Pulmonary alveolar proteinosis in a woman with respiratory failure and crazy-paving pattern on chest computed tomography

History of present illness

A 47-year-old Philippine woman was referred to the pulmonology clinic due to progressively worsening exertional dyspnea. She also complained of a 6-month dry cough with occasional production of whitish sputum. She reported no fever, chest pain, hemoptysis, or weight loss.

Past medical history

The patient was a caretaker without any exposure to pneumotoxic agents and had no smoking habit. No familial history of respiratory diseases was reported. Her medical history included systemic arterial hypertension in treatment with a β-blocker and hypercholesterolemia that was not pharmacologically treated.

Physical examination and early clinical findings

At the first evaluation, the patient was apyretic, with severe dyspnea at rest. Oxygen saturation measured by pulse oximetry (SpO ₂ ) was 87% on room air, heart rate was 96 beats/min, and blood pressure was 130/90 mmHg. Chest auscultation revealed fine bibasilar end-inspiratory fixed crackles. Cardiac and abdominal physical examinations were normal, and there was no peripheral edema or jugular vein distention. Chest radiograph showed bilateral parenchymal infiltrates in the mid- and lower-lung fields ( Fig. 16.1 ). Blood tests were unremarkable as hemoglobin, leukocytes, and renal and hepatic function indexes were in the normal range; serum procalcitonin was negative, C-reactive protein was 6 mg/dL (normal value: <0.5 mg/dL), and lactate dehydrogenase (LDH) was 348 mU/mL (normal range: 125-220 mU/mL). No significant antinuclear antibody (ANA) titer was detected (1:80). Extractable nuclear antigens (ENA) were negative. Arterial blood gas analysis (ABGA) confirmed acute hypoxemic respiratory failure with PaO ₂ 51 mmHg, PaCO ₂ 33.1 mmHg, pH 7.45, and HCO ₃ ^– 28.5 mmol/L. Alveolar-arterial oxygen gradient (A-aDO ₂ ) was 59.2 (expected normal value <12). Oxygen supplementation was necessary to improve gas exchange. Pulmonary function tests (PFTs) showed severe restrictive ventilatory defect, with forced expiratory volume in 1 second (FEV ₁ ) 43%, forced vital capacity (FVC) 47%, and total lung capacity (TLC) 65% of the predicted value. The diffusing capacity of the lungs for carbon monoxide (DLCO) was severely impaired with a percentage of predicted values of 19%.

Clinical course

Due to worsening of respiratory conditions, the patient was admitted to the pulmonology unit. The supplement of 50% oxygen through the Venturi mask, allowed the patient to obtain an SpO ₂ of 96%. She underwent CT scan of the chest ( Fig. 16.2 ), which revealed a bilateral, symmetrical “crazy paving” pattern, due to ground-glass opacities delimited by interlobular septal thickening, with craniocaudal gradient.

No signs of pulmonary embolism were found.

A bronchoscopy was performed: opaque, milky, periodic acid–Schiff (PAS)-positive lipoproteinaceous BAL fluid was collected. Transbronchial lung biopsies revealed well-preserved alveoli filled with eosinophilic, granular, and PAS-positive material and foamy alveolar macrophages. CT scan, BAL fluid appearance, and histology were compatible with pulmonary alveolar proteinosis (PAP) ( Fig. 16.3 ). Serum granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody concentration was abnormal (44 μg/mL) (normal range: ≤3.1 μg/mL), thus supporting a diagnosis of autoimmune PAP.

Recommended therapy and further indications

Due to severely impaired respiratory conditions, the patient underwent WLL. As Enterobacter aerogenes was isolated from BALF culture, targeted antibiotic therapy was administered before the lavage. The patient was transferred to the ICU and intubated with a double-lumen endotracheal tube. The left lung was lavaged first: 15 L of warmed saline solution (37°C = 98.6°F), divided in aliquots of 500 mL, was instilled and drained by gravity. Concurrently, the other lung was mechanically ventilated. When the collected fluid began to be clear, manual chest percussions were added to improve drainage. The patient was in lateral decubitus, which offers some advantages: 1) more effective manual percussions on the lung and 2) blood perfusion diverted toward the ventilated lung, with subsequent reduction of ventilation-perfusion mismatch and hypoxemia. The entire procedure continued until the effluent fluid was completely clear. Sequentially, the right lung was lavaged with 17 L of saline solution. Fig. 16.4 shows the typical milky appearance of collected effluent fluid.