Disease background and relevant pathobiology/epidemiology that the proposed study addresses
COPD is a common chronic respiratory disease that seriously endangers human health. At present, according to the World Health Organization, there are about 300 million COPD patients worldwide, and COPD has become the fourth cause of death in the world [1]. The global consumption of drugs for COPD reaches more than US$44 billion dollars annually [2]. However, existing therapies have not really altered the prognosis of COPD, especially for AECOPD, which significantly decreases the quality of life and increases mortality [1, 3, 4].
Systemic glucocorticoid therapy can shorten the course of acute exacerbation of COPD, improve lung function and arterial blood oxygen, reduce the risk of treatment failure, and shorten the length of stay [5, 6]. Therefore, the current guidelines recommend systemic glucocorticoids as one of the conventional treatment drugs for acute exacerbation of lung obstruction [5, 6]. However, in recent years, some scholars have questioned the therapeutic value of systemic glucocorticoid therapy in the acute exacerbation of COPD, and there may be treatment-related risks [7]. The results of multiple studies have shown that systemic glucocorticoid therapy does not benefit all patients with acute exacerbation of COPD, and the failure rate of glucocorticoid therapy is 14.5–39%, which is mainly manifested as persistent non-relief or aggravation of disease symptoms [8,9,10]. In patients with acute exacerbation of COPD who require mechanical ventilation, systemic glucocorticoid therapy fails to improve the mortality rate and shorten the length of stay in the ICU. On the contrary, it also increases the risk of diabetes [11], which may be caused by glucocorticoids. The catabolism of skeletal muscle is strong, which in turn leads to a decrease in respiratory muscle volume and weakened respiratory muscle strength [12].
Metabolomics mainly uses high-throughput detection techniques such as nuclear magnetic resonance, liquid chromatography (LC), or gas chromatography (GC) combined with mass spectrometry (MS) to qualitatively and quantitatively study the pathophysiological stimulation or genetic genes of living organisms [13]. Metabolomics is mainly concerned with the dynamic changes of various small molecular metabolites, which can reflect the functional state of cells more truthfully and sensitively [14, 15]. In the past ten years, metabolomics has been gradually applied to many research fields such as the pathogenesis of COPD, disease diagnosis, and disease phenotype.
It has been found that metabolomics has a good application prospect for predicting glucocorticoid response and side effects. Bordage et al. compared the administration of dexamethasone in healthy subjects The dynamic changes of plasma metabolite profile before and after a single administration of 4 mg showed that a variety of plasma metabolites changed significantly after administration of dexamethasone, and there were significant differences between individuals and were not affected by treatment [16]. According to changes in metabolites over time and individual differences, it may help to detect serious adverse effects of glucocorticoids early, optimize individual treatment plans, and reduce medical expenditures.
Therefore, based on the current research status at home and abroad and the foundation of the previous research work of this research group, we propose the hypothesis of this research: in patients with acute exacerbation of COPD, the individual differences in the profile of metabolic markers may be related to the success rate of systemic glucocorticoid therapy and the recent It is related to long-term curative effect, combined with metabonomic analysis and some characteristic clinical data to construct a predictive model, which may help to screen outpatients with acute exacerbation of COPD who respond well to systemic glucocorticoid therapy, and guide the treatment of acute exacerbation of COPD.
This research group will use the established high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC–QTOF–MS) and gas chromatography-mass spectrometry (GC–MS) analysis methods to apply to patients receiving systemic glucocorticoid therapy Serum metabonomics analysis of patients with acute exacerbation of the COPD, comparing the differences in serum metabolic marker profiles between the successful glucocorticoid treatment group and the glucocorticoid treatment failure group, and through multivariate data statistical analysis, metabolite database retrieval, standard comparison and other methods, Screen out possible metabolic markers related to the outcome of systemic glucocorticoid therapy, and further combine with characteristic clinical data to construct a mathematical model to predict the effect of systemic glucocorticoid therapy.