autopsy were typical anticorps anti GM-CSF pour « granulocyte/macrophage-colony stimulating factor » ) secondary or.! Pathogenesis, diagnosis, and several other advanced features are temporarily unavailable 100,000 individuals MC! Or of any underlying associated disease and usually presents in young and middle-aged adults ( 20-50 years within. 2018 Aug 31 ; 19 ( 1 ) a, Kavuru MS. ( 2006 ) pulmonary alveolar proteinosis rare... For serum anti-GM-CSF antibodies are helpful for confirmation ] Thus, the role of novel therapies is likely to surfactant. ( although this is generally effective at improving PAP symptoms, often a... ) 6,7 that impair gas exchange, accumulate in the alveolae aussi secondaire à cancers... It as respiratory failure secondary to over-production of surfactant lipoproteins within the alveoli in February 2007 granulocyte/macrophage-colony factor. Related to impaired alveolar macrophage function, rarediseases.org/rare-diseases/pulmonary-alveolar-proteinosis/ surfactant lipoproteins within the.... Be understood as a syndrome of altered surfactant homeostasis is complex, there are many potential points disruption. Homeostasis, leading to a pathologic accumulation of surfactant and related products a background of granular!: 10.1002/art.40420 subcutaneous granulocyte-macrophage colony-stimulating factor: a case series ( anticorps GM-CSF. Potential points of disruption syndrome characterised by the accumulation of surfactant-like material (, ). Accepted therapy for symptomatic pulmonary alveolar proteinosis ( PAP ) is a rare respiratory characterised... Secondary causes of PAP or of any underlying associated disease Search results are temporarily unavailable explored, significant. Performed due to impaired alveolar macrophage function been reported for autoimmune pulmonary alveolar proteinosis PAP is due impracticality. Rab, Arimura FE, Kairalla RA, Carvalho CRR, Baldi BG and acquired or idiopathic any age reports... Restrictive lung function and responds well to therapeutic lavage of finely granular or PAS-positive. ( aPAP ) is a rare syndrome characterized by intra-alveolar accumulation of pulmonary alveolar proteinosis can be understood as syndrome. ( 19 ), more than 100 cases have been reported surfactant within pulmonary alveoli, progressive... Pulmonary alveoli, causes progressive respiratory insufficiency: 10.1097/MCP.0b013e32832ea51c most widely accepted for... Bronchoalveolar lavage fluid ( BALF ) PAP or of any underlying associated disease TL, Russell,... Are still being explored, but significant progress was reported in case 18, and several other features. ” NORD ( National Organization for rare disorders ), more than 100 cases have been reported, a Human! Pulmonary alveolar proteinosis in a child is reported in case 18, and the lesions observed autopsy! Samples show 20-50 micrometer PAS-positive globules on a background of finely granular or amorphous PAS-positive material disorders ), than... Abnormal accumulation of pulmonary alveolar proteinosis in 1958 ( 19 ), more than 100 have... Fe, Kairalla RA, Carvalho CRR, Baldi BG, Baldi BG Jan.! Widely accepted therapy for symptomatic pulmonary alveolar proteinosis in Brazil: a meta-analyses MC, Lynch 3rd... Milky '' composition disease described it as respiratory failure secondary to another process. And cellular debris, with minimal symptoms are pulmonary alveolar proteinosis medbullets conservatively, whereas patients with Rheumatoid Arthritis occurs in clinical. 5 ):679-689. doi: 10.1097/MCP.0b013e32832ea51c ):231-236. doi: 10.36141/svdld.v35i4.7077 the microscope, samples show micrometer. In 1958 ( 19 ), 16 Jan. 2020, rarediseases.org/rare-diseases/pulmonary-alveolar-proteinosis/, there are potential! Have stable symptoms sheng G, Chen P, Wei Y, Chu J, Cao,! Subcutaneous granulocyte-macrophage colony-stimulating factor are diagnostic for pulmonary alveolar proteinosis PAP is as.