Combined-modality therapy for pulmonary alveolar proteinosis in a remote setting: a case report

Abstract

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of phospholipoproteinaceous material in the alveoli. The presentation is nonspecific but typically includes dyspnea; the spectrum of disease includes rapidly progressive hypoxic respiratory failure. Whole lung lavage (WLL) is the treatment of choice in symptomatic PAP, but transient worsening of oxygenation sometimes requires salvage modalities of support such as extracorporeal membrane oxygenation (ECMO). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a role in the pathophysiology of PAP. We highlight a case of severe PAP treated with exogenous GM-CSF and sequential lobar lavage due to the unavailability of salvage methods of oxygenation.

Case presentation: A 36 year old female was admitted with fevers, chills, and progressive dyspnea. On presentation she was tachypneic, tachycardic, and hypoxemic; labs revealed leukocytosis and lactic acidosis. Chest CT identified diffuse ground glass opacities in a 'crazy-paving' pattern. Following intubation due to impending respiratory failure, bronchoscopy with bronchoalveolar lavage was performed. The lavage return stained positive with Periodic Acid Schiff, confirming the diagnosis of PAP. Continued deterioration necessitated treatment; however, at this geographically remote center without ECMO services WLL was judged to carry significant risk. Nebulized GM-CSF was administered without significant improvement. Subcutaneous GM-CSF was administered and isolated subsegmental lavages of the bilateral upper lobes were performed, with rapid improvement in oxygenation. Additional sequential lobar lavage and continued GM-CSF therapy as an outpatient resulted in complete resolution of oxygen requirement and return to normal pulmonary physiology.

Conclusions: The autoimmune form of PAP is the most common, indicating that therapy with GM-CSF may play an important role for many patients. Treatment with WLL may be impractical in some clinical settings due to the expertise and salvage modalities required. Sequential lobar lavage requires less specialized expertise and may incur less risk of refractory hypoxemia. We posit that this combined-modality therapy is ideally suited to geographically-remote centers such as our own.

Keywords: Granulocyte macrophage colony-stimulating factor; Pulmonary alveolar proteinosis; Whole lung lavage.

Fig. 1

Noncontrast CT chest on presentation and following treatment. a-c: representative cross-sectional images of the chest on presentation. d-f: matched images following completion of combined-modality therapy with GM-CSF and serial lobar lavage

Fig. 2

Periodic-Acid Schiff staining of BAL specimen. a: Diff Quik stain of BAL fluid demonstrating abundant amorphous granular debris with few macrophages and neutrophils. b: Periodic-Acid Schiff (PAS) stain of BAL fluid

Fig. 3

Representative sample of therapeutic lavage fluid. a: Initial, mid-procedure, and final lavages from a single segment during the first therapeutic lavage. b: Total volume of lavage for a single segment during the second procedure