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Observational Study
. 2022 Oct 25:2022:1589660.
doi: 10.1155/2022/1589660. eCollection 2022.

Assessment of Statin Treatment for Pulmonary Alveolar Proteinosis without Hypercholesterolemia: A 12-Month Prospective, Longitudinal, and Observational Study

Shenyun Shi  1 , Xianhua Gui  1 , Jingjing Ding  1 , Shangwen Yang  2 , Xiaoyan Xin  2 , Kaifeng Xu  3 , Yonglong Xiao  1
Affiliations
Observational Study

Assessment of Statin Treatment for Pulmonary Alveolar Proteinosis without Hypercholesterolemia: A 12-Month Prospective, Longitudinal, and Observational Study

Shenyun Shi et al. Biomed Res Int. .

Abstract

Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia.

Methods: In a prospective real-world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow-up.

Results: Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody and baseline total cholesterol/high-density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035, respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738-0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study.

Conclusions: In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flow diagram of the study population.
Figure 2
Figure 2
Changes in PaO2, A-aDO2, and quantitative analysis of HRCT from baseline to 1, 3, 6, 9, and 12 months of follow-up.
Figure 3
Figure 3
Correlation between baseline TC/HDL level and ΔPaO2, ΔA-aDO2, ΔDLCO%pred, and Δtotal opacification of whole lung(%) in 40 PAP patients after 12 months of statin treatment.
Figure 4
Figure 4
Comparison HRCT scans of one PAP patient with complete response between baseline and 9 months follow-up by AI.
Figure 5
Figure 5
(a) Comparison the dose of atorvastatin between responders and nonresponders. (b) Receiver operating characteristic (ROC) curve of dose of atorvastatin for predicting the response to statin therapy for PAP.
See this image and copyright information in PMC

References

    1. Trapnell B. C., Whitsett J. A., Nakata K. Pulmonary alveolar proteinosis. The New England Journal of Medicine . 2003;349(26):2527–2539. doi: 10.1056/NEJMra023226. - DOI - PubMed
    1. Trapnell B. C., Nakata K., Bonella F., et al. Pulmonary alveolar proteinosis. Nature Reviews. Disease Primers . 2019;5(1):p. 16. doi: 10.1038/s41572-019-0066-3. - DOI - PubMed
    1. Beccaria M., Luisetti M., Rodi G., et al. Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. The European Respiratory Journal . 2004;23(4):526–531. doi: 10.1183/09031936.04.00102704. - DOI - PubMed
    1. Trapnell B. C., Inoue Y., Bonella F., et al. Inhaled Molgramostim therapy in autoimmune pulmonary alveolar Proteinosis. The New England Journal of Medicine . 2020;383(17):1635–1644. doi: 10.1056/NEJMoa1913590. - DOI - PMC - PubMed
    1. McCarthy C., Lee E., Bridges J. P., et al. Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis. Nature Communications . 2018;9(1):p. 3127. doi: 10.1038/s41467-018-05491-z. - DOI - PMC - PubMed

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