Prevalence and healthcare burden of pulmonary alveolar proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare syndrome of alveolar surfactant accumulation, resulting hypoxemic respiratory failure, and increased infection risk. Despite advances in our understanding of disease pathogenesis and the availability of improved diagnostics, the epidemiology and healthcare burden of PAP remain poorly defined. To determine the prevalence, and healthcare utilization and costs associated with PAP, we interrogated a large health insurance claims database containing comprehensive data for approximately 15 million patients in the United States. We also evaluated data from a referral-based diagnostic testing program collected over a 15-year period. The prevalence of PAP was determined to be 6.87 ± 0.33 per million in the general population, similar in males and females, and increased with age, however considering difficulties and delays in diagnosing this is likely a minimum estimate of true prevalence. PAP patients had significantly more comorbidities, health care utilization and associated costs compared to control patients precisely matched for age and gender. Between 2004 and 2018, 249 patients confirmed to have PAP were evaluated to identify the PAP-causing disease; 91.5% had autoimmune PAP, 3% had hereditary PAP caused by GM-CSF receptor mutations, 4% had secondary PAP, and 1.5% had congenital PAP. Considering the high diagnostic accuracy of serum GM-CSF autoantibody testing and predominance of autoimmune PAP, these results emphasize the importance of utilizing blood-based testing in PAP syndrome to identify the PAP-causing disease rather than invasive lung biopsies, resulting in earlier diagnosis, reduced morbidity and lower healthcare costs.

Keywords: GM-CSF autoantibody; Healthcare burden; Prevalence; Pulmonary alveolar proteinosis.

Fig. 1

Prevalence of PAP syndrome and detection of autoimmune PAP in the United States (US). a Annual prevalence of PAP syndrome was determined retrospectively between January 1, 2008 and December 31, 2012 using data from the OptumInsight health insurance claims database. Bars represent the mean (±SD) prevalence stratified by age (left) or gender (right). Statistical comparisons were done with ANOVA or Student’s t-test, respectively. b Relationship between detection of autoimmune PAP and population size. Autoimmune PAP was identified among individuals with PAP syndrome across the US between 2004 and 2018 by serum GM-CSF autoantibody testing [6] with confirmation by blood-based STAT5 phosphorylation index testing to document impaired GM-CSF signaling [7] at the Translational Pulmonary Science Center in Cincinnati. Data are expressed as the number of individuals with autoimmune PAP by state plotted against the state population obtained from the 2010 US Census [8]. The correlation between GM-CSF autoantibody positive PAP patients and state population size was evaluated by Spearman correlation