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Thorax 55:67-77 doi:10.1136/thorax.55.1.67
  • Review series
  • Rare diseases • 6

Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis

  1. Pallav L Shaha,
  2. David Hansella,
  3. Peter R Lawsonb,
  4. Kenneth B M Reidb,
  5. Cliff Morgana
  1. aRoyal Brompton Hospital and Imperial College School of Medicine at the National Heart & Lung Institute, London SW3 6NP, UK, bMRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
  1. Dr C Morgan, Department of Anaesthesia & Intensive Care Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK

    Pulmonary alveolar proteinosis was first described by Rosenet al in 1958.1 It is an unusual diffuse lung disease characterised by the accumulation of large amounts of a phospholipoproteinaceous material in the alveoli. It has a variable clinical presentation and course. Most cases are primary but occasionally the condition is secondary to other conditions or inhalation of chemicals. Whole lung lavage remains the most effective treatment and the overall prognosis is good. Surfactant homeostasis is abnormal and animal experiments suggest that this may relate, in some instances at least, to defects in GM-CSF signalling. There are at least two congenital forms of the disease and several different animal models suggesting that pulmonary alveolar proteinosis is unlikely to be a single disease entity and more likely to represent a clinical syndrome.

    Epidemiology

    Pulmonary alveolar proteinosis is a rare lung disease and accurate estimates of incidence are not available. Current estimates suggest an incidence of one in two million people. The series reported in the literature suggest a male preponderance (male:female ratio 3:1).1-11 Peak onset is in the third or fourth decade of life with over 80% of reported cases occurring in this age group.1-9 However, there are reports of the disease occurring in neonates,12 children,13-15 and the elderly.11

    Clinical features

    CLINICAL PRESENTATION

    Dyspnoea is the most common presenting symptom. It usually occurs on moderate exertion but in a few patients occurs at rest.1-11 Cough is the other common symptom. These symptoms are often trivial and some patients do not present until they develop a supervening infection. This may explain the acute onset of symptoms and fever observed in some patients. A low grade fever may also occur as a consequence of pulmonary alveolar proteinosis in the absence of secondary infection.6

    Physical examination is often normal and inspiratory crackles …