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.

Pulmonary alveolar proteinosis in Korea: analysis of prevalence and incidence via a nationwide population-based study

“…Our results showed a low prevalence of PAP in Korea (4.44 per 10 6 people from 2010 to 2016), similar to that in Japan [4,11]. Inoue Y. et al, using national cohort data from 9 primary clinical research centres in Japan, reported that the prevalence of autoimmune PAP was 6.2 per 10 6 population between 1999 and 2006 [4].…”

“…This could explain the late diagnostic age of PAP observed in our current study. Recent prevalence of PAP in United States between 2008 and 2012 peaked at over 75 years followed by the aged 65-74 years also supports the global aging of PAP patients [11].…”

“…Ben-Dov I. et al, based on the results from a nationwide survey, showed that the prevalence of PAP in Israel from 1976 to 1998 was 3.7 per 10 6 population [3]. In the study using the health insurance claims data covering approximately 30 million people in the United States, the prevalence of PAP in the United States was reported as 6.9 per 10 6 population between 2008 and 2012 [11]. In addition, the incidence rate of PAP in our study (0.56 per 10 6 population at risk) was similar to that in other countries (0.49 [Japan], 0.36 [Israel]) [3,4], suggesting that the racial differences of the epidemiology of PAP are not large.…”

“…Based on several case reports and series, the peak incidence of PAP is between 30 and 40 years and it predominantly occurs in men [2][3][4][5][6][7][8][9][10]. In previous studies, the prevalence of PAP was estimated to be 3.7-6.9 per 10 6 population and incidence was estimated to be less than 1 person per 10 6 population at risk [2][3][4]11]; however, there are still limited data on the prevalence and incidence of PAP, especially in the Asian population.…”

Pulmonary Alveolar Proteinosis Syndrome

“…The prevalence of PAP in the United States determined from claims database of 15 million patients was estimated at 6.87 per million. 55 A recent report from Japan which employed a Poisson distribution to the number of cases diagnosed annually in a specific region estimated that the incidence and prevalence of autoimmune PAP is 1.65 and 26.6 per million, respectively, suggesting the prior numbers were underestimates. Autoimmune PAP accounts for approximately 90% of the cases 4,55 and the average age of diagnosis is between 39 and 43 years, with a slight male predominance.…”