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Relevance of superoxide dismutase type 1 to lipoid pneumonia: the first retrospective case-control study
Yinan Hu1, Yanhong Ren1, Yinzhen Han1,2
1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, P. R. China.
Background:
Lipoid pneumonia (LP) is a rare disease caused by the accumulation of lipids and lipid-laden macrophages in the alveoli inducing damage. LP is difficult to differentiate from other similar diseases without pathological evidence, such as upper respiratory tract infection (URTI), pneumonia, cryptogenic organizing pneumonia (COP), pulmonary alveolar proteinosis (PAP), lung mucinous adenocarcinoma and pulmonary edema. Given the high misdiagnosis rate and limited statistical clinical and treatment data, there is an urgent need for novel indicators of LP. Superoxide dismutase type1 (SOD1) plays an essential role in macrophage polarization, promoting inflammation and oxidative stress, but its association with LP remains unknown.
Methods:
The clinical data of 22 patients with proven LP from January 2008 to June 2024 and their prognostic information up to June 2024 were retrospectively gathered (ClinicalTrials.gov, NCT06430008). Additionally, information on patients with URTI, bacterial and fungal pneumonia, COP, PAP, lung mucinous adenocarcinoma and pulmonary edema, was collected totaling 140 patients as control subjects. Receiver operating characteristic curve, machine learning (ML), regression and survival analyses were performed to analyze the data.
Results:
In multivariate regression analysis, the sole independent risk factor of LP was the level of SOD1 (OR 0.922, 95% CI: 0.878 ~ 0.967, P < 0.001), while smoking status (β= -0.177, 95% CI -18.645~-2.836, P = 0.008), diabetes mellitus (β= -0.191, 95% CI: -20.442~-3.592, P = 0.005), and total sialic acid (TSA) (β= -0.426, 95% CI: -0.915~ -0.433, P < 0.001) independently influenced the level of SOD1. SOD1 had the highest importance score in ML-based LP predictive models. Additionally, advanced age may be associated with higher mortality in LP.
Conclusion:
SOD1 is a potential biomarker for LP, but the smoking status, diabetes comorbidities, and TSA level need to be considered.
Insights
Superoxide dismutase type 1 (SOD1) is identified as a potential biomarker for diagnosing lipoid pneumonia (LP). Smoking, diabetes, and total sialic acid levels also influence SOD1 and LP risk.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Medical Diagnostics
Background:
- Lipoid pneumonia (LP) is a rare lung disease characterized by lipid accumulation, often misdiagnosed due to similar symptoms with other respiratory conditions.
- Accurate diagnosis of LP is challenging without pathological confirmation, highlighting the need for novel diagnostic indicators.
- Superoxide dismutase type 1 (SOD1) is implicated in macrophage function and inflammation, but its role in LP pathogenesis is unexplored.
Purpose of the Study:
- To investigate the potential of Superoxide Dismutase Type 1 (SOD1) as a diagnostic biomarker for Lipoid Pneumonia (LP).
- To identify clinical factors associated with SOD1 levels and their influence on LP.
- To develop and validate predictive models for LP using machine learning.
Main Methods:
- Retrospective analysis of clinical data from 22 LP patients and 140 control subjects with various respiratory conditions.
- Utilized receiver operating characteristic curve, machine learning (ML), regression, and survival analyses.
- Assessed the association between SOD1 levels and clinical factors including smoking status, diabetes mellitus, and total sialic acid (TSA).
Main Results:
- SOD1 level was the sole independent risk factor for LP in multivariate regression analysis (OR 0.922, P < 0.001).
- Smoking status, diabetes mellitus, and TSA levels independently influenced SOD1 levels (P < 0.01).
- SOD1 demonstrated the highest importance score in ML-based predictive models for LP; advanced age correlated with higher LP mortality.
Conclusions:
- SOD1 emerges as a promising biomarker for the diagnosis of Lipoid Pneumonia.
- Smoking status, diabetes comorbidities, and TSA levels are crucial factors to consider alongside SOD1 in LP assessment.
- Further research may integrate these factors into improved diagnostic and prognostic tools for LP.
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