Current management strategies and the potential of inhaled GM-CSF for the treatment of autoimmune pulmonary alveolar proteinosis

ABSTRACT

Introduction: Pulmonary alveolar proteinosis (PAP) is an ultra-rare syndrome the peculiarity of which is the accumulation of surfactant within the alveolar spaces, which can lead to respiratory failure and death. The autoimmune form (approximately 90% of cases) is characterized by the presence of neutralizing autoantibodies anti granulocyte monocyte-colony stimulating factor (GM-CSF), which impair alveolar macrophage functions.

Areas covered: This review delineates the standard therapeutic strategy based on whole lung lavage (WLL) and the potentiality of the incoming inhaled treatment for PAP.

Expert opinion: WLL is the current gold standard treatment for PAP, however a number of non responders have been reported and the requirement of repeated lavages is not unusual. In addition, WLL is an invasive procedure that has not yet been standardized, which needs to be performed in specialized centers, under general anesthesia in an intensive care unit, even if associated with a low rate of complications. Inhaled GM-CSF is feasible as ‘at home’ therapy and might be a promising therapeutic option for PAP, nevertheless, definite guidelines for GM-CSF therapy are still lacking and the data supporting GM-CSF supplementation as first line treatment are not conclusive.

KEYWORDS:

• Inhaled therapy
• GM-CSF
• pulmonary alveolar proteinosis
• whole lung lavage

Article highlights

• Pulmonary alveolar proteinosis is a diffuse pulmonary syndrome characterized by the accumulation of lipoproteinaceous material, in the distal air spaces.

• Autoimmune PAP (aPAP), is the most common form of the disease (90% of patients) and is due to autoantibodies directed towards GM-CSF which impair alveolar macrophage functions.

• Bilateral sequential WLL is the current standard of care for PAP, but this technique still needs international guidelines.

• Inhaled GM-CSF is a promising therapy for PAP and randomized trials aimed at investigating its safety and efficacy in autoimmune PAP patients are currently ongoing.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.