Ian M Adcock

Imperial College London, Londinium, England, United Kingdom

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Publications (409)1980.37 Total impact

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    ABSTRACT: Respiratory virus infections are commonly associated with COPD exacerbations but little is known about the mechanisms linking virus infection to exacerbations. Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2) but their roles in COPD exacerbations is unknown. We investigated oxidative/nitrosative stress and HDAC2 in COPD exacerbations using experimental rhinovirus infection. 9 subjects with COPD (GOLD stage II), 10 smokers and 11 non-smokers were successfully infected with rhinovirus. Markers of oxidative and nitrosative-stress associated cellular damage, inflammatory mediators and proteases were measured in sputum, and HDAC2 activity measured in sputum and bronchoalveolar macrophages. In an in vitro model monocyte derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 measured. Rhinovirus infection induced significant increases in airways inflammation and markers of oxidative and nitrosative stress in COPD subjects. Oxidative/nitrosative stress markers correlated with virus load and inflammatory markers. Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers and nitrosative stress. Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory makers during exacerbation. Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity, inhibition of oxidative/nitrosative stress inhibited rhinovirus-induced inflammatory cytokines. Oxidative and nitrosative stress, airways inflammation and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations. Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.
    Chest 03/2015; DOI:10.1378/chest.14-2637 · 7.13 Impact Factor
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    ABSTRACT: The role of mitogen-activated protein kinases (MAPK) in regulating the inflammatory response in the airways of patients with chronic obstructive pulmonary disease (COPD) and asthmatic patients is unclear. To investigate the expression of activated MAPK in lungs of COPD patients and in bronchial biopsies of asthmatic patients and to study MAPK expression in bronchial epithelial cells in response to oxidative and inflammatory stimuli. Immunohistochemical expression of phospho (p)-p38 MAPK, p-JNK1 and p-ERK1/2 was measured in bronchial mucosa in patients with mild/moderate (n = 17), severe/very severe (n = 16) stable COPD, control smokers (n = 16), control non-smokers (n = 9), in mild asthma (n = 9) and in peripheral airways from COPD patients (n = 15) and control smokers (n = 15). Interleukin (IL)-8 and MAPK mRNA was measured in stimulated 16HBE cells. No significant differences in p-p38 MAPK, p-JNK or p-ERK1/2 expression were seen in bronchial biopsies and peripheral airways between COPD and control subjects. Asthmatics showed increased submucosal p-p38 MAPK expression compared to COPD patients (p < 0.003) and control non-smokers (p < 0.05). Hydrogen peroxide (H2O2), cytomix (tumour necrosis factor-α + IL-1β + interferon-γ) and lipopolysaccharide (LPS) upregulated IL-8 mRNA at 1 or 2 h. p38 MAPKα mRNA was significantly increased after H2O2 and LPS treatment. JNK1 and ERK1 mRNA were unchanged after H2O2, cytomix or LPS treatments. p-p38 MAPK expression is similar in stable COPD and control subjects but increased in the bronchi of mild asthmatics compared to stable COPD patients. p38 MAPK mRNA is increased after bronchial epithelial challenges in vitro. These data together suggest a potential role for this MAPK in Th2 inflammation and possibly during COPD exacerbations. © 2015 S. Karger AG, Basel.
    Respiration 03/2015; DOI:10.1159/000375168 · 2.92 Impact Factor
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    ABSTRACT: Abstract Background; Sarcoidosis is a systemic disease of unknown etiology characterized histologically by the observation of non-caseating granulomas and several immunological abnormalities. Sarcoidosis is a multi-organ disorder which involves formation of granulomas in many tissues including the lungs (pulmonary) and others such as skin, bone, heart (extra pulmonary). Associations between human leukocyte antigens (HLA), the encoded cell surface receptor (HLA-DR) and sarcoidosis have been reported in several studies. Several HLA-DR alleles have been described as potential risk factors for sarcoidosis in distinct ethnic groups however evidence for a relationship between HLA-DR alleles and pulmonary and extra-pulmonary sarcoidosis (EPS) is still scarce. Although the etiology of the disease remains unclear, infectious and environmental factors have been postulated. Inflammatory cytokines and chemokines may play important roles in the pathogenesis of sarcoidosis and serum free light chain (FLC) numbers have been implicated in several immunologic disorders. Purpose of the study; The aim of the present study was to investigate HLA associations with serum cytokines and FLC in Iranian patients with pulmonary (n= 86) and EPS (n=46). Results; We found that among the 16 HLA DRB alleles only *7 and *12 were different in sarcoidosis patients. The levels of TNF- and IL-8 in pulmonary sarcoidosis patients were higher than in EPS (P<0.05) whereas the levels of FLC subunits in EPS were higher than in pulmonary sarcoidosis. Conclusion; This data may suggests a link between HLA-DRB *12 and sarcoidosis in Iranian population.
    Journal of Inflammation 03/2015; · 2.22 Impact Factor
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    ABSTRACT: Rationale Airway smooth muscle (ASM) mass is increased in asthma and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8. The bromo- and extra-terminal (BET) family of proteins (Brd2, Brd3 and Brd4) govern the assembly of histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation and cytokine expression in asthmatic ASM cells by studying the effect of BET bromodomain mimics, JQ1/SGCBD01 and I-BET762. Methods ASM cells from healthy individuals, non-severe and severe asthmatics were pre-treated with JQ1/SGCBD01 and I-BET762 prior to stimulation with fetal calf serum (FCS) and transforming growth factor-β (TGF-β). Proliferation was measured by BrdU incorporation. IL-6 and CXCL8 release was measured by ELISA, and mRNA expression was measured by RT-qPCR. Chromatin immunoprecipitation (ChIP) using a specific anti-Brd4 antibody and PCR primers directed against the transcriptional start site of IL-6 and CXCL8 gene promoters was performed. Results Neither JQ1/SGCBD01 nor I-BET762 had any effect on ASM cell viability. JQ1/SGCBD01 and I-BET762 inhibited FCS+TGF-β-induced ASM cell proliferation, IL-6 and CXCL8 release in healthy individuals (≥ 30nM) and in non-severe and severe asthma patients (≥ 100nM), the latter requiring higher concentrations of these mimics. JQ1/SGCBD01 reduced Brd4 binding to IL8 and IL6 promoters induced by FCS+TGF-β. Conclusions Mimics of BET bromodomains inhibit aberrant ASM cell proliferation and inflammation with lesser efficiency in those from asthmatic patients. They may be effective in reducing airway remodelling in asthma. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 02/2015; DOI:10.1074/jbc.M114.612671 · 4.60 Impact Factor
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    Mark M Perry, Ian M Adcock, Kian Fan Chung
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    ABSTRACT: Purpose of review: MicroRNAs (miRNAs) modulate gene transcription in response to environmental stressors and other stimuli. A role for miRNAs in inflammation and immunity has been demonstrated and further evidence suggests that miRNAs also play a role in allergic asthma. Recent findings: Studies investigating the differential expression of miRNAs in biological fluids between asthma patients and controls have been published, as have their role in immune cell subsets. Further development of miRNAs in therapy has been addressed. miRNA-146a has been implicated in autoimmunity and allergic inflammation and miRNA-155 in the development of atopy. Targeting of miRNA-1 and miRNA-145 has been used to inhibit lung inflammation in mouse models of asthma. Although these recent findings need to be confirmed, miRNAs may prove to be useful as potential biomarkers of disease. However, their use as therapeutic targets in the lung remains unclear. Summary: There may be a potential role for using circulating miRNAs as biomarkers of disease status or response to therapy. The use of miRNAs as asthma therapy remains to be determined.
    Current Opinion in Allergy and Clinical Immunology 02/2015; doi: 10.1097/ACI.0000000000000147. DOI:10.1097/ACI.0000000000000147 · 3.40 Impact Factor
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    ABSTRACT: Recent studies have been established high degree of genetic diversity in solid organ tumors among individuals and even between individual tumor cells. This intratumor and intertumor genetic diversity results in a heterogeneous tumor with unique characteristics which potentially allows effective drug therapy. The goal of pharmacogenomics is to elucidate the genetic network(s) that underlie drug efficacy and drug resistance. Advances in targeted and personalized therapy plays an increasingly important role in many common cancers, notably lung cancer, due to the high incidence, prevalence, mortality and the greater tendency towards drug resistance seen in these patients. Non-small cell lung cancer (NSCLC) is characterized by mutations in the epidermal growth factor receptor (EGFR) and or downstream kinase pathways. This has led to the development of highly selective monoclonal antibodies and EGFR tyrosine kinase inhibitors (EGFR-TKIs) to prevent cancer initiation, proliferation, differentiation, angiogenesis, survival, and invasion. However, resistance to many of these new treatments is induced and further pharmacogenomic analysis has revealed mutations associated with increased or reduced drug efficacy. Combinations of kinase inhibitors or potentially the targeting of cancer stem cells may further increase the success of pharmacogenomics in treating patients with lung cancer. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 02/2015; DOI:10.1016/j.ejphar.2015.02.029 · 2.59 Impact Factor
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    ABSTRACT: The use of flow cytometry in the clinical laboratory has grown substantially in the past decade. Flow cytometric analysis provides a rapid qualitative and quantitative description of multiple characteristics of individual cells. For example, it is possible to detect the cell size and granularity, aspects of DNA and RNA content and the presence of cell surface and nuclear markers which are used to characterize the phenotype of single cells. Flow cytometry has been used for the immunophenotyping of a variety of specimens including whole blood, bone marrow, serous cavity fluids, (cerebrospinal fluid) CSF, urine and all types of body fluids. The technique has also been applied to human bronchoalveolar lavage (BAL) fluid, peritoneal fluids and blood. In this review, we describe the current status of the application of flow cytometry as a diagnostic tool in various lung diseases. We focus on the analysis of BAL cell composition in chronic obstructive lung disease (COPD), asthma, lung cancer, sarcoidosis, tuberculosis and idiopathic eosinophilic pneumonia (IEP).
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    ABSTRACT: The 2nd Cross Company Respiratory Symposium (CCRS), held in Horsham, U.K. in 2012, brought together representatives from across the pharmaceutical industry with expert academics, in the common interest of improving the design and translational predictiveness of in vivo models of respiratory disease. Organized by the respiratory representatives of the European Federation of Pharmaceutical Industries and Federations (EFPIA) group of companies involved in the EU-funded project (U-BIOPRED), the aim of the symposium was to identify state-of-the-art improvements in the utility and design of models of respiratory disease, with a view to improving their translational potential and reducing wasteful animal usage. The respiratory research and development community is responding to the challenge of improving translation in several ways: greater collaboration and open sharing of data, careful selection of the species, complexity and chronicity of the models, improved practices in preclinical research, continued refinement in models of respiratory diseases and their sub-types, greater understanding of the biology underlying human respiratory diseases and their sub-types, and finally greater use of human (and especially disease-relevant) cells, tissues and explants. The present review highlights these initiatives, combining lessons from the symposium and papers published in Clinical Science arising from the symposium, with critiques of the models currently used in the settings of asthma, idiopathic pulmonary fibrosis and COPD. The ultimate hope is that this will contribute to a more rational, efficient and sustainable development of a range of new treatments for respiratory diseases that continue to cause substantial morbidity and mortality across the world.
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    ABSTRACT: Inflammation is a central feature of stable chronic obstructive pulmonary disease (COPD) and involves both activation of structural cells of the airways and the lungs and the activation and/or recruitment of infiltrating inflammatory cells. This results in enhanced expression of many pro-inflammatory proteins and reduced expression of some anti-inflammatory mediators. An altered protein expression is generally associated with concomitant changes in gene expression profiles in a cell-specific manner. Increased understanding of the role of transcription factors and of the signaling pathways leading to their activation in stable COPD will provide new targets to enable the development of potential anti-inflammatory drugs. Several new compounds targeting these pathways and/or transcription factors are now in development for the treatment of stable COPD. Furthermore, glucocorticoids drugs already in clinical use act through their own transcription factor, the glucocorticoid receptor, to control the expression of inflammatory and anti-inflammatory genes.
    Annals of the New York Academy of Sciences 01/2015; DOI:10.1111/nyas.12619 · 4.38 Impact Factor
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    ABSTRACT: Necrotizing sarcoid granulomatosis (NSG) is a rare syndrome with unknown etiology. The disease is frequently confused with sarcoidosis and other granulomatous diseases. Diagnosis is made based on typical histologic criteria. No specific laboratory finding can confirm NSG diagnosis. The gender ratio of women to men has been reported as being as high as 4:1 and has a good prognosis.
    01/2015; 4. DOI:10.1016/j.ijmyco.2014.11.044
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    ABSTRACT: Tuberculosis (TB) is one of the most common infections world-wide, and in 2012, an estimated 8.6 million people developed TB and 1.3 million died from the disease (including 320,000 deaths among HIV-positive people). Mycobacterium tuberculosis (MTB) is an intracellular pathogen capable of infecting and surviving within the hosts mononuclear cells, particularly macrophages. This involves sequestration of MTB within organized granulomas. Nontuberculous mycobacteria refers to all the species in the family of mycobacteria that may cause human disease, but does not cause TB. Every year in the world approximately 2 people per 100,000 population develop infections caused by these lesser-known “cousins” of TB and leprosy. In this study, the focus is on a rare case of a patient with chronic granulomatous disease presenting with both MTB and nontuberculous Mycobacteria. As far as this research is concerned, this is the first report of a carrier patient with chronic granulomatous disease combined with MTB and nontuberculous mycobacteria. The presented information may help to improve the diagnosis and open a new light in the investigation of susceptibility of patients to mycobacterium infections.
    01/2015; 4. DOI:10.1016/j.ijmyco.2014.11.045
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    ABSTRACT: Tuberculosis (TB) has previously been linked to acute respiratory distress syndrome (ARDS). Here this study investigates the link between inflammation and TB in ARDS by measuring inflammatory cytokine and chemokine levels in bronchoalveolar lavage (BAL) from 90 patients with TB or ARDS alone and in patients with TB-induced ARDS (ARDS + TB). BAL was collected by fiber-optic bronchoscopy, and the concentrations of interleukin (IL)-6, CXCL8, TNF α and IL-1β were measured by ELISA. CXCL8 levels in BAL were significantly higher in the ARDS + TB group compared with TB and ARDS alone groups. Disease severity in the ARDS + TB group as determined by Murray score correlated with BAL CXCL8 and neutrophils, but not with IL-6, IL-1β and TNF α concentrations. In addition, CXCL8 levels and neutrophils were increased in non-miliary TB versus miliary TB. This difference in CXCL8 was lost in the presence of ARDS. It was concluded from this study that CXCL8 may play an important role in the pathogenesis of this form of ARDS. This further suggests that CXCL8 inhibitors or blockers may be useful to control the onset and/or development of these combined diseases.
    01/2015; 4. DOI:10.1016/j.ijmyco.2014.11.039
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    ABSTRACT: Long noncoding RNAs (lncRNAs) play an important role in the pathogenesis of many human diseases. In this study, we provide the description of genome-wide lncRNA expression in the lung tissue of non-smokers without Chronic obstructive pulmonary disease (COPD), of smokers without COPD and of smokers with COPD. RNA was extracted from human lung tissue and analysed using an Agilent Human lncRNA + mRNA Array v2.0 system. 39,253 distinct lncRNA transcripts were detected in the lung tissues of all subjects. In smokers without COPD 87 lncRNAs were significantly up-regulated and 244 down-regulated compared to non-smokers without COPD with RNA50010|UCSC-9199-1005 and RNA58351| CombinedLit_316_550, the most over- and under-regulated, respectively. In contrast, in COPD patients 120 lncRNAs were over-expressed and 43 under-expressed compared with smokers without COPD with RNA44121|UCSC-2000-3182 and RNA43510|UCSC-1260-3754 being the most over- and under-regulated, respectively. Gene Ontology (GO) and pathway analysis indicated that cigarette smoking was associated with activation of metabolic pathways, whereas COPD transcripts were associated with 'hematopoietic cell lineage', intermediary metabolism and immune system processes. We conclude that the altered expression of lncRNAs might play partial role in pathways implicated in COPD onset and progression such as intermediary metabolism and the immune response.
    Inflammation Research 12/2014; 64(2). DOI:10.1007/s00011-014-0790-9 · 2.14 Impact Factor
  • Kian Fan Chung, Ian M Adcock
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    ABSTRACT: Asthma is a common disease which presents in various clinical forms and levels of severity. The current 'one size fits all' approach to treatment is suboptimal. Using unbiased cluster analysis has identified several asthma phenotypes. Understanding the underlying mechanisms driving these clusters may lead to better patient-orientated medicines. Clustering was initially performed on clinical features only, but the addition of biomarkers that characterize sputum and blood cellular profiles has enabled the prediction of responses to targeted therapies. Clusters of severe asthma include those on high-dose corticosteroid treatment associated with severe airflow obstruction and those with discordance between symptoms and sputum eosinophilia. Sputum eosinophilia can predict therapeutic responses to T-helper type 2 cytokine blockade. Further molecular phenotyping or endotyping of asthma will be necessary to determine new treatment strategies. Low T-helper type 2 expression may be predictive of poor therapeutic response to inhaled corticosteroids, but much less is known about this type of asthma. Phenotype-driven treatment of asthma will be further boosted by the integration of genetic, transcriptomic and proteomic technologies to defining distinct severe asthma phenotypes and biomarkers of therapeutic responses. This will lead towards stratified medicine for asthma.
    Current Opinion in Allergy and Clinical Immunology 12/2014; 15(1). DOI:10.1097/ACI.0000000000000134 · 3.66 Impact Factor
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    ABSTRACT: Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities.
    Journal of Clinical Immunology 10/2014; DOI:10.1007/s10875-014-0103-7 · 2.65 Impact Factor
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    ABSTRACT: The immunopathology of sarcoidosis remains elusive despite years of research into this multiorgan disease.However, recent studies have provided new insights into the genetics and immune components involved in the clinical manifestation of the disease. Granulomatous inflammation is due to the host immune response to a persistent poorly degradable unknown antigen.Mycobacterium tuberculosis (MTB) is the major disease driver in many patients. The immune mechanisms that cause this disease start with the antigenic stimulus, followed by T-cell, macrophage and dendritic cell activation via a classic MHC II-mediated pathway. In addition, the profile of immune mediators reported in sarcoidosis indicates that the inflammasome pathway plays a critical role in disease pathogenesis. Increased understanding of the signal transductions pathways involved in the induction of inflammatory processes in sarcoidosis could give rise to new therapeutic approaches in future.
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    ABSTRACT: Abstract : Tuberculosis remains a major public health problem in most of the developing world and the emerging epidemic of acquired immunodeficiency syndrome has resulted in a resurgence of Tuberculosis throughout the world. Nontuberculous mycobacteria refers to all the species in the family of mycobacteria that may cause human disease, but do 56 not cause Tuberculosis. Every year in the world approximately two people per 100,000 populations develop infections caused by these lesser-known "cousins" of Tuberculosisand leprosy. In this study we focus on a rare case of a patient with chronic granulomatous disease presenting with both Mycobacterium Tuberculosis and 60 Nontuberculous mycobacteria. To our knowledge this is the first report of patient with carrier of chronic granulomatous disease combined with Mycobacterium Tuberculosis and Nontuberculous mycobacteria. The presented information may help to improve the diagnosis and open a new light in investigation of susceptibility of patients to mycobacterium infections.
    BioMed Research International 09/2014; · 2.71 Impact Factor
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    Esmaeil Mortaz, Ian M. Adcock, Peter Barens
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    ABSTRACT: Sarcoidosis is a granulomatous inflammatory disease that is induced by unknown antigen(s) in a genetically susceptible host. Although the direct link between Mycobacterium tuberculosis (MTB) infection and sarcoidosis can be excluded on the basis of current knowledge, non-infectious mechanisms may explain the causative role of mycobacterial antigens. Ever since sarcoidosis was first described, its relationship with tuberculosis (TB) has been under-investigated. Whereas some researchers consider sarcoidosis and TB as two examples of the same disease process, others have rejected mycobacteria as playing any causative role in sarcoidosis. Whether they are linked causally or not, clinical evidence makes a differential diagnosis between the two conditions very challenging, particularly in countries with high burden of TB. The present study analyzes the relationship between sarcoidosis and TB and its implications in clinical practice. The coincidence of TB and sarcoidosis and the higher incidence of mycobacterial DNA in biological samples of sarcoid patients have been reported by many authors. In addition, new evidence of a similarity in MTB phenotype in sarcoidosis is provided. Overall, these observations suggest that TB and sarcoidosis may not only share the same etiology, but may even be different aspects of one disease.
    09/2014; DOI:10.1016/j.ijmyco.2014.10.008
  • European Respiratory Journal 09/2014; 44(3):578-84. DOI:10.1183/09031936.00109314 · 7.13 Impact Factor
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    ABSTRACT: BackgroundTuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS). The role of inflammatory cytokines in the progression of ARDS in TB patients is unknown.ObjectivesIn this study we investigated the possible link between the levels of inflammatory cytokines in bronchoalveolar lavage (BAL) in patients with TB or ARDS alone or in patients with TB-induced ARDS (ARDS + TB).Methods90 patients were studied: 30 with TB alone, 30 with ARDS alone and 30 with ARDS + TB. BAL was collected by fiberoptic bronchoscopy and the concentrations of interleukin(IL)-6, CXCL8, TNF-α and IL-1β and the amounts of total protein were measured by ELISA and bicinchoninic acid assay (BCA) methods respectively. The correlation between disease severity measured by Murray scores, SOFA and APACHE II analysis and BAL mediators and cells was also determined.ResultsCXCL8 levels in BAL were significantly higher in the ARDS + TB group compared to TB and ARDS alone groups. Disease severity in the ARDS + TB group as determined by Murray score correlated with BAL CXCL8 and neutrophils but not with IL-6, IL-1β and TNF-α concentrations. In addition, CXCL8 levels and neutrophils were increased in non-miliary TB versus miliary TB. This difference in CXCL8 was lost in the presence of ARDS.ConclusionsBAL CXCL8 levels were significantly higher in patients with ARDS induced by TB and could suggest an important role of CXCL8 in the pathogenesis of this form of ARDS. This further suggests that CXCL8 inhibitors or blockers may be useful to control the onset and/or development of these combined diseases.
    Journal of Inflammation 08/2014; 11:21. DOI:10.1186/1476-9255-11-21 · 2.22 Impact Factor
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Publication Stats

18k Citations
1,980.37 Total Impact Points


  • 1996–2015
    • Imperial College London
      • • Faculty of Medicine
      • • Section of Airway Disease
      • • Division of Cell and Molecular Biology
      Londinium, England, United Kingdom
  • 1993–2014
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 2003–2013
    • Universita degli studi di Ferrara
      • Research Center for the Research of Asthma and BPCO
      Ferrara, Emilia-Romagna, Italy
  • 2012
    • Utrecht University
      • Division of Pharmacology
      Utrecht, Utrecht, Netherlands
  • 2011
    • Università degli Studi di Salerno
      • Department of BioMedical and Pharmaceutical Sciences FARMABIOMED
      Fisciano, Campania, Italy
  • 2008
    • University of Wisconsin–Madison
      • Department of Medicine
      Madison, Wisconsin, United States
  • 1998–2008
    • Royal Brompton and Harefield NHS Foundation Trust
      Harefield, England, United Kingdom
  • 2006
    • University of Rochester
      • Department of Environmental Medicine
      Rochester, New York, United States
  • 2005
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2004
    • University of Cologne
      • Division of Cardiology, Pneumology, Angiology and Intensive Care
      Köln, North Rhine-Westphalia, Germany
  • 2001
    • Imperial Valley College
      IPL, California, United States