eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Alveolar Proteinosis: Treatment & Medication

Author: Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Coauthor(s): Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland; Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Contributor Information and Disclosures

Updated: Aug 5, 2008

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 pulmonary alveolar proteinosis (PAP). Reports describe spontaneous remission of primary PAP without medical intervention.1,10 Treatment of congenital PAP is often difficult.

  • 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.3
  • Gene therapy: Because congenital PAP is a single-gene defect, it may be a candidate disease for gene therapy.
  • GM-CSF therapy: In addition, several trials of GM-CSF therapy for acquired PAP have shown encouraging results.20,21

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.10,22 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.10

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.2

  • 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.23
    • 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.
  • 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.2
    • PAP has recurred in lungs transplanted into adults.24

Consultations

  • 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.

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.

Activity

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

Medication

To date, no medical therapy has proven effective against pulmonary alveolar proteinosis (PAP). Numerous investigators report the successful use of GM-CSF in adults with PAP.2 Evidence suggests that GM-CSF leads to therapeutic responses in pediatric patients as well.25  One case report described successful therapy with intravenous immunoglobulin (IVIG) for a single case of CAP.26

Colony-stimulating factors

Seymour et al (2001) reported their experience in treating PAP with GM-CSF.20 Fourteen patients received GM-CSF at an initial dosage of 5 mcg/kg/d for 6-12 weeks. The alveolar-arterial oxygen gradient, carbon monoxide diffusing capacity, chest CT scans, and exercise test results were serially monitored. Nonresponders underwent a stepwise dose increase; 5 of 14 patients (34%) responded to a dosage of 5 mcg/kg/d, and 1 patient responded to 20 mcg/kg/d. Overall, 43% of patients responded. Among responders, the mean improvement in the difference in partial pressures of oxygen in mixed alveolar gas and mixed arterial blood (A-a DO2) was 23.2 mm Hg. Responses lasted a median of 39 weeks, and the effects were reproducible with the resumption of therapy. No serious adverse effects were noted. GM-CSF–related eosinophilia was predictive of a successful response to therapy.

Another prospective phase II trial of subcutaneous GM-CSF showed that A-a DO2 values improved in 3 of 4 patients treated with 5-9 mcg/kg/d. Values changed from 48.3 ± 20.1 mm Hg at baseline to 18.3 ± 4.2 mm Hg at week 16.21

One case report described the successful treatment of a 13-year-old patient who was given inhaled GM-CSF after whole-lung lavage failed.25


Sargramostim (Leukine)

GM-CSF stimulates division and maturation of early myeloid and macrophage precursor cells. Reported to increase granulocytes in 48-91% of patients.

Adult

Data limited; 5-20 mcg/kg/d SC reported in series and case reports

Pediatric

Not established.

Documented hypersensitivity; excessive myeloid blasts (>10%) in bone marrow or peripheral blood

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Diffuse bone ache or pain may result from stimulation of bone marrow cells; caution in malignancies with myeloid characteristics; may cause local reactions at injection site, fever, myalgia, headache, and flulike reactions; more serious complications include anaphylaxis, cardiac failure, or leaky capillary syndrome

More on Alveolar Proteinosis

Overview: Alveolar Proteinosis
Differential Diagnoses & Workup: Alveolar Proteinosis
Treatment & Medication: Alveolar Proteinosis
Follow-up: Alveolar Proteinosis
References
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Further Reading

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Keywords

alveolar proteinosis, pulmonary alveolar proteinosis, PAP, respiratory failure, congenital alveolar proteinosis, CAP, secondary pulmonary alveolar proteinosis, pulmonary macrophage dysfunction, smoking, tobacco use, neonatal respiratory distress, respiratory distress syndrome, pneumonia, sepsis, failure to thrive, dyspnea, pneumothorax, lysinuric protein intolerance, Nocardia species, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, human immunodeficiency virus, HIV, Pneumocystis species, Cryptococcus species, cytomegalovirus, polycythemia, respiratory alkalosis, hyperventilation

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Contributor Information and Disclosures

Author

Anne E Stone, MD, Fellow, Division of Pediatric Pulmonary Medicine, Columbia University Medical Center, Children's Hospital of New York-Presbyterian
Anne E Stone, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

David J Vaughan, MBBCh, Consultant Pediatrician, Department of Pediatrics, Our Lady of Lourdes Hospital, Ireland
David J Vaughan, MBBCh is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Jerry Zimmerman, MD, PhD, Professor, Department of Pediatrics/Anesthesia, University of Washington School of Medicine; Director, Division of Pediatric Critical Care Medicine, Children's Hospital of Seattle
Jerry Zimmerman, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, Society for Pediatric Research, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Susanna A McColley, MD, Director of Cystic Fibrosis Center; Head, Division of Pulmonary Medicine; Associate Professor, Department of Pediatrics, Children's Memorial Medical Center of Chicago, Northwestern University
Susanna A McColley, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Sleep Disorders Association, and American Thoracic Society
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Consulting fee Consulting; Novartis Consulting fee Consulting; Altus Consulting fee Consulting; Axcan Scandi Consulting fee Consulting; Boston Scientific Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Michael R Bye, MD, Attending Physician, Pediatric Pulmonary Medicine, Columbia University Medical Center; Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching

 
 
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