How is pulmonary alveolar proteinosis (PAP) treated?

Updated: Dec 18, 2019
  • Author: Rodolfo Laucirica, MD; Chief Editor: Philip T Cagle, MD  more...
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Answer

The most widely accepted and effective treatment for PAP is therapeutic whole-lung lavage(WLL). [1, 6, 7, 39] This form of therapy is instituted when significant dyspnea limits activity and progressive deterioration of arterial oxygenation. [40, 41]  Bronchoscopic serial lobar lavages have also been used to treat patients with PAP. [42]

The patient’s respiratory function improves due to the removal of proteinaceous material and local anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. This helps restore the migration and phagocytic functions of alveolar macrophages. [43, 44] Although a significant number of patients exhibit clinical, radiologic, and functional improvement after a single treatment, most require repeat lavage at intervals between 6 and 15 months. [45, 46] Patients receiving whole-lung lavage have shown a significant improvement in their 5-year survival rate compared to those who do not receive this form of therapy. [1, 45] For patients with secondary PAP, in addition to whole-lung lavage, treatment of the underlying condition should also be instituted. [6, 7]

The administration of exogenous GM-CSF or suppression of ant-GM-CSF antibodies has been used to treat those patients with autoimmune PAP. The goal of this treatment is to relieve the deficiency of functional GM-CSF, and this can be administered simultaneously or as an alternate to whole-lung lavage. [47, 48, 49, 50] Although predictors of response to treatment with GM-CSF have yet to be established, those patients with pretreatment variables such as longer time from diagnosis, high vital capacity, normal serum lactate dehydrogenase level, and higher plasma surfactant-protein-B level appear to respond better to GM-CSF. [50]

Novel forms of therapy are being explored for those patients who do not respond to GM-CSF or whole-lung lavage. Plasmapharesis, rituximab, trypsin, chymotrypsin, ambroxol, immunoglobulin G, and antibiotics have been investigated. [51, 52, 53, 54, 55, 56] For refractory PAP, rituximab, plasmapheresis, and lung transplantation may be therapeutic considerations. [6]

Attempts have also been made to use stem cells to treat some forms of PAP. Lachmann et al have investigated the use of induced pluripotent stem cells derived from monocytes and macrophages to treat patients with the hereditary form of PAP. [57]

As a means to monitor disease progression, research has evaluated several ancillary tests, including high molecular weight human MUC-1 mucin and serum KL-6. Both of these makers are increased in most patients with PAP. Based on the work of Bonella et al, it appears that serum KL-6 levels are a strong predictor of disease progression in patients with PAP. [58]


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