Sections

Overview

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 surfactant, namely 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.^[2]

Three clinically distinct forms of PAP have been described: autoimmune (primary or idiopathic), secondary, and genetic (congenital).^{[3, 4, 5]}Genetic PAP is seen more commonly in children, while adult forms are usually autoimmune.^{[1, 3, 6, 7, 8]}The 3 distinct types of PAP differ in respect to etiology, clinical course, therapy, and outcome.^{[1, 9, 10]}

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.^{[7, 11, 12]}Surfactant production, secretion, and reuptake are normal, while surfactant catabolism in alveolar macrophages is impaired.^[13]This surfactant-derived alveolar fluid may cause increased work of breathing, a diminished surface area for gas diffusion, and, ultimately, respiratory failure.^[11]The pulmonary interstitium and airways are relatively spared.

Secondary iatrogenic lung damage may occur in the congenital form as a consequence of the required high levels of ventilator support and high-inspired oxygen concentrations.^{[14, 15]}Pulmonary macrophage dysfunction occurs, resulting in increased risk of superinfection^{[13, 16, 17]}

International statistics

PAP is extremely rare. In a 2002 report, at least 410 cases in the literature were identified.^[18]The estimated annual incidence was 0.36, and the prevalence was 3.76 cases per million population worldwide.

A 2002 French retrospective study reported 41 patients, while a 2008 Japanese study reported 248 patients.^[19]

Race-, sex-, and age-related demographics

No race predilection is reported in children or adults.

Most patients with acquired PAP are men (male-to-female ratio of 2.65:1), and 56-72% have a history of smoking.^{[1, 12, 18]} 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.^[18]

More than 90% of all cases of PAP are the autoimmune type. The median age at the time of diagnosis is between 39 and 51 years.^{[1, 12, 18]} The age distribution of PAP in children is unknown. The congenital form occurs shortly after birth.^{[11, 14, 20]}

Morbidity/mortality

In neonates with congenital alveolar proteinosis (CAP), the mortality rate associated with conventional therapy is 100%.^{[11, 14]} Lung transplantation improves survival.

In a retrospective analysis of 343 cases of acquired pulmonary alveolar proteinosis, the 5-year survival rate was 75%.^[18] 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.^[18]

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.^[18]

Clinical Presentation

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Author

Danielle M Goetz, MD Clinical Assistant Professor of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Women and Children's Hospital of Buffalo; Associate Cystic Fibrosis Center Director, Director of Pediatric Resident and Medical Student Rotation in Pediatric Pulmonology at Women's and Children's Hospital of Buffalo

Danielle M Goetz, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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, Chief, Department of Pediatrics and Pediatric Pulmonology, Tripler 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, Christian Medical and Dental Associations

Disclosure: Nothing to disclose.

Chief Editor

Girish D Sharma, MD, FCCP, FAAP Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and Rush Cystic Fibrosis Center, Rush Children's Hospital, Rush University Medical Center

Girish D Sharma, MD, FCCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Additional Contributors

Michael R Bye, MD Professor of Clinical Pediatrics, State University of New York at Buffalo School of Medicine; Attending Physician, Pediatric Pulmonary Division, Women's and Children's Hospital of Buffalo

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

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, American Thoracic Society

Disclosure: Received honoraria from Genentech for speaking and teaching; Received honoraria from Genentech for consulting; Partner received consulting fee from Boston Scientific for consulting; Received honoraria from Gilead for speaking and teaching; Received consulting fee from Caremark for consulting; Received honoraria from Vertex Pharmaceuticals for speaking and teaching.

Acknowledgements

Michael Bye, MD, Professor of Clinical Pediatrics, Division of Pediatric Pulmonology, Women & Children's Hospital of Buffalo and State University of New York at Buffalo School of Medicine

Pediatric Alveolar Proteinosis

Background

Pathophysiology

Epidemiology

International statistics

Race-, sex-, and age-related demographics

Prognosis

Morbidity/mortality

Pediatric Alveolar Proteinosis

Background

Pathophysiology

Epidemiology

International statistics

Race-, sex-, and age-related demographics

Prognosis

Morbidity/mortality

References

Tables

Contributor Information and Disclosures

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