Approach Considerations
Management of pulmonary alveolar proteinosis (PAP) depends on the progression of the illness, the presence of coexisting infections, and the degree of physiologic impairment. The standard of care for PAP is mechanical removal of the lipoproteinaceous material by whole-lung lavage (WLL), as well as management of the underlying cause. [1, 2, 3]
Supplemental granulocyte-macrophage colony-stimulating factor (GM-CSF) is useful; however, there is continued debated regarding its indications, agent selection, and dosing. [3] Inhaled GM-CSF was initially shown to be safe and effective in providing a sustained therapeutic effect in autoimmune PAP [13] ; more recently, it appears to have only modest salutary laboratory effects on arterial oxygen tension without clinical benefits in mild-to-moderate autoimmune PAP. [14] For refractory PAP, rituximab, plasmapheresis, and lung transplantation may be therapeutic considerations. [3]
Historically, patients have been treated with systemic steroids, mucolytics (aerosol), and proteinase (aerosol) without much success. In secondary PAP, appropriate treatment of the underlying cause is warranted.
Inpatient care is uncommon in primary PAP, except for concomitant superinfection or severe hypoxemia. Treatment of secondary PAP might require inpatient care and outpatient follow-up.
Medical Care
Surgical Care
Whole-lung lavage (WLL) remains the gold standard of therapy for PAP. [1, 2, 3] Current indications for WLL vary from center to center, but the most common indications appear to be declining lung function, declining oxygenation, and radiographic worsening. [34, 35] The main indication is limitation in daily activities due to dyspnea. [35] An alveolar-arterial oxygen gradient of at least 40 mmHg and a PaO2 below 70 mmHg on room air are additional indications, as these patients are more likely to have disease progression. [35]
WLL is performed with a double-lumen endotracheal tube designed to allow simultaneous ventilation and lavage. Lung lavage is performed under general anesthesia, and the lung is ventilated briefly with 100% oxygen before lavage with isotonic sodium chloride solution. The standard is lavage with up to 50 L of fluid. Upon completion of the procedure, the lung is suctioned of most of the isotonic sodium chloride solution and allowed to recover before lavaging the other lung. Lung lavage has been performed in hyperbaric chambers, which has made lavage of both lungs possible on the same day. Lung lavage may require several hours.
Although WLL is an invasive procedure, it has been determined to be safe and associated with a low rate of procedure-related morbidity. The results of a global practice survey of 20 centers in 14 countries found the most complications to be fever (18%), worsened hypoxemia (14%), wheezing (6%), pneumonia (5%) and pleural effusion (3%). [34, 35]
Rarely, hyperbaric chamber or extracorporeal membrane oxygenation (ECMO) has been used to perform WLL in cases of severe hypoxemia. [36]
Lung transplantation is the treatment of choice in patients with congenital PAP and in adult patients with end-stage interstitial fibrosis and cor pulmonale.
Long-Term Monitoring
Patients with pulmonary alveolar proteinosis (PAP) usually improve dramatically with whole-lung lavage, but relapses may occur. Repeated lavage usually is necessary. Patients should have regular follow-up with a pulmonologist.
Patients prone to alveolar proteinosis related to inhalation of inorganic dusts or insecticides should avoid further exposure.
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Pulmonary alveolar proteinosis. A periodic acid-Schiff histochemical stain of transbronchial biopsy: Alveolar spaces contain considerable amounts of granular material.
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Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (A) (hematoxylin and eosin, x400) and broncheoalveolar lavage (BAL).
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Pulmonary alveolar proteinosis. Contrast between the granular exudate of pulmonary alveolar proteinosis (PAP) and frothy exudate of pneumocystis pneumonia in the transbronchial biopsy (B) (Papanicolaou, x600). Note the negative images of the cysts impart the foamy characteristic of the exudate.
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Pulmonary alveolar proteinosis. Intra-alveolar material is strongly periodic acid-Schiff (PAS) positive (diastase-PAS, x200).
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Pulmonary alveolar proteinosis. Cytologic appearance of intra-alveolar granular material from a bronchoalveolar lavage sample (diastase-periodic acid-Shiff [DPAS], x400).
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Pulmonary alveolar proteinosis. Bronchoalveolar lavage sample depicting dense globules with sharp borders seen in patients with pulmonary alveolar proteinosis (PAP) (Papanicolaou, x400).
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Pulmonary alveolar proteinosis. Alveoli are filled with an eosinophilic granular material. Note the preservation of the normal lung architecture (hematoxylin and eosin, x200).
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Pulmonary alveolar proteinosis. High magnification illustrating the granular material and alveolar macrophages surrounded by intact alveolar septal tissue with minimal reaction (hematoxylin and eosin, x400).
