Genetic association and causal inference between lung function and venous thromboembolism

Zhang, Qiaoyun; Zhang, Xiaoyu; Zhang, Jie; Jiang, Mengyang; Zhang, Yiqiang; Zheng, Deqiang; Wu, Lijuan; Wang, Wei; Wang, Baoguo; Wang, Youxin

doi:10.1186/s12931-023-02335-3

Cited by 5 publications

(4 citation statements)

References 60 publications

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“…Pre-FEV1 and Pre-FVC are considered objective measures of respiratory health ( Zhang et al, 2023 ). As previous studies have demonstrated, reduced microbiota alpha diversity is associated with a worsening of FEV1 and an increased risk of COPD exacerbation ( Erb-Downward et al, 2011 ; Han et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)

Yue,

Zhang,

et al. 2024

Front. Pharmacol.

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Objective: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD) patients as a treatment option. However, ICS may also increase the risk of pneumonia and alter the composition of airway microbiota. In clinical application, the overuse of ICS exists pervasively and may potentially lead to adverse effects. Whether the long-term use of ICS confers enough benefit to COPD patients to justify its use so far remains unknown. Therefore, this study employed a single-center retrospective cohort study to compare alterations in airway function and the sputum microbial community structure between COPD patients who had undergone either long-term or short-term treatment with ICS.Methods: Sixty stable COPD patients who had used ICS were recruited and classified into the long-term use group (more than 3 months) and short-term use group (less than 3 months). The demographic features and clinical information of the subjects were investigated and their sputum samples were collected and subjected to metagenomic next-generation sequencing (mNGS).Results: The study found that compared with short-term ICS use, long-term ICS use did not further improve the clinical airway function, decrease the number of acute exacerbations, or decrease hospital readmission. In terms of sputum microbiota, the long-term use of ICS significantly altered the beta diversity of the microbial community structure (p < 0.05) and the top three phyla differed between the two groups. At the genus level, long-term ICS induced higher relative abundances of Abiotrophia, Schaalia, Granulicatella, Mogibacterium, Sphingobium, and Paraeggerthella compared to short-term ICS use. Additionally, alpha diversity was positively associated with clinical airway indicators (pre-bronchodilatory FEV1 and pre-bronchodilatory FVC) in the long-term ICS group. The relative abundances of Rothia, Granulicatella, Schaalia, and Mogibacterium genera had positive correlations with the eosinophil % (of all white blood cells). Conclusion: This study reveals the effect of long-term and short-term ICS use on sputum microbiota among COPD patients and provides a reference for the appropriate application of clinical ICS treatment in COPD patients.

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Section: Discussionmentioning

confidence: 99%

Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)

Yue,

Zhang,

et al. 2024

Front. Pharmacol.

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“…An exposure's causal effect was deemed indicative with a nominally significant false discovery rate (FDR < 0.05) in the IVW method, bolstered by consistent results across sensitivity tests. The heterogeneity of instrumental variables was scrutinized using Cochran’s Q test, with significant heterogeneity marked by Q _ p < 0.05 [ 21 ]. Further, the MR pleiotropy residual sum and outlier (MR-PRESSO) test was utilized to identify and adjust for horizontal pleiotropic outliers, refining our effect estimations [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Immune cell signatures and inflammatory mediators: unraveling their genetic impact on chronic kidney disease through Mendelian randomization

Hu,

Hao,

et al. 2024

Clin Exp Med

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Prior research has established associations between immune cells, inflammatory proteins, and chronic kidney disease (CKD). Our Mendelian randomization study aims to elucidate the genetic causal relationships among these factors and CKD. We applied Mendelian randomization using genetic variants associated with CKD from a large genome-wide association study (GWAS) and inflammatory markers from a comprehensive GWAS summary. The causal links between exposures (immune cell subtypes and inflammatory proteins) and CKD were primarily analyzed using the inverse variance-weighted, supplemented by sensitivity analyses, including MR-Egger, weighted median, weighted mode, and MR-PRESSO. Our analysis identified both absolute and relative counts of CD28 + CD45RA + CD8 + T cell (OR = 1.01; 95% CI = 1.01–1.02; p < 0.001, FDR = 0.018) (OR = 1.01; 95% CI = 1.00–1.01; p < 0.001, FDR = 0.002), CD28 on CD39 + CD8 + T cell(OR = 0.97; 95% CI = 0.96–0.99; p < 0.001, FDR = 0.006), CD16 on CD14–CD16 + monocyte (OR = 1.02; 95% CI = 1.01–1.03; p < 0.001, FDR = 0.004) and cytokines, such as IL-17A(OR = 1.11, 95% CI = 1.06–1.16, p < 0.001, FDR = 0.001), and LIF-R(OR = 1.06, 95% CI = 1.02–1.10, p = 0.005, FDR = 0.043) that are genetically predisposed to influence the risk of CKD. Moreover, the study discovered that CKD itself may causatively lead to alterations in certain proteins, including CST5(OR = 1.16, 95% CI = 1.09–1.24, p < 0.001, FDR = 0.001). No evidence of reverse causality was found for any single biomarker and CKD. This comprehensive MR investigation supports a genetic causal nexus between certain immune cell subtypes, inflammatory proteins, and CKD. These findings enhance the understanding of CKD's immunological underpinnings and open avenues for targeted treatments.

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“…Therefore, it is likely that the risk of VTE development in CTD-ILD patients will increase with their increasing lung fibrosis and decreasing DLCO levels [ 84 ]. Lower lung function is also thought to be associated with the development of VTE [ 85 ]. Severe pulmonary fibrosis and decline in lung function can trigger hypoxia in patients, and hypoxia-inducible factor (HIF) will activate the hypoxia signaling pathway, induce platelet activation and regulate the levels of prothrombotic and antithrombotic factors, which can promote thrombosis and even lead to VTE [ 86 ], in which the activation of the nucleotide binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammatory vesicle complex mediated by HIF-1α plays a key role [ 87 ].…”

Section: Vte Associated With Ctd-ildmentioning

confidence: 99%

Under the dual effect of inflammation and pulmonary fibrosis, CTD-ILD patients possess a greater susceptibility to VTE

Jiang,

Jia,

Dong

2024

Thrombosis J

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As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient’s pre-existing pulmonary fibrosis, which will continue to increase the patient’s risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients’ coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention.

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Genetic association and causal inference between lung function and venous thromboembolism

Cited by 5 publications

References 60 publications

Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)

Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)

Immune cell signatures and inflammatory mediators: unraveling their genetic impact on chronic kidney disease through Mendelian randomization

Under the dual effect of inflammation and pulmonary fibrosis, CTD-ILD patients possess a greater susceptibility to VTE

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