Peter J Barnes

Summary

Affiliation: Imperial College
Country: UK

Publications

  1. pmc Correlation of exhaled breath temperature with bronchial blood flow in asthma
    Paolo Paredi
    Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK
    Respir Res 6:15. 2005
  2. pmc Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study
    Christiane Lex
    Department of Paediatric Respiratory Medicine, Imperial College of Science, Technology and Medicine, Royal Brompton Hospital, National Heart and Lung Institute, London, UK
    Respir Res 7:63. 2006
  3. pmc Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children
    Paolo Montuschi
    Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy
    Respir Res 6:119. 2005
  4. ncbi request reprint Synergy between tumor necrosis factor alpha and interleukin 1beta in inducing transcriptional down-regulation of muscarinic M2 receptor gene expression. Involvement of protein kinase A and ceramide pathways
    E B Haddad
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology, and Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    J Biol Chem 271:32586-92. 1996
  5. ncbi request reprint New treatments for COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
    Nat Rev Drug Discov 1:437-46. 2002
  6. ncbi request reprint Alveolar macrophages as orchestrators of COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, SW3 6LY, London, UK
    COPD 1:59-70. 2004
  7. ncbi request reprint Achieving asthma control
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Curr Med Res Opin 21:S5-9. 2005
  8. ncbi request reprint New concepts in chronic obstructive pulmonary disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, United Kingdom
    Annu Rev Med 54:113-29. 2003
  9. ncbi request reprint Molecular mechanisms and cellular effects of glucocorticosteroids
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
    Immunol Allergy Clin North Am 25:451-68. 2005
  10. ncbi request reprint Therapy of chronic obstructive pulmonary disease
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Pharmacol Ther 97:87-94. 2003

Detail Information

Publications111 found, 100 shown here

  1. pmc Correlation of exhaled breath temperature with bronchial blood flow in asthma
    Paolo Paredi
    Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK
    Respir Res 6:15. 2005
    ..0 +/- 2.3 mul/ml/min, p < 0.05) but was not affected by salbutamol.Deltae degrees T correlates with Qaw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids...
  2. pmc Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in childhood asthma: a pilot study
    Christiane Lex
    Department of Paediatric Respiratory Medicine, Imperial College of Science, Technology and Medicine, Royal Brompton Hospital, National Heart and Lung Institute, London, UK
    Respir Res 7:63. 2006
    ..The aim of this study was to evaluate the relationship between cysLTs in EBC and another marker of airway remodeling, reticular basement membrane (RBM) thickening, in endobronchial biopsies in children...
  3. pmc Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children
    Paolo Montuschi
    Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy
    Respir Res 6:119. 2005
    ..We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO) was measured as an independent marker of airway inflammation...
  4. ncbi request reprint Synergy between tumor necrosis factor alpha and interleukin 1beta in inducing transcriptional down-regulation of muscarinic M2 receptor gene expression. Involvement of protein kinase A and ceramide pathways
    E B Haddad
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology, and Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    J Biol Chem 271:32586-92. 1996
    ..Furthermore, these results suggest that M2 receptor expression is under the control of a cytokine network...
  5. ncbi request reprint New treatments for COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
    Nat Rev Drug Discov 1:437-46. 2002
    ....
  6. ncbi request reprint Alveolar macrophages as orchestrators of COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, SW3 6LY, London, UK
    COPD 1:59-70. 2004
    ..These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase-4 inhibitors...
  7. ncbi request reprint Achieving asthma control
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Curr Med Res Opin 21:S5-9. 2005
    ..When choosing an inhaler device it is essential that it is easy to use correctly, dosing is consistent, adequate drug is deposited in the lungs (both central and peripheral airways) and that drug deposition is independent of airflow...
  8. ncbi request reprint New concepts in chronic obstructive pulmonary disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, United Kingdom
    Annu Rev Med 54:113-29. 2003
    ..Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease...
  9. ncbi request reprint Molecular mechanisms and cellular effects of glucocorticosteroids
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
    Immunol Allergy Clin North Am 25:451-68. 2005
    ..These new insights into GCS action may lead to new approaches to treating inflammatory lung diseases and in particular to increasing effectiveness of steroids in situations where they are less effective...
  10. ncbi request reprint Therapy of chronic obstructive pulmonary disease
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Pharmacol Ther 97:87-94. 2003
    ..There is a pressing need to develop new classes of therapy, and several new drugs are current in development, including interleukin-8 antagonists, phosphodiesterase-4 inhibitors, protease inhibitors, and antioxidants...
  11. ncbi request reprint Corticosteroids: the drugs to beat
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Eur J Pharmacol 533:2-14. 2006
    ..Corticosteroids are likely to remain the mainstay of asthma therapy and new therapeutic strategies may reverse the corticosteroid insensitivity in COPD and severe asthma...
  12. ncbi request reprint Update on asthma
    Peter J Barnes
    Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Isr Med Assoc J 5:68-72. 2003
  13. ncbi request reprint Theophylline: new perspectives for an old drug
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Am J Respir Crit Care Med 167:813-8. 2003
  14. ncbi request reprint Anti-leukotrienes: here to stay?
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
    Curr Opin Pharmacol 3:257-63. 2003
    ..It is unlikely that this class of drug will be improved greatly in the future, and so will remain as a weak second-line therapy...
  15. ncbi request reprint Cytokine-directed therapies for the treatment of chronic airway diseases
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Cytokine Growth Factor Rev 14:511-22. 2003
    ....
  16. ncbi request reprint How do corticosteroids work in asthma?
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London, United Kingdom
    Ann Intern Med 139:359-70. 2003
  17. pmc Chronic obstructive pulmonary disease * 12: New treatments for COPD
    P J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, London SW3 6LY, UK
    Thorax 58:803-8. 2003
  18. ncbi request reprint Mechanisms in COPD: differences from asthma
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, London, UK
    Chest 117:10S-4S. 2000
    ..The eosinophilic inflammation in asthma is markedly suppressed by corticosteroids, but they have no appreciable effect on the inflammation in COPD, consistent with a failure of long-term corticosteroids to alter the progression of COPD...
  19. ncbi request reprint Anti-IgE therapy in asthma: rationale and therapeutic potential
    P J Barnes
    National Heart and Lung Institute, London, UK
    Int Arch Allergy Immunol 123:196-204. 2000
    ..Thus, the clinical effectiveness of rhuMAb-E25 supports the central role of IgE in allergic reactions and the viability of anti-IgE therapy as a potentially effective treatment option for asthma...
  20. ncbi request reprint Neurogenic inflammation in the airways
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, SW3 6LY, London, UK
    Respir Physiol 125:145-54. 2001
    ....
  21. ncbi request reprint Tiotropium bromide
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK
    Expert Opin Investig Drugs 10:733-40. 2001
    ..Since, anticholinergics are the bronchodilators of choice in COPD it is likely that tiotropium bromide will become the most widely used bronchodilator for COPD patients in the future...
  22. ncbi request reprint Clinical outcome of adding long-acting beta-agonists to inhaled corticosteroids
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK
    Respir Med 95:S12-6. 2001
    ..In conclusion, the addition of formoterol to established treatment with inhaled corticosteroids provides superior asthma control compared with an increase in the dose of corticosteroid alone...
  23. ncbi request reprint Therapeutic strategies for allergic diseases
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK
    Nature 402:B31-8. 1999
    ..Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments...
  24. ncbi request reprint Pharmacology of airway smooth muscle
    P J Barnes
    Department of Thoracic Medicine, Imperial College, National Heart and Lung Institute, London, United Kingdom
    Am J Respir Crit Care Med 158:S123-32. 1998
    ..Airway smooth muscle cells are now seen as playing an important interactive role with inflammatory and structural cells in the response to injury and repair of the airways...
  25. ncbi request reprint Future Advances in COPD Therapy
    P J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Respiration 68:441-8. 2001
    ..Small molecule protease inhibitors, including neutrophil elastase inhibitors and selective matrix metalloproteinase inhibitors are also in development. Future drug targets may be identified by gene array and proteomics...
  26. ncbi request reprint New treatments for chronic obstructive pulmonary disease
    P J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Curr Opin Pharmacol 1:217-22. 2001
    ..Several new drugs are now in development that may affect the underlying inflammatory and destructive processes in this increasingly common disease...
  27. ncbi request reprint Cytokine modulators as novel therapies for asthma
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom
    Annu Rev Pharmacol Toxicol 42:81-98. 2002
    ..Several such classes of drug are now in clinical development, and the risk of side effects with these nonspecific inhibitors may be reduced by the inhaled route of delivery...
  28. ncbi request reprint The role of inflammation and anti-inflammatory medication in asthma
    P J Barnes
    National Heart and Lung Institute, Department of Thoracic Medicine, London, UK
    Respir Med 96:S9-15. 2002
    ..For many people asthma is associated with complex therapy; thus treatment developments that simplify asthma treatment are an mportant step forward n asthma management...
  29. ncbi request reprint Interview: interview with peter barnes
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, UK
    Future Med Chem 3:1575-9. 2011
    ..He speaks to Future Medicinal Chemistry about the molecular mechanisms currently under investigation by his group, and discusses his views on the latest therapeutic breakthroughs and the future of respiratory research...
  30. ncbi request reprint Inhibitory cytokines in asthma
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Mol Med Today 4:452-8. 1998
    ....
  31. ncbi request reprint Cytokine modulators for allergic diseases
    P J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK
    Curr Opin Allergy Clin Immunol 1:555-60. 2001
    ..Inhibitory cytokines, such as interleukin-10, interferons and interleukin-12, are also being considered in the treatment of allergic diseases...
  32. doi request reprint Peroxynitrite elevation in exhaled breath condensate of COPD and its inhibition by fudosteine
    Grace O Osoata
    Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
    Chest 135:1513-20. 2009
    ..Nitrative stress is implicated in COPD pathogenesis, but PN has not been detected due to a short half-life (< 1 s) at physiologic condition. Instead, 3-nitrotyrosine has been measured as a footprint of PN release...
  33. ncbi request reprint Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy
    Omar S Usmani
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Am J Respir Crit Care Med 172:704-12. 2005
    ..Together, our data confirm that GR nuclear translocation may underlie the complementary interactions between LABAs and corticosteroids, although the precise signal transduction mechanisms remain to be determined...
  34. pmc Suppression of GATA-3 nuclear import and phosphorylation: a novel mechanism of corticosteroid action in allergic disease
    Kittipong Maneechotesuwan
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
    PLoS Med 6:e1000076. 2009
    ..We investigated the effect of the corticosteroid fluticasone propionate on GATA-3 regulation in human T-lymphocytes in vitro and in vivo...
  35. ncbi request reprint Decreased histone deacetylase activity in chronic obstructive pulmonary disease
    Kazuhiro Ito
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
    N Engl J Med 352:1967-76. 2005
    ..HDAC is a key molecule in the repression of production of proinflammatory cytokines in alveolar macrophages...
  36. doi request reprint Rapid effect of inhaled ciclesonide in asthma: a randomized, placebo-controlled study
    Edward M Erin
    National Heart and Lung Institute Clinical Studies Unit, Imperial College, London, UK
    Chest 134:740-5. 2008
    ....
  37. pmc Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages
    Borja G Cosio
    Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, England, UK
    J Exp Med 200:689-95. 2004
    ..Therefore, theophylline might restore steroid responsiveness in COPD patients...
  38. pmc Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression
    Kazuhiro Ito
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY, England, UK
    J Exp Med 203:7-13. 2006
    ..Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-kappaB-mediated, but not GRE-mediated, gene expression...
  39. doi request reprint Effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, on nitric oxide production and its metabolites in healthy control subjects, healthy smokers, and COPD patients
    Caterina Brindicci
    Section of Airway Disease, National Heart and Lung Institute, Imperial College London, London, UK
    Chest 135:353-67. 2009
    ..NO production is increased in patients with COPD, and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD...
  40. pmc Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma
    Nicolas Mercado
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London, United Kingdom
    PLoS ONE 7:e41582. 2012
    ..We investigated the effects of a p38MAPK inhibitor in corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from severe asthmatics and the profile of its responders...
  41. ncbi request reprint Effects of corticosteroids on noninvasive biomarkers of inflammation in asthma and chronic obstructive pulmonary disease
    Sergei A Kharitonov
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 1:191-9. 2004
    ....
  42. pmc Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease
    Yasuo To
    Airway Disease Section, NHLI Imperial College, London, United Kingdom
    Am J Respir Crit Care Med 182:897-904. 2010
    ..Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids. This has been linked to a reduction of histone deacetylase-2 as a result of oxidative stress and is reversed by theophylline...
  43. doi request reprint Oxidative stress modulates theophylline effects on steroid responsiveness
    John A Marwick
    National Heart and Lung Institute, Airways Disease Section, Imperial College London, Guy Scadding Building, Dovehouse Steet, London SW3 6LY, UK
    Biochem Biophys Res Commun 377:797-802. 2008
    ..In conclusion, oxidative stress alters theophylline binding profile and gene expression which may result in restoration of corticosteroid function...
  44. ncbi request reprint Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers
    Katsuyuki Tomita
    Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, London, United Kingdom
    Am J Respir Crit Care Med 166:724-31. 2002
    ..Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis...
  45. ncbi request reprint Expression and activity of histone deacetylases in human asthmatic airways
    Kazuhiro Ito
    Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY UK
    Am J Respir Crit Care Med 166:392-6. 2002
    ..The increase in HAT activity and reduced HDAC activity in asthma may underlie the increased expression of multiple inflammatory genes, and this is reversed, at least in part, by treatment with inhaled steroids...
  46. ncbi request reprint Redox regulation of histone deacetylases and glucocorticoid-mediated inhibition of the inflammatory response
    Ian M Adcock
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, UK
    Antioxid Redox Signal 7:144-52. 2005
    ..This may account for the lack of glucocorticoid sensitivity in patients with chronic obstructive pulmonary disease. Antioxidants should reduce the inflammation and restore glucocorticoid sensitivity in these subjects...
  47. ncbi request reprint Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E release
    Joanna E Chivers
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Faculty of Medicine, London, UK
    Eur J Biochem 271:4042-52. 2004
    ....
  48. doi request reprint Nitric oxide synthase isoenzyme expression and activity in peripheral lung tissue of patients with chronic obstructive pulmonary disease
    Caterina Brindicci
    National Heart and Lung Institute, Imperial College London, UK
    Am J Respir Crit Care Med 181:21-30. 2010
    ..However, expression of the NO synthase(s) responsible for elevated NO has not been identified in the peripheral lung tissue of patients with COPD of varying severity...
  49. doi request reprint Long-acting fluticasone furoate has a superior pharmacological profile to fluticasone propionate in human respiratory cells
    Christos Rossios
    Airway Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, United Kingdom
    Eur J Pharmacol 670:244-51. 2011
    ..The longer duration of action and oxidative stress insensitivity of FF compared with FP has potential clinical implications for the control of inflammation in respiratory diseases, such as COPD...
  50. ncbi request reprint Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes
    Susan J Smith
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, United Kingdom
    Mol Pharmacol 66:1679-89. 2004
    ..Furthermore, although BRL 50481 had only a modest inhibitory effect per se on the proinflammatory cells studied, it acted at least additively with other cAMP-elevating drugs, especially when HSPDE7A1 was up-regulated...
  51. ncbi request reprint Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3
    Kittipong Maneechotesuwan
    Section of Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom
    J Immunol 178:2491-8. 2007
    ..This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases...
  52. ncbi request reprint Role of nitric oxide in allergic inflammation and bronchial hyperresponsiveness
    Paul R Eynott
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
    Eur J Pharmacol 452:123-33. 2002
    ..NO generated through NOS2 contributes to allergen-induced bronchial hyperresponsiveness but not to bronchial eosinophilia, indicating that these are independently expressed...
  53. ncbi request reprint Histone deacetylation: an important mechanism in inflammatory lung diseases
    Ian M Adcock
    National Heart and Lung Institute, Imperial College London, UK
    COPD 2:445-55. 2005
    ..The modulation of HAT/HDAC activity may lead to the development of novel anti-inflammatory approaches to inflammatory lung diseases that are currently difficult to treat...
  54. ncbi request reprint NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription
    Kang Yun Lee
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Immunol 176:603-15. 2006
    ..Our results suggest that IL-1beta-stimulated transcription of TGF-beta1 is temporally regulated by NF-kappaB and AP-1 and involves histone hyperacetylation at distinct promoter sites...
  55. ncbi request reprint Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89
    Koremu K Meja
    Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Pharmacol Exp Ther 309:833-44. 2004
    ..Furthermore, these data suggest that H-89 is not a selective inhibitor of PKA and should be avoided...
  56. pmc A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression
    Kazuhiro Ito
    Thoracic Medicine, Imperial College School of Science, Technology, and Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom
    Proc Natl Acad Sci U S A 99:8921-6. 2002
    ..Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes...
  57. ncbi request reprint Breath condensate pH in children with cystic fibrosis and asthma: a new noninvasive marker of airway inflammation?
    Giovanna E Carpagnano
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK
    Chest 125:2005-10. 2004
    ..The pH of exhaled breath condensate (EBC) is a promising marker. Although pH has been measured in the EBC of adults with inflammatory airway diseases, no study has measured this in children...
  58. ncbi request reprint The role of IkappaB kinase 2, but not activation of NF-kappaB, in the release of CXCR3 ligands from IFN-gamma-stimulated human bronchial epithelial cells
    Susan J Tudhope
    Airway Disease, National Heart and Lung Institute, Imperial College, London, United Kingdom
    J Immunol 179:6237-45. 2007
    ..These data suggest that IKK2 is also involved in the IFN-gamma-stimulated release of the CXCR3 ligands through a novel mechanism that is independent NF-kappaB...
  59. ncbi request reprint Formoterol attenuates neutrophilic airway inflammation in asthma
    Kittipong Maneechotesuwan
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, UK
    Chest 128:1936-42. 2005
    ..While beta2-agonists may affect neutrophil function in vitro, it is uncertain whether they have effects on neutrophilic inflammation in asthmatic patients in vivo...
  60. doi request reprint A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model
    Coen H Wiegman
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LY, U K
    Clin Sci (Lond) 126:425-40. 2014
    ....
  61. doi request reprint Comparison of Symbicort® versus Pulmicort® on steroid pharmacodynamic markers in asthma patients
    Sarah Essilfie-Quaye
    Airway Disease, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Respir Med 105:1784-9. 2011
    ..Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophages...
  62. ncbi request reprint The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma
    Edward M Erin
    National Heart and Lung Institute, Imperial College, London, UK
    Am J Respir Crit Care Med 174:753-62. 2006
    ..Neutralization of tumor necrosis factor-alpha (TNF-alpha) is an effective antiinflammatory therapy for several chronic inflammatory diseases...
  63. ncbi request reprint Validation of the anti-inflammatory properties of small-molecule IkappaB Kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle
    Matthew C Catley
    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Mol Pharmacol 70:697-705. 2006
    ..We therefore suggest that IKK inhibitors may be of considerable benefit in inflammatory airways diseases, particularly in COPD or severe asthma, in which corticosteroids are ineffective...
  64. doi request reprint Pathophysiology of allergic inflammation
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London, UK
    Immunol Rev 242:31-50. 2011
    ..Corticosteroids are highly effective with a broad spectrum of anti-inflammatory effects, including epigenetic modulation of the inflammatory response and suppression of GATA3...
  65. ncbi request reprint Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers
    Caterina Brindicci
    Section of Airway Disease, National Heart and Lung Institute, Imperial College, Dovehouse St, London SW3 6LY, UK
    Chest 132:581-8. 2007
    ....
  66. doi request reprint Inhibition of PI3Kdelta restores glucocorticoid function in smoking-induced airway inflammation in mice
    John A Marwick
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Am J Respir Crit Care Med 179:542-8. 2009
    ..Recent studies have shown that histone deacetylase activity, which is critical to glucocorticoid function, is altered by oxidant stress and may be involved in the development of glucocorticoid insensitivity...
  67. pmc Evidence for post-transcriptional regulation of interleukin-5 by dexamethasone
    Karl J Staples
    Department of Thoracic Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, UK
    Immunology 109:527-35. 2003
    ..Taken together, the results presented here suggest that, whilst transcriptional processes predominantly regulate IL-5 release, the mechanism by which dexamethasone inhibits IL-5 is post-transcriptional...
  68. pmc Steroid-resistant neutrophilic inflammation in a mouse model of an acute exacerbation of asthma
    Kazuhiro Ito
    Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK
    Am J Respir Cell Mol Biol 39:543-50. 2008
    ..We conclude that impaired nuclear recruitment of HDAC2 could be an important mechanism of steroid resistance of the neutrophilic inflammation in exacerbations of asthma. Oxidative stress may contribute to decreased HDAC2 activity...
  69. ncbi request reprint Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD
    Paul A Ford
    Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, England
    Chest 137:1338-44. 2010
    ..This may account, at least in part, for the relative corticosteroid resistance. Thus, combination therapy with an ICS and low-dose theophylline may be of benefit in the treatment of COPD...
  70. pmc Glucocorticoids reverse IL-1beta-induced impairment of beta-adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases
    Judith C W Mak
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY
    Br J Pharmacol 135:987-96. 2002
    ..In light of data obtained in this study, we propose that both the decrease in AC activity and the increase in GRK activity, which are reversed by dexamethasone, may underlie beta(2)-adrenoceptor desensitization...
  71. ncbi request reprint Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
    Lancet 363:731-3. 2004
    ..This hypothesis raises the possibility that novel therapeutic approaches might unlock this corticosteroid resistance, leading to more effective anti-inflammatory treatments for COPD and other severe inflammatory diseases...
  72. ncbi request reprint Overcoming steroid insensitivity in smoking asthmatics
    Tehireem Ahmad
    Imperial College London, National Heart and Lung Institute, Airways Disease Section, Dovehouse Street, London, SW3 6LY, UK
    Curr Opin Investig Drugs 9:470-7. 2008
    ..This review summarizes the various hypotheses underlying corticosteroid insensitivity in smoking asthmatics and discusses the development of potential novel therapies based on these concepts...
  73. ncbi request reprint Corticosteroid resistance in airway disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 1:264-8. 2004
    ....
  74. ncbi request reprint Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma
    Adam Antczak
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK
    Am J Respir Crit Care Med 166:301-6. 2002
    ..Exhaled PGE(2) levels are not reduced, so that it is unlikely that a deficiency of PGE(2) is an important mechanism, whereas exhaled LTB(4) levels are unchanged, indicating an abnormality beyond 5-lipoxygenase...
  75. ncbi request reprint Theophylline in chronic obstructive pulmonary disease: new horizons
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 2:334-9; discussion 340-1. 2005
    ..Better understanding of the molecular basis for the action of theophylline might lead to the development of novel drugs...
  76. doi request reprint Glucocorticoid resistance in inflammatory diseases
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London, UK
    Lancet 373:1905-17. 2009
    ....
  77. ncbi request reprint Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator
    Omar S Usmani
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Nucl Med 45:69-73. 2004
    ..Here, we report our methodology for radiolabeling and imaging monodisperse pharmacologic aerosols in order to study basic aerosol science concepts of drug delivery within the human airways...
  78. ncbi request reprint Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator
    Martyn F Biddiscombe
    Nuclear Medicine, Royal Brompton Hospital, and National Heart and Lung Institute, Imperial College London, London, United Kingdom
    J Aerosol Med 19:245-53. 2006
    ..The aerosols generated by the STAG can allow investigators to study the scientific principles of inhaled drug deposition and lung physiology for a range of therapeutic agents...
  79. doi request reprint New therapies for chronic obstructive pulmonary disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK
    Med Princ Pract 19:330-8. 2010
    ..This might be achieved by theophylline-like drugs, phosphoinositide 3 kinase-delta inhibitors, more effective antioxidants and non-antibiotic macrolides...
  80. ncbi request reprint p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma
    Elvis Irusen
    Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
    J Allergy Clin Immunol 109:649-57. 2002
    ..IL-2 combined with IL-4 can alter glucocorticoid receptor (GR) ligand-binding affinity and modulate glucocorticoid function...
  81. ncbi request reprint Distribution of receptor targets in the lung
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
    Proc Am Thorac Soc 1:345-51. 2004
    ..Many novel receptors, including orphan receptors, have now been identified as these may be future targets for developing novel therapies for asthma and chronic obstructive pulmonary disease...
  82. ncbi request reprint Analysis of expired air for oxidation products
    Paolo Paredi
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, London, United Kingdom
    Am J Respir Crit Care Med 166:S31-7. 2002
    ..Longitudinal studies are required to assess the clinical usefulness of these measurements in the monitoring of chronic inflammatory lung disease...
  83. ncbi request reprint Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients
    John G Matthews
    Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Dovehouse Street, London SW3 6LY, United Kingdom
    J Allergy Clin Immunol 113:1100-8. 2004
    ..Most chronic inflammatory diseases are well controlled by glucocorticoids. However, a minority of patients fails to respond adequately to this treatment...
  84. ncbi request reprint Exhaled biomarkers
    Sergei A Kharitonov
    National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
    Chest 130:1541-6. 2006
    ....
  85. ncbi request reprint Long-acting beta 2-adrenoceptor agonists or tiotropium bromide for patients with COPD: is combination therapy justified?
    Rachel C Tennant
    Clinical Studies Unit, National Heart and Lung Institute, Imperial College, London, UK
    Curr Opin Pharmacol 3:270-6. 2003
    ..However, because LABAs are given twice daily but tiotropium bromide is required only once daily, the challenge is to develop a combined inhaler that can be employed on a daily basis...
  86. ncbi request reprint Increased leukotrienes in exhaled breath condensate in childhood asthma
    Zsuzsanna Csoma
    Department of Thoracic Medicine and Department of Pediatric Respiratory Care, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom
    Am J Respir Crit Care Med 166:1345-9. 2002
    ..05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma...
  87. doi request reprint New therapies for asthma: is there any progress?
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London, UK
    Trends Pharmacol Sci 31:335-43. 2010
    ..Improved immunotherapy approaches have the prospect of disease modification, although prospects for a cure are currently remote. The most promising therapeutic developments for asthma are discussed in this review...
  88. ncbi request reprint Emerging pharmacotherapies for COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, London, UK
    Chest 134:1278-86. 2008
    ..This might be achieved by theophylline-like drugs, more effective antioxidants, and nonantibiotic macrolide agents...
  89. doi request reprint Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London SW3 6LY, UK
    Proc Am Thorac Soc 6:693-6. 2009
    ....
  90. doi request reprint Histone deacetylase-2 and airway disease
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London, UK
    Ther Adv Respir Dis 3:235-43. 2009
    ..In the future selective PI3Kdelta inhibitors and more direct activators of HDAC2 may be used to treat corticosteroid-resistant inflammatory diseases of the lung, including COPD, severe asthma and asthma in smokers...
  91. ncbi request reprint Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols
    Omar S Usmani
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom
    J Appl Physiol (1985) 95:2106-12. 2003
    ..Aerosols delivered in monodisperse form can enable large reductions of the inhaled dose without loss of clinical efficacy...
  92. ncbi request reprint Normal bronchial blood flow in COPD is unaffected by inhaled corticosteroids and correlates with exhaled nitric oxide
    Paolo Paredi
    National Heart and Lung Institute, Airway Disease Section, Dovehouse St, London, SW3 6LY, UK
    Chest 131:1075-81. 2007
    ..We studied the relationship of QAW with the fraction of exhaled nitric oxide (FENO), which is a potent vasodilator. We also investigated the vascular response to budesonide and a beta(2)-agonist...
  93. doi request reprint New drugs for exacerbations of chronic obstructive pulmonary disease
    Trevor T Hansel
    National Heart and Lung Institute, Imperial College, London, UK
    Lancet 374:744-55. 2009
    ..Such concepts have been used to generate a range of molecular targets, and clinical trials are taking place to identify effective drugs for the prevention and treatment of COPD exacerbations...
  94. ncbi request reprint Treatment of airway mucus hypersecretion
    Duncan F Rogers
    Section of Airway Disease, National Heart and Lung Institute, Imperial College London, UK
    Ann Med 38:116-25. 2006
    ..More information is required on these differences to identify specific therapeutic targets which, in turn, should lead to rational design of anti-hypersecretory drugs for treatment of airway mucus hypersecretion in asthma and COPD...
  95. ncbi request reprint Role of HDAC2 in the pathophysiology of COPD
    Peter J Barnes
    National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom
    Annu Rev Physiol 71:451-64. 2009
    ..Antioxidants and inhibitors of nitric oxide synthesis may therefore restore corticosteroid sensitivity in COPD, but this can also be achieved by low concentrations of theophylline and curcumin, which act as HDAC activators...
  96. pmc Drugs for asthma
    Peter J Barnes
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, SW3 6LY London
    Br J Pharmacol 147:S297-303. 2006
    ..It seems likely that pharmacology, rather than molecular genetics, will remain the main approach to the further improvement of treatment for asthma...
  97. ncbi request reprint Loss of control of asthma following inhaled corticosteroid withdrawal is associated with increased sputum interleukin-8 and neutrophils
    Kittipong Maneechotesuwan
    Airways Disease Section, Dovehouse St, London, SW3 6LY, UK
    Chest 132:98-105. 2007
    ..The role of neutrophils in exacerbations of asthma is poorly understood. We examined the effect of withdrawal of inhaled corticosteroids on sputum inflammatory indexes in a double-blind study in patients with moderate, stable asthma...
  98. ncbi request reprint Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease
    Sarah V Culpitt
    Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom
    Am J Respir Crit Care Med 167:24-31. 2003
    ..We conclude that the lack of efficacy of corticosteroids in COPD might be due to the relative steroid insensitivity of macrophages in the respiratory tract...
  99. ncbi request reprint 5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene
    Hiroo Wada
    Airway Disease Section, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK
    Biochem Biophys Res Commun 331:93-9. 2005
    ....
  100. doi request reprint Molecular mechanisms of corticosteroid resistance
    Ian M Adcock
    National Heart and Lung Institute, Imperial College London, Dovehouse St, London SW3 6LY, UK
    Chest 134:394-401. 2008
    ..Understanding the molecular mechanisms of GR action, and inaction, may lead to the development of new antiinflammatory drugs or may reverse the relative steroid insensitivity that is characteristic of patients with these diseases...