Yang Hao,1,* Hanyu Zheng,2,3,* Wenqiong Xiang,4,* Fangjun Chen,1,5 Guangliang Qiang6 

1Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2China-Japan Friendship Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3National 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, People’s Republic of China; 4Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, People’s Republic of China; 5China-Japan Friendship Institute of Clinical Medicine, Beijing, 100029, People’s Republic of China; 6Department of Thoracic Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Guangliang Qiang, Department of Thoracic Surgery, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Email pkudd@bjmu.edu.cn

Background: Epidemiological study has confirmed an association between hypothyroidism and pneumonia, but the causal relationship between the two remains unclear.
Methods: The National Health and Nutrition Examination Survey (NHANES) data were used to confirm the correlation between hypothyroidism and pneumonia. Mendelian randomization (MR) studies were conducted to explore the potential causal relationship. Co-expressed differential genes were used to identify potential mechanisms and potential drugs for pneumonia treatment, CCK8 and qPCR were used to detect the safety and efficacy of potential drugs. Molecular docking and Western blot assays were used to explore potential underlying mechanism of pneumonia treatment.
Results: The NHANES and MR (Training set: OR=47.88, 95% CI: 8.432– 271.8, P=1.3e-5; Test set: OR=1.849, 95% CI: 1.029– 3.323, P=4.0e-5) analyses indicated that hypothyroidism may increase the risk of pneumonia. Moreover, increasing the usual walking pace was associated with a reduced risk of pneumonia, and sensitivity analysis indicated these results were robust. Hypothyroidism may increase the risk of pneumonia through the JAK-STAT signaling pathway. Garcinol was identified as a compound that attenuates lipopolysaccharide (LPS)-induced pneumonia via inhibiting the expression level of p-STAT1.
Conclusion: Hypothyroidism may elevate the risk of pneumonia, highlighting the need for preventive measures among hypothyroid patients, such as increasing walking pace. Additionally, garcinol shows potential therapeutic effects for pneumonia management.
Plain Language Summary: Why was the study done - The clinical, economic, and humanistic burdens caused by pneumonia have always been a concern. It is particularly important to further analyze the potential risk factors, protective factors and therapeutic drugs of pneumonia.
What did the researchers do and find - There is a potential causal relationship between hypothyroidism and the risk of pneumonia, increasing the usual walking pace may help reduce the risk of pneumonia, and garcinol may have a therapeutic effect on LPS-induced pneumonia by reducing the phosphorylation level of STAT1.
What do these results mean - The relationship between hypothyroidism and pneumonia will receive further attention and increased walking speed and garcinol may play a further role in the prevention and treatment of pneumonia.

Keywords: hypothyroidism, pneumonia, mendelian randomization, nhanes, walking, garcinol