Dataset Information

Characteristics of hospital admissions for pulmonary alveolar proteinosis: analysis of the nationwide inpatient sample (2012-2014).

ABSTRACT:

Background

Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome involving the accumulation of lipid-rich proteinaceous material in the alveoli. There is a paucity of published studies on this condition. To better characterize the demographics, complication rates, mortality, and healthcare costs of patients hospitalized for PAP in the United States, a secondary analysis on the Hospital Cost and Utilization Project's Nationwide Inpatient Sample (NIS) was performed on patients admitted from 2012 to 2014 with a diagnosis of pulmonary alveolar proteinosis.

Methods

Using the NIS database, a secondary analysis was performed on 500 admissions with the diagnosis "pulmonary alveolar proteinosis." The clinical variables and outcome measures extracted were: patient demographics, hospital costs, length of stay, frequency of admissions, and inpatient mortality rate.

Results

Among a weighted estimate of 500 hospital admissions from 2012 to 2014, the number of PAP admissions averaged 4.7 per million. The population was predominantly male (55%) with a mean age of 41.45 (CI 38.3-44.5) from all socioeconomic levels. Inpatient mortality was calculated to be 5%, which may result from the fact that the majority of admitted patients had few or no comorbid conditions (CCI 0.72). The most common procedure performed during admission was a bronchoalveolar lavage. Mean length of stay was 6.2 days (CI 3.9-8.5) and average cost of admission was $29,932.20 (CI 13,739-46,124). Of note, 50% of these admissions were considered "elective."

Conclusions

Demographics of patients with PAP who have been hospitalized in the United States are similar to previously reported demographics from prior patient cohorts, specifically a male predominance and a mean age in the 40 s. The inpatient mortality rate of 5% we found is consistent with prior studies demonstrating good disease-specific survival rates. Notably, the cost per admission and overall annual cost associated with PAP hospitalization was calculated to be $29932.20 and $5 million respectively. This reflects the high economic cost associated with hospitalization of PAP patients, and provokes thought about ways to make treatment more cost-effective.

SUBMITTER: Kim C

PROVIDER: S-EPMC9509629 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Characteristics of hospital admissions for pulmonary alveolar proteinosis: analysis of the nationwide inpatient sample (2012-2014).

Kim Chongiin C Garcia-Tome Rodrigo R Hurtado Carolina C Ding Li L Wang Tisha T Chang Ching-Fei CF

BMC pulmonary medicine 20220924 1

<h4>Background</h4>Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome involving the accumulation of lipid-rich proteinaceous material in the alveoli. There is a paucity of published studies on this condition. To better characterize the demographics, complication rates, mortality, and healthcare costs of patients hospitalized for PAP in the United States, a secondary analysis on the Hospital Cost and Utilization Project's Nationwide Inpatient Sample (NIS) was performed on patients a ...[more]

PMID: 36153570

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Project description:Pulmonary alveolar proteinosis (PAP) is an umbrella term used to refer to a pulmonary syndrome which is characterized by excessive accumulation of surfactant in the lungs of affected individuals. In general, PAP is a rare lung disease affecting children and adults, although its prevalence and incidence is variable among different countries. Even though PAP is a rare disease, it is a prime example on how modern medicine can lead to new therapeutic concepts, changing ways and techniques of (genetic) diagnosis which ultimately led into personalized treatments, all dedicated to improve the function of the impaired lung and thus life expectancy and quality of life in PAP patients. In fact, new technologies, such as new sequencing technologies, gene therapy approaches, new kind and sources of stem cells and completely new insights into the ontogeny of immune cells such as macrophages have increased our understanding in the onset and progression of PAP, which have paved the way for novel therapeutic concepts for PAP and beyond. As of today, classical monocyte-derived macrophages are known as important immune mediator and immune sentinels within the innate immunity. Furthermore, macrophages (known as tissue resident macrophages (TRMs)) can also be found in various tissues, introducing e. g. alveolar macrophages in the broncho-alveolar space as crucial cellular determinants in the onset of PAP and other lung disorders. Given recent insights into the onset of alveolar macrophages and knowledge about factors which impede their function, has led to the development of new therapies, which are applied in the context of PAP, with promising implications also for other diseases in which macrophages play an important role. Thus, we here summarize the latest insights into the various forms of PAP and introduce new pre-clinical work which is currently conducted in the framework of PAP, introducing new therapies for children and adults who still suffer from this severe, potentially life-threatening disease.

Project description:Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPAR?) and the PPAR?-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation.This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages.BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes.Mean PPAR? and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p???0.05) after treatment. Lysosomal phospholipase A2 (LPLA2) (a key enzyme in surfactant degradation) mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPAR? KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy.Reduction in GM-CSF autoantibodies by rituximab therapy improves alveolar macrophage lipid metabolism by increasing lipid transport and surfactant catabolism. Mechanisms may involve GM-CSF stimulation of alveolar macrophage ABCG1 and LPLA2 activities by distinct pathways.

Project description:IntroductionPulmonary alveolar proteinosis (PAP) is a rare lung syndrome characterized by the accumulation of surfactant in the alveoli. Using a longitudinal claims database, we compared measures of clinical and economic burden between a sample of diagnosed PAP patients and non-PAP matched controls.MethodsPAP patients were identified leveraging IPM.ai's longitudinal U.S. claims database spanning January 1, 2009, through May 1, 2022. PAP patients were selected based on the presence of ICD-10: J84.01 or ICD-9: 516.0 in their claims history and were indexed for observation. An age, gender, and geographically matched control cohort was created (ratio of 1:4) for comparison. A third cohort, consisting of likely undiagnosed PAP patients, was identified using a machine learning model. The PAP and control cohorts were tracked longitudinally, depending on individual index dates, from January 1, 2018, through May 1, 2023. Inclusion criteria required evidence of continual claims activity 12 months prior to and after the index date, which reduced the total number of diagnosed PAP and control patients in the analysis. Demographics, comorbidities, procedures, medication use, annual healthcare resource utilization (HCRU), and costs were calculated for eligible PAP and control patients and were compared 12 months prior to, and 12 months after each patient's index date.ResultsAfter inclusion criteria were applied, 2312 confirmed PAP patients and 9247 matched controls were included in the analysis. Compared with matched controls, PAP patients had significantly higher rates of diagnosed conditions at baseline as defined by the Charlson Comorbidity Index (CCI). During the follow-up period, PAP patients had higher rates of diagnosed conditions, procedures, medication use, and cost-of-care compared with controls. PAP patients also had higher rates of emergency room visits (35% vs. 14%; P < 0.001), outpatient visits (87% vs. 56%; P < 0.001), inpatient visits (20% vs. 5%; P < 0.001) and had longer lengths of stay for inpatient hospitalizations (2.8 days vs. 0.56 days; P < 0.001), respectively.ConclusionThis study represents the largest dataset of PAP patients and matched controls to be analyzed to date. Findings indicate that PAP patients have higher rates of diagnosed conditions, procedures, medication use, HCRU, and costs compared with non-PAP patients.

Project description:BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP.MethodsIn a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24.ResultsIn total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group.ConclusionsIn patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

Dataset Information

Characteristics of hospital admissions for pulmonary alveolar proteinosis: analysis of the nationwide inpatient sample (2012-2014).

Background

Methods

Results

Conclusions

Publications

Characteristics of hospital admissions for pulmonary alveolar proteinosis: analysis of the nationwide inpatient sample (2012-2014).

Similar Datasets

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