Pediatric Alveolar Proteinosis Treatment & Management

Updated: Jan 16, 2021
  • Author: Danielle M Goetz, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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Treatment

Medical Care

The appropriate management depends on the patient's age at presentation, the severity of symptoms, and the anticipated course of the disease. Any predisposing conditions (eg, malignancy, infection) should be treated because resolution of the primary condition may lead to remission of secondary pulmonary alveolar proteinosis (PAP). Reports describe spontaneous remission of primary PAP without medical intervention. [9, 18] Treatment of congenital (genetic) PAP is often difficult. [31] In lysinuric protein intolerance, even after lung transplant, PAP can recur and lead to relapse and death.

Mechanical ventilation

Mechanical ventilation is necessary in children with congenital PAP. No reports show any benefit from the use of high-frequency oscillatory ventilation (HFOV) or other unconventional forms of mechanical ventilation. [7]

Gene therapy

Because congenital (genetic) PAP is a single-gene defect, it may be a candidate disease for gene therapy. GM-CSF therapy does not seem to be effective in these cases. [12]

Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy

Several trials of GM-CSF therapy for autoimmune PAP have shown encouraging results. [32, 33] In a meta-analysis of the efficacy of GM-CSF therapy in autoimmune PAP, there were 5 observational studies (94 patients), which showed a response rate of 43-92%, with the pooled response rate being 58.6% (95% confidence interval, 42.7-72.9). [24]  In a more recent randomized, controlled trial, inhaled GM-CSF appeared to have only modest salutary laboratory effects on arterial oxygen tension without clinical benefits in mild-to-moderate autoimmune PAP. [34]

GM-CSF may be inhaled or subcutaneously administered and may be considered an alternative to whole-lung lavage. However, sargramostim (Bayer) was withdrawn from several national markets and may require specific permission from national health authorities, depending on the country. [12]

Rituximab

Rituximab (monoclonal antibody against B lymphocyte specific antigen CD20) treatment decreased anti-GM-CSF antibody levels in BAL fluid in 7 of 9 patients. Rituximab appeared to improve alveolar macrophage lipid metabolism (reduction in Oil Red O intensity in alveolar macrophages) and increased total protein and surfactant protein A levels. [35]

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Surgical Care

The mainstay of therapy in PAP is whole-lung lavage. Patients who undergo lavage during the course of their illness have improved survival rates. In addition, 84% of the published cases reported clinical, physiologic, and radiographic improvements after initial therapeutic lavage. [18, 36] Response rates substantially differ when patients are divided into cohorts by age. Patients younger than 20 years old have a 58% response compared with 90% patients older than 40 years. [18]

The mechanism of improvement is unknown but is presumed to be the removal of surfactant buildup or minimizing the effect of macrophage dysfunction. Successful treatment with lobar lavage with fiberoptic bronchoscopy is also reported.

Other surgical options include extracorporeal membrane oxygenation (ECMO) and lung transplantation. [1, 37]

  • Lung lavage

    • In brief, the procedure involves single-lung ventilation while the contralateral lung is lavaged with sodium chloride solution. A double-lumen endotracheal tube (ETT) is used in older children to allow for simultaneous ventilation of one lung and lavage of the contralateral lung with the patient under general anesthesia. [38, 39, 40, 41, 42]

    • Isotonic sodium chloride solution with or without heparin is generally instilled into the lungs. The patient is ventilated with 100% oxygen, and the dependent lung is filled with 3-5 mL/kg of fluid and drained. Lavage is repeated until no sediment material is obtained.

    • The lungs retain variable amounts of fluid. Chest percussion is reported to improve the yield of material. The patient should be intermittently suctioned through the ETT after the procedure to remove any residual fluid.

    • Serum electrolyte levels should be monitored because fluid fluxes may cause electrolyte imbalances.

    • The use of whole-lung lavage is less well established in young infants and newborns than in others primarily because of the technical difficulties associated with passing a necessarily large ETT through a small glottis. However, the success rate of this procedure is described in infants as small as 5 kg. In smaller infants, whole-lung lavage performed while the infant is receiving cardiopulmonary bypass or ECMO is reported.

    • A technique was described using a balloon-wedge pressure catheter into a main bronchus through the endotracheal tube. Complete filling of the lung was indicated by slight proximal movement of the catheter balloon. [43]

    • Spock reported the use of a nasotracheal tube and a hyperbaric chamber to prevent hypoxemia. [44]

  • ECMO: ECMO may provide a bridge to lung transplantation or definitive lung lavage in patients who are either too critically ill or too small to undergo lavage.

  • Lung transplantation

    • At this time, the only definitive therapy for CAP is bilateral lung transplantation. [1]

    • PAP has recurred in lungs transplanted into adults. [45] It has also recurred in lysinuric protein intolerance in children after lung transplantation. [12]

    • Twenty-four cases of spontaneous resolution of secondary PAP were reported, suggesting some surviving patients, with or without therapy, may enter a quiescent state.

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Consultations

See the list below:

  • CAP

    • Consult a neonatologist and a pulmonologist when a patient has congenital PAP. An opinion from or a referral to a center with expertise in neonatal lung transplantation is required when this option is being considered.

    • Consultation with a geneticist should be offered to parents of a child with congenital PAP. Antenatal screening for this condition is now possible.

  • Acquired PAP

    • For the older child, consultation with a pulmonologist is mandatory.

    • The opinions of an immunologist, an infectious disease specialist, or a hematologist may also be necessary, depending on clinical findings and suspicion for secondary PAP.

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Diet

No specific diet is necessary. However, as in any chronic disease, attention should be paid to the provision of sufficient calories to maintain adequate growth. Young infants with feeding difficulties due to dyspnea may require feeding through a nasogastric or gastrostomy tube. When prescribing a high-calorie diet, ensure that the carbohydrate load is not excessive because this may exacerbate respiratory difficulties due to a high respiratory quotient and subsequent high CO2 burden.

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Activity

In general, the patient's degree of dyspnea limits his or her activity. No limitations on activity are necessary.

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