Translational respiratory medicine最新文献

{"title":"Inhaled corticosteroid influence toll like receptor 2 expression in induced sputum from patients with COPD.","authors":"Haixing Zhu,&nbsp;Yuheng Shi,&nbsp;Wei Tang,&nbsp;Guocao Shi,&nbsp;Huanyin Wan","doi":"10.1186/2213-0802-1-7","DOIUrl":"https://doi.org/10.1186/2213-0802-1-7","url":null,"abstract":"<p><strong>Background: </strong>The link between long-term ICS therapy and respiratory infection in COPD patients is controversial. We investigated the effect of long-term use of inhaled corticosteroid on Toll like receptor 2 (TLR2) expression in induced sputum from COPD patients.</p><p><strong>Methods: </strong>51 patients were divided into two groups according to their treatment history: long-term ICS treatment group (patients who have used ICS (equivalent to Fluticasone Propionate (FP) ≥ 500 ug/day for more than 1 year) (n = 21) and ICS naive group (who have never routinely used ICS before, n = 29). In their induced sputum, we tested TLR2 extracellular and intracellular expression on macrophages using flowcytometry. TLR2 and tumor necrosis factor αmRNA expression were also evaluated by real-time PCR.</p><p><strong>Results: </strong>TLR2 extracellular expression on the macrophages from induced sputum in long-term ICS treatment group was lower than the ICS naïve group (13.69% ± 1.17% vs 20.12% ± 4.37%, p = 0.019). TLR2 intracellular expression in the macrophages, the TLR2 and TNFαmRNA in the induced sputum also showed a trend towards decreased endpoint in ICS long-term treatment group compare to ICS naïve group but did not reach significance. TLR2 extracellular and TLR2 intracellular expression were strongly related (r = 0.645, p = P = 0.017) as well as TNFαmRNA and TLR2 mRNA expression (r = 0.894, p = 0.0001).</p><p><strong>Conclusion: </strong>Long-term use of ICS may have negative influence on TLR2 expression in the airway of severe COPD patient.</p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of high concentration oxygen therapy on PaCO2 in acute and chronic respiratory disorders.","authors":"Janine Pilcher,&nbsp;Kyle Perrin,&nbsp;Richard Beasley","doi":"10.1186/2213-0802-1-8","DOIUrl":"https://doi.org/10.1186/2213-0802-1-8","url":null,"abstract":"<p><p>There is evidence that the potential for high concentration oxygen therapy to increase PaCO2 is not limited to stable and acute exacerbations of COPD, but also to other acute respiratory disorders with abnormal gas exchange such as asthma and pneumonia, and chronic respiratory conditions with hypercapnia such as obesity hypoventilation syndrome. This evidence forms the basis of consensus guidelines which recommend that oxygen therapy is titrated in COPD and other respiratory conditions, to ensure the maximal benefits of oxygen therapy are achieved while reducing the potential for harm due to hyperoxia. </p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD.","authors":"Rekha Chaudhuri,&nbsp;Charles McSharry,&nbsp;Mark Spears,&nbsp;Jeffrey Brady,&nbsp;Christal Grierson,&nbsp;C Martina Messow,&nbsp;Gino Miele,&nbsp;Karl Nocka,&nbsp;William MacNee,&nbsp;Martin Connell,&nbsp;John T Murchison,&nbsp;Michael Sproule,&nbsp;Omar Hilmi,&nbsp;Douglas K Miller,&nbsp;Neil C Thomson","doi":"10.1186/2213-0802-1-11","DOIUrl":"10.1186/2213-0802-1-11","url":null,"abstract":"<p><strong>Background: </strong>Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD.</p><p><strong>Findings: </strong>In 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units). Sputum MMP-9 concentrations and mRNA expression in COPD subjects were significantly greater than in healthy never-smokers (p = 0.007 and p = 0.001 respectively) and similar to those in healthy smokers. Disease severity when assessed by the extent of emphysema measured by CT, but not by spirometry or DLco values, was directly associated with sputum MMP-9 concentrations [r = 0.442 (0.171, 0.634), p = 0.020], and MMP-9 activity [r = 0.447 (0.219, 0.643), p = 0.010]. In moderate to severe COPD, increased MMP-9 mRNA expression levels were associated with reduced post-bronchodilator FEV1 [r = -0.530 (-0.686, -0.327), p < 0.001], FEV1/FVC ratio [r = -0.551 (-0.701, -0.354), p < 0.001] and reduced DLco [r = -0.399 (-539, -0.102), p = 0.048].</p><p><strong>Conclusions: </strong>Sputum MMP-9 concentrations in COPD are directly associated with the extent of emphysema measured by CT and MMP-9 expression levels are inversely associated with DLco. These findings support a role for MMP-9 in the pathogenesis of COPD.</p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic driver mutations in lung cancer.","authors":"Susan Y Luo,&nbsp;David Cl Lam","doi":"10.1186/2213-0802-1-6","DOIUrl":"https://doi.org/10.1186/2213-0802-1-6","url":null,"abstract":"<p><p>Lung cancer is a heterogeneous and complex disease. Genomic and transcriptomic profiling of lung cancer not only further our knowledge about cancer initiation and progression, but could also provide guidance on treatment decisions. The fact that targeted treatment is most successful in a subset of tumors indicates the need for better classification of clinically related molecular tumor phenotypes based on better understanding of the mutations in relevant genes, especially in those oncogenic driver mutations. EGFR gene mutations, KRAS gene mutations, EML4-ALK rearrangements and altered MET signaling are widely recognized alterations that play important roles in both the biological mechanisms and the clinical sensitivity to treatment in lung cancer. In this article, we reviewed the discovery of the clinical values of these oncogenic driver mutations and the clinical studies revealing the prognostic and predictive values of these biomarkers for clinical sensitivity and resistance to anti-EGFR therapy or other targeted therapies. These form the basis of personalized treatment in lung cancer based on biomarker profiles of individual tumor, leading to therapeutic advancement and betterment. </p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The acute respiratory distress syndrome in 2013.","authors":"Michael A Matthay,&nbsp;Yuanlin Song,&nbsp;Chunxue Bai,&nbsp;Kirk D Jones","doi":"10.1186/2213-0802-1-10","DOIUrl":"https://doi.org/10.1186/2213-0802-1-10","url":null,"abstract":"<p><p>Acute lung injury and the acute respiratory distress syndrome are major causes of morbidity and mortality in critically ill patients. This review focuses on new developments in definitions, epidemiology, clinical and basic research, and promising new directions in treatment. There is new information about the potential contribution of environmental factors, especially exposure to cigarette smoke. Pathologic findings in ARDS have been limited to case reports of open lung biopsies and post-mortem studies but there is some new information from a recent pathology study relative to the frequency of diffuse alveolar damage and the severity of arterial hypoxemia. Further, therapy with lung-protective ventilation and fluid conservative protocol has improved outcomes, but several new trials are in progress to test several promising strategies. </p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood viscosity as a forgotten factor and its effect on pulmonary flow.","authors":"Gulfidan Cakmak,&nbsp;Fatma Ates Alkan,&nbsp;Kazim Korkmaz,&nbsp;Zuhal Aydan Saglam,&nbsp;Denizhan Karis,&nbsp;Mustafa Yenigun,&nbsp;Meltem Ercan","doi":"10.1186/2213-0802-1-3","DOIUrl":"https://doi.org/10.1186/2213-0802-1-3","url":null,"abstract":"<p><strong>Background: </strong>The effect of smoking on blood viscosity is widely known. There are, however, few studies on the effect of blood viscosity on pulmonary circulation.</p><p><strong>Methods: </strong>We aimed to observe the relationship between blood viscosity and pulmonary circulation among smokers and non-smokers. The study comprised 114 subjects in three groups: group 1, ex-smokers; group 2, smoked at least 10 packs/year and still smoking; group 3, never smoked. Blood viscosity (BV), pulmonary blood flow (PBF), and right ventricular systolic pressure (RVSP) were measured in all subjects.</p><p><strong>Results: </strong>PBF was significantly lower in group 1 compared with group 3 (p < 0.05). BV in group 1 was significantly higher than group 3 (p < 0.05) while BV in group 2 was significantly higher than group 3 (p < 0.05). PBF in group 2 was significantly lower than group 3 (p = 0.01).</p><p><strong>Conclusions: </strong>We believe that BV is a significant and forgotten factor that plays an important role in pulmonary and cardiovascular diseases. BV may affect PF even during the course of smoking, and before the clinical onset of chronic obstructive pulmonary disease (COPD). Therefore, individuals at risk of pulmonary hypertension could be detected earlier with a simple blood test.</p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34588950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A half doubling dose change in bronchial hyperresponsiveness in a population represents an important difference.","authors":"Mark Weatherall,&nbsp;James Fingleton,&nbsp;Sally Eyers,&nbsp;Richard Beasley","doi":"10.1186/2213-0802-1-4","DOIUrl":"https://doi.org/10.1186/2213-0802-1-4","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of asthma has increased over recent decades and the reasons for this are poorly understood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness (BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference in BHR for an individual is accepted to be around one doubling dose, the minimum important change in a population is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and cholesterol, a change that is not clinically important in an individual may be extremely important in public health terms.</p><p><strong>Findings: </strong>To assess the potential impact of a small absolute change in BHR across a population, we modelled the effect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population. We calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR by 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe asthma, this would be highly significant in public health terms.</p><p><strong>Conclusions: </strong>We propose that a one half doubling dose worsening in BHR across a population may represent an important change.</p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34524547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of WWOX and NF-κB in lung cancer progression.","authors":"Szu-Jung Chen,&nbsp;Shenq-Shyang Huang,&nbsp;Nan-Shan Chang","doi":"10.1186/2213-0802-1-15","DOIUrl":"https://doi.org/10.1186/2213-0802-1-15","url":null,"abstract":"<p><p>It is generally agreed that the pro-inflammatory, pro-survival transcription factor NF-κB is a tumor promoter. Tumor necrosis factor alpha (TNF-α or TNF) mediates NF-κB activation. Tumor suppressor WWOX (FOR or WOX1) is a downstream effector of the TNF signaling. Thus, activation of both WWOX (FOR or WOX1) and NF-κB may occur during TNF signaling and/or under stress conditions. Indeed, the first WW domain of WWOX induces the activation of NF-κB-responsive promoter without TNF participation. It appears that WWOX counteracts with NF-κB in regulating cell survival and death. For example, WWOX becomes activated with Tyr33 phosphorylation and relocates together with NF-κB and many transcription factors to the nucleus to cause neuronal death in sciatic nerve-transected rats. While WWOX is frequently lost in lung cancer and many other cancers, NF-κB activation-induced cancer promotion probably requires WWOX-independent signaling networks to induce expression of pro-survival factors. The antagonistic role of WWOX and NF-κB in the regulation of lung cancer progression is discussed. </p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34525583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs Implicated in Dysregulation of Gene Expression Following Human Lung Transplantation.","authors":"Wei Zhang,&nbsp;Tong Zhou,&nbsp;Shwu-Fan Ma,&nbsp;Robert F Machado,&nbsp;Sangeeta M Bhorade,&nbsp;Joe G N Garcia","doi":"10.1186/2213-0802-1-12","DOIUrl":"https://doi.org/10.1186/2213-0802-1-12","url":null,"abstract":"<p><strong>Background: </strong>Lung transplantation remains the only viable treatment option for the majority of patients with advanced lung diseases. However, 5-year post-transplant survival rates remain low primarily secondary to chronic rejection. Novel insights from global gene expression profiles may provide molecular phenotypes and therapeutic targets to improve outcomes after lung transplantation.</p><p><strong>Methods: </strong>Whole-genome gene expression profiling was performed in a cohort of patients that underwent lung transplantation as well as healthy controls using the Affymetrix Human Exon 1.0ST Array. To explore the potential roles of microRNAs (miRNAs) in regulating lung transplantation-associated gene dysregulation, miRNA expression levels were also profiled in the same samples using the Exiqon miRCURY(™) LNA Array.</p><p><strong>Results: </strong>In a cohort of 18 lung transplant patients, 364 dysregulated genes were identified in Caucasian lung transplant patients relative to normal individuals. Pathway enrichment analysis of the dysregulated genes pointed to Gene Ontology biological processes such as \"defense response\", \"immune response\" and \"response to wounding\". We then compared the expression profiles of potential regulating miRNAs, suggesting that dysregulation of a number of lung transplantation-associated genes (e.g., ATR, FUT8, LRRC8B, NFKBIA) may be attributed to the dysregulation of their respective regulating miRNAs.</p><p><strong>Conclusions: </strong>Following human lung transplantation, a substantial proportion of genes, particularly those genes involved in certain biological processes like immune response, were dysregulated in patients relative to their healthy counterparts. This exploratory analysis of the relationships between miRNAs and their gene targets in the context of lung transplantation warrants further investigation and may serve as novel therapeutic targets in lung transplant complications.</p>","PeriodicalId":90074,"journal":{"name":"Translational respiratory medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2213-0802-1-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32022339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}