Pathogenesis
Type II alveolar cells have many important functions in the lung, including the production of pulmonary surfactant, maintenance of fluid balance and composition in the airspace. Phospholipids that make up pulmonary surfactant are broken down by macrophages, releasing phosphate into the alveolar lining fluid. The loss of the Npt2b phosphate transported eliminates the ability of alveolar type II cells to pump phosphorus ions from the alveolar space back into the bloodstream, and leads to microlith formation.Epithelial deletion of Npt2b in mice results in an authentic mimic of the human condition, including accumulation of calcium phosphate microliths in the lung tissue and progressive diffuse radiographic opacities. The mouse model provides a useful platform for preclinical studies, including therapeutic trials of EDTA lavage and low phosphate diet/phosphate binders. Pathology
PAM may be confined to certain areas or show diffuse distribution through the lungs. Lung biopsy and autopsy specimens demonstrate characteristic intra-alveolar lamellar microliths. Calcium deposits in the alveoli begin in the lower lobes and spread over a period of years throughout the lungs. Diagnosis
PAM is usually diagnosed on the basis of a typical radiological pattern, namely a very fine, sand-like micronodulation of calcific density diffusely involving both lungs, with basal predominance. Many authors argue that this pattern precludes the need for a lung biopsy in most cases. After PAM is diagnosed in a given patient, family members should be screened by chest radiography, and parents should be counseled that future children are also at risk of developing the disease.
Radiology
Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs. High-resolution computed tomography
The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects. Ground-glass opacities, probably due to small calculi in the air space, are the most common finding in children and in patients with early-stage PAM. Magnetic resonance imaging
On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images. Pulmonary function studies
Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC. Treatment
To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired.Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases. Epidemiology
Since the disease was first described in 1918, over 500 case reports have appeared in the literature.