Mayo Clinic Proceedings Home

Pulmonary Alveolar Proteinosis

Crazy Paving to Whole Lung Lavage

      Abbreviations and Acronyms:

      PAP (pulmonary alveolar proteinosis), PAS (periodic acid–Schiff)
      Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous material accumulates in alveoli. A 47-year-old white man with a 15–pack-year smoking history visited his primary care physician for progressive shortness of breath. A chest radiograph showed diffuse pulmonary opacification. A high-resolution chest computed tomographic scan showed the crazy-paving pattern of diffuse interstitial and ground-glass opacification throughout the lung fields (Figure 1). A wedge lung biopsy was performed; histologic examination showed periodic acid–Schiff (PAS)–positive granular material (Supplemental Figure, available online at and alveolar macrophages with intracytoplasmic debris consistent with PAP.
      Figure thumbnail gr1
      Figure 1High-resolution chest computed tomographic scan shows the crazy-paving pattern of diffuse interstitial and ground-glass opacification throughout the lung fields.
      Pulmonary alveolar proteinosis is a diffuse lung disease characterized by accumulation of PAS-positive lipoproteinaceous material in alveoli, with little lung inflammation and preserved architecture. Clinical presentation is usually the insidious onset of dyspnea and cough in a middle-aged male smoker. However, one-third of patients are asymptomatic. Physical examination findings are usually unremarkable; expectoration of white gelatinous material may occur. Laboratory abnormalities include polycythemia and increased lactate dehydrogenase levels. Typical findings on high-resolution chest computed tomographic scans are the crazy-paving pattern, and bronchoalveolar lavage or lung biopsy staining positive for PAS is diagnostic. The autoimmune form of PAP accounts for 90% of cases and is characterized by the presence of granulocyte-macrophage colony-stimulating factor autoantibodies that are believed to contribute to macrophage dysfunction and impaired surfactant processing.
      Whole lung lavage is a widely accepted form of treatment (Figure 2). The median duration of clinical benefit from lavage is approximately 15 months. Administration of subcutaneous or inhalational granulocyte-macrophage colony-stimulating factor for PAP remains experimental, but shows promise. Lung transplant has been performed in refractory patients.
      Figure thumbnail gr2
      Figure 2The fluid retrieved from the whole lung lavage shows milky lipoproteinaceous material. The first bottle is more milky and turbid.


      We thank Nada Siddique Khan, MBBS; Thomas Vacek, MD; Abdulmonam Ali, MD; Natalya Kozodoi, MD; Zaidi Ammari, MD; and Ragheb Assaly, MD, for their assistance with this submission.

      Supplemental Online Material

      Figure thumbnail figs1
      Supplemental FigureCytologic examination shows intra-alveolar, periodic acid–Schiff (PAS)–positive granular material consistent with pulmonary alveolar proteinosis.

      Supplemental Online Material

      Supplemental material can be found online at: Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.