Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management

被引:38
作者
Huizar, Isham [1 ]
Kavuru, Mani S. [1 ]
机构
[1] E Carolina Univ, Brody Sch Med, Div Pulm Crit Care & Sleep Med, Greenville, NC 27834 USA
关键词
alveolar proteinosis; autoimmune disease; GM-CSF; PPAR-gamma; surfactant proteins and lipids; whole lung lavage; COLONY-STIMULATING FACTOR; ANTI-GM-CSF; INTERSTITIAL LUNG-DISEASE; ACTIVATED-RECEPTOR-GAMMA; HIGH-RESOLUTION CT; BRONCHOPULMONARY LAVAGE; SURFACTANT HOMEOSTASIS; FACTOR AUTOANTIBODIES; GENE; MACROPHAGES;
D O I
10.1097/MCP.0b013e32832ea51c
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Purpose of review This review discusses the most recent clinical and basic research literature on pulmonary alveolar proteinosis (PAP) as it relates to pathogenesis, diagnosis, and management. Recent findings The discovery of Granulocyte macrophage-colony stimulating factor (GM-CSF) and the alveolar macrophage as critical regulators of surfactant protein and lipid homeostasis has led to significant advances in PAP. Adults affected by PAP have circulating neutralizing anti-GM-CSF antibodies. Reduced localized GM-CSF activity in the lung (from neutralizing anti-GM-CSF antibodies), decreases alveolar macrophage surfactant degradation with surfactant excess and accumulation. Cause, source of antibodies or downstream effects of GM-CSF deficiency is speculative. GM-CSF antibodies above a threshold level have proved to be a useful diagnostic test. Research towards therapy has focused on improving the technique for therapeutic whole lung lavage as well as overcoming effects of neutralizing anti-GM-CSF, which include GM-CSF therapy (systemic and inhaled) and anecdotal reports of anti-B cell therapy. Whereas this approach has been somewhat successful for primary PAP, other causes of PAP (i.e. alveolar macrophage dysfunction, surfactant protein alterations) are still without therapy. Summary Understanding of the pathogenesis of PAP has greatly increased in the last decade; study has brought better comprehension of lung biology and recognition of the critical role for GM-CSF and alveolar macrophage in surfactant clearance. Balance between resident immune cell population and normal lung function still needs further study. Resident alveolar macrophages have an essential role in surfactant homeostasis. With this knowledge more effective diagnostic tests (e.g. anti-GM-CSF antibody) and therapies for PAP are under investigation.
引用
收藏
页码:491 / 498
页数:8
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