BackgroundCOPD, characterized by chronic inflammation and airway remodeling, has significant pathological alterations in composition and deposition of the extracellular matrix. The expression of procollagen 1 C-terminal peptide (PICP) and collagen type 1 C-terminal telopeptide (ICTP), two major by-products in the synthesis and degradation of collagen, was shown to be positively correlated with inflammatory mediator levels in previous studies.PurposeIn this study, we investigated whether the serum concentrations of PICP and ICTP were associated with the inflammation level for patients with stable COPD.Patients and methodsWe collected serum samples from 25 control subjects and 20 patients with stable COPD from December 2011 to October 2012 in Shanghai Zhongshan Hospital and Shanghai Dahua Hospital. We determined concentrations of PICP, ICTP, C-reactive protein (CRP), IL-6, IL-8, and tumor necrosis factor (TNF)-α by using enzyme-linked immunosorbent assay methods.ResultsDemographic characteristics were comparable between the two groups. In patients with stable COPD, serum levels of CRP, IL-6, IL-8, and TNF-α were all elevated compared to control subjects, but only changes of IL-6 achieved statistical significance. Serum concentration of PICP was significantly elevated in patients with COPD, and level of ICTP was slightly decreased. Moreover, serum concentrations of PICP were positively correlated with the levels of both IL-6 and IL-8.ConclusionThe increased levels of serum PICP in COPD might indicate the condition of airway remodeling, and IL-6 and/or IL-8 might play an important role in stimulating collagen synthesis.

PurposeBy reanalyzing the gene expression profile GSE76925 in the Gene Expression Omnibus database using bioinformatic methods, we attempted to identify novel candidate genes promoting the development of emphysema in patients with COPD.Patients and methodsAccording to the Quantitative CT data in GSE76925, patients were divided into mild emphysema group (%LAA-950<20%, n=12) and severe emphysema group (%LAA-950>50%, n=11). Differentially expressed genes (DEGs) were identified using Agilent GeneSpring GX v11.5 (corrected P-value <0.05 and |Fold Change|>1.3). Known driver genes of COPD were acquired by mining literatures and retrieving databases. Direct protein–protein interaction network (PPi) of DEGs and known driver genes was constructed by STRING.org to screen the DEGs directly interacting with driver genes. In addition, we used STRING.org to obtain the first-layer proteins interacting with DEGs’ products and constructed the indirect PPi of these interaction proteins. By merging the indirect PPi with driver genes’ PPi using Cytoscape v3.6.1, we attempted to discover potential pathways promoting emphysema’s development.ResultsAll the patients had COPD with severe airflow limitation (age=62±8, FEV1%=28±12). A total of 57 DEGs (including 12 pseudogenes) and 135 known driving genes were identified. Direct PPi suggested that GPR65, GNB4, P2RY13, NPSR1, BCR, BAG4, and IMPDH2 were potential pathogenic genes. GPR65 could regulate the response of immune cells to the acidic microenvironment, and NPSR1’s expression on eosinophils was associated with asthma’s severity and IgE level. Indirect merging PPi demonstrated that the interacting network of TP53, IL8, CCR2, HSPA1A, ELANE, PIK3CA was associated with the development of emphysema. IL8, ELANE, and PIK3CA were molecules involved in the pathological mechanisms of emphysema, which also in return proved the role of TP53 in emphysema.ConclusionCandidate genes such as GPR65, NPSR1, and TP53 may be involved in the progression of emphysema.

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Background It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case–control study. Methods A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period. Results Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs. Conclusions Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.