Publications by authors named "Rongchang Chen"

169 Publications

Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2021 Apr 28. Epub 2021 Apr 28.

Pathology and Molecular Medicine, McMaster University, Canada.

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesised to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalised Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in COPD subjects compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in COPD subjects, asymptomatic smokers and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilisation of autoantibodies for diagnostic purposes.
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http://dx.doi.org/10.1152/ajplung.00518.2020DOI Listing
April 2021

Optimized combination of circulating biomarkers as predictors of prognosis in AECOPD patients complicated with Heart Failure.

Int J Med Sci 2021 4;18(7):1592-1599. Epub 2021 Feb 4.

Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, China.

Systematic inflammation, nutritional status, and cardiovascular function have been associated with the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with heart failure (HF). However, the value of their relevant biomarkers in predicting mortality has not been well defined yet. We aimed to investigate the prognostic value of circulating biomarkers including C-reaction protein (CRP)/albumin (ALB), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and N-terminal pro-brain natriuretic peptide (NT-proBNP) for AECOPD patients with HF. A retrospective study was carried out in the Second Clinical College of Jinan University from January 1, 2013 to January 31, 2019. A total of 146 cases of AECOPD complicated with HF were enrolled and classified into survivor group (n=94) and non-survivor group (n=52). The baseline characteristics, CRP/ALB ratio, NLR, PLR, serum levels of NT-proBNP, and other indicators were collected. The predictors for prognosis were analyzed by multivariate logistic regression, and the ability to predict 28-day mortality was evaluated by receiver operating characteristics curve (ROC) and the area under the curve (AUC). The patients in non-survivors had significantly higher levels of CRP, CRP/ALB, NLR, PCT and NT-proBNP, but lower ALB levels compared to the survivors [111.7 (56.9, 186.5) VS. 43.8 (10.3, 96.1) mg/L, 4.6 (2.0, 8.0) VS. 1.4 (0.3, 3.4), 22.2 (11.1, 40.1) VS. 12.0 (6.2, 24.8), 2.6 (0.2, 10.3) VS. 0.08 (0.1, 0.5) ng/ml, 17912.5 (9344.0, 34344.5) VS. 9809.0 (4415.9, 16387.2) ng/ml, 25.8 (23.2, 30.5) VS. 30.7 (27.9, 34.1) g/L; < 0.001, <0.001, 0.001, <0.001, <0.001, and < 0.001, respectively]. No significant difference in PLR was found between the two groups (=0.413). The logistic analysis revealed that CRP/ALB (OR=1.303, 95%CI: 1.145-1.483, <0.001), NT-proBNP (OR=1.041, 95%CI: 1.010-1.073, =0.009) and NLR (OR=1.010, 95%CI: 0.999-1.022, <0.001) are independent risk factors for predicting the 28-day mortality. The AUC of the ROC curves were 0.768, 0.767, 0.757, 0.723, 0.716, and 0.668 for CRP/ALB, PCT, CRP, NT-proBNP, ALB, and NLR, respectively. The combination of CRP/ALB, NLR and NT-proBNP as biomarkers was shown to have better accuracy for predicting prognosis (AUC=0.830, 95%CI: 0.761-0.899, <0.001), with a higher specificity of 80.8% and specificity of 77.7% as compared with each single biomarkers. High levels of NLR, CRP/ALB and NT-proBNP may be clinical usefully predictors for death in AECOPD patients with HF. Combination of NLR with CRP/ALB and NT-proBNP can provide a higher accuracy for predicting 28-day mortality in these patients.
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http://dx.doi.org/10.7150/ijms.52405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976571PMC
February 2021

Effect of inferior vena cava filters on pulmonary embolism-related mortality and major complications: a systematic review and meta-analysis of randomized controlled trials.

J Vasc Surg Venous Lymphat Disord 2021 May 19;9(3):792-800.e2. Epub 2021 Feb 19.

Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, People's Republic of China; State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.

Objective: Inferior vena cava (IVC) filters are often used. However, no clear consensus has been reached regarding the benefits and risks from randomized, controlled trials. Therefore, we investigated benefits and risks of IVC filter use.

Methods: The PubMed and Cochrane Library databases were searched from inception to October 31, 2019 to identify randomized, controlled trials for inclusion in our meta-analysis. The primary outcome was mortality related to pulmonary embolism (PE). The secondary outcomes were overall mortality, PE, deep vein thrombosis, and major bleeding. Risk ratios were pooled using the Mantel-Haenszel method with the fixed effects model for low heterogeneity. Otherwise, the random effects model was used. Risk differences were considered candidates of effect size if some of the data could not be pooled in the calculations.

Results: Seven articles with 1274 patients were included. We found no significant difference in mortality related to PE between the IVC filter and control groups within 3 months (risk difference, -0.01; 95% confidence interval, -0.03 to 0.00; P = .11) nor during the entire follow-up period with low heterogeneity (I = 0%). The new occurrence of PE within 3 months and during the whole follow-up period was lower in the IVC filter group than in the control group (0.81% vs 5.98%; risk ratio, 0.17; 95% CI, 0.04-0.65; P = .01; and 3.2% vs 7.79%; risk ratio, 0.42; 95% CI, 0.25-0.71; P = .001, respectively). No significant differences were found in the rates of the new occurrence of deep vein thrombosis, major bleeding, and mortality during the whole follow-up period between the two groups (P > .05).

Conclusions: We found insufficient evidence to conclude that the use of IVC filters can reduce mortality. However, the use of IVC filters decreased the new occurrence of PE without increasing deep vein thrombosis or major bleeding.
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http://dx.doi.org/10.1016/j.jvsv.2021.02.008DOI Listing
May 2021

A novel host of MCR-5 belonging to Enterobacter spp. isolated from hospital sewage water.

Environ Microbiol Rep 2021 Apr 17;13(2):234-237. Epub 2021 Feb 17.

Shenzhen Institute of Respiratory Diseases, Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, the First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, China.

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http://dx.doi.org/10.1111/1758-2229.12937DOI Listing
April 2021

Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response.

Int Immunopharmacol 2021 May 9;94:107444. Epub 2021 Feb 9.

The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China. Electronic address:

Toluene diisocyanate (TDI) exhibits an ability to induce steroid insensitive asthma with the involvement of Th17 cells. And emerging evidence has indicated that DLL4 signaling promotes Th17 differentiation through directly upregulating Rorc and IL-17 transcription. Thus, we sought to evaluate the effects of DLL4 blocking antibody on TDI-induced asthma model. Female BALB/c mice were sensitized and challenged with TDI to generate an asthma model. TDI-exposed mice were intraperitoneally injected with anti-DLL4 antibody and then analyzed for various parameters of the airway inflammatory responses. Increased expression of DLL4 in spleen and lung was detected in TDI-exposed mice. Furthermore, anti-DLL4 treatment alleviated TDI-induced airway hyperreactivity (AHR), airway inflammation, airway epithelial injury and airway smooth muscle (ASM) thickening. In the meantime, neutralizing DLL4 also blunted Th17 response via downregulation of ROR-γt expression, while had no effect on Th2 cells and regulatory T (Treg) cells. Overall, anti-DLL4 ameliorated TDI-induced experimental asthma by inhibiting Th17 response, implying the feasibility of targeting DLL4 for therapy of Th17-predominant severe asthma.
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http://dx.doi.org/10.1016/j.intimp.2021.107444DOI Listing
May 2021

Scutellarin protects against diabetic cardiomyopathy via inhibiting oxidative stress and inflammatory response in mice.

Ann Palliat Med 2021 Mar 2;10(3):2481-2493. Epub 2021 Feb 2.

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.

Background: Scutellarin (Scu) shows both anti-inflammatory and antioxidant activities. The study investigates cardioprotective effects of Scu in mice with type 1 diabetes and the underlying molecular mechanism.

Methods: Streptozotocin (STZ) was used to induce diabetic cardiomyopathy (DCM) in C57BL/6 mice by intraperitoneal injection (i.p.). Normal and diabetic mice were divided into 6 groups: control, diabetic model group (DM), DM + Scu (5 mg/kg), DM + Scu (10 mg/kg), DM + Scu (20 mg/kg), DM + pioglitazone (Pio) (10 mg/kg). Scu was administered to the mice intraperitoneally and Pio was administrated by oral. Mice in control and DM groups were simply treated normal saline. Four weeks later, myocardial function, myocardial fibrosis, the levels inflammatory factors and oxidative stress were detected.

Results: Scu improved cardiac function and reduced heart injury in diabetic mice, which was indicated by increasing Left ventricular (LV) end-diastolic volume (LVVd), fractional shortening (FS), and ejection fraction (EF) levels and decreased pathological changes of heart. Scu inhibited the level of myocardial fibrosis by reducing the release of inflammatory cytokines and increasing activities of antioxidant enzymes. Further study showed that Scu inhibited the activation of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and nuclear factor-kappa B (NF-κB) and activated phospho-protein kinase B (p-AKT), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase (HO-1).

Conclusions: Scu protects against DCM in STZ-induced diabetic mice by inhibiting oxidative stress and inflammatory responses and might be a potential therapeutic agent to treat DCM.
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http://dx.doi.org/10.21037/apm-19-516DOI Listing
March 2021

National Prevalence of Salmonella enterica Serotype Kentucky ST198 with High-Level Resistance to Ciprofloxacin and Extended-Spectrum Cephalosporins in China, 2013 to 2017.

mSystems 2021 Jan 12;6(1). Epub 2021 Jan 12.

Shenzhen Institute of Respiratory Diseases, The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, China

serotype Kentucky is frequently associated with high-level fluoroquinolone resistance and has gained epidemiological importance globally. A retrospective screening was performed to understand the national prevalence of ciprofloxacin-resistant Kentucky in China. strains (=15,405) were collected within the frame of two national surveillance networks between 2013 and 2017. Thirty-three Kentucky strains were detected in 5 of 10 provinces, and 27 were assigned to sequence type 198 (ST198). The 27 isolates were multidrug resistant, with high-level resistance to ciprofloxacin, and 21 isolates were further resistant to extended-spectrum cephalosporins (ESCs). Phylogenomic analysis classified ST198 isolates into two clades (198.1 and 198.2), and recent occurrences of inter-/intraregion and interhost transmission were identified. Phylogenetic reconstruction with a global collection showed that one subclade of clade 198.2 was clustered with historical strains from Egypt, and the other one was clustered with strains from Southeast Asia. Isolates of clade 198.1 were clustered with strains isolated from North America. The various patterns of mutations detected in quinolone resistance-determining regions of GyrA and ParC are accordant with the phylogenetic structure. These findings indicate that our isolates may have various origins. SGI1 was exclusively detected in isolates of clade 198.2 with a highly mosaic structure, which were mainly identified as SGI1-K derivatives. Plasmid-mediated quinolone resistance genes and were identified in three isolates, and and were detected in 20 of 21 ESC-resistant isolates. This is the first report of the genetic and epidemiological characterization for the Kentucky epidemic clone ST198 in China, warranting the necessity of surveillance for the high-risk clone. Ciprofloxacin and extended-spectrum cephalosporins are the choice for treatment of severe nontyphoidal infections in adults. serotype Kentucky ST198 has gained epidemiological importance globally, because the clone is frequently resistant to both of these high-level-resistance drug groups. The genetic and epidemiological characterization of Kentucky has been well studied in Western countries; however, the information is unclear for China. To fill in the gap, we here did a retrospective screening on a large collection in China, and ST198 isolates were systematically analyzed by whole-genome sequencing. Our study revealed that multidrug-resistant ST198 has spread in five provinces, and the occurrences of interregion and cross-host clonal disseminations were detected. Of note, phylogenomic analysis suggests that the Chinese isolates may have emerged with diverse origins, including Egypt, Southeast Asia, and North America. This study warrants the necessity of surveillance for the high-risk clone to prevent its further dissemination in China.
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http://dx.doi.org/10.1128/mSystems.00935-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901479PMC
January 2021

A narrative review of research advances in mesenchymal stem cell therapy for asthma.

Ann Transl Med 2020 Nov;8(21):1461

Department of Respiratory and Critical Care Medicine, Shenzhen People's Hospital (Second Clinical Medical College of Jinan University & First Affiliated Hospital of Southern University of Science and Technology), Shenzhen Institute of Respiratory Diseases, Shenzhen, China.

Asthma is a chronic inflammatory disease of the airways that involves multiple cells, including inflammatory cells, structural cells, and cellular components. Glucocorticoids and beta-receptor agonists are still the first choices for asthma treatment. However, the asthma symptoms may still be poorly controlled in some patients after an optimal treatment. Mesenchymal stem cells (MSCs) are characterized by the potential for multi-directional differentiation and can exert immunomodulatory and anti-inflammatory effects. Its role in treating asthma has increasingly been recognized in recent years. In this review article, we sought to summarize the recent advances in the therapeutic effects of MSCs on several types of asthma and explain the relevant mechanisms. Articles on asthma treatment with MSCs as of January 2020 were searched in PubMed, Google Scholar, and Web of Science databases. It was found that MSCs have therapeutic effects on allergic asthma, non-allergic asthma and occupational asthma; gene-modified or pretreated MSCs improves the therapeutic effects of MSCs in asthma; MSC-derived conditioned medium or extracellular vesicles possess the considerable curative effect as MSC on asthma; and MSCs exert their therapeutic effects on asthma by restoring Th1/Th2 balance, reversing Th17/Tregs imbalance, inhibiting DC maturation, and promoting the switch of M1 to M2 and repairing epithelial injury. Thus, MSCs may be a promising treatment for asthma.
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http://dx.doi.org/10.21037/atm-20-6389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723541PMC
November 2020

Noninvasive ventilation with a helmet in patients with acute respiratory failure caused by chest trauma: a randomized controlled trial.

Sci Rep 2020 12 8;10(1):21489. Epub 2020 Dec 8.

Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China.

Noninvasive ventilation (NIV) is beneficial in acute respiratory failure (ARF) caused by chest trauma; however, NIV-related complications affect the efficacy. We evaluated whether NIV with helmet decreases the incidence of complications and improves its effects in a single center. Patients with ARF after chest trauma were randomized to receive NIV with helmet or face mask. The primary outcome was the rate of NIV-related complications. Secondary outcomes were PaO/FiO, patient's tolerance, intubation rate, length of intensive care unit (ICU) stay, and ICU mortality. The trial was terminated early after an interim analysis with 59 patients. The incidence of complications was lower in the helmet group [10% (3/29) vs 43% (13/30), P = 0.004], and PaO/FiOs were higher at 1 h and at the end of NIV (253.14 ± 64.74 mmHg vs 216.06 ± 43.86 mmHg, 277.07 ± 84.89 mmHg vs 225.81 ± 63.64 mmHg, P = 0.013 and 0.012) compared with them in face mask group. More patients reported excellent tolerance of the helmet vs face mask after 4 h of NIV [83% (24/29) vs 47% (14/30), P = 0.004] and at the end of NIV [69% (20/29) vs 30% (9/30), P = 0.03]. Differences in intubation rate, ICU stay, and mortality were non-significant (P = 0.612, 0.100, 1.000, respectively). NIV with helmet decreased NIV-related complications, increased PaO/FiO, and improved tolerance compared with NIV with face mask in patients with chest trauma.Trial registration: Registered in the Chinese Clinical Trial Registry (ChiCTR1900025915), a WHO International Clinical Trials Registry Platform ( http://www.chictr.org.cn/searchprojen.aspx ).
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http://dx.doi.org/10.1038/s41598-020-78607-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722864PMC
December 2020

Casticin Improves Respiratory Dysfunction and Attenuates Oxidative Stress and Inflammation via Inhibition of NF-ĸB in a Chronic Obstructive Pulmonary Disease Model of Chronic Cigarette Smoke-Exposed Rats.

Drug Des Devel Ther 2020 17;14:5019-5027. Epub 2020 Nov 17.

Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People's Republic of China.

Objective: The present study was conducted to elucidate the protective effect of Casticin against chronic obstructive pulmonary disease (COPD) in rats.

Methods: The COPD in rats was induced by the controlled cigarette smoke, and CST (10, 20, and 30 mg/kg) was injected into the cigarette-smoke exposed rats. Blood was taken from the abdominal vein and centrifuged (1500×g, 4°C, 15min); plasma was collected and used for the determination of various biochemical parameters.

Results: The results of the study suggested that CST significantly improved the lung functions of the rats in a dose-dependent manner. It also causes a reduction of white blood cells, neutrophils, and macrophages in BALF of rats. The plasma level of leptin and C-reactive protein together with pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were also significantly restored to near to normal in CST-treated group. In Western blot analysis, CST causes significant inhibition of the NF-ĸB and iNOS pathway.

Conclusion: Our study demonstrated that the CST protects lungs against COPD via improving lung functions and inhibition of oxidative stress and inflammation.
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http://dx.doi.org/10.2147/DDDT.S277126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680168PMC
November 2020

ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling.

Food Nutr Res 2020 31;64. Epub 2020 Aug 31.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Background: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of to protect against DCM in db/db mice.

Methods: Male wild-type (WT) and db/db mice were administered ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting.

Results: Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and cle-caspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions.

Conclusion: Our results indicate that ECL treatment can markedly reduce pathological cardiac damage in db/db mice through antiapoptotic, antifibrotic, and anti-inflammatory mechanisms. Specifically, this extract was able to suppress NF-κB activation via the PI3K/Akt signaling pathway. Given its diverse activities and lack of significant side effects, ECL may thus have therapeutic value for the treatment of DCM.
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http://dx.doi.org/10.29219/fnr.v64.4267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534947PMC
August 2020

The Impact of Lung Function on Extra-Pulmonary Diseases and All-Cause Mortality in US Adult Population with and without COPD.

Clin Epidemiol 2020 25;12:997-1005. Epub 2020 Sep 25.

Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People's Republic of China.

Objective: Spirometric lung function is usually used to evaluate respiratory health. However, the impact of lung function on extra-pulmonary diseases and all-cause mortality has not been fully elucidated, especially in people without chronic obstructive pulmonary disease (COPD).

Patients And Methods: Participants aged ≥20 and underwent spirometry test from the US National Health and Nutrition Examination Surveys (NHANES) 2007-2012 were analyzed in this study. Multivariate logistic and Cox regressions were used to evaluate the impact of forced expiratory volume in 1 second percent of predicted (FEV% predicted) and forced vital capacity percent of predicted (FVC% predicted) on 14 extra-pulmonary diseases and all-cause morbidity after adjusting for multiple confounders.

Results: During 2007-2012, 1800 COPD patients and 11,437 non-COPD subjects were included. The prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, metabolic syndrome (MS), congestive heart failure (CHF), coronary disease, stroke, chronic kidney disease (CKD), arthritis, cancer, underweight and osteoporosis in COPD patients was higher than that in the non-COPD population. After adjusting for confounders, the decrease of FEV% predicted and FVC% predicted was related with higher odds of having hypertension, DM, obesity, MS, CHF, coronary disease and depression (OR > 1, <0.05) in both the COPD and non-COPD populations. These 2 indices were also related with higher odds of dyslipidemia, CKD, arthritis and osteoporosis in the non-COPD population. The risk of stroke, anemia and cancer was not related with the decrease of lung function. In addition, the decrease of lung function was independent risk factors for the increase of all-cause mortality. These risks were gradually increased with the decrease of lung function.

Conclusion: The decrease of FEV% predicted and FVC% predicted was related with higher risk of multiple extra-pulmonary diseases and all-cause mortality in both the COPD and non-COPD population.
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http://dx.doi.org/10.2147/CLEP.S270599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524173PMC
September 2020

Management of COVID-19 patients in Fangcang shelter hospital: clinical practice and effectiveness analysis.

Clin Respir J 2021 Mar 28;15(3):280-286. Epub 2020 Oct 28.

Department of Respiratory and Critical Care Medicine, Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, South University of Science and Technology), Shenzhen, China.

Fangcang shelter (Cabin) hospitals were set up in order to cope with the rapid growth of confirmed cases of coronavirus disease 2019 (COVID-19) in Wuhan, China at a time when there were insufficient beds in designated hospitals. This paper describes the layout and functioning of a typical Fangcang shelter hospital, Wuhan Dongxihu Fangcang shelter Hospital, where the author has worked, the working mechanism, experience and effectiveness. A set of patient management protocols was employed for daily practice, which included preset criteria and procedure for admission, examination, medication treatment, referral and discharge. WeChat platform with different groups was used for communication, ward round, test appointments and patient data communication. All these procedures and mechanisms of working enabled the effective management of a larger number of patients with relatively few doctors. As a result, 442 mild or moderate COVID-19 patients in Hall C were successfully managed by a team of 40 doctors, with 246 (56%) patients were cured and discharged from the Fangcang shelter hospital while the remaining 196 (44%) patients were referred on to designated hospitals for further treatment. The reasons for referral included poor resolution in computerized tomography (CT) scan (59%), persistently positive severe acute respiratory syndrome coronavirus 2 by PCR after 9 days of admission (16%), deterioration in CT image (4%), development of dyspnoea (1%) and other (4%) or unclear reasons (16%) due to no record of reasons for referral on the document. There were no deaths and no complaints from the patients in Hall C. In summary, the Fangcang shelter hospital could be run successfully with a set of patient management protocols under conditions of limited facilities and medical staff. It was effective and safe in isolating patients, providing basic medical care and early identification of potential severe cases. This experience may provide a successful example of a working mechanism for the prevention and control of the COVID-19 pandemic worldwide.
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http://dx.doi.org/10.1111/crj.13293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675548PMC
March 2021

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

Eur Respir Rev 2020 Sep 5;29(157). Epub 2020 Oct 5.

Dept of Medicine, Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine, New Haven CT, USA.

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research.

Methods: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion.

Results: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder.

Conclusions: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.
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http://dx.doi.org/10.1183/16000617.0287-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537943PMC
September 2020

Practical strategies to reduce nosocomial transmission to healthcare professionals providing respiratory care to patients with COVID-19.

Crit Care 2020 09 23;24(1):571. Epub 2020 Sep 23.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University Medical Center, 1620 W Harrison St, Tower LL1202, Chicago, IL, 60612, USA.

Coronavirus disease (COVID-19) is an emerging viral infection that is rapidly spreading across the globe. SARS-CoV-2 belongs to the same coronavirus class that caused respiratory illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). During the SARS and MERS outbreaks, many frontline healthcare workers were infected when performing high-risk aerosol-generating medical procedures as well as when providing basic patient care. Similarly, COVID-19 disease has been reported to infect healthcare workers at a rate of ~ 3% of cases treated in the USA. In this review, we conducted an extensive literature search to develop practical strategies that can be implemented when providing respiratory treatments to COVID-19 patients, with the aim to help prevent nosocomial transmission to the frontline workers.
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http://dx.doi.org/10.1186/s13054-020-03231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509502PMC
September 2020

Dissociation between airway and systemic autoantibody responses in chronic obstructive pulmonary disease.

Ann Transl Med 2020 Aug;8(15):918

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Autoimmune processes have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship between airway and systemic autoantibody responses remains unclear. The aim of this study was to elucidate this relationship in patients with stable COPD by investigating the correlation patterns between sputum and serum autoantibodies.

Methods: In this cross-sectional study, sputum supernatant and serum obtained from 47 patients with stable COPD were assayed for the presence of IgG antibodies against ten autoantigens: Smith antigen (Sm), ribosomal phosphoprotein P0 (P0), Ro/Sjögren syndrome type A antigen (Ro/SSA), La/Sjögren syndrome type B antigen (La/SSB), DNA topoisomerase I (Scl-70), histidyl-tRNA synthetase (Jo-1), U1 small nuclear ribonucleoprotein (U1-SnRNP), thyroid peroxidase (TPO), proteinase-3 (PR3), and myeloperoxidase (MPO). A second cohort of 55 stable COPD patients was recruited for validation, and a group of 59 non-COPD controls and a group of 20 connective-tissue disease-associated interstitial lung disease (CTD-ILD) patients were also recruited for comparison. Hierarchical clustering and network analysis were used to evaluate the correlation patterns between sputum and serum autoantibody profiles.

Results: Both hierarchical clustering and network analysis showed that sputum and serum autoantibody profiles were distinct in either analytic COPD cohort or validation cohort. In contrast, the autoantibodies of the two compartments in non-COPD controls and CTD-ILD patients were inadequately distinguished using either hierarchical clustering or network analysis. Many autoantibodies in the sputum were found to have significant correlations with lung function, symptom score and frequency of prior exacerbations in COPD patients, but the antibodies in the serum were not.

Conclusions: We observed a dissociation between sputum autoantibodies and serum autoantibodies in patients with stable COPD, suggesting that airway and systemic immune status may play very different roles in the disease. Sputum autoantibodies are more clinically relevant than serum autoantibodies. Focusing on airway autoimmunity may help improve understanding of the immunopathological mechanism of COPD.
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http://dx.doi.org/10.21037/atm-20-944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475442PMC
August 2020

Short-term oral corticosteroids for initial treatment of moderate-to-severe persistent asthma: A double-blind, randomized, placebo-controlled trial.

Respir Med 2020 10 21;172:106126. Epub 2020 Aug 21.

Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University (National Clinical Research Center for Respiratory Diseases), Guangzhou, China. Electronic address:

Background And Purpose: The purpose of this study was to investigate that on the basis of ICS-LABA treatment, whether or not adding on short course of oral corticosteroid could increase the rate of asthma control.

Methodology: This was a double blind, randomized controlled study. Patients with moderate to severe persistent asthma who are maintenance treatment naïve were recruited from the out-patients clinic. All patients included in the study received ICS-LABA as initial treatment. Two weeks oral corticosteroid or placebo were added on at the beginning of treatment. All the subjects were followed-up by daily measurement of PEF and asthma diary for 12 week and spirometry at 4 weeks and 12 weeks.

Results: 13 cases were randomized to Corticosteroid group (M/F: 9/4, age: 45.0 ± 5.0 yrs), 11 to Placebo group (M/F: 4/7, age: 35.7 ± 9.6yrs). After treatment, significant improvement in ACT、ACQ、AQLQ、FEV1、FEV1% were observed in both groups as compared with baseline data (all P < 0.05). However, there were no significant difference between two groups in the improvement of ACT、ACQ、AQLQ、FEV1、FEV1% (all P > 0.05). After 4 weeks of treatment, total control was achieved in 3 (30.8%) in corticosteroid group and 2 (18.2%) in placebo group; Partial control was achieved in 7 (61.5%)in corticosteroid group and in 7 (63.6%) in placebo group. There was no significant difference in control rates between two groups (X = 0.919, P = 0.632). Similar findings were observed after 12 weeks of treatment.

Conclusion: In maintenance treatment naïve moderate to severe persistent asthma, ICS-LABA therapy was adequate initial treatment for achieving asthma control in majority of the patients. Add on short course of oral corticosteroid provided no significant clinical benefit.
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http://dx.doi.org/10.1016/j.rmed.2020.106126DOI Listing
October 2020

Current smoking status is associated with reduced sputum immunoglobulin M and G expression in COPD.

Eur Respir J 2021 Feb 4;57(2). Epub 2021 Feb 4.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.

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http://dx.doi.org/10.1183/13993003.02338-2019DOI Listing
February 2021

A Refined View of Airway Microbiome in Chronic Obstructive Pulmonary Disease at Species and Strain-Levels.

Front Microbiol 2020 30;11:1758. Epub 2020 Jul 30.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Little is known about the underlying airway microbiome diversity in chronic obstructive pulmonary disease (COPD) at in-depth taxonomic levels. Here we present the first insights on the COPD airway microbiome at species and strain-levels. The full-length 16S rRNA gene was characterized from sputum in 98 COPD patients and 27 age-matched healthy controls, using the Pacific Biosciences sequencing platform. Individual species within the same genus exhibited reciprocal relationships with COPD and disease severity. Species dominant in health can be taken over by another species within the same genus but with potentially increasing pathogenicity in severe COPD patients. , an opportunistic pathogen, was significantly increased in frequent exacerbators (fold-change = 4.94, FDR = 0.005). There were distinct patterns of interaction between bacterial species and host inflammatory mediators according to neutrophilic or eosinophilic inflammations, two major airway inflammatory phenotypes in COPD. e, , and were associated with enhanced Th1, Th17 and pro-inflammatory mediators, while a group of seven species including were specifically associated with Th2 mediators related to eosinophilia. We developed an automated pipeline to assign strain-level taxonomy leveraging bacterial intra-genomic 16S allele frequency. Using this pipeline we further resolved three non-typeable strains PittEE, PittGG and 86-028NP with reasonable precision and uncovered strain-level variation related to airway inflammation. In particular, 86-028NP and PittGG strains exhibited inverse associations with Th2 chemokines CCL17 and CCL13, suggesting their abundances may inversely predict eosinophilic inflammation. A systematic comparison of 16S hypervariable regions indicated V1V3 instead of the commonly used V4 region was the best surrogate for airway microbiome. The full-length 16S data augmented the power of functional inference, which slightly better recapitulated the actual metagenomes. This led to the unique identification of butyrate-producing and nitrate reduction pathways as depleted in COPD. Our analysis uncovered finer-scale airway microbial diversity that was previously underappreciated, thus enabled a refined view of the airway microbiome in COPD.
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http://dx.doi.org/10.3389/fmicb.2020.01758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406711PMC
July 2020

The interstitial lung disease spectrum under a uniform diagnostic algorithm: a retrospective study of 1,945 individuals.

J Thorac Dis 2020 Jul;12(7):3688-3696

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis.

Methods: This retrospective study enrolled ILDs cases from Guangzhou Institute of Respiratory Health (GIRH). All cases were classified into specific subgroups of ILDs according to updated guidelines.

Results: A total of 1,945 subjects were enrolled from January 2012 to December 2017. The mean age was 57.9 years, and 1,080 (55.5%) patients were male. The most common subtype of ILDs was idiopathic pulmonary fibrosis (IPF, 20.3%), followed by interstitial pneumonia with autoimmune features (IPAF, 17.9%), connective tissue disease associated ILD (CTD-ILD, 18.3%) and unclassifiable idiopathic interstitial pneumonia (UIIP, 14.7%). A total of 818 (42.1%) patients underwent lung biopsy in order to obtain a histological diagnose. TBLB was performed in 565 (29.0%) patients, eleven of whom underwent SLB because TBLB failed to obtain lung samples. SLB was performed in 213 (11.0%) patients and TBCB was performed in 51 (2.6%) patients. Among them, histological results were considered clinically helpful in 722 (88.3%) cases, and provided definitive histopathological diagnoses in 368 cases. Surgical lung biopsy (SLB) was performed in 213 (10.9%) subjects, while 115 (54.0%) cases were performed among the idiopathic interstitial pneumonia (IIP). Among SLB cases in IIP, the highest rate of SLB was desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease (DIP/RB-ILD, 10/10), lymphoid interstitial pneumonia (LIP, 9/9), followed by cryptogenic organizing (COP, 18/26), nonspecific interstitial pneumonia (NSIP, 22/53), IPF (43/395), UIIP (13/285).

Conclusions: IPF was the most common ILDs in our ILD center, followed by IPAF, CTD-ILD and UIIP. Histological information may help to establish diagnostic algorithm in ILD.
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http://dx.doi.org/10.21037/jtd-19-4021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399396PMC
July 2020

Exploration of n-6 and n-3 Polyunsaturated Fatty Acids Metabolites Associated with Nutritional Levels in Patients with Severe Stable Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 10;15:1633-1642. Epub 2020 Jul 10.

Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.

Background And Objective: Severe chronic obstructive pulmonary disease (COPD) is the terminal stage of the disease characterized by declined lung function, malnutrition, and poor prognosis. Such patients cannot tolerate long-time sports rehabilitation owing to dyspnea and fail to achieve the desired therapeutic effect; therefore, increasing nutritional support will be an important strategy for them. The present study applied metabolomics technology to evaluate the correlation between serum concentrations of polyunsaturated fatty acid (PUFA) metabolites, nutritional status, and lung function in patients with COPD to provide a theoretical basis for accurate nutritional support.

Materials And Methods: We enrolled 82 patients with stable severe COPD in our hospital. The general characteristics including height, weight, and lung function were recorded. Metabolomics was used to detect the concentrations of serum metabolites of n-3 and n-6 at baseline and at 24 and 52 weeks after enrollment. The correlations between nutrition level and pulmonary function and clinical indicators were evaluated.

Results: The concentrations of n-3 and n-6 increased over time along with the progression of COPD. Body mass index (BMI) and percent of ideal body weight (IBW%) decreased with disease development, and BMI was found to be significantly correlated with FEV1% predicted and FEV1/FVC. Serum levels of n-6 metabolites such as linoleic acid (LA), γ-linoleic acid (GLA), and arachidonic acid (ARA) (all < 0.01) and the n-3 metabolites such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (all < 0.05) showed significant correlations with BMI and were closely correlated with FEV1% predicted and FEV1/FVC of lung function (all < 0.05).

Conclusion: This study demonstrates that malnutrition in patients with severe COPD is progressive and is positively correlated with n-3 and n-6 polyunsaturated fatty acids and lung function.
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http://dx.doi.org/10.2147/COPD.S245617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360408PMC
July 2020

Association of sputum microbiome with clinical outcome of initial antibiotic treatment in hospitalized patients with acute exacerbations of COPD.

Pharmacol Res 2020 10 28;160:105095. Epub 2020 Jul 28.

Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, China; South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Guangzhou, China. Electronic address:

Identification of risk factors for antibiotic treatment failure is urgently needed in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Here we investigated the relationship between sputum microbiome and clinical outcome of choice of initial antibiotics during hospitalization of AECOPD patients. Sputum samples of 41 AECOPD patients and 26 healthy controls were collected from Guangzhou Medical University, China. Samples were processed for 16S rRNA gene-based microbiome profiling. Thirty patients recovered with initial antibiotic treatment (antibiotic success or AS), while 11 patients showed poor outcome (antibiotic failure or AF). Substantial differences in microbiome were observed in AF versus AS patients and healthy controls. There was significantly decreased alpha diversity and increased relative abundances of Pseudomonas, Achromobacter, Stenotrophomonas and Ralstonia in AF patients. Conversely, Prevotella, Peptostreptococcus, Leptotrichia and Selenomonas were depleted. The prevalence of Selenomonas was markedly reduced in AF versus AS patients (9.1 % versus 60.0 %, P = 0.004). The AF patients with similar microbiome profiles in general responded well to the same new antibiotics in the adjusted therapy, indicating sputum microbiome may help guide the adjustment of antibiotics. Random forest analysis identified five microbiome operational taxonomic units together with C-reactive protein, procalcitonin and blood neutrophil count showing best predictability for antibiotic treatment outcome (area under curve 0.885). Functional inference revealed an enrichment of microbial genes in xenobiotic metabolism and antimicrobial resistance in AF patients, whereas genes in DNA repair and amino acid metabolism were depleted. Sputum microbiome may determine the clinical outcome of initial antibiotic treatment and be considered in the risk management of antibiotics in AECOPD.
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http://dx.doi.org/10.1016/j.phrs.2020.105095DOI Listing
October 2020

Multi-omic meta-analysis identifies functional signatures of airway microbiome in chronic obstructive pulmonary disease.

ISME J 2020 11 27;14(11):2748-2765. Epub 2020 Jul 27.

Institute of Ecological Science, School of Life Science, South China Normal University, Guangzhou, Guangdong Province, China.

The interaction between airway microbiome and host in chronic obstructive pulmonary disease (COPD) is poorly understood. Here we used a multi-omic meta-analysis approach to characterize the functional signature of airway microbiome in COPD. We retrieved all public COPD sputum microbiome datasets, totaling 1640 samples from 16S rRNA gene datasets and 26 samples from metagenomic datasets from across the world. We identified microbial taxonomic shifts using random effect meta-analysis and established a global classifier for COPD using 12 microbial genera. We inferred the metabolic potentials for the airway microbiome, established their molecular links to host targets, and explored their effects in a separate meta-analysis on 1340 public human airway transcriptome samples for COPD. 29.6% of differentially expressed human pathways were predicted to be targeted by microbiome metabolism. For inferred metabolite-host interactions, the flux of disease-modifying metabolites as predicted from host transcriptome was generally concordant with their predicted metabolic turnover in microbiome, suggesting a synergistic response between microbiome and host in COPD. The meta-analysis results were further validated by a pilot multi-omic study on 18 COPD patients and 10 controls, in which airway metagenome, metabolome, and host transcriptome were simultaneously characterized. 69.9% of the proposed "microbiome-metabolite-host" interaction links were validated in the independent multi-omic data. Butyrate, homocysteine, and palmitate were the microbial metabolites showing strongest interactions with COPD-associated host genes. Our meta-analysis uncovered functional properties of airway microbiome that interacted with COPD host gene signatures, and demonstrated the possibility of leveraging public multi-omic data to interrogate disease biology.
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http://dx.doi.org/10.1038/s41396-020-0727-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784873PMC
November 2020

Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.

Cell 2020 08 10;182(3):734-743.e5. Epub 2020 Jun 10.

Department of Pathology, University of Iowa, Iowa City, Iowa 52242, USA.

COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.
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http://dx.doi.org/10.1016/j.cell.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284240PMC
August 2020

Sputum and serum autoantibody profiles and their clinical correlation patterns in COPD patients with and without eosinophilic airway inflammation.

J Thorac Dis 2020 Jun;12(6):3085-3100

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Autoimmunity plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the autoantibody responses and their clinical correlation patterns in COPD patients with and without airway eosinophilic inflammation are unknown. The aim of this study was to compare the autoantibody profiles and their clinical associations in stable COPD patients, stratified by airway inflammatory phenotypes.

Methods: Matched sputum and serum, obtained from 62 stable COPD patients and 14 age-matched controls, were assayed for the presence of IgG and IgM antibodies against 13 autoantigens using protein array. A sputum eosinophil count ≥3% was used as cut-off value to stratify COPD patients into eosinophilic and non-eosinophilic groups. Correlation network analysis was used to evaluate the correlation patterns among autoantibody and clinical variables in each group.

Results: There were no significant differences of clinical parameters and autoantibody levels between the two COPD groups. In non-eosinophilic COPD, sputum anti-CytochromeC_IgG and anti-Aggrecan_IgM were significantly higher than those in healthy controls, and prior exacerbation was positively associated with lung function and sputum anti-Collagen-IV_IgG. While in eosinophilic COPD, sputum/serum anti-heat shock protein (HSP)47_IgG, serum anti-HSP70_IgG and serum anti-Amyloid-beta_IgG were significantly lower than those in healthy controls, and no significant correlation between prior exacerbations and lung function was found. Differences were also observed in network hubs, with the network for non-eosinophilic COPD possessing 9 hubs comprising two lung function parameters and seven autoantibodies, compared with eosinophilic COPD possessing 12 hubs all comprising autoantibodies.

Conclusions: Autoantibody responses were heterogeneous and differentially correlated with the exacerbation risk and other clinical parameters in COPD patients of different inflammatory phenotypes. These findings provide useful insight into the need for personalized management for preventing COPD exacerbations.
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http://dx.doi.org/10.21037/jtd-20-545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330801PMC
June 2020

Kinetics of viral load and antibody response in relation to COVID-19 severity.

J Clin Invest 2020 10;130(10):5235-5244

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, and.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and N IgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.
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http://dx.doi.org/10.1172/JCI138759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524490PMC
October 2020

Effect of a bundle of intervention strategies for the control of COVID-19 in Henan, a neighboring province of Wuhan, China.

Wien Klin Wochenschr 2020 Jul 16;132(13-14):396-399. Epub 2020 Jun 16.

Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China.

The novel coronavirus disease 2019 (COVID-19) occurred in China (mainly in Wuhan, Hubei Province) at the end of December 2019. Henan province is located in the center of China, borders on Hubei province by land in the south with the nearest distance of 200 kilometers to Wuhan. As the inland provinces in mainland China, frequent communication in transportation and population flow make it difficult to confine the pandemic, which is similar to that in the landlocked countries in Europe. The expected cases in Henan were mainly imported. A bundle of intervention strategies were adopted from 26 January 2020 to cut off the spread between the infected patients and the native residents. The pandemic was controlled 2 month later after the bundle of strategies was adopted although the number of cases continued to increase explosively during the first 10 days. A total of 1273 cases were confirmed, 1251 patients were cured, 22 patients died, and 1 patient was still in hospital until 29 March 2020. The peak of daily increased cases was 109 cases. Our data show that COVID-19 is highly infectious and easy to cause an outbreak, but it can be controlled by early effective interventions. A bundle of strategies according to the specific situation of each country is suggested to be implemented as early as possible.
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http://dx.doi.org/10.1007/s00508-020-01688-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296893PMC
July 2020

Non-invasive ventilation in the treatment of early hypoxemic respiratory failure caused by COVID-19: considering nasal CPAP as the first choice.

Crit Care 2020 06 11;24(1):333. Epub 2020 Jun 11.

Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen Institute of Respiratory Diseases, 1017 Dong Men Road, Shenzhen, 518020, China.

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http://dx.doi.org/10.1186/s13054-020-03054-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289232PMC
June 2020

Improved mechanical ventilation requires more than just increased ventilator availability: A word of caution.

Clin Transl Med 2020 Jun 4;10(2):e43. Epub 2020 Jun 4.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

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http://dx.doi.org/10.1002/ctm2.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300635PMC
June 2020

Association Between Adherence to Maintenance Medication in Patients with COPD and Acute Exacerbation Occurrence and Cost in China: A Retrospective Cohort Database Study.

Int J Chron Obstruct Pulmon Dis 2020 4;15:963-971. Epub 2020 May 4.

Health Economics Research Institute, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Background: This study aimed to evaluate the association between adherence to maintenance medication (ie, inhaled bronchodilators, inhaled corticosteroid/long-acting beta-2 agonist [ICS/LABA] combinations, and oral therapy) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and related costs among patients with chronic obstructive pulmonary disease (COPD) in China.

Patients And methods: Claims data from the hospitals of a metropolitan city in south China between January 2014 and December 2016 were obtained. Patients with COPD with ≥2 maintenance medication claims during 1 year were included. Adherence was measured by the proportion of days covered (PDC). The interaction of medication class×adherence was considered when building models.

Results: A total of 11,708 patients met the inclusion criteria, of whom 10.8% were highly adherent (PDC≥0.8). There were significant interaction effects of drug category on hospitalized AECOPD risk (P≤0.001), hospitalized AECOPD rate (P<0.001), and 1-year hospitalized AECOPD treatment costs (P=0.012). There was a relationship between high adherence and outcomes for ICS/LABA combinations (n=3,419), ie, relative risk of hospitalized AECOPD was reduced by 34.8% (adjusted odds ratio=0.65; 95% confidence interval (CI): 0.54-0.79; P<0.001) while the frequency of hospitalized AECOPD per patient-year was reduced by 24.4% (adjusted rate ratio=0.76; 95% CI: 0.65 to 0.87; P<0.001). Mean 1-year per-patient hospitalized AECOPD costs were reduced by 37.8% (mean difference=-848 USD; 95% CI: -1435-262 USD; P<0.001). Patients taking oral mucolytics and having high adherence had worse AECOPD outcomes than patients with poor adherence.

Conclusion: High adherence to ICS/LABA maintenance therapy was associated with reduced hospitalized AECOPD rates and costs in Chinese patients with COPD.
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http://dx.doi.org/10.2147/COPD.S234349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210029PMC
May 2020