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Pulmonary Alveolar Proteinosis - Treatment by Serial Whole Lung Lavage

Iftikhar A Jan¹, Nighat Ghias², Nadeem Rizvi³, Rhubab Naqvi²

¹Zayed Military Hospital, Abu Dhabi, United Arab Emirates

²National Institute of Child Health Karachi, Karachi, Pakistan

³Jinnah Postgraduate Medical Center Karachi, Karachi, Pakistan

 

Correspondence

Iftikhar Ahmad Jan

Zayed Military Hospital

Abu Dhabi, United Arab Emirates

Phone: 00971508213073

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Abstract

Pulmonary alveolar proteinosis is a rare cause of recurrent chest infections in children. It is characterized by intra alveolar accumulation of lipid and proteinaceous material that is periodic acid Schiff positive. Clinically is associated with respiratory difficulty and derangement of gas exchange. We report the case of a 13 years old boy who presented with recurrent chest infections for the last four years. He was treated in another hospital with antibiotics also for pulmonary tuberculosis due to the respiratory symptoms. On presentation he had dyspnea with signs of respiratory insufficiency. X-ray chest showed bilateral pulmonary involvement with diffuse infiltration of the lung parenchyma. CT scan of lungs showed diffuse alveolar shadowing. Echocardiography showed mild right ventricular hypertrophy. Thoracoscopic biopsy confirmed the diagnosis of pulmonary alveolar proteinosis. The child was treated with four sessions of whole lung saline lavage and showed significant improvements of symptoms. He was well at 6 months follow up.

Keywords: alveolar proteinosis, thoracoscopic biopsy, lung lavage

 

 

Introduction

Pulmonary alveolar proteinosis (PAP) was first described by Rosen in 1958 [1]. This is a rare disorder in which lipoproteinaceous material accumulates within alveoli and is visualized on light microscope as periodic acid Schiff (PAS) positive-staining fluid within the alveoli [2]. The thick secretions decrease the alveolar surface tension, leading to increased work of breathing, diminished surface area of gas diffusion, and ultimately respiratory failure. Pulmonary interstitium and airways are relatively spared. The clinical course of the disease is variable, ranging from spontaneous resolution to respiratory failure. Two forms are encountered which include congenital alveolar proteinosis (CAP) and a less severe later-onset form [3]. The diagnosis of PAP may be delayed due to rarity of condition. Lung biopsy is diagnostic and thoracoscopic biopsy avoids unnecessary thoracotomy [4]. Serial whole lung lavage is the treatment of choice in these patients which causes significant improvement of symptoms and may be curative [2].

Case Report

A 13 years old male presented with the complaints of chest pain and exertional dyspnea for the last 4 years. The patient also had productive cough with history of blood stained sputum. On examination he was a healthy looking child but developed mild cyanosis on coughing. His heart rate was 96 beats/min and respiratory rate 30 breaths per minute. Chest examination revealed bilateral crepitations and low pitched rhonchi. His hemoglobin was 10 grams%. Sputum for acid fast bacilli (AFB) was negative. X-ray chest showed bilateral diffuse pulmonary involvement, prominent broncho-vascular markings and hilar shadows (Fig.1).

Figure 1: Chest X-ray showing bilateral pulmonary involvement

JPSS 9.1.7.1

Echo-cardiography suggested right ventricular hypertrophy. Abdomen ultrasound was normal. CT- scan of the lungs showed diffuse alveolar shadowing with no evidence of bronchiectasis (Fig. 2). Thoracoscopic biopsy was performed from right lung. Child tolerated the procedure well and recovered in few days. Histopathology suggested pulmonary alveolar proteinosis (Fig. 3). Serial whole lung lavage was planned. Procedures were performed under general anesthesia with single lumen endotracheal intubation. About 500 ml of warm saline was used for each lavage. He had four sessions of whole lung lavage at two weeks intervals. Child showed significant improved of symptoms and was advised nebulization and chest physiotherapy at home. He was symptom free at six months follow-up.

Figure 2: Chest CT scan showing diffuse pul- monary involvement

JPSS 9.1.7.2

 

Figure 3: Histopathology image showing PA positive proteinaceous material in the alveoli

JPSS 9.1.7.3

Discussion

Pulmonary alveolar proteinosis, also known as pulmonary alveolar phospholipoproteinosis, is a diffuse lung disease. There is little or no lung inflammation, and the underlying lung architecture is well preserved. The disease is characterized by accumulation of surfactant-rich proteinacious material, resulting in impaired phagocytes [1, 2]. It is suggested that impaired processing of surfactant by alveolar macrophages is responsible for the pathogenesis of PAP. Findings similar to pulmonary alveolar proteinosis have been found in other conditions like acute silicosis (silicoproteinosis), aluminum or titanium dust exposure, infection with pneumocystis carnii, hematological malignancies, and immunosuppressive disorders [4].

Antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF) have been suggested to cause disease in mice buts its definitive role has not yet been established in human PAP especially in pediatric patients [5]. PAP is usually seen in adults and is less common in children [1]. It is twice more common in male than female. It usually presents with progressive exertional dyspnea, fatigue, weight loss and low-grade fever thus mimicking pulmonary tuberculosis [6]. This was also the case in our patient who received anti TB treatment for a long time before the diagnosis was made. A non-productive cough is common, but occasionally expectoration of “chunky” gelatinous material may occur. Our patient had occasional bouts of productive cough and hemamtemesis. The physical examination may be normal but clubbing and cyanosis may be present in advance cases [1].

Due to impaired macrophage phagocytic function; there is an increased risk of superinfection in PAP patients by opportunistic organisms such as Nocardia, mycobacterium, and various endemic or opportunistic fungi. Some patients may be asymptomatic with little or no physiologic impairment despite extensive radiographic abnormalities; these patients often do not require immediate treatment. In classical PAP chest radiograph shows bilateral symmetric alveolar opacities located centrally in mid and lower lung zones, resulting in a “bat wing” distribution. This appearance was also present in our patient and is highly suggestive of PAP. High resolution CT scanning (HRCT) reveals ground-glass opacification [7].

There may also be thickened intralobular structures and interlobular septa in typical polygonal shapes, referred to as “crazy-paving”. Crazy-paving is not specific for PAP and can also be observed in patients with other pulmonary conditions [8]. Our patient showed ground glass opacifications on conventional CT chest. Laboratory abnormalities include polycythemia, and hypergammaglobulinemia. Our patient did not have polycythemia and gammaglobulin levels were not done. The diagnosis may be confirmed by bronchio-alveolar lavage or transbronchial lung biopsy with periodic acid-Schiff (PAS) positive lipoproteinaceous material in alveoli. In selected cases thoracoscopic or open lung biopsy may be required for confirmation of the diagnosis. The most widely accepted and effective form of treatment has been therapeutic whole lung lavage (WLL) via a double-lumen endotracheal tube (DETT) [9-11].

The procedure is performed under general anesthesia. Lavage is done using warm saline in each lung while the other lung is independently ventilated and oxygenated. In adults 1 to 1.5 liters of warm saline is required for each lavage [11]. In some cases 10 to 15 sessions may be required for complete clearing of the lungs. We were able to get good response with four session of lung lavage and used a single lumen endotracheal tube due to non-availability of DETT.

Oxygen saturation was monitored during WLL but we did not encounter any event of respiratory compromise during the procedure. It is suggested that chest percussion during the lavage significantly increases the recovery of the lipoproteinaceous material [10]. Complications of whole lung lavage include malpositioning of the endotracheal tube, saline spillover into the unlavaged ventilated lung and hydropneumothorax. We did not encounter any of these complications even with the single endotracheal tube lavage and we experienced that if lavage fluid was sucked in time it did not cause any respiratory compromise. Immediate improvement in symptoms is seen after WLL, which we also observed in our patient. It is suggested that 30-40 % patients may require only one lavage, while others require repeated lung lavage for longer period at regular intervals [7].

Good chest physiotherapy after steam inhalation will decrease the necessity of repeated lavage in many patients. In some cases that show poor response to WLL, high doses of growth factor are used but the response in variable [7]. Lung transplantation has been performed in patients who deteriorate despite whole lung lavage, but recurrence in the allograft has been reported [12]. There is limited role of corticosteroids or other immunosuppressive agents in PAP; corticosteroids may actually increase mortality [13].

In summary the diagnosis of PAP may be delayed due to the rarity of the condition; however, bronchio-alveolar lavage and lung biopsy is confirmatory. Once the diagnosis is made treatment by whole lung saline lavage will give immediate relief in most patients.

 

 

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