Pulmonary alveolar proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic ''crazy paving'' pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

Procedimento e complicações anestésicas no manejo de lavagem pulmonar total em paciente obeso com proteinose alveolar pulmonar: relato de caso

“…Clinical presentation is variable and non-specific 2 , often leading to months or years of misdiagnosis 11,13 .…”

“…The later is the one of most importance concerning prevalence (approximately 0.2 cases per million of population) and response to treatment 8,9,14 . Investigations reveal radiographic bilateral patchy air-space infiltration 6,9,11,12,14 , restrictive pulmonary function 5,6,12,17 , impaired diffusion capacity 12 and milky brochoalveolar lavage (BAL) fluid-rich in alveolar macrophages 6,11,16 .…”

“…The affected individuals suffer a progressive accumulation of lipoproteins in the alveolar space 2,3,[6][7][8]11,12,18 as a result of defective macrophage clearance 2,8,11,12,14 , yet with minimal local lung inflammation or distortion of architecture on biopsy 3,9,12 . Recent insights into the pathogenesis of PAP suggest that in most cases of PAP autoimmunity against pulmonary granulocytemacrophage colony-stimulating factor (GM-CSF) plays a major role 2,6,8,9,11,12,14,18 .…”

“…Recent insights suggest that, in the most common form, acquired (idiopathic) PAP, autoimmunity against pulmonary granulocyte-macrophage colonystimulating factor (GM-CSF) plays a major role 2,3,6,8,[10][11][12]14 . Recombinant Granulocyte-Macrophage colony stimulating factor appears to benefit a subset of adult patient with PAP and may represent an alternative in the treatment of this disease 8,10,11,14 , but the success rate is not yet sufficient to displace WLL 16 .…”

“…PAP is characterized by deposition of lipoproteinaceous material secondary to abnormal processing of surfactant by macrophages 2,3,[5][6][7][8][9][10][11] .…”