Publications
160 results found
Hattotuwa K, Gamble EA, O'Shaughnessy T, et al., 2002, Safety of bronchoscopy, biopsy, and BAL in research patients with COPD, CHEST, Vol: 122, Pages: 1909-1912, ISSN: 0012-3692
- Author Web Link
- Cite
- Citations: 59
Jeffery PK, Venge P, Gizycki MJ, et al., 2002, Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study, EUROPEAN RESPIRATORY JOURNAL, Vol: 20, Pages: 1378-1385, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 57
Zhu J, Kilty L, Granger H, et al., 2002, Gene expression and immunolocalization of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 27, Pages: 666-677, ISSN: 1044-1549
- Author Web Link
- Cite
- Citations: 35
Gizycki MJ, Hattotuwa KL, Barnes N, et al., 2002, Effects of fluticasone propionate on inflammatory cells in COPD: an ultrastructural examination of endobronchial biopsy tissue, THORAX, Vol: 57, Pages: 799-803, ISSN: 0040-6376
- Author Web Link
- Cite
- Citations: 84
Hattotuwa KL, Gizycki MJ, Ansari TW, et al., 2002, The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease - A double-blind, placebo-controlled biopsy study, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 165, Pages: 1592-1596, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 200
Griesenbach U, Cassady RL, Ferrari S, et al., 2002, The nasal epithelium as a factory for systemic protein delivery, MOLECULAR THERAPY, Vol: 5, Pages: 98-103, ISSN: 1525-0016
- Author Web Link
- Cite
- Citations: 23
Jeffery P, Zhu J, 2002, Mucin-producing elements and inflammatory cells, MUCUS HYPERSECRETION IN RESPIRATORY DISEASE, Vol: 248, Pages: 51-75, ISSN: 1528-2511
- Author Web Link
- Cite
- Citations: 38
Zhu J, Majumdar S, Qiu Y, et al., 2001, Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis -: Lack of relationship with CD8<SUP>+</SUP> cells, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 164, Pages: 2220-2228, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 50
Jeffery PK, 2001, Remodeling in asthma and chronic obstructive lung disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 164, Pages: S28-S38, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 697
Jeffery PK, 2001, Remodeling in asthma and chronic obstructive lung disease, 16th Annual Transatlantic Airway Conference (TAC), Pages: S28-S38
Asthma and chronic obstructive lung disease (COPD) are both inflammatory conditions of the lung associated with structural "remodeling" inappropriate to the maintenance of normal lung function. The clinically observed distinctions between asthma and COPD are reflected by differences in the remodeling process, the patterns of inflammatory cells and cytokines, and also the predominant anatomic site at which these alterations occur. In asthma the epithelium appears to be more fragile than that of COPD, the epithelial reticular basement membrane (RBM) is significantly thicker, there is marked enlargement of the mass of bronchial smooth muscle, and emphysema does not occur in the asthmatic nonsmoker. In COPD, there is epithelial mucous metaplasia, airway wall fibrosis, and inflammation associated with loss of surrounding alveolar attachments to the outer wall of small airways: bronchiolar smooth muscle is increased also. Emphysema is a feature of severe COPD: in spite of the destructive process, alveolar wall thickening and focal fibrosis may be detected. The hypertrophy of submucosal mucus-secreting glands is similar in extent in asthma and COPD. The number of bronchial vessels and the area of the wall occupied by them increase in severe corticosteroid-dependent asthma: it is likely that these increases also occur in severe COPD as they do in bronchiectasis. Pulmonary vasculature is remodeled in COPD. In asthma several of these structural alterations begin early in the disease process, even in the child. In COPD the changes begin later in life and the associated inflammatory response differs from that in asthma. The following synopsis defines and compares the key remodeling processes and proposes several hypotheses.
Coker RK, Laurent GJ, Jeffery PK, et al., 2001, Localisation of transforming growth factor β<sub>1</sub> and β<sub>3</sub> mRNA transcripts in normal and fibrotic human lung, THORAX, Vol: 56, Pages: 549-556, ISSN: 0040-6376
- Author Web Link
- Cite
- Citations: 93
Zhu J, Qiu YS, Majumdar S, et al., 2001, Exacerbations of bronchitis - Bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 164, Pages: 109-116, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 134
Jeffery PK, 2001, Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease, CHRONIC OBSTRUCTIVE PULMONARY DISEASE: PATHOGENESIS TO TREATMENT, Vol: 234, Pages: 149-168
- Author Web Link
- Cite
- Citations: 39
Jeffery PK, 2001, Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease, Symposium on Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment, Pages: 149-168
Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and/or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosincophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD3 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance an
Jeffery PK, Laitinen A, Venge P, 2000, Biopsy markers of airway inflammation and remodelling, RESPIRATORY MEDICINE, Vol: 94, Pages: S9-S15, ISSN: 0954-6111
- Author Web Link
- Cite
- Citations: 64
Jeffery PK, Laitinen A, Venge P, 2000, Biopsy markers of airway inflammation and remodelling, Biopsy Workshop on Anti-inflammatory Therapy - Assessment using Bronchial Biopsy, Pages: S9-S15
Bronchial inflammation is a consistent feature of asthma and its chronicity probably determines disease progression. Clinical evaluation of drugs with potential disease-modifying activity requires measurement of their effects on the inflammatory and remodelling process using a variety of techniques including bronchial biopsy, and analysis of sputum, broncholaveolar lavage, blood, urine and exhaled air.Markers of the key components of the inflammatory process, such as the number and activation of T-cells, the number of mast cells, cytokine and chemokine release or gene expression and eosinophil and neutrophil recruitment, can be determined in biopsy samples. Biopsies also allow assessment of the integrity and structure of the airway epithelium, the thickness of the reticular basement membrane and the numbers and ultrastructure of contractile cells. These and other markers may allow differentiation between subtypes of asthma patient according to atopic status and will help to distinguish asthma from chronic obstructive pulmonary disease.Airway remodelling may be a consequence of chronic bronchial inflammation and is a characteristic of chronic asthma, particularly in severe asthma and when there is progressive decline in lung function. There are changes in the surface epithelium, reticular basement membrane, bronchial smooth muscle, blood vessels and mucous glands. Reliable markers of remodelling need to be identified to improve our ability to evaluate chronic asthma therapy.
Yonemitsu Y, Kitson C, Ferrari S, et al., 2000, Efficient gene transfer to airway epithelium using recombinant Sendai virus, NATURE BIOTECHNOLOGY, Vol: 18, Pages: 970-973, ISSN: 1087-0156
- Author Web Link
- Cite
- Citations: 182
Jeffery PK, 2000, Comparison of the structural and inflammatory features of COPD and asthma. Giles F. Filley Lecture., Chest, Vol: 117, Pages: 251S-260S, ISSN: 0012-3692
At least three conditions contribute to COPD. (1) Chronic bronchitis (mucous hypersecretion) is an inflammatory condition in which CD8+ T-lymphocytes, neutrophils, and CD68+ monocytes/macrophages predominate. The condition is defined clinically by the presence of chronic cough and recurrent increases in bronchial secretions sufficient to cause expectoration. There is enlargement of mucus-secreting glands and goblet cell hyperplasia, which can occur in the absence of airflow limitation. (2) Adult chronic bronchiolitis (small or peripheral airways disease) is an inflammatory condition of small bronchi and bronchioli in which there are predominantly CD8+ and pigmented macrophages. The functional defect is difficult to detect clinically but may be recognized by sophisticated tests of small airway function. There is mucous metaplasia, enlargement of the mass of bronchiolar smooth muscle, and loss of alveolar attachments. (3) Emphysema is an inflammatory condition of the alveoli in which T-lymphocytes, neutrophils, and pigmented alveolar macrophages are involved, associated with the release of excessive amounts of elastases. It is defined anatomically by permanent, destructive enlargement of airspaces distal to terminal bronchioli without obvious fibrosis. In contrast, asthma is a clinical syndrome characterized by allergic inflammation of bronchi and bronchioli in which CD4+ (helper) T-lymphocytes and eosinophils predominate. There is increased production and release of interleukin (IL)-4 and IL-5, which is referred to as a Th2-type response. There is usually increased tracheobronchial responsiveness to a variety of stimuli, and the condition is usually manifest as variable airflow obstruction. While differences between COPD and asthma have been highlighted, new data are emerging that indicate there may also be similarities.
Jeffery PK, 2000, Comparison of the structural and inflammatory features of COPD and asthma, Thomas L Petty 42nd Annual Aspen Lung conference - Mechanisms of COPD, Publisher: ELSEVIER SCIENCE BV, Pages: 251S-260S, ISSN: 0012-3692
- Author Web Link
- Cite
- Citations: 160
Bousquet J, Jeffery PK, Busse WW, et al., 2000, Asthma - From bronchoconstriction to airways inflammation and remodeling, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 161, Pages: 1720-1745, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 1390
Jeffery PK, 1999, Chairman's summary - Inflammation in chronic obstructive lung disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 160, Pages: S3-S4, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 13
Majumdar S, Li D, Ansari T, et al., 1999, Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis - A quantitative study of open lung biopsies, EUROPEAN RESPIRATORY JOURNAL, Vol: 14, Pages: 251-257, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 72
Erjefält JS, Greiff L, Andersson M, et al., 1999, Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 160, Pages: 304-312, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 101
Jeffery PK, 1999, Differences and similarities between chronic obstructive pulmonary disease and asthma, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 29, Pages: 14-26, ISSN: 0954-7894
- Author Web Link
- Cite
- Citations: 85
Jeffery PK, 1999, Differences and similarities between chronic obstructive pulmonary disease and asthma, Symposium on the Link Between Asthma and COPD, Pages: 14-26
Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions, which make definitive morphological comparisons difficult. The airways in asthma are occluded by tenacious plugs of exudate and mucus, and there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina (the last two not usually features of COPD), and bronchial vessel congestion and oedema. There is an increased inflammatory infiltrate comprising 'activated' lymphocytes and eosinophils with release of granular content in the latter, and enlargement of bronchial smooth muscle, particularly in medium-sized bronchi. CD4(+)ve lymphocytes predominate over CD8(+)ve cells and neutrophils are sparse.In contrast, three conditions contribute to COPD. In chronic bronchitis there is cough and mucous hypersecretion with enlargement of tracheobronchial submucosal glands and a disproportionate increase of mucous acini. CD8(+)ve lymphocytes predominate over CD4(+)ve cells and there are increased numbers of subepithelial macrophages and intraepithelial neutrophils. Exacerbations of bronchitis are associated with a tissue eosinophilia, apparent absence of IL-5 protein but gene expression for IL-4 and IL-5 is present. In small or peripheral airways disease, there is inflammation of bronchioli and mucous metaplasia and hyperplasia, with increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses (also referred to as chronic obstructive bronchiolitis). Respiratory bronchiolitis involving increased numbers of pigmented macrophages is a critically important early lesion. Increasingly severe peribronchiolitis includes infiltration of T lymphocytes in which the CD8(+) subset again predominates. These inflammatory changes may predispose to the development of centrilobular emphysema and reduced FEV1 via the destruction of alveolar attachments. In emphysema there is abnormal, permanent enlargement of airspaces d
Zhu J, Rogers AV, Burke-Gaffney A, et al., 1999, Cytokine-induced airway epithelial ICAM-1 upregulation: quantification by high-resolution scanning and transmission electron microscopy, EUROPEAN RESPIRATORY JOURNAL, Vol: 13, Pages: 1318-1328, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 24
Alton EWFW, Stern M, Farley R, et al., 1999, Cationic lipid-mediated <i>CFTR</i> gene transfer to the lungs and nose of patients with cystic fibrosis:: a double-blind placebo-controlled trial, LANCET, Vol: 353, Pages: 947-954, ISSN: 0140-6736
- Author Web Link
- Cite
- Citations: 328
Gizycki MJ, Ansari TW, Adelroth E, et al., 1999, Diversity of allergen-induced myofibroblasts in mild asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A259-A259, ISSN: 1073-449X
Gizycki MJ, Ädelroth E, Rogers AV, et al., 1999, Disruption of reticular basement membrane in mild asthma following allergen challenge, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A407-A407, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 1
Lukacs KV, Steel RM, Oakley RE, et al., 1998, Towards a clinical trial of HSP65 gene therapy for malignant mesothelioma, Thorax, Vol: 53, ISSN: 0040-6376
We have previously reported the effectiveness of single and repeat application of the heat shock protein-65 gene in murine models of malignant mesothelioma (Thorax, 52 Supplement 6, A27. In preparation for a clinical trial we have now optimised a number of key parameters needed for liposome mediated gene transfer. Both in vitro and in vivo studies have been undertaken to assess the optimal cationic lipid to achieve gene transfer. In vitro studies did not predict in vivo efficacy in a murine model in which asbestos-induced malignant mesothelioma cells were injected into the peritoneal cavity of syngenic mice. In the latter model, the lipids DC-Cholesterol and Genzyme lipid#89 were particularly effective. After 4 intraperitoneal injections of DNA-liposome complexes, 93% of mice were alive after one year. Histological analysis showed the presence of tumour infiltrating lymphocytes one month after the last of four injections, and the absence of tumours in the majority of animals after one year. Mice surviving for one year were re-challenged with a tumour dose lethal for naive mice and showed protection, indicating long term memory had been induced by the treatment. These data provide further evidence for the efficacy of Hsp65 gene therapy for malignant mesothelima.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.