Imperial College London

Emeritus ProfessorPeterJeffery

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor
 
 
 
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p.jeffery

 
 
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Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
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160 results found

Zhu J, Mallia P, Footitt J, Yusheng Q, Message SD, Kebadze T, Aniscenko J, Barnes PJ, Adcock I, Kon OM, Johnson M, Contoli M, Stanciu L, Papi A, Jeffery PK, Johnston Set al., 2020, Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 840-850.e7, ISSN: 0091-6749

BackgroundRespiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.ObjectivesWe sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity.MethodsBronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.ResultsRV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.ConclusionsExperimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflamma

Journal article

Qiu S, Nikolaou S, Zhu J, Jeffery P, Goldin R, Kinross J, Alexander J, Rasheed S, Tekkis P, Kontovounisios Cet al., 2020, Characterisation of the expression of neurotensin and its receptors in human colorectal cancer and its clinical implications, Biomolecules, Vol: 10, Pages: 1-15, ISSN: 2218-273X

Introduction: Colorectal Cancer (CRC) accounts for 9% of cancer deaths globally. Hormonal pathways play important roles in some cancers. This study investigated the association of CRC expression of neurotensin (NTS), NTS receptors 1 and 3 (NTSR1 and NTSR3) and clinical outcomes. Methods: A prospective cohort study which quantifies the protein expression of NTS, NTSR1 and NTSR3 in human CRCs using immunohistochemistry. Expression levels were then compared with clinico-pathological outcome including histological grade, overall survival (OS) and disease-free survival (DFS). Results: Sixty-four patients were enrolled with median follow-up of 44.0 months. There was significantly higher expression of NTS in cancer tissue in CRC with higher T stages (p < 0.01), N stages (p = 0.03), and AJCC clinical stages (p = 0.04). There was significantly higher expression of NTS, NTSR1 and NTSR3 in cancer tissue compared to surrounding normal epithelium (median H-score 163.5 vs 97.3, p < 0.01). There was significantly shorter DFS in individuals with CRC with high levels of NTS compared to lower levels of NTS (35.8 months 95% CI 28.7–42.8 months vs 46.4 months 95% CI 42.2–50.5 months, respectively, p = 0.02). Above median NTS expression in cancer tissue was a significant risk factor for disease recurrence (HR 4.10, 95% CI 1.14–14.7, p = 0.03). Discussion: The expression of NTS and its receptors has the potential to be utilised as a predictive and prognostic marker in colorectal cancer for postoperative selection for adjuvant therapy and identify individuals for novel therapies targeting the neurotensinergic pathways. Conclusions: High NTS expression appears to be associated with more advanced CRC and worse DFS.

Journal article

Zhu J, Message SD, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, Papi A, Stanciu LA, Edwards MR, Jeffery PK, Johnston SLet al., 2019, Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 114-125.e4, ISSN: 0091-6749

BACKGROUND: The innate immune system senses viral infection via pattern recognition receptors (PRRs) leading to type I interferon (IFN) production: their roles in rhinovirus (RV)-induced asthma exacerbations in vivo are uncertain. OBJECTIVES: To compare bronchial mucosal type I IFN and PRR expression at baseline and following RV infection in atopic asthmatic and control subjects. METHODS: Immunohistochemistry was used to detect expression of IFN-α, IFN-β and the PRRs, toll-like receptor (TLR)-3, melanoma-differentiation-associated gene-5 (MDA-5) and retinoic-acid-inducible protein-I (RIG-I) in bronchial biopsies from 10 atopic asthmatics and 15 non-asthmatic non-atopic controls at baseline and on day four and six weeks following RV infection. RESULTS: We observed IFN-α/β deficiency in bronchial epithelium at three time points in asthma in vivo. Lower epithelial IFN-α/β expression was related to greater virus load, worse airway symptoms, airway hyperresponsiveness (AHR) and reductions in lung function during RV infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthma during infection. IFN deficiency at baseline was not accompanied by deficient PRR expression in asthma. Both epithelial and subepithelial PRR expression was induced during RV infection. RV infection increased numbers of subepithelial IFN/PRRs-expressing inflammatory cells were related to greater virus load, AHR and reductions in lung function. CONCLUSIONS: Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β-expressing monocytes/macrophages during infection were both deficient in asthma. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes following RV infection in vivo. Increases in subepithelial cells expressing IFN/PRRs during infection were also related to greater virus load/illness severity.

Journal article

Zhu J, Message SD, Qiu Y, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, Papi A, Stanciu LA, Jeffery PK, Johnston SLet al., 2014, Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma, Chest, Vol: 145, Pages: 1219-1229, ISSN: 0012-3692

BackgroundThe nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations.MethodsWe used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects.ResultsCompared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = −0.89, P = .029), the PC10 correlated inversely with CD4+ (r = −0.67, P = .023) and CD8+ cells (r = −0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = −0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = −0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024).ConclusionsIn subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during in

Journal article

Agusti A, Barbera JA, Wouters EFM, Peinado VI, Jeffery PKet al., 2013, Lungs, Bone Marrow, and Adipose Tissue A Network Approach to the Pathobiology of Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 188, Pages: 1396-1406, ISSN: 1073-449X

Journal article

O'Reilly R, Ullmann N, Irving S, Bossley C, Sonnappa S, Zhu J, Oates T, Banya W, Jeffery PK, Bush A, Saglani Set al., 2012, Increased airway smooth muscle in preschool wheezers who have asthma at school age., J Allergy Clin Immunol

BACKGROUND: Increased airway smooth muscle (ASM) is a feature of established asthma in schoolchildren, but nothing is known about ASM in preschool wheezers.OBJECTIVE: We sought to determine endobronchial biopsy specimen ASM area fraction in preschool wheezers and its association with asthma at school age.METHODS: ASM area, reticular basement membrane thickness, and mucosal eosinophil and ASM mast cell values were quantified in endobronchial biopsy specimens previously obtained from preschool children undergoing clinically indicated bronchoscopy: severe recurrent wheezers (n = 47; median age, 26 months) and nonwheezing control subjects (n = 21; median age, 15 months). Children were followed up, and asthma status was established at age 6 to 11 years. Preschool airway pathology was examined in relation to asthma at school age.RESULTS: Forty-two (62%) of 68 children had 1 or more evaluable biopsy specimens for ASM. At school age, 51 of 68 children were followed up, and 15 (40%) of 37 preschool wheezers had asthma. Children who had asthma and an evaluable biopsy specimen had increased preschool ASM area fraction (n = 8; median age, 8.2 years [range, 6-10.4 years]; median ASM, 0.12 [range, 0.08-0.16]) compared with that seen in children without asthma (n = 24; median age, 7.3 years [range, 5.9-11 years]; median ASM, 0.07 [range, 0.02-0.23]; P = .007). However, preschool reticular basement membrane thickness and mucosal eosinophil or ASM mast cell values were not different between those who did or did not have asthma at school age.CONCLUSION: Increased preschool ASM is associated with those children who have asthma at school age. Thus a focus on early changes in ASM might be important in understanding the subsequent development of childhood asthma.

Journal article

Zhu J, Bandi V, Qiu S, Figueroa DJ, Evans JF, Barnes N, Guntupalli KK, Jeffery PKet al., 2012, Cysteinyl Leukotriene 1 Receptor Expression Associated With Bronchial Inflammation in Severe Exacerbations of COPD, CHEST, Vol: 142, Pages: 347-357, ISSN: 0012-3692

Journal article

Hewson CA, Haas JJ, Bartlett NW, Message SD, Laza-Stanca V, Kebadze T, Caramori G, Zhu J, Edbrooke R, Stanciu LA, Kon OM, Papi A, Jeffery PK, Edwards MR, Johnston SLet al., 2012, Rhinovirus induces MUC5AC in a human infection model and in vitro via NF-kappa B and EGFR pathways (vol 36, pg 1425, 2010), EUROPEAN RESPIRATORY JOURNAL, Vol: 39, Pages: 793-793, ISSN: 0903-1936

Journal article

Regamey N, Tsartsali L, Hilliard TN, Fuchs O, Tan H-L, Zhu J, Qiu Y-S, Alton EWFW, Jeffery PK, Bush A, Davies JCet al., 2012, Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis, THORAX, Vol: 67, Pages: 170-176, ISSN: 0040-6376

Journal article

Regamey N, Jeffery PK, Alton EWFW, Bush A, Davies JCet al., 2012, Should bronchoscopy be advocated to study airway remodelling and inflammation in adults with cystic fibrosis? Authors' response, THORAX, Vol: 67, Pages: 177-177, ISSN: 0040-6376

Journal article

Regamey N, Jeffery PK, Alton EWFW, Bush A, Davies JCet al., 2011, Airway remodelling and its relationship to inflammation in cystic fibrosis, THORAX, Vol: 66, Pages: 624-629, ISSN: 0040-6376

Journal article

Tsartsali L, Hislop AA, McKay K, James AL, Elliot J, Zhu J, Rosenthal M, Payne DN, Jeffery PK, Bush A, Saglani Set al., 2011, Development of the bronchial epithelial reticular basement membrane: relationship to epithelial height and age, THORAX, Vol: 66, Pages: 280-285, ISSN: 0040-6376

Journal article

Malmstrom K, Pelkonen AS, Malmberg LP, Sarna S, Lindahl H, Kajosaari M, Turpeinen M, Saglani S, Bush A, Haahtela T, Jeffery PK, Makela MJet al., 2011, Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years, THORAX, Vol: 66, Pages: 157-162, ISSN: 0040-6376

Journal article

Hewson CA, Haas JJ, Bartlett NW, Message SD, Laza-Stanca V, Kebadze T, Caramori G, Zhu J, Edbrooke MR, Stanciu LA, Kon OM, Papi A, Jeffery PK, Edwards MR, Johnston SLet al., 2010, Rhinovirus induces MUC5AC in a human infection model and in vitro via NF-kappa B and EGFR pathways, EUROPEAN RESPIRATORY JOURNAL, Vol: 36, Pages: 1425-1435, ISSN: 0903-1936

Journal article

Slater L, Bartlett NW, Haas JJ, Zhu J, Message SD, Walton RP, Sykes A, Dahdaleh S, Clarke DL, Belvisi MG, Kon OM, Fujita T, Jeffery PK, Johnston SL, Edwards MRet al., 2010, Co-ordinated Role of TLR3, RIG-I and MDA5 in the Innate Response to Rhinovirus in Bronchial Epithelium, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366

Journal article

Malmberg LP, Malmstrom K, Kotaniemi-Syrjanen A, Lindahl H, Kajosaari M, Turpeinen M, Haahtela T, Saglani S, Bush A, Jeffery PK, Pelkonen AS, Makela MJet al., 2010, Does tidal exhaled nitric oxide reflect mucosal airway inflammation in infants?, THORAX, Vol: 65, Pages: 1027-1027, ISSN: 0040-6376

Journal article

Xenariou S, Liang H-D, Griesenbach U, Zhu J, Farley R, Somerton L, Singh C, Jeffery PK, Scheule RK, Cheng SH, Geddes DM, Blomley M, Alton EWFWet al., 2010, Low-frequency ultrasound increases non-viral gene transfer to the mouse lung, ACTA BIOCHIMICA ET BIOPHYSICA SINICA, Vol: 42, Pages: 45-51, ISSN: 1672-9145

Journal article

Tsoumakidou M, Koutsopoulos AV, Tzanakis N, Dambaki K, Tzortzaki E, Zakynthinos S, Jeffery PK, Siafakas NMet al., 2009, Decreased Small Airway and Alveolar CD83+ Dendritic Cells in COPD, CHEST, Vol: 136, Pages: 726-733, ISSN: 0012-3692

Journal article

Ramsay CF, Sullivan P, Gizycki M, Wang D, Swern AS, Barnes NC, Reiss TF, Jeffery PKet al., 2009, Montelukast and bronchial inflammation in asthma: A randomised, double-blind placebo-controlled trial, RESPIRATORY MEDICINE, Vol: 103, Pages: 995-1003, ISSN: 0954-6111

Journal article

Tsoumakidou M, Kemp SJ, Thorley AJ, Zhu J, Dewar A, Jeffery PK, Tetley TDet al., 2009, Expression of blood dendritic cell antigens (BDCAs) by CD1a(+) human pulmonary cells, RESPIRATORY MEDICINE, Vol: 103, Pages: 935-938, ISSN: 0954-6111

Journal article

Pavord ID, Jeffery PK, Qiu Y, Zhu J, Parker D, Carlsheirner A, Naya I, Barnes NCet al., 2009, Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 123, Pages: 1083-1089, ISSN: 0091-6749

Journal article

Tsoumakidou M, Bouloukaki I, Koutala H, Kouvidi K, Mitrouska I, Zakynthinos S, Tzanakis N, Jeffery PK, Siafakas NMet al., 2009, Decreased Sputum Mature Dendritic Cells in Healthy Smokers and Patients with Chronic Obstructive Pulmonary Disease, INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, Vol: 150, Pages: 389-397, ISSN: 1018-2438

Journal article

Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SLet al., 2008, Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 105, Pages: 13562-13567, ISSN: 0027-8424

Journal article

Hilliard TN, Zhu J, Farley R, Escudero-Garcia S, Wainwright BJ, Jeffery PK, Griesenbach U, Bush A, Davies JC, Alton EWFWet al., 2008, Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol: 39, Pages: 19-25, ISSN: 1044-1549

Journal article

Tsoumakidou M, Demedts IK, Brusselle GG, Jeffery PKet al., 2008, Dendritic cells in chronic obstructive pulmonary disease - New players in an old game, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 177, Pages: 1180-1186, ISSN: 1073-449X

Journal article

Regamey N, Ochs M, Hilliard TN, Muehlfeld C, Cornish N, Fleming L, Saglani S, Alton EWFW, Bush A, Jeffery PK, Davies JCet al., 2008, Increased airway smooth muscle mass in children with asthma, cystic fibrosis, and non-cystic fibrosis bronchiectasis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 177, Pages: 837-843, ISSN: 1073-449X

Journal article

Bartlett NW, Walton RP, Edwards MR, Aniscenko J, Caramori G, Zhu J, Glanville N, Choy KJ, Jourdan P, Burnet J, Tuthill TJ, Pedrick MS, Hurle MJ, Plumpton C, Sharp NA, Bussell JN, Swallow DM, Schwarze J, Guy B, WAlmond J, Jeffery PK, Lloyd CM, Papi A, Killington RA, Rowlands DJ, Blair ED, Clarke NJ, Johnston SLet al., 2008, Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation, NATURE MEDICINE, Vol: 14, Pages: 199-204, ISSN: 1078-8956

Journal article

Rogers AV, Adelroth E, Hattotuwa K, Dewar A, Jeffery PKet al., 2008, Bronchial mucosal dendritic cells in smokers and exsmokers with COPD: an electron microscopic study, THORAX, Vol: 63, Pages: 108-114, ISSN: 0040-6376

Journal article

Regamey N, Hilliard TN, Saglani S, Zhu J, Balfour-Lynn IM, Rosenthal M, Jeftery PK, Alton EWFV, Bush A, Davies JCet al., 2008, Endobronchial biopsy in childhood, CHEST, Vol: 133, Pages: 312-312, ISSN: 0012-3692

Journal article

Xenariou S, Griesenbach U, Liang HD, Zhu J, Farley R, Somerton L, Singh C, Jeffery PK, Blomley M, Alton Eet al., 2007, Assessing ultrasound as a method to enhance non-viral gene transfer to the lung, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A105-A105, ISSN: 0040-6376

Conference paper

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