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Wang H, Wang R, Shen K, Huang R, Wang Z. Biological Roles and Clinical Applications of Exosomes in Breast Cancer: A Brief Review. Int J Mol Sci 2024; 25:4620. [PMID: 38731840 PMCID: PMC11083446 DOI: 10.3390/ijms25094620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 04/20/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Breast cancer (BC) is a global health risk for women and has a high prevalence rate. The drug resistance, recurrence, and metastasis of BC affect patient prognosis, thus posing a challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells; they have a double-layered lipid membrane structure and contain rich biological information. They mediate intercellular communication and have pivotal roles in tumor development, progression, and metastasis and drug resistance. Exosomes are important cell communication mediators in the tumor microenvironment (TME). Exosomes are utilized as diagnostic and prognostic biomarkers for estimating the treatment efficacy of BC and have the potential to function as tools to enable the targeted delivery of antitumor drugs. This review introduces recent progress in research on how exosomes influence tumor development and the TME. We also present the research progress on the application of exosomes as prognostic and diagnostic biomarkers and drug delivery tools.
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Affiliation(s)
| | | | | | - Renhong Huang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (H.W.); (R.W.); (K.S.)
| | - Zheng Wang
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; (H.W.); (R.W.); (K.S.)
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Huang SY, Hsu CM, Yang YH, Tsai YH, Tsai MS, Chang GH, Liu CY, Lee YC, Huang EI, Tsai YT. Elevated risk of acute epiglottitis in patients with chronic obstructive pulmonary disease: A nationwide cohort study. PLoS One 2022; 17:e0273437. [PMID: 35984835 PMCID: PMC9390908 DOI: 10.1371/journal.pone.0273437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 08/08/2022] [Indexed: 11/18/2022] Open
Abstract
Objective
In individuals with epiglottitis, chronic obstructive pulmonary disease (COPD) is a common comorbidity; however, the impact of COPD under such circumstances is not well documented. Therefore, we performed this population-based study to determine whether, in adults, COPD is a risk factor for epiglottitis.
Methods
In this retrospective matched-cohort study, data obtained from the Taiwan National Health Insurance Research Database were analyzed. We identified all patients newly diagnosed as having COPD in 2000–2011 and performed frequency matching and propensity-score matching for every patient with COPD individually to another patient without a COPD diagnosis. We used epiglottitis occurrence as the study endpoint, and we investigated the hazard ratio of epiglottitis by using the Cox proportional hazards model after adjustment for potential confounders.
Results
In the frequency matching, the cumulative epiglottitis incidence was significantly higher (p = 0.005) in the COPD cohort. According to the adjusted Cox proportional hazard model, COPD exhibited a significant association with elevated epiglottitis incidence (adjusted hazard ratio: 1.76; 95% confidence interval: 1.15–2.70, p = 0.009). Similar trend was observed in the propensity-score matching analysis (adjusted hazard ratio: 1.50; 95% confidence interval: 0.99–2.29, p = 0.057). Our subgroup analysis revealed COPD to be an epiglottitis risk factor in male patients and those aged 40–64 years.
Conclusions
This is the first nationwide matched-cohort research to examine the association of COPD with epiglottitis. Our results revealed that COPD may be a potential risk factor for epiglottitis; thus, clinicians should be mindful of the potential increased risk of epiglottitis following COPD.
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Affiliation(s)
- Shu-Yi Huang
- Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Cheng-Ming Hsu
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yuan-Hsiung Tsai
- Department of Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ming-Shao Tsai
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Geng-He Chang
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chia-Yen Liu
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yi-Chan Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ethan I. Huang
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Te Tsai
- Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- * E-mail:
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Biswas M, Suvarna R, Krishnan S V, Devasia T, Shenoy Belle V, Prabhu K. The mechanistic role of neutrophil lymphocyte ratio perturbations in the leading non communicable lifestyle diseases. F1000Res 2022; 11:960. [PMID: 36619602 PMCID: PMC9780608 DOI: 10.12688/f1000research.123245.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/08/2022] [Indexed: 01/13/2023] Open
Abstract
Inflammation plays a critical role in the development and progression of chronic diseases like type 2 diabetes mellitus, coronary artery disease, and chronic obstructive pulmonary disease. Inflammatory responses are indispensable for pathogen control and tissue repair, but they also cause collateral damage. A chronically activated immune system and the resultant immune dysregulation mediated inflammatory surge may cause multiple negative effects, requiring tight regulation and dampening of the immune response to minimize host injury. While chronic diseases are characterized by systemic inflammation, the mechanistic relationship of neutrophils and lymphocytes to inflammation and its correlation with the clinical outcomes is yet to be elucidated. The neutrophil to lymphocyte ratio (NLR) is an easy-to-measure laboratory marker used to assess systemic inflammation. Understanding the mechanisms of NLR perturbations in chronic diseases is crucial for risk stratification, early intervention, and finding novel therapeutic targets. We investigated the correlation between NLR and prevalent chronic conditions as a measure of systemic inflammation. In addition to predicting the risk of impending chronic conditions, NLR may also provide insight into their progression. This review summarizes the mechanisms of NLR perturbations at cellular and molecular levels, and the key inflammatory signaling pathways involved in the progression of chronic diseases. We have also explored preclinical studies investigating these pathways and the effect of quelling inflammation in chronic disease as reported by a few in vitro, in vivo studies, and clinical trials.
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Affiliation(s)
- Monalisa Biswas
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Renuka Suvarna
- Division of Ayurveda, Center for Integrative Medicine and Research, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vimal Krishnan S
- Department of Emergency Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Tom Devasia
- Department of Cardiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vijetha Shenoy Belle
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India,
| | - Krishnananda Prabhu
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India,
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Uliński R, Kwiecień I, Domagała-Kulawik J. Lung Cancer in the Course of COPD-Emerging Problems Today. Cancers (Basel) 2022; 14:cancers14153819. [PMID: 35954482 PMCID: PMC9367492 DOI: 10.3390/cancers14153819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/26/2022] [Accepted: 08/03/2022] [Indexed: 11/16/2022] Open
Abstract
Tobacco smoking remains the main cause of tobacco-dependent diseases like lung cancer, chronic obstructive pulmonary disease (COPD), in addition to cardiovascular diseases and other cancers. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. A patient with COPD has a four- to six-fold greater risk of developing lung cancer independent of smoking exposure, when compared to matched smokers with normal lung function. The 10 year risk is about 8.8% in the COPD group and only 2% in patients with normal lung function. COPD is not a uniform disorder: there are different phenotypes. One of them is manifested by the prevalence of emphysema and this is complicated by malignant processes most often. Here, we present and discuss the clinical problems of COPD in patients with lung cancer and against lung cancer in the course of COPD. There are common pathological pathways in both diseases. These are inflammation with participation of macrophages and neutrophils and proteases. It is known that anticancer immune regulation is distorted towards immunosuppression, while in COPD the elements of autoimmunity are described. Cytotoxic T cells, lymphocytes B and regulatory T cells with the important role of check point molecules are involved in both processes. A growing number of lung cancer patients are treated with immune check point inhibitors (ICIs), and it was found that COPD patients may have benefits from this treatment. Altogether, the data point to the necessity for deeper analysis and intensive research studies to limit the burden of these serious diseases by prevention and by elaboration of specific therapeutic options.
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Affiliation(s)
- Robert Uliński
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Iwona Kwiecień
- Laboratory of Hematology and Flow Cytometry, Department of Internal Medicine and Hematology, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Joanna Domagała-Kulawik
- Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, 02-097 Warsaw, Poland
- Correspondence:
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Association between Chronic Obstructive Pulmonary Disease and Ménière's Disease: A Nested Case-Control Study Using a National Health Screening Cohort. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18094536. [PMID: 33923368 PMCID: PMC8123129 DOI: 10.3390/ijerph18094536] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/21/2021] [Accepted: 04/21/2021] [Indexed: 11/16/2022]
Abstract
This study explored the relation between Ménière's disease and chronic obstructive pulmonary disease (COPD). The ≥40-year-old population of the Korean National Health Insurance Service-Health Screening Cohort was included. In total, 7734 Ménière's disease patients and 30,936 control participants were enrolled. Control participants were matched for age, sex, income, and region of residence with Ménière's disease participants. The odds of having Ménière's disease given a history of COPD were analyzed using conditional logistic regression. Subgroup analyses were conducted according to age, sex, income, and region of residence. The odds of having Ménière's disease were found to be 1.18-fold higher with a history of COPD than with no history of COPD (95% confidence intervals (CI) = 1.06-1.32, E-value (CI) = 1.64 (1.31)). The ≥60 years old, male, low-income, and rural subgroups showed increased odds of developing Ménière's disease when a history of COPD was reported. A history of COPD was associated with an increased risk of Ménière's disease in the adult population.
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Impact of reduced pulmonary function in the Japanese general population: Lessons from the Yamagata-Takahata study. Respir Investig 2019; 57:220-226. [PMID: 30773474 DOI: 10.1016/j.resinv.2019.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/09/2019] [Accepted: 01/24/2019] [Indexed: 12/19/2022]
Abstract
Regional epidemiological studies for respiratory diseases have been rarely performed in Japan, because spirometry is not regularly conducted in the standard annual health checks. The Yamagata-Takahata Study is an epidemiological study utilizing regional characteristics based on the 21st Century Centers of Excellence (COE) Program and the Global COE Program. Spirometric examination and other specific measurements via blood sampling were performed for the study participants in annual health check-ups held in Takahata, a town in Yamagata Prefecture. The Yamagata-Takahata Study revealed the impact of cigarette smoking habit on pulmonary function, the impact of reduced pulmonary function on mortality, and the situation regarding COPD comorbidities in Japan. Additionally, the study identified biomarkers of decline in pulmonary function among active smokers, and the risk factors for respiratory mortality in Japan. In this review, we summarize the findings of the Yamagata-Takahata study regarding the association between lower pulmonary function and the clinical characteristics of a Japanese general population.
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Cervilha DAB, Ito JT, Lourenço JD, Olivo CR, Saraiva-Romanholo BM, Volpini RA, Oliveira-Junior MC, Mauad T, Martins MA, Tibério IFLC, Vieira RP, Lopes FDTQS. The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association. Sci Rep 2019; 9:1921. [PMID: 30760822 PMCID: PMC6374436 DOI: 10.1038/s41598-019-38600-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 01/03/2019] [Indexed: 12/22/2022] Open
Abstract
We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4+ and CD8+ T cells, Treg cells, and IL-10+ and IL-17+ cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4+ and CD8+ T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17+ cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5+ cells corroborated the increased numbers of IL-17+ and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10+ cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.
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Affiliation(s)
- Daniela A B Cervilha
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
| | - Juliana T Ito
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Juliana D Lourenço
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Clarice R Olivo
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
- Department of post-graduation of Institute of Medical Assistance to the State Public Servant, University City of Sao Paulo, Sao Paulo, Brazil
| | - Beatriz M Saraiva-Romanholo
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
- Department of post-graduation of Institute of Medical Assistance to the State Public Servant, University City of Sao Paulo, Sao Paulo, Brazil
| | - Rildo A Volpini
- Nephrology Department, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | | | - Thais Mauad
- Department of Pathology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Milton A Martins
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Iolanda F L C Tibério
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Rodolfo P Vieira
- Post-graduation Program in Bioengineering and in Biomedical Engineering, Universidade Brasil, Sao Paulo, Brazil
- Post-graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of Sao Paulo (UNIFESP), Santos, Brazil
- Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Sao Jose dos Campos, Brazil
| | - Fernanda D T Q S Lopes
- Department of Medicine, Laboratory of Experimental Therapeutics (LIM-20), School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
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Shindi R, Almehairi A, Negm OH, Kalsheker N, Gale NS, Shale DJ, Harrison TW, Bolton CE, John M, Todd I, Tighe PJ, Fairclough LC. Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease. Clin Immunol 2017; 183:344-353. [DOI: 10.1016/j.clim.2017.09.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/10/2017] [Accepted: 09/22/2017] [Indexed: 12/22/2022]
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Comella K, Blas JAP, Ichim T, Lopez J, Limon J, Moreno RC. Autologous Stromal Vascular Fraction in the Intravenous Treatment of End-Stage Chronic Obstructive Pulmonary Disease: A Phase I Trial of Safety and Tolerability. J Clin Med Res 2017; 9:701-708. [PMID: 28725319 PMCID: PMC5505307 DOI: 10.14740/jocmr3072w] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 05/23/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a consistently progressive, ultimately fatal disease for which no treatment exists capable of either reversing or even interrupting its course. It afflicts more than 5% of the population in many countries, and it accordingly represents the third most frequent cause of death in the US, where it accounts for more than 600 billion in health care costs, morbidity, and mortality. Adipose tissue contains within its stromal compartment a high abundance of adipose stem/stromal cells (ASCs), which can be readily separated from the adipocyte population by methods which require less than 2 h of processing time and yield a concentrated cellular preparation termed the stromal vascular fraction (SVF). The SVF contains all cellular elements of fat, excluding adipocytes. Recent clinical studies have begun to explore the feasibility and safety of the local injection or intravascular delivery of SVF or more purified populations of ASCs derived by culture protocols. Several pre-clinical studies have demonstrated a remarkable ability of ASC to nearly fully ameliorate the progress of emphysema due to cigarette smoke exposure as well as other causes. However, no prior clinical studies have evaluated the safety of administration of either ASC or SVF in subjects with COPD. We hypothesized that harvest, isolation, and immediate intravenous infusion of autologous SVF would be feasible and safe in subjects with COPD; and that such an approach, if ultimately determined to be efficacious as well as safe, would provide a highly practical method for treatment of COPD. METHODS In this study, an initial phase I trial evaluating the early and delayed safety of SVF infusion was performed. Twelve subjects were enrolled in the study, in which adipose tissue was harvested using standard liposuction techniques, followed by SVF isolation and intravenous infusion of 150 - 300 million cells. Standardized questionnaires were administered to study feasibility as well as immediate and delayed outcomes and adverse events as primary endpoints. Secondary endpoints included subjective wellness and attitudes towards the procedure, as well as willingness to undergo the procedure a second time. The follow-up time ranged from 3 to 12 months, averaging 12 months. RESULTS Of the 12 subjects, only one experienced an immediate adverse event, related to bruising from the liposuction. No observed pulmonary or cardiac issues were observed as related to the procedure. There were no deaths over the 12-month study period, and none identified in the subsequent telephonic follow-up. Attitudes toward the procedure were predominantly positive, and 92% of the study subjects expressed a desire to undergo the procedure a second time. CONCLUSIONS This study is the first to demonstrate safety of SVF infusion in humans with serious pulmonary disease. Specifically, the use of intravenous infusion as a route to achieve pulmonary cellular targeting did not lead to clinical pulmonary compromise. The intravenous administration of SVF should be further explored as a potentially feasible and safe method for delivery leading to possible therapeutic benefit.
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Affiliation(s)
- Kristin Comella
- US Stem Cell, Inc., 13794 NW 4th Street, Suite 212, Sunrise, FL 33325, USA
| | - Jesus A. Perez Blas
- University of Baja California, Mexico and Hospital Angeles, Tijuana, Mexico, Regenerative Medicine Institute, Mexico
| | - Tom Ichim
- University of Baja California, Mexico and Hospital Angeles, Tijuana, Mexico, Regenerative Medicine Institute, Mexico
| | - Javier Lopez
- University of Baja California, Mexico and Hospital Angeles, Tijuana, Mexico, Regenerative Medicine Institute, Mexico
| | - Jose Limon
- University of Baja California, Mexico and Hospital Angeles, Tijuana, Mexico, Regenerative Medicine Institute, Mexico
| | - Ruben Corral Moreno
- University of Baja California, Mexico and Hospital Angeles, Tijuana, Mexico, Regenerative Medicine Institute, Mexico
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Hampson JA, Stockley RA, Turner AM. Free light chains: potential biomarker and predictor of mortality in alpha-1-antitrypsin deficiency and usual COPD. Respir Res 2016; 17:34. [PMID: 27036487 PMCID: PMC4815123 DOI: 10.1186/s12931-016-0348-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 03/18/2016] [Indexed: 12/15/2022] Open
Abstract
Background Circulating free light chains (FLCs) can alter neutrophil migration, apoptosis and activation and may be a biomarker of autoimmune disease and adaptive immune system activation. These pathogenic roles could be relevant to lung disease in alpha 1 antitrypsin deficiency (A1ATD) and chronic obstructive pulmonary disease (COPD). Methods Total combined (c)FLCs were measured using the FreeLite® assay in 547 patients with A1ATD and 327 patients with usual COPD in the stable state, and assessed for association with clinical phenotype, disease severity, airway bacterial colonisation and mortality. Univariate and multivariate analyses were undertaken. Results Circulating cFLCs were static in the stable state when measured on 4 occasions in A1ATD and twice in usual COPD. Levels were inversely related to renal function (A1ATD and COPD p = <0.01), and higher in patients with chronic bronchitis (p = 0.019) and airway bacterial colonisation (p = 0.008). After adjusting for renal function and age the relationship between cFLCs and lung function was weak. Kaplan Meier curves showed that cFLC > normal (43.3 mg/L) significantly associated with mortality in both cohorts (A1ATD p = 0.001, COPD p = 0.013). Conclusions cFLCs may be a promising biomarker for risk stratification in A1ATD and COPD. Electronic supplementary material The online version of this article (doi:10.1186/s12931-016-0348-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Judith A Hampson
- Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK.,ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK
| | - Robert A Stockley
- Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK.,ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK
| | - Alice M Turner
- Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK. .,ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK. .,Heart of England NHS Foundation Trust, Birmingham, B9 5SS, UK.
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11
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Saeedi P, Salimian J, Ahmadi A, Imani Fooladi AA. The transient but not resident (TBNR) microbiome: a Yin Yang model for lung immune system. Inhal Toxicol 2015; 27:451-61. [PMID: 26307905 DOI: 10.3109/08958378.2015.1070220] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The concept of microbial content of the lung is still controversial. What make this more complicated are controversial results obtaining from different methodologies about lung microbiome and the definition of "lung sterility". Lungs may have very low bacteria but are not completely germ-free. Bacteria are constantly entering from the upper respiratory tract, but are then quickly being cleared. We can find bacterial DNA in the lungs, but it is much harder to ask about living bacteria. Here, we propose that if there is any trafficking of the microorganisms in the lung, it should be a "Transient But Not Resident (TBNR)" model. So, we speculate a "Yin Yang model" for the lung immune system and TBNR. Despite beneficial roles of microbiome on the development of lung immune system, any disruption and alteration in the microbiota composition of upper and lower airways may trigger or lead to several diseases such as asthma, chronic obstructive pulmonary disease and mustard lung disease.
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Affiliation(s)
| | - Jafar Salimian
- b Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences , Tehran , Iran
| | - Ali Ahmadi
- a Applied Microbiology Research Center and
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Jia Z, Feng Z, Tian R, Wang Q, Wang L. Thymosinα1 plus routine treatment inhibit inflammatory reaction and improve the quality of life in AECOPD patients. Immunopharmacol Immunotoxicol 2015; 37:388-92. [DOI: 10.3109/08923973.2015.1069837] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Daffa NI, Tighe PJ, Corne JM, Fairclough LC, Todd I. Natural and disease-specific autoantibodies in chronic obstructive pulmonary disease. Clin Exp Immunol 2015; 180:155-63. [PMID: 25469980 PMCID: PMC4367103 DOI: 10.1111/cei.12565] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2014] [Indexed: 12/01/2022] Open
Abstract
Autoimmunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Studies have identified disease-specific autoantibodies (DSAAbs) in COPD patients, but natural autoantibodies (NAAbs) may also play a role. Previous studies have concentrated on circulating autoantibodies, but lung-associated autoantibodies may be most important. Our aim was to investigate NAAbs and DSAAbs in the circulation and lungs of COPD smoking (CS) patients compared to smokers (S) without airway obstruction and subjects who have never smoked (NS). Immunoglobulin (Ig)G antibodies that bind to lung tissue components were significantly lower in the circulation of CS patients than NS (with intermediate levels in S), as detected by enzyme-linked immunosorbent assay (ELISA). The levels of antibodies to collagen-1 (the major lung collagen) detected by ELISA were also reduced significantly in CS patients’ sera compared to NS. The detection of these antibodies in NS subjects indicates that they are NAAbs. The occurrence of DSAAbs in some CS patients and S subjects was indicated by high levels of serum IgG antibodies to cytokeratin-18 and collagen-5; furthermore, antibodies to collagen-5 eluted from homogenized lung tissue exposed to low pH (0·1 M glycine, pH 2·8) were raised significantly in CS compared to S and NS. Thus, this study supports a role in COPD for both NAAbs and DSAAbs.
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Affiliation(s)
- N I Daffa
- School of Life Sciences, University of Nottingham, Nottingham, UK; Medical Microbiology Department, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
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The role of serum soluble urokinase-type plasminogen activator receptor in stable chronic obstructive pulmonary disease. J Investig Med 2015; 62:938-43. [PMID: 25127435 DOI: 10.1097/jim.0000000000000105] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory response of the lungs to noxious particles or gases. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during infections and inflammation. The main goal of this study was to evaluate the serum suPAR level in stable COPD patients compared with a control group. METHODS Forty-six stable COPD patients and 41 control subjects were included in the study. Blood samples were collected from 46 stable COPD patients (40 men, 6 women; mean [SD] age, 55.92 [7.91] years; the forced expiratory volume in 1 second, 45.32% [19.1%] of predicted). Forty-one healthy subjects were selected as control subjects and were matched to COPD patients with respect to age and body mass index. Serum suPAR and plasma fibrinogen levels were measured in stable COPD patients and control subjects. RESULTS Serum suPAR levels of the COPD patients were significantly higher than those of the control subjects (4.94 [2.79] and 2.40 [2.01] ng/mL, respectively; P < 0.001). Plasma fibrinogen levels of the COPD patients were significantly higher than those of the control subjects (406.77 [172.6] and 336.53 [96.1] g/L, respectively; P < 0.05). CONCLUSIONS Our study indicated that serum suPAR may play an important role in the inflammatory process of COPD, and this increase may be particularly large for patients in Global Initiative for Chronic Obstructive Lung Disease stages III and IV. Serum suPAR and plasma fibrinogen level measurements may be useful for the evaluation of stable COPD.
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15
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Duan M, Huang Y, Zhong X, Tang H. IL-21 is increased in peripheral blood of emphysema mice and promotes Th1/Tc1 cell generation in vitro. Inflammation 2013; 37:745-55. [PMID: 24357415 DOI: 10.1007/s10753-013-9793-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Interleukin-21 (IL-21) has been reported to be involved in many Th1-associated diseases. However, the alteration and immune regulation of IL-21 in emphysema remains unknown. In this study, we tested the levels of IFN-γ and IL-21 and the frequencies of Th1 and Tc1 in peripheral blood from cigarette smoke (CS)-exposed mice and air-exposed mice and explored the effect of IL-21 on generation of Th1 and Tc1 cells in vitro. It was found that the levels of IFN-γ and IL-21 and the frequencies of Th1, Tc1, CD4(+) IL-21(+), CD4(+) IL-21R(+), and CD8(+) IL-21R(+) T cells were much higher in CS-exposed mice. Moreover, the levels of IL-21 were correlated positively with Th1 cells and with Tc1 cells. Finally, the in vitro experiments showed that IL-21 could promote Th1/Tc1 cell generation in CS-exposed mice. These results indirectly provide evidence that IL-21 produced by CD4(+) T cells could promote Th1/Tc1 response, leading to systemic inflammation in emphysema.
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Affiliation(s)
- Minchao Duan
- Department of Respiratory Medicine, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Avenue, Nanning, Guangxi, 530021, China
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16
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Brebner JA, Turner AM. Early chronic obstructive pulmonary disease: Beyond spirometry. World J Respirol 2013; 3:57-66. [DOI: 10.5320/wjr.v3.i3.57] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 07/24/2013] [Accepted: 08/17/2013] [Indexed: 02/06/2023] Open
Abstract
The significant healthcare burden associated with chronic obstructive pulmonary disease (COPD) is driving us to improve our understanding of the natural history of this disease. Historically, the focus has been largely centred on diagnosing and treating individuals with moderate and severe disease. However, it is now recognised that the speed of decline in lung function as measured by forced expiratory volume in 1 s occurs faster in the earlier stages of the disease process. As a result, a clearer understanding of the potential benefits of treatment in early COPD is needed. It is recognised that many patients with COPD remain undiagnosed in the community which has prompted global case-finding initiatives. In this review we discuss the difficulties in diagnosing COPD in its early stages, examine the role of case-finding and look at the evidence for early intervention with therapeutic agents. There is a growing interest in the phenotypic variation amongst patients with COPD and we explore the role of phenotyping in early COPD and its potential benefits in providing a more individualised approach to COPD management. The majority of patients with COPD are known to die from non-respiratory causes such as cardiovascular disease. The mechanistic link is thought to relate to systemic inflammation, causing us to question whether earlier interventions could have a beneficial impact on the burden of co-morbidities for patients with COPD.
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17
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Podolin PL, Foley JP, Carpenter DC, Bolognese BJ, Logan GA, Long E, Harrison OJ, Walsh PT. T cell depletion protects against alveolar destruction due to chronic cigarette smoke exposure in mice. Am J Physiol Lung Cell Mol Physiol 2013; 304:L312-23. [DOI: 10.1152/ajplung.00152.2012] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The role of T cells in chronic obstructive pulmonary disease (COPD) is not well understood. We have previously demonstrated that chronic cigarette smoke exposure can lead to the accumulation of CD4+ and CD8+ T cells in the alveolar airspaces in a mouse model of COPD, implicating these cells in disease pathogenesis. However, whether specific inhibition of T cell responses represents a therapeutic strategy has not been fully investigated. In this study inhibition of T cell responses through specific depleting antibodies, or the T cell immunosuppressant drug cyclosporin A, prevented airspace enlargement and neutrophil infiltration in a mouse model of chronic cigarette smoke exposure. Furthermore, individual inhibition of either CD4+ T helper or CD8+ T cytotoxic cells prevented airspace enlargement to a similar degree, implicating both T cell subsets as critical mediators of the adaptive immune response induced by cigarette smoke exposure. Importantly, T cell depletion resulted in significantly decreased levels of the Th17-associated cytokine IL-17A, and of caspase 3 and caspase 7 gene expression and activity, induced by cigarette smoke exposure. Finally, inhibition of T cell responses in a therapeutic manner also inhibited cigarette smoke-induced airspace enlargement, IL-17A expression, and neutrophil influx in mice. Together these data demonstrate for the first time that therapeutic inhibition of T cell responses may be efficacious in the treatment of COPD. Given that broad immunosuppression may be undesirable in COPD patients, this study provides proof-of-concept for more targeted approaches to inhibiting the role of T cells in emphysema development.
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Affiliation(s)
- Patricia L. Podolin
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Joseph P. Foley
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Donald C. Carpenter
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Brian J. Bolognese
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Gregory A. Logan
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Edward Long
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Oliver J. Harrison
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
| | - Patrick T. Walsh
- Respiratory Therapeutic Area, GlaxoSmithKline, King Of Prussia, Pennsylvania; and
- School of Medicine, Trinity College Dublin, National Childrens Research Centre, Our Ladys Childrens Hospital, Crumlin, Dublin, Ireland
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18
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Epidemiology of comorbidities in chronic obstructive pulmonary disease: clusters, phenotypes and outcomes. ITALIAN JOURNAL OF MEDICINE 2012. [DOI: 10.1016/j.itjm.2012.02.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Erythromycin enhances CD4+Foxp3+ regulatory T-cell responses in a rat model of smoke-induced lung inflammation. Mediators Inflamm 2012; 2012:410232. [PMID: 22701274 PMCID: PMC3371355 DOI: 10.1155/2012/410232] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 04/01/2012] [Accepted: 04/01/2012] [Indexed: 01/12/2023] Open
Abstract
Heavy smoking can induce airway inflammation and emphysema. Macrolides can modulate inflammation and effector T-cell response in the lungs. However, there is no information on whether erythromycin can modulate regulatory T-cell (Treg) response. This study is aimed at examining the impact of erythromycin on Treg response in the lungs in a rat model of smoking-induced emphysema. Male Wistar rats were exposed to normal air or cigarette smoking daily for 12 weeks and treated by gavage with 100 mg/kg of erythromycin or saline daily beginning at the forth week for nine weeks. The lung inflammation and the numbers of inflammatory infiltrates in bronchoalveolar lavage fluid (BALF) were characterized. The frequency, the number of Tregs, and the levels of Foxp3 expression in the lungs and IL-8, IL-35, and TNF-α in BALF were determined by flow cytometry, RT-PCR and ELISA, respectively. Treatment with erythromycin reduced smoking-induced inflammatory infiltrates, the levels of IL-8 and TNF-α in the BALF and lung damages but increased the numbers of CD4+Foxp3+ Tregs and the levels of Foxp3 transcription in the lungs, accompanied by increased levels of IL-35 in the BALF of rats. Our novel data indicated that erythromycin enhanced Treg responses, associated with the inhibition of smoking-induced inflammation in the lungs of rats.
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20
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Ludvigsson JF, Inghammar M, Ekberg M, Egesten A. A nationwide cohort study of the risk of chronic obstructive pulmonary disease in coeliac disease. J Intern Med 2012; 271:481-489. [PMID: 21880073 DOI: 10.1111/j.1365-2796.2011.02448.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality and healthcare costs in the western world. Although smoking is an important trigger of COPD, other factors such as chronic inflammation and malnutrition are known to influence its development. Because coeliac disease (CD) is characterized both by dysregulated inflammation and malnutrition, the possibility of an association between CD and COPD was investigated. METHODS Through biopsy data from all Swedish pathology departments, we identified 10 990 individuals with CD who were biopsied between 1987 and 2008 (Marsh 3: villous atrophy). As controls, 54 129 reference individuals matched for age, sex, county and calendar year of first biopsy were selected. Cox regression analysis was then performed to estimate hazard ratios (HRs) for having a diagnosis of COPD according to the Swedish Patient Register. RESULTS During follow-up, 380 individuals with CD (3.5%) and 1391 (2.6%) controls had an incident diagnosis of COPD, which corresponds to an HR of 1.24 (95% CI: 1.10-1.38) and an excess risk of COPD of 79/100 000 person-years in CD. The risk increase remained 5 years after biopsy (HR = 1.17; 95% CI: 1.00-1.37). Risk estimates did not change with adjustment for type 1 diabetes, thyroid disease, rheumatoid arthritis, country of birth or level of education. Men with CD were at a higher risk of COPD (HR = 1.39; 95% CI: 1.18-1.62) than women with CD (HR = 1.11; 95% CI: 0.94-1.30). Of note, CD was also associated with COPD before CD diagnosis (odds ratio = 1.22; 95% CI: 1.02-1.46). Conclusion. Patients with CD seem to be at a moderately increased risk of COPD both before and after CD diagnosis.
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Affiliation(s)
- J F Ludvigsson
- Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
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21
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22
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Hodge G, Mukaro V, Reynolds PN, Hodge S. Role of increased CD8/CD28(null) T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease. Clin Exp Immunol 2011; 166:94-102. [PMID: 21910726 DOI: 10.1111/j.1365-2249.2011.04455.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease; it is a leading cause of death and existing treatments have no proven disease-modifying effect. The mechanisms underlying this resistance are largely unknown, but suggest the presence of some self-maintaining pathogenic process, possibly initiated by cigarette smoking, that prevents the normal resolution of inflammation. We have previously reported increased production of proinflammatory cytokines and granzyme b by CD8(+) T cells in COPD; costimulatory receptor/ligand interactions required include CD80:86/CD28, B7-1/CTLA4, 4-1BB/1BBL and OX40/OX40L. We hypothesized that a dysregulated expression/function of these molecules may play a role in inflammatory/autoimmune components of COPD. We analysed T cell co-stimulatory molecules in blood from 34 controls, 15 smokers and 48 COPD subjects. We assessed the potential functional relevance of CD8/CD28(null) cells in COPD by measuring their production of proinflammatory cytokines, co-stimulatory molecules, granzyme and perforin. A smoke-exposed murine model was applied to investigate the relative expression of CD8/CD28(null) T cells in blood, lung tissue and airway. CD8/CD28(null) cells were increased in both current- and ex-smoker COPD groups; these cells expressed significantly more interferon (IFN)-γ, OX40, 4-1BB, CTLA4, granzyme and perforin when stimulated than CD8/CD28(+) T cells. There were no changes in CD4/CD28(null) T cells. In mice exposed to cigarette smoke for 12 weeks, CD8/CD28(null) T cells were significantly increased in the airway with a trend for an increase in lung tissue and blood. Increased production of proinflammatory cytokines and expression of alternative co-stimulatory molecules by CD8/CD28(null) T cells may play a role in inflammatory or autoimmune responses in COPD and identify therapeutic targets.
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Affiliation(s)
- G Hodge
- Lung Research Laboratory, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, Australia.
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23
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Suskovic S, Keser D. Chronic obstructive pulmonary disease status 2011: long walk home. Respir Med 2011; 105 Suppl 1:S4-6. [DOI: 10.1016/s0954-6111(11)70003-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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24
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Elsais A, Johansen B, Kerty E. Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients. Acta Neurol Scand 2010:12-7. [PMID: 20586729 DOI: 10.1111/j.1600-0404.2010.01369.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Myasthenia gravis (MG) is an autoimmune disease of neuromuscular synapses, characterized by muscular weakness and reduced endurance. Remission can be obtained in many patients. However, some of these patients complain of fatigue. The aim of this study was to assess exercise capacity and lung function in well-regulated MG patients. PATIENTS AND METHODS Ten otherwise healthy MG patients and 10 matched controls underwent dynamic spirometry, and a ramped symptom-limited bicycle exercise test. Spirometric variables included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV). Exercise variables included maximal oxygen uptake (VO(2) max), anaerobic threshold (VO(2) AT) maximum work load (W), maximum ventilation (VE max), and limiting symptom. RESULTS Myasthenia gravis patients had significantly lower FEV1/FVC ratio than controls. This was more marked in patients on acetylcholine esterase inhibitors. On the contrary, patients not using acetylcholine esterase inhibitors had a significantly lower exercise endurance time. CONCLUSION Well-regulated MG patients, especially those using pyridostigmine, tend to have an airway obstruction. The modest airway limitation might be a contributing factor to their fatigue. Patients who are not using acetylcholinesterase inhibitor seem to have diminished exercise endurance in spite of their clinically complete remission.
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Affiliation(s)
- A Elsais
- Department of Neurology, Oslo University Hospital, Oslo, Norway.
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25
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Nava RG, Li W, Gelman AE, Krupnick AS, Miller MJ, Kreisel D. Two-photon microscopy in pulmonary research. Semin Immunopathol 2010; 32:297-304. [PMID: 20589501 DOI: 10.1007/s00281-010-0209-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2010] [Accepted: 05/28/2010] [Indexed: 12/12/2022]
Abstract
As the lung is constantly exposed to both innocuous and potentially noxious antigens, a thorough understanding of both innate and adaptive immune responses in this organ is of the essence. Imaging modalities such as magnetic resonance imaging, positron emission tomography, and confocal microscopy have expanded our knowledge about various molecular processes and cellular responses in the lung. Two-photon microscopy has evolved into a powerful tool to observe cellular interactions in real time and has markedly expanded our understanding of the immune system. Recently, two-photon microscopy has also been utilized to image the murine lung. As immune responses in the lung differ from those in other non-lymphoid tissues, this technique holds great promise to advance our knowledge of the biology that underlies a wide spectrum of pulmonary diseases.
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Affiliation(s)
- Ruben G Nava
- Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
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26
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Current World Literature. Curr Opin Pulm Med 2010; 16:162-7. [DOI: 10.1097/mcp.0b013e32833723f8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Lin F, Josephs SF, Alexandrescu DT, Ramos F, Bogin V, Gammill V, Dasanu CA, De Necochea-Campion R, Patel AN, Carrier E, Koos DR. Lasers, stem cells, and COPD. J Transl Med 2010; 8:16. [PMID: 20158898 PMCID: PMC2830167 DOI: 10.1186/1479-5876-8-16] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2010] [Accepted: 02/16/2010] [Indexed: 12/13/2022] Open
Abstract
The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.
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Affiliation(s)
- Feng Lin
- Entest BioMedical, San Diego, CA, USA
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Abstract
Chronic obstructive pulmonary disease (COPD) is still a poorly understood disease. Its pathogenesis is excitingly complex and has systemic consequences caused not only by increased production of certain cytokines but also by neurohumoral activation, chronic bacterial infection, muscle wasting and cachexia. Asthma and COPD have many overlapping clinical features so it should not be surprising that in the pathogenesis of COPD mediators such as leukotrienes, complement activation, atopic or even autoimmune processes are possibly involved. The pathogenesis of cardiovascular system involvement in COPD is also multifaceted and includes chronic heart hypoxia, damage by smoking and pulmonary hypertension; it must also be viewed as a consequence of systemic inflammation and neurohormonal activation. COPD is among the leading causes of morbidity and mortality worldwide and therefore it should be studied intensively beyond the lung itself. Treatments directed at neurohumoral activation in COPD have not been fully addressed; this aspect of COPD should be better understood, as it may direct novel therapeutic approaches.
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