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1.
Lancet Oncol ; 21(4): e180, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32142622
2.
J Immunol ; 204(6): 1437-1447, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32034061

RESUMO

DNA damage could lead to the accumulation of cytosolic DNA, and the cytosolic DNA-sensing pathway has been implicated in multiple inflammatory diseases. However, the role of cytosolic DNA-sensing pathway in asthma pathogenesis is still unclear. This article explored the role of airway epithelial cyclic GMP-AMP synthase (cGAS), the major sensor of cytosolic dsDNA, in asthma pathogenesis. Cytosolic dsDNA accumulation in airway epithelial cells (ECs) was detected in the setting of allergic inflammation both in vitro and in vivo. Mice with cGAS deletion in airway ECs were used for OVA- or house dust mite (HDM)-induced allergic airway inflammation. Additionally, the effects of cGAS knockdown on IL-33-induced GM-CSF production and the mechanisms by which IL-33 induced cytosolic dsDNA accumulation in human bronchial epithelial (HBE) cells were explored. Increased accumulation of cytosolic dsDNA was observed in airway epithelium of OVA- or HDM-challenged mice and in HBE cells treated with IL-33. Deletion of cGAS in the airway ECs of mice significantly attenuated the allergic airway inflammation induced by OVA or HDM. Mechanistically, cGAS participates in promoting TH2 immunity likely via regulating the production of airway epithelial GM-CSF. Furthermore, Mito-TEMPO could reduce IL-33-induced cytoplasmic dsDNA accumulation in HBE cells possibly through suppressing the release of mitochondrial DNA into the cytosol. In conclusion, airway epithelial cGAS plays an important role via sensing the cytosolic dsDNA in asthma pathogenesis and could serve as a promising therapeutic target against allergic airway inflammation.

3.
Appl Microbiol Biotechnol ; 104(5): 2039-2050, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31950219

RESUMO

The biotechnology-based production of xylitol has received widespread attention because it can use cheap and renewable lignocellulose as a raw material, thereby decreasing costs and pollution. The simultaneous use of various sugars in lignocellulose hydrolysates is a primary prerequisite for efficient xylitol production. In this study, a ΔptsG and crp* combinatorial strategy was used to generate Escherichia coli W3110 strain IS5-dI, which completely eliminated glucose repression and simultaneously used glucose and xylose. This strain produced 164 g/L xylitol from detoxified corncob hydrolysates during a fed-batch fermentation in a 15-L bioreactor, which was 14.7% higher than the xylitol produced by the starting strain, IS5-d (143 g/L), and the xylitol productivity was 3.04 g/L/h. These results represent the highest xylitol concentration and productivity reported to date for bacteria and hemicellulosic sugars. Additionally, strain IS5-dG, which differs from IS5-dI at CRP amino acid residue 127 (I127G), was tolerant to the toxins in corncob hydrolysates. In a fed-batch fermentation experiment involving a 15-L bioreactor, IS5-dG produced 137 g/L xylitol from non-detoxified corncob hydrolysates, with a productivity of 1.76 g/L/h. On the basis of these results, we believe that IS5-dI and IS5-dG may be useful host strains for the industrial-scale production of xylitol from detoxified or non-detoxified corncob hydrolysates.

4.
Eur Respir J ; 55(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31558662

RESUMO

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using a blood eosinophil cut-point ≥150 µL-1 to guide anti-IL-5 initiation in adult patients with severe asthma; 3) suggest considering specific eosinophil (≥260 µL-1) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy; 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4-5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies; 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.

5.
Autophagy ; 16(3): 435-450, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31203721

RESUMO

Particulate matter (PM) is able to induce airway epithelial injury, while the detailed mechanisms remain unclear. Here we demonstrated that PM exposure inactivated MTOR (mechanistic target of rapamycin kinase), enhanced macroautophagy/autophagy, and impaired lysosomal activity in HBE (human bronchial epithelial) cells and in mouse airway epithelium. Genetic or pharmaceutical inhibition of MTOR significantly enhanced, while inhibition of autophagy attenuated, PM-induced IL6 expression in HBE cells. Consistently, club-cell-specific deletion of Mtor aggravated, whereas loss of Atg5 in bronchial epithelium reduced, PM-induced airway inflammation. Interestingly, the augmented inflammatory responses caused by MTOR deficiency were markedly attenuated by blockage of downstream autophagy both in vitro and in vivo. Mechanistically, the dysregulation of MTOR-autophagy signaling was partially dependent on activation of upstream TSC2, and interacted with the TLR4-MYD88 to orchestrate the downstream NFKB activity and to regulate the production of inflammatory cytokines in airway epithelium. Moreover, inhibition of autophagy reduced the expression of EPS15 and the subsequent endocytosis of PM. Taken together, the present study provides a mechanistic explanation for how airway epithelium localized MTOR-autophagy axis regulates PM-induced airway injury, suggesting that activation of MTOR and/or suppression of autophagy in local airway might be effective therapeutic strategies for PM-related airway disorders.Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; ALI: air liquid interface; AP2: adaptor related protein complex 2; ATG: autophagy related; BALF: bronchoalveolar lavage fluid; COPD: chronic obstructive pulmonary disease; CXCL: C-X-C motif chemokine ligand; DOX: doxycycline; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPS15: epidermal growth factor receptor pathway substrate 15; HBE: human bronchial epithelial; H&E: hematoxylin & eosin; IKK: IKB kinase; IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTEC: mouse tracheal epithelial cells; MTOR: mechanistic target of rapamycin kinase; MYD88: MYD88 innate immune signal transduction adaptor; NFKB: nuclear factor of kappa B; NFKBIA: NFKB inhibitor alpha; PM: particulate matter; PtdIns3K: phosphatidylinositol 3-kinase; Rapa: rapamycin; RELA: RELA proto-oncogene, NFKB subunit; SCGB1A1: secretoglobin family 1A member 1; siRNA: small interfering RNAs; SQSTM1: sequestosome 1; TEM: transmission electronic microscopy; TLR4: toll like receptor 4; TSC2: TSC complex subunit 2.

6.
Eur. respir. j ; 54(3): 1900588, Sept. 2019.
Artigo em Inglês | BIGG | ID: biblio-1026251

RESUMO

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on 6 specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) Suggest using anti-IL5 and anti IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using blood eosinophil cut-point of ≥150/µL to guide anti-IL5 initiation in adult patients with severe asthma; and 3) Suggest considering specific eosinophil (≥260/µL) and FeNO (≥19.5 ppb) cutoffs to identify adolescents or adults with the greatest likelihood or response to anti-IgE therapy; 4) Suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite GINA step 4-5 or NAEPP step 5 therapies; 5) Suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; 6) Suggest using anti-IL4/13 for adult patients with severe eosinophilic asthma, and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.


Assuntos
Humanos , Asma/complicações , Asma/diagnóstico , Asma/prevenção & controle , Estado Asmático/prevenção & controle
7.
Lancet ; 394(10196): 407-418, 2019 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-31230828

RESUMO

BACKGROUND: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population. METHODS: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 µg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma. FINDINGS: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45·7 million Chinese adults. The prevalence of asthma with airflow limitation was 1·1% (0·9-1·4), representing 13·1 million adults. Cigarette smoking (odds ratio [OR] 1·89, 95% CI 1·26-2·84; p=0·004), allergic rhinitis (3·06, 2·26-4·15; p<0·0001), childhood pneumonia or bronchitis (2·43, 1·44-4·10; p=0·002), parental history of respiratory disease (1·44, 1·02-2·04; p=0·040), and low education attainment (p=0·045) were associated with prevalent asthma. In 2032 people with asthma, only 28·8% (95% CI 19·7-40·0) reported ever being diagnosed by a physician, 23·4% (13·9-36·6) had a previous pulmonary function test, and 5·6% (3·1-9·9) had been treated with inhaled corticosteroids. Furthermore, 15·5% (11·4-20·8) people with asthma reported at least one emergency room visit and 7·2% (4·9-10·5) at least one hospital admission due to exacerbation of respiratory symptoms within the preceding year. INTERPRETATION: Asthma is prevalent but largely undiagnosed and undertreated in China. It is crucial to increase the awareness of asthma and disseminate standardised treatment in clinical settings to reduce the disease burden. FUNDING: National Key R&D Program of China, Ministry of Science and Technology of China; the Special Research Foundation for Public Welfare of Health, Ministry of Health of China; the Chinese National Research Program for Key Issues in Air Pollution Control; and the National Natural Science Foundation of China.


Assuntos
Asma/tratamento farmacológico , Asma/epidemiologia , Bronquite/epidemiologia , Fumar Cigarros/epidemiologia , Pneumonia/epidemiologia , Rinite Alérgica/epidemiologia , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Asma/etiologia , Bronquite/complicações , China/epidemiologia , Fumar Cigarros/efeitos adversos , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Prevalência , Rinite Alérgica/complicações , Fatores de Risco , Inquéritos e Questionários
8.
Int J Chron Obstruct Pulmon Dis ; 14: 1009-1018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190786

RESUMO

Dysregulated lipid metabolism plays crucial roles in various diseases, including diabetes mellitus, cancer, and neurodegeneration. Recent studies suggest that alterations in major lipid metabolic pathways contribute to pathogenesis of lung diseases, including chronic obstructive pulmonary disease (COPD). These changes allow lung tissue to meet the energy needs and trigger anabolic pathways that initiate the synthesis of active molecules directly involved in the inflammation. In this review, we summarize the changes of catabolism and anabolism of lipids, lipid molecules including lipid mediators, lipid synthesis transcription factors, cholesterol, and phospholipids, and how those lipid molecules participate in the initiation and resolution of inflammation in COPD.


Assuntos
Metabolismo Energético , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Humanos , Pulmão/metabolismo , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Transdução de Sinais
9.
Toxicol Lett ; 307: 1-10, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30658152

RESUMO

BACKGROUND: Paraquat (PQ) poisoning is one of the leading causes of suicide attempts in China signature by acute onset of respiratory distress with massive matrix production resulting in progressive pulmonary fibrosis. There is no specific antidote and mortality remains high without effective treatment available. The cellular mechanisms underlying PQ-induced pulmonary fibrosis remain largely unknown. OBJECTIVES: To determine the origin of mesenchymal stem cells (MSCs) migrated to the lung after PQ exposure and their roles in PQ-induced pulmonary fibrosis, to further explore the possible mechanisms involved in these processes, and to help finding novel therapies. METHODS: We used a combination of lineage tracking techniques to investigate the contributions of several cells of MSCs, marked by Nestin or CXCL12, and traced their co-expression of α-smooth muscle actin (α-SMA), a marker for fibrosis, or their co-location with matrix production, marked by collagen-1 production (Col1-GFP) following PQ exposure. Then, we used a CXCL12flox/flox; Prx1-Cre mice and a pharmacologic agent AMD3100 to selectively deplete chemotactic mechanism of the MSCs, and tested pro-fibrotic pathways, fibrotic processes and survival of mice after PQ exposure. RESULTS: Our results showed that after paraquat exposure, the residential Nestin + MSCs were quickly expanded and contributed to extracellular matrix production. Moreover, when we used a CXCL12flox/flox; Prx1-Cre mice to selectively deplete chemotactic mechanism of the MSC, we found that PQ exposure in these mice failed to activate pro-fibrotic pathways including TGF-ß, Wnt and EGFR signaling. Furthermore, when the chemotactic effect of MSCs via CXCL12 was blocked by a pharmacologic agent, AMD3100, it alleviated the development of the fibrotic process and improved survival rate in mice exposed to PQ. CONCLUSION: Collectively, our data suggest paraquat intoxication rapidly activated Nestin + MSCs and that blocking chemotactic effects of MSCs by perivascular CXCL12 inhibition may effectively protect pulmonary injury following paraquat exposure. Our results revealed a novel mechanism for post-PQ lung injury and indicated a novel therapeutic option to attenuate fibrosis induced by paraquat.


Assuntos
Inibição de Migração Celular , Células-Tronco Mesenquimais/efeitos dos fármacos , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Animais , Linhagem da Célula , Inibição de Migração Celular/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Feminino , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Nestina/metabolismo , Fibrose Pulmonar/patologia , Fibrose Pulmonar/terapia
11.
Acta Pharmacol Sin ; 40(6): 769-780, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30446733

RESUMO

Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31+ cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury. The expression of TF and PARs on the EC in lungs was upregulated after ALI. In the two strains of transgenic mice, expression of either of hTFPI or hirudin by EC was associated with significant reduction of inflammation, as assessed by the extent of leukocyte infiltration or the levels of proinflammatory cytokines, and promoted survival after LPS-induced ALI. The beneficial outcomes were associated with inhibition of the expression of chemokine CCL2 in lung tissues. The protection observed in the CD31-TFPI-transgenic strain was abolished by injection of an anti-hTFPI antibody, but not by prior engraftment of the transgenic strains with WT bone marrow, confirming that the changes observed were a specific transgenic expression of anticoagulants by EC. These results demonstrate that the inflammation in ALI is TF and thrombin dependent, and that expression of anticoagulants by EC significantly inhibits the development of ALI via repression of leukocyte infiltration, most likely via inhibition of chemokine gradients. These data enhance our understanding of the pathology of ALI and suggest a novel therapeutic strategy for treatment.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Células Endoteliais/metabolismo , Hirudinas/metabolismo , Inflamação/metabolismo , Lipoproteínas/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Coagulação Sanguínea/fisiologia , Quimiocinas/metabolismo , Quimiotaxia de Leucócito/fisiologia , Hirudinas/genética , Humanos , Inflamação/induzido quimicamente , Sanguessugas/química , Lipopolissacarídeos , Lipoproteínas/genética , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pseudomonas aeruginosa/química , Receptores Ativados por Proteinase/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Trombina/metabolismo , Tromboplastina/metabolismo
12.
Biomaterials ; 192: 429-439, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30500724

RESUMO

Elimination of airway inflammatory cells is essential for asthma control. As Bcl-2 protein is highly expressed on the mitochondrial outer membrane in inflammatory cells, we chose a Bcl-2 inhibitor, ABT-199, which can inhibit airway inflammation and airway hyperresponsiveness by inducing inflammatory cell apoptosis. Herein, we synthesized a pH-sensitive nanoformulated Bcl-2 inhibitor (Nf-ABT-199) that could specifically deliver ABT-199 to the mitochondria of bronchial inflammatory cells. The proof-of-concept study of an inflammatory cell mitochondria-targeted therapy using Nf-ABT-199 was validated in a mouse model of allergic asthma. Nf-ABT-199 was proven to significantly alleviate airway inflammation by effectively inducing eosinophil apoptosis and inhibiting both inflammatory cell infiltration and mucus hypersecretion. In addition, the nanocarrier or Nf-ABT-199 showed no obvious influence on cell viability, airway epithelial barrier and liver function, implying excellent biocompatibility and with non-toxic effect. The nanoformulated Bcl-2 inhibitor Nf-ABT-199 accumulates in the mitochondria of inflammatory cells and efficiently alleviates allergic asthma.

13.
Cell Death Differ ; 26(9): 1859-1860, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30546073

RESUMO

Since the publication of the article, the authors became aware that Figs. 1c, 5k and 6m contained errors in representative image and PAS score in control groups. The corrected Figs. 1c, 5k, and 6m are given below, and the figure legends are the same as original.

14.
Am J Physiol Lung Cell Mol Physiol ; 316(1): L269-L279, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407865

RESUMO

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/- mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/- mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.


Assuntos
Asma/imunologia , Histona Desacetilase 2/imunologia , Interleucina-17/imunologia , Pyroglyphidae/imunologia , Animais , Asma/genética , Asma/patologia , Modelos Animais de Doenças , Feminino , Histona Desacetilase 2/genética , Interleucina-17/genética , Masculino , Camundongos , Camundongos Knockout , Células Th2/patologia
15.
Respiration ; 97(5): 416-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30554211

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. OBJECTIVES: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. METHODS: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). RESULTS: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. CONCLUSION: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.

16.
J Thorac Dis ; 10(10): 5939-5945, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30505504

RESUMO

Airway stent implantation is a highly effective treatment for airway stenosis. However, it is presently unclear whether patients with airway stents can safely undergo magnetic resonance imaging (MRI). Such stents may be metallic or non-metallic, and MRI may induce stent dislodgment or heating and may be associated with stent-induced artifacts. We thoroughly reviewed the literature, experimental data, and manufacturer information on non-metallic, stainless steel (SS) and nickel-titanium alloy stents. Non-metallic stents are made of non-ferromagnetic materials associated with no MRI concerns. SS stents may shift in a magnetic field, generating significant artifacts. Nickel-titanium alloy stents are not at risk of dislodgement or heating, but may create some artifacts affecting image quality. Both non-metallic and nickel-titanium alloy stents are safe for patients who must undergo MRI. However, the safety of SS stents depends on the type of steel used.

17.
PLoS One ; 13(12): e0207994, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517168

RESUMO

INTRODUCTION: We performed a meta-analysis on whether heated humidification during positive airway pressure (PAP) could improve compliance and subjective daytime sleepiness in obstructive sleep apnea syndrome (OSAS) patients. MATERIALS AND METHODS: We searched PubMed, EMBASE, Medline, Cochrane Library, Clinical Trials, Web of Science and Scopus from inception to Oct 29, 2017. We made meta-analysis on the all available randomized controlled trials (RCTs) which assessed effects of heated humidification intervention on PAP compliance and subjective daytime sleepiness, by subgroups of automatic adjusting positive airway pressure/ continuous positive airway pressure (APAP/CPAP) usage and patients with/without upper airway symptoms prior to PAP therapy. RESULTS: A total of nine RCTs were evaluated finally in this meta-analysis. When all the studies were pooled, heated humidification did not improve PAP usage time [weighted mean difference(WMD) = 13.28, 95% confidence interval(CI): -5.85 to 32.41, P = 0.17] or Epworth sleepiness scale (ESS) score (WMD = -0.63, 95% CI: -1.32 to 0.07, P = 0.08). In terms of PAP usage time, heated humidification failed to enhance compliance in both APAP (WMD = 22.34, 95%CI: -21.08 to 65.77, P = 0.31) or CPAP subgroup (WMD = 11.09, 95%CI: -10.21 to 32.40, P = 0.31) and it was also ineffective among patients with upper airway symptoms prior to PAP therapy (WMD = 22.74, 95% CI: -7.77 to 53.24, P = 0.14) or without (WMD = 13.22, 95%CI: -35.84 to 62.29, P = 0.60). In terms of ESS score, heated humidification did not reduce ESS scores in both APAP (WMD = -1.59, 95% CI: -3.81 to 0.64, P = 0.16) or CPAP subgroup (WMD = -0.39, 95% CI: -1.16 to 0.37, P = 0.32) and it was also helpless among patients with upper airway symptoms prior to PAP therapy (WMD = -1.17, 95% CI: -3.10 to 0.75, P = 0.23) or without (WMD = -0.30, 95%CI: -2.25 to 1.66, P = 0.76). CONCLUSION: Heated humidification during PAP therapy improves neither the compliance nor ESS scores in OSAS patients, no matter what types of PAP or whether the patients had upper airway symptoms prior to PAP therapy. But to the population with upper airway symptoms and the APAP users, the conclusions were limited because of small sample size and possible selection bias. More attentions should be paid to these potentially possible benefited subgroups.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida/psicologia , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Viés , Pressão Positiva Contínua nas Vias Aéreas/psicologia , Feminino , Temperatura Alta , Humanos , Umidade , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/psicologia , Sonolência , Fatores de Tempo , Resultado do Tratamento
18.
Cochrane Database Syst Rev ; 12: CD010593, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30536956

RESUMO

BACKGROUND: Sepsis and septic shock are potentially life-threatening complications of infection that are associated with high morbidity and mortality in adults and children. Fluid therapy is regarded as a crucial intervention during initial treatment of sepsis. Whether conservative or liberal fluid therapy can improve clinical outcomes in patients with sepsis and septic shock remains unclear. OBJECTIVES: To determine whether liberal versus conservative fluid therapy improves clinical outcomes in adults and children with initial sepsis and septic shock. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, intensive and critical care conference abstracts, and ongoing clinical trials on 16 January 2018, and we contacted study authors to try to identify additional studies. SELECTION CRITERIA: We planned to include all randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs comparing liberal fluid therapy versus conservative fluid therapy for adults and children with sepsis or septic shock. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We assessed risk of bias of all included trials by using the Cochrane risk of bias tool. When appropriate, we calculated risk ratios (RRs) and 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. Our primary outcomes were all-cause mortality in hospital and at follow-up. Secondary outcomes included adverse events (organ dysfunction, allergic reaction, and neurological sequelae). We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We identified no adult studies that met our selection criteria.This review included three paediatric RCTs (N = 3402), but we were able to extract data from only two of the three trials (n = 3288). These trials were conducted in India (two studies) and Africa. Participants were children from one month to 12 years old with sepsis or septic shock. All three included trials investigated liberal versus conservative fluid therapy, although definitions of liberal and conservative fluid therapy varied slightly across included studies. Results of the two trials included in the analyses show that liberal fluid therapy may increase risk of in-hospital mortality by 38% (2 studies; N = 3288; RR 1.38, 95% CI 1.07 to 1.77; number needed to treat for an additional harmful outcome (NNTH) = 34; moderate-quality evidence) and may increase risk of mortality at follow-up (at four weeks) by 39% (1 study; N = 3141; RR 1.39, 95% CI 1.11 to 1.74; NNTH = 29; high-quality evidence). The third study reported inconclusive results for in-hospital mortality (very low-quality evidence).We are uncertain whether there is a difference in adverse events between liberal and conservative fluid therapy because the single-study results are imprecise (organ dysfunction - hepatomegaly: RR 0.95, 95% CI 0.60 to 1.50; n = 147; low-quality evidence; organ dysfunction - need for ventilation: RR 1.17, 95% CI 0.83 to 1.65; n = 147; low-quality evidence; allergic reaction: RR 1.74, 95% CI 0.36 to 8.37; n = 3141; low-quality evidence; neurological sequelae: RR 1.03, 95% CI 0.61 to 1.75; n = 2983; low-quality evidence). Results are also uncertain for other adverse events such as desaturation, tracheal intubation, increased intracranial pressure, and severe hypertension. AUTHORS' CONCLUSIONS: No studies compared liberal versus conservative fluid therapy in adults. Low- to high-quality evidence indicates that liberal fluid therapy might increase mortality among children with sepsis or septic shock in hospital and at four-week follow-up. It is uncertain whether there are any differences in adverse events between liberal and conservative fluid therapy because the evidence is of low quality. Trials including adults, patients in other settings, and patients with a broader spectrum of pathogens are needed. Once published and assessed, three ongoing studies may alter the conclusions of this review.


Assuntos
Hidratação/métodos , Sepse/terapia , Adulto , Causas de Morte , Criança , Pré-Escolar , Hidratação/efeitos adversos , Mortalidade Hospitalar , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Choque Séptico/terapia
19.
Crit Care ; 22(1): 301, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442203

RESUMO

BACKGROUND: Aerosolized antibiotics have been proposed as a novel and promising treatment option for the treatment of ventilator-associated pneumonia (VAP). However, the optimum aerosolized antibiotics for VAP remain uncertain. METHODS: We included studies from two systematic reviews and searched PubMed, EMBASE, and Cochrane databases for other studies. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. RESULTS: Eight observational and eight randomized studies were identified for this analysis. By pairwise meta-analysis using intravenous antibiotics as the reference, patients treated with aerosolized antibiotics were associated with significantly higher rates of clinical recovery (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.09-1.34; P = 0.001) and microbiological eradication (RR 1.42, 95% CI 1.22-1.650; P < 0.0001). There were no significant differences in the risks of mortality (RR 0.88, 95% CI 0.74-1.04; P = 0.127) or nephrotoxicity (RR 1.00, 95% CI 0.72-1.39; P = 0.995). Using network meta-analysis, clinical recovery benefits were seen only with aerosolized tobramycin and colistin (especially tobramycin), and microbiological eradication benefits were seen only with colistin. Aerosolized tobramycin was also associated with significantly lower mortality when compared with aerosolized amikacin and colistin and intravenous antibiotics. The assessment of rank probabilities indicated aerosolized tobramycin presented the greatest likelihood of having benefits for clinical recovery and mortality, and aerosolized colistin presented the best benefits for microbiological eradication. CONCLUSIONS: Aerosolized antibiotics appear to be a useful treatment for VAP with respect to clinical recovery and microbiological eradication, and do not increase mortality or nephrotoxicity risks. Our network meta-analysis in patients with VAP suggests that clinical recovery benefits are associated with aerosolized tobramycin and colistin (especially tobramycin), microbiological eradication with aerosolized colistin, and survival with aerosolized tobramycin, mostly based on observational studies. Due to the low levels of evidence, definitive recommendations cannot be made before additional, large randomized studies are carried out.


Assuntos
Administração por Inalação , Antibacterianos/administração & dosagem , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Antibacterianos/uso terapêutico , Teorema de Bayes , Humanos , Meta-Análise em Rede , Resultado do Tratamento
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