scholarly journals Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges

2012 ◽  
Vol 7 ◽  
Author(s):  
Ilaria Campo ◽  
Zamir Kadija ◽  
Francesca Mariani ◽  
Elena Paracchini ◽  
Giuseppe Rodi ◽  
...  
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Gene Mutations ◽  
Spontaneous Remission ◽  
Lung Lavage ◽  
Current Standard ◽  
Gm Csf ◽  
Genes Encoding ◽  
Current Standard Treatment ◽  
Alveolar Proteinosis ◽  
Macrophage Colony

Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals and in distinct clinical forms: autoimmune (previously referred to as the idiopathic form, represents the vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) auto-antibodies; GMAbs), secondary (is a consequence of underlying disorders), congenital (caused by mutations in the genes encoding for the GM-CSF receptor), and PAP-like syndromes (disorders associated with surfactant gene mutations). The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole lung lavage (WLL) is the current standard treatment for PAP patients and although it is effective in the majority of cases, disease persistence is not an unusual outcome, even if disease is well controlled by WLL. In this paper we review the therapeutic strategies which have been proposed for the treatment of PAP patients and the progress which has been made in the understanding of the disease pathogenesis.

scholarly journals Congenital Pulmonary Alveolar Proteinosis

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Saber Hammami ◽  
Khaled Harrathi ◽  
Khaled Lajmi ◽  
Samir Hadded ◽  
Chebil Ben Meriem ◽  
...  
Keyword(s):  
Pulmonary Surfactant ◽  
Standard Treatment ◽  
Pulmonary Alveolar Proteinosis ◽  
Late Onset ◽  
Spontaneous Remission ◽  
Lung Lavage ◽  
Current Standard ◽  
Whole Lung Lavage ◽  
Current Standard Treatment ◽  
Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals. Two clinically different pediatric types have been defined as congenital PAP which is fatal and a late-onset PAP which is similar to the adult form and less severe. The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole-lung lavage is the current standard treatment for PAP patients. We report a new congenital case of PAP.

scholarly journals Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy

Thorax ◽  
2001 ◽  
Vol 56 (8) ◽  
pp. 664-665
Author(s):  
R M Barraclough ◽  
A J Gillies
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Rare Condition ◽  
Complete Response ◽  
Lung Lavage ◽  
Whole Lung Lavage ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Alveolar Proteinosis ◽  
Macrophage Colony ◽  
New Treatment

Pulmonary alveolar proteinosis is a rare condition traditionally requiring treatment with whole lung lavage. The case is presented of a young man who obtained complete remission following treatment with granulocyte-macrophage colony stimulating factor, a new treatment option.

scholarly journals Pulmonary alveolar proteinosis in children

Breathe ◽  
2020 ◽  
Vol 16 (2) ◽  
pp. 200001
Author(s):  
Andrew Bush ◽  
Rishi Pabary
Keyword(s):  
Pulmonary Alveolar Proteinosis ◽  
Lung Lavage ◽  
List Type ◽  
Colony Stimulating Factor ◽  
Whole Lung Lavage ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Alveolar Proteinosis ◽  
Macrophage Colony ◽  
Stimulating Factor

Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. 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. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations.Educational aimsTo understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.

Pulmonary Alveolar Proteinosis Syndrome

2020 ◽  
Vol 41 (02) ◽  
pp. 288-298 ◽  
Author(s):  
Alan Kelly ◽  
Cormac McCarthy
Keyword(s):  
Alveolar Macrophage ◽  
Immune Modulation ◽  
Pulmonary Alveolar Proteinosis ◽  
Systemic Infection ◽  
Lung Lavage ◽  
Response To Therapy ◽  
Cholesterol Homeostasis ◽  
Current Standard ◽  
Gm Csf ◽  
Alveolar Proteinosis

AbstractPulmonary alveolar proteinosis (PAP) is a syndrome characterized by progressive accumulation of pulmonary surfactant. This results in dyspnea, secondary pulmonary and systemic infection, and in some cases respiratory failure. PAP syndrome occurs in distinct diseases, classified according to pathogenetic mechanism; these include primary PAP (due to disruption of granulocyte-macrophage colony-stimulating factor [GM-CSF] signaling), secondary PAP (due to reduction in alveolar macrophage numbers/functions), and congenital PAP (due to disruption of surfactant production). In primary PAP, the most common cause is autoimmune PAP, which accounts for over 90% of all PAP syndrome. The pathogenesis is driven by reduced GM-CSF-signaling causing abnormal alveolar macrophage function which subsequently results in impaired alveolar surfactant clearance. Autoimmune PAP can be accurately diagnosed by serum GM-CSF autoantibody levels and there now exist other diagnostic tests for rare causes of PAP syndrome. The current standard treatment is whole lung lavage; however, there is emerging evidence to support the use of novel therapeutic approaches, including inhaled GM-CSF, immune modulation, gene and cell therapy, and targeting macrophage cholesterol homeostasis. Furthermore, several innovative approaches to monitor disease severity and response to therapy have recently been developed.

scholarly journals The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation.

1996 ◽  
Vol 183 (6) ◽  
pp. 2657-2662 ◽  
Author(s):  
R Nishinakamura ◽  
R Wiler ◽  
U Dirksen ◽  
Y Morikawa ◽  
K Arai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Pulmonary Alveolar Proteinosis ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Alveolar Proteinosis ◽  
Macrophage Colony ◽  
Stimulating Factor

Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.

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