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Clinical and histological comparison of smoking and non-smoking patients with severe asthma in the U-BIOPRED cohort

P.P.W. Hekking, S.J. Wilson, A.H. Wagener, A.R. Sousa, J. Corfield, D.E. Shaw, S.J. Fowler, L.J. Fleming, J.H. Riley, E. Jeyasingham, A. Rowe, W. Seibold, G. Roberts, P. Bakke, F. Singer, T. Geiser, U. Frey, I. Horvath, R. Polosa, N. Krug, J. Musial, L. Pahus, D. Myles, C. Compton, T.W. Higenbottam, P. Montuschi, U. Nihlén, T. Sandstrom, S.S. Wagers, P.H. Howarth, R. Djukanovic, K.F. Chung, I. Pandis, Y. Guo, A.T. Bansal, E.H. Bel, P.J. Sterk
European Respiratory Journal 2014 44: 1688; DOI:
P.P.W. Hekking
1Respiratory Medicine, AMC, Amsterdam, Netherlands
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S.J. Wilson
2Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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A.H. Wagener
1Respiratory Medicine, AMC, Amsterdam, Netherlands
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A.R. Sousa
3GSK, GSK, London, United Kingdom
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J. Corfield
4AZ, AstraZeneca R&D Molndalm Sweden & Areteva Ltd, Nottingham, United Kingdom
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D.E. Shaw
5Respiratory Medicine, Nottingham city Hospital, Nottingham, United Kingdom
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S.J. Fowler
6Faculty of Medicine, University of Manchester and Lancashire Teaching Hospitals NHS Foundation Trust, Manchester, United Kingdom
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L.J. Fleming
7Faculty of Medicine, Imperial College, London, United Kingdom
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J.H. Riley
3GSK, GSK, London, United Kingdom
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E. Jeyasingham
3GSK, GSK, London, United Kingdom
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A. Rowe
8R&D IT, Janssen Research and Development, London, United Kingdom
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W. Seibold
9Pharma GmbH&Co KG, Boehringer Ingelheim, Biberach an der Riss, Germany
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G. Roberts
2Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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P. Bakke
10Respitatory Medicine, Haukeland University Hospital, Bergen, Norway
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F. Singer
11Faculty of Medicine, Inselspital and University of Bern, Bern, Switzerland
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T. Geiser
11Faculty of Medicine, Inselspital and University of Bern, Bern, Switzerland
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U. Frey
11Faculty of Medicine, Inselspital and University of Bern, Bern, Switzerland
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I. Horvath
12Faculty of Medicine, Semnmelweis University, Budapest, Hungary
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R. Polosa
13Faculty of Medicine, University of Catania, Catania, Italy
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N. Krug
14Fraunhofer, Institute for Toxocology and Exp. Medicine, Hannover, Germany
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J. Musial
23Faculty of Medicine, Jagoellonian University, Krakow, Poland
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L. Pahus
16Faculty of Medicine, Université de la Méditerranee, Marseille, France
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D. Myles
3GSK, GSK, London, United Kingdom
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C. Compton
17Novartis, Pharma AG, Horsham, United Kingdom
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T.W. Higenbottam
18Chiesi, Chiesi, London, United Kingdom
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P. Montuschi
19Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
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U. Nihlén
4AZ, AstraZeneca R&D Molndalm Sweden & Areteva Ltd, Nottingham, United Kingdom
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T. Sandstrom
20University Hospital, Umea, Umea, Sweden
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S.S. Wagers
21U-BIOPRED, BioSci Consulting, Maasmechelen, Belgium
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P.H. Howarth
2Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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R. Djukanovic
2Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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K.F. Chung
7Faculty of Medicine, Imperial College, London, United Kingdom
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I. Pandis
24Discovery Sciences Group, Imperial College, London, United Kingdom
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Y. Guo
24Discovery Sciences Group, Imperial College, London, United Kingdom
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A.T. Bansal
22Acclarogen, Acclarogen, Cambridge, United Kingdom
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E.H. Bel
1Respiratory Medicine, AMC, Amsterdam, Netherlands
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P.J. Sterk
1Respiratory Medicine, AMC, Amsterdam, Netherlands
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Abstract

Rationale: Smoking results in deteriorated clinical and inflammatory outcomes in severe asthma [Thomson et al; JACI 2013]. We aimed to compare clinical, inflammatory and histological characteristics between smoking and non-smoking severe asthma patients.

Methods: This was a cross-sectional analysis of the U-BIOPRED adult severe asthma cohort. Clinical, sputum and endobronchial biopsy (immunohistochemistry) data were collected. Group comparisons were undertaken between smokers, ex-smokers and non-smokers and between (ex-)smokers and non-smokers with one-way ANOVA, independent T-test, Mann-Whitney U and Chi-square analyses.

Results: Current smokers had significantly lower post-salbutamol FEV1/FVC %predicted (mean±SD; 75.8±13.2%) than ex-smokers and non-smokers (84.6±15.1 and 84.7±16.2; p=0.014). There was a significantly higher number of mast cells within the airway smooth muscle layer in (ex-)smokers compared with non-smokers (median(interquartile range); 18.4(9.6-35.8)cells/mm2 versus 10.3(3.0-14.2); p=0.044), in contrast to the mast cells in the epithelium and submucosa (p=0.113 and p=0.787). The lamina reticularis was thicker in (ex-)smokers compared with non-smokers (9.7±2.0µm versus 8.5±1.4; p=0.006) and thicker in current smokers compared with ex-smokers and non-smokers (10.4±2.8µm versus 9.4±1.5 versus 8.6±1.4; p=0.010).

Conclusion: Severe asthma patients who smoke have lower post-bronchodilator lung function than ex-smokers and non-smokers. Notably, smokers and ex-smokers also exhibit a greater number of mast cells within the airway smooth muscle layer and a thicker lamina reticularis suggesting more prominent airway remodeling by smoking in severe asthma.

  • Asthma - mechanism
  • Smoking
  • Airway smooth muscle
  • © 2014 ERS
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Clinical and histological comparison of smoking and non-smoking patients with severe asthma in the U-BIOPRED cohort
P.P.W. Hekking, S.J. Wilson, A.H. Wagener, A.R. Sousa, J. Corfield, D.E. Shaw, S.J. Fowler, L.J. Fleming, J.H. Riley, E. Jeyasingham, A. Rowe, W. Seibold, G. Roberts, P. Bakke, F. Singer, T. Geiser, U. Frey, I. Horvath, R. Polosa, N. Krug, J. Musial, L. Pahus, D. Myles, C. Compton, T.W. Higenbottam, P. Montuschi, U. Nihlén, T. Sandstrom, S.S. Wagers, P.H. Howarth, R. Djukanovic, K.F. Chung, I. Pandis, Y. Guo, A.T. Bansal, E.H. Bel, P.J. Sterk
European Respiratory Journal Sep 2014, 44 (Suppl 58) 1688;

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Clinical and histological comparison of smoking and non-smoking patients with severe asthma in the U-BIOPRED cohort
P.P.W. Hekking, S.J. Wilson, A.H. Wagener, A.R. Sousa, J. Corfield, D.E. Shaw, S.J. Fowler, L.J. Fleming, J.H. Riley, E. Jeyasingham, A. Rowe, W. Seibold, G. Roberts, P. Bakke, F. Singer, T. Geiser, U. Frey, I. Horvath, R. Polosa, N. Krug, J. Musial, L. Pahus, D. Myles, C. Compton, T.W. Higenbottam, P. Montuschi, U. Nihlén, T. Sandstrom, S.S. Wagers, P.H. Howarth, R. Djukanovic, K.F. Chung, I. Pandis, Y. Guo, A.T. Bansal, E.H. Bel, P.J. Sterk
European Respiratory Journal Sep 2014, 44 (Suppl 58) 1688;
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