Pulmonary alveolar proteinosis
ICD-10 J84.0 · ICD-11 CB04.31

Confirmed autoimmune PAP with raised GM-CSF autoantibodies — treatment when whole lung lavage or inhaled GM-CSF has not worked

Clinical scenario

This protocol is for patients with confirmed autoimmune pulmonary alveolar proteinosis (aPAP) who have raised GM-CSF autoantibody titres and who have active or worsening disease. Treatment is indicated when disease is active or deteriorating.

When first-line treatment has not reached its goals

Bilateral whole lung lavage (WLL) and/or inhaled GM-CSF are the established first-line approaches in aPAP. Escalation to the next step is indicated when a patient remains symptomatic and has not achieved the expected outcomes at 6 months — including symptomatic improvement, improved walking distance, a reduced alveolar–arterial oxygen gradient, and improved oxygenation and diffusion capacity.

Next-line treatment approach partial

For patients with confirmed aPAP who remain symptomatic and require supplemental oxygen despite WLL or inhaled GM-CSF, the protocol involves rituximab, a B-cell depleting monoclonal antibody. The complete regimen — including schedule, monitoring, and follow-up plan — is in the full structured protocol.

Treatment goals (assessed at 6–12 months)

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References

DOI: 10.1183/20734735.0224-2024

Treatment is indicated in patients with active or worsening disease.

GM-CSF antibody measurement is objective, reproducible and has high accuracy for diagnosing aPAP with a level of 10.2 µg·mL−1 or above the threshold of the individual laboratory references.

We recommend inhaled GM-CSF for symptomatic patients with confirmed aPAP (strong recommendation for the intervention; very low certainty of evidence).

We suggest the use of rituximab for patients with confirmed aPAP who remain symptomatic, requiring supplemental oxygen, despite WLL therapy or exogenous GM-CSF treatment (conditional recommendation, very low certainty).

Pooled analysis suggest rituximab may improve PA–aO2 (MD −11.83 mmHg, 95% CI −23.76, 0.10) and PaO2 on room air (MD 11.94 mmHg; 95% CI −4.17, 28.05).

There was also a suggestion of improvement in DLCO, FVC and 6-minute walk test distance.

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