Pediatric Alveolar Proteinosis 

  • Author: Anne E Stone, MD; Chief Editor: Michael R Bye, MD   more...
 
Updated: Nov 23, 2011
 

Background

Pulmonary alveolar proteinosis (PAP) is an extremely rare cause of respiratory failure in the pediatric age group. PAP is characterized by intra-alveolar accumulation of lipid and proteinaceous material that is periodic acid-Schiff (PAS) positive when visualized on light microscopy.[1, 2] The disease is not associated with inflammation, and lung architecture is typically preserved. The clinical course of PAP varies and ranges from respiratory failure and death to spontaneous resolution.

Three clinically distinct forms of PAP have been described: congenital, secondary, and acquired.[2] More than 90% of cases occur as an acquired (idiopathic) disorder, typically in adults.[3, 2] The 3 distinct types of PAP differ in respect to etiology, clinical course, therapy, and outcome.[1, 2, 4]

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Pathophysiology

The alveolar airspaces are filled with a dense proteinaceous-lipid fluid mix, which is thought to occur secondary to impaired clearance of surfactant by alveolar macrophages.[5, 3] This surfactant-derived alveolar fluid may cause increased work of breathing, a diminished surface area for gas diffusion, and, ultimately, respiratory failure.[5] The pulmonary interstitium and airways are relatively spared.

Secondary iatrogenic lung damage may occur in the neonatal form as a consequence of the required high levels of ventilator support and high-inspired oxygen concentrations.[6, 7] The development of superinfection, which is thought to be a relatively common consequence of pulmonary macrophage dysfunction, may further complicate the condition.[8, 9]

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Epidemiology

Frequency

International

  • PAP is extremely rare. In a 2002 report, at least 410 cases in the literature were identified.[10] The estimated annual incidence was 0.36, and the prevalence was 3.76 cases per million population worldwide.

Mortality/Morbidity

  • In neonates with congenital alveolar proteinosis (CAP), the mortality rate associated with conventional therapy is 100%.[5, 6] Lung transplantation improves survival.
  • In a retrospective analysis of 343 cases of acquired pulmonary alveolar proteinosis, the 5-year survival rate was 75%.[10] The same retrospective analysis estimated the 5-year survival rate for children younger than 5 years to be 14% ±13%, with only one of 7 young children surviving beyond 10 months. Children with late-onset disease appear to have the best likelihood for survival, but they generally require treatment with repeated lung lavage.[10]
  • Many children have prolonged oxygen dependence and other symptoms of respiratory compromise, including dyspnea, chronic cough, and failure to gain weight in the absence of recurrent PAP.[10]

Race

  • No race predilection is reported in children or adults.

Sex

  • Most patients with acquired PAP are men (male-to-female ratio of 2.65:1), and 72% have a history of smoking.[2, 10]
  • No male predominance is observed among nonsmokers with PAP; this observation suggests that the overall male predominance is secondary to a more common use of tobacco by men than by women.[10]

Age

  • More than 90% of all cases of PAP are the acquired type. The median age at the time of diagnosis is 39 years.[10, 2]
  • The age distribution of PAP in children is unknown.
  • The congenital form occurs shortly after birth.[5, 6, 11]
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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  Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

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: Nothing to disclose.

Specialty Editor Board

Susanna A McColley, MD  Professor of Pediatrics, Northwestern University, The Feinberg School of Medicine; Director of Cystic Fibrosis Center, Head, Division of Pulmonary Medicine, Children's Memorial Medical Center of Chicago

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 Honoraria Consulting; Boston Scientific Consulting fee Consulting; Gilead Honoraria Speaking and teaching; Caremark Consulting fee Consulting; Vertex Pharmaceuticals Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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.

Mary E Cataletto, MD  Director of Children's Sleep Services, Winthrop Sleep Disorders Center, Mineola, NY; Professor of Clinical Pediatrics, State University of New York at Stony Brook, Stony Brook, NY

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  Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University Medical Center

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: Nothing to disclose.

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