The burden of autoimmune pulmonary alveolar proteinosis: a systematic review

Clinical Snapshot

Key Findings

• Effect Size: Not applicable - descriptive systematic review

• Primary Outcome: Multifactorial disease burden including clinical manifestations, diagnostic delays, treatment burden, and healthcare costs

• Nnt Or Sensitivity: Not applicable - burden assessment study

• Confidence Interval: Not reported

Clinical Application

High - findings inform clinical awareness and diagnostic approaches Relevant to Australian practice; aPAP is rare globally requiring specialist respiratory care. May inform PBS considerations for emerging therapies and guide referral patterns to tertiary centres Patients with suspected or confirmed autoimmune pulmonary alveolar proteinosis

Abstract

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is characterised by abnormal alveolar surfactant accumulation and reduced pulmonary gas transfer. Disease severity and progression depend on pulmonary surfactant accumulation, the rate of which varies widely among patients. Currently, whole-lung lavage (WLL) is the most widely accepted therapy. This review addresses the burden of aPAP on patients, caregivers and society. METHODS: MEDLINE and Embase databases were systematically searched for reports on the manifestations, treatment burden, caregiver impact and healthcare costs of aPAP published after 2000. RESULTS: Out of 1023 publications identified, 50 reported relevant data (for 2855 aPAP patients), including 43 observational studies and seven phase 2/3 trials. Commonly reported symptoms included dyspnoea, cough and sputum production. Clinical manifestations included progressive hypoxaemia, reduced exercise capacity, reduced quality of life, and an increased rate of serious infections. Low prevalence and nonspecific signs and symptoms contributed to delayed diagnosis of aPAP, frequent misdiagnoses, use of multiple tests with nondiagnostic results, and therapies that were inappropriate or exacerbated the disease. WLL was the most frequently administered therapy, and many patients required repeat procedures. Medical care costs were higher for PAP patients than for non-PAP control patients. CONCLUSIONS: The results highlight the multifactorial and substantial burden of aPAP on patients. Significant unmet needs remain, particularly in achieving timely and accurate diagnosis and in providing effective, well-tolerated therapies that address the underlying pathophysiology of the disease.

References

1. 1.McCarthy, C., Bonella, F., Wang, T., Inoue, Y., Robinson, B., & Trapnell, B. C. (2026). The burden of autoimmune pulmonary alveolar proteinosis: a systematic review. European Respiratory Review, 35(160). https://doi.org/10.1183/16000617.0237-2025