scholarly journals Pulmonary alveolar proteinosis: from classification to therapy

Breathe ◽  
2020 ◽  
Vol 16 (2) ◽  
pp. 200018
Author(s):  
Elena Salvaterra ◽  
Ilaria Campo
Keyword(s):  
Disease Severity ◽  
Pulmonary Alveolar Proteinosis ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Lung Lavage ◽  
List Type ◽  
Gm Csf ◽  
Surfactant Production ◽  
Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare respiratory syndrome characterised by the accumulation of surfactant lipoproteins within the alveoli. According to various pathogenetic mechanisms and aetiologies, PAP is classified as primary, secondary or congenital. Primary PAP is led by a granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling disruption; the autoimmune form is driven by the presence of anti GM-CSF autoantibodies and represents 90% of all the PAP cases; and the hereditary form is the result of mutations in genes encoding GM-CSF receptor. Secondary PAP is associated with various diseases causing a reduction in function and/or number of alveolar macrophages. Congenital PAP emerges as a consequence of corrupted surfactant production, due to mutations in surfactant proteins or lipid transporter, or mutations affecting lung development. The clinical manifestations are various, ranging from insidious onset to acute or progressive respiratory failure, including premature death within the first days of life in neonates with congenital surfactant production disorders. The diagnostic workup includes clinical and radiological assessment (respiratory function test, high-resolution chest computed tomography), laboratory tests (anti-GM-CSF autoantibodies dosage, GM-CSF serum level and GM-CSF signalling test), and genetic tests. Whole-lung lavage is the current gold standard of care of PAP; however, the therapeutic approach depends on the pathogenic form and disease severity, including GM-CSF augmentation strategies in autoimmune PAP and other promising new treatments.Educational aimsTo update knowledge about a rare respiratory syndrome, pulmonary alveolar proteinosis, in order to promote early diagnosis and correct management.To highlight recent treatment options based on pathogenesis and disease severity.

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.

scholarly journals PULMONARY ALVEOLAR PROTEINOSIS - A CASE REPORT AND REVIEW OF LITERATURE

2020 ◽  
pp. 1-3
Author(s):  
Abhilash Narvenkar ◽  
Uday C. Kakodkar* ◽  
Chetan Kerkar ◽  
John Muchahary
Keyword(s):  
Case Report ◽  
Lower Respiratory Tract ◽  
Pulmonary Alveolar Proteinosis ◽  
Lung Lavage ◽  
Review Of Literature ◽  
Whole Lung Lavage ◽  
Gm Csf ◽  
Radiological Features ◽  
History Of ◽  
Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised by accumulation of lipoproteinaceous material in the alveolar air spaces. Diagnosis depends on histopathological and radiological features. Treatment includes whole lung lavage (WLL) and GM-CSF therapy. We present a case report of primary idiopathic PAP treated with bilateral whole lung lavage. A 50 year old female presented with history of progressive breathlessness and recurrent lower respiratory tract infection. There were bilateral basal ne crepitations on auscultation and she was maintaining saturation of 70% at room air. Serial chest radiographs showed persistent bilateral alveolar opacities. HRCT thorax showed crazy paving pattern involving both lungs. BAL uid showed lipoproteinaceous material which was PAS stain positive. Patient was subsequently treated with bilateral WLLfollowing which there was radiological and clinical improvement

scholarly journals Serum neutralizing capacity of GM-CSF reflects disease severity in a patient with pulmonary alveolar proteinosis successfully treated with inhaled GM-CSF

2004 ◽  
Vol 98 (12) ◽  
pp. 1227-1230 ◽  
Author(s):  
Toru Arai ◽  
Emi Hamano ◽  
Yoshikazu Inoue ◽  
Ryushi Tazawa ◽  
Toshihiro Nukiwa ◽  
...  
Keyword(s):  
Disease Severity ◽  
Pulmonary Alveolar Proteinosis ◽  
Gm Csf ◽  
Neutralizing Capacity ◽  
Alveolar Proteinosis

A combination therapy of whole lung lavage and GM-CSF inhalation in pulmonary alveolar proteinosis

2008 ◽  
Vol 43 (8) ◽  
pp. 828-830 ◽  
Author(s):  
Hajime Yamamoto ◽  
Etsuro Yamaguchi ◽  
Hiroatsu Agata ◽  
Nobuhisa Kandatsu ◽  
Toru Komatsu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Pulmonary Alveolar Proteinosis ◽  
Lung Lavage ◽  
Whole Lung Lavage ◽  
Gm Csf ◽  
Alveolar Proteinosis

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: 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.

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