Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles - 06/06/18
Abstract |
Background |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.
Objective |
We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.
Methods |
Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.
Results |
The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.
Conclusions |
A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Asthma, chronic obstructive pulmonary disease, asthma and chronic obstructive pulmonary disease heterogeneity, inflammatory profiles, microbiome abundances, phylum and genus levels, factor and cluster analyses
Abbreviation used : COPD, IL-6R, P/F ratio, T1, T2, TNF-R, VAS, VEGF
Plan
| Supported by MedImmune and a Wellcome Trust Senior Fellowship (to C.E.B.). The research was performed in laboratories funded in part by the European Regional Development Fund (ERDF 05567). This study was also part supported by the Medical Research Council; the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, United Kingdom; and AirPROM (FP7-270194). S.L.J. was supported by the Asthma UK Clinical Chair (CH11SJ) and an MRC Centre grant (no. G1000758). The views expressed are those of the author or authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. |
|
| Disclosure of potential conflict of interest: P. H. Pang reports personal fees from Teva UK Limited outside the submitted work. D. Desai reports personal fees from AstraZeneca, Boehringer Ingelheim, and Chiesi outside the submitted work. M. Bafadhel reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Pfizer outside the submitted work. S. Cohen, P. Newbold, L. Rapley, J. Woods, and P. Rugman are employees of MedImmune, which supported the study. I. D. Pavord reports personal fees and nonfinancial support from AstraZeneca and Boehringer Ingelheim and personal fees from Aerocrine, Almirall, Novartis, GlaxoSmithKline, Genentech, Regeneron, Merck & Co, Schering-Plough, Mylan Specialty (Dey Pharma), Napp Pharmaceuticals and Respivert outside the submitted work. S. L. Johnston reports grants/personal fees from Apollo Therapeutics, AstraZeneca, Boehringer Ingelheim, Bioforce, Chiesi, Genentech, GlaxoSmithKline, Merck, Novartis, Sanofi/Regeneron, Synairgen, and Therapeutic Frontiers; is a director of Therapeutic Frontiers; and holds patents on the use of inhaled interferons as treatments for exacerbations of airway disease outside the submitted work. R. D. May is a former employee of MedImmune, which supported the study. C. E. Brightling has received grants and personal fees paid to his institution from MedImmune (AstraZeneca), GlaxoSmithKline, Roche/Genentech, Novartis, Chiesi, Pfizer, Teva, Sanofi/Regeneron, Glenmark, Mologic, PreP, and Vectura, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 6
P. 2027 - juin 2018 Retour au numéro
Article précédent
- Is 9 more than 2 also in allergic airway inflammation?
- Holger Garn
- Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease
- Jeong H. Yun, Andrew Lamb, Robert Chase, Dave Singh, Margaret M. Parker, Aabida Saferali, Jørgen Vestbo, Ruth Tal-Singer, Peter J. Castaldi, Edwin K. Silverman, Craig P. Hersh, COPDGene and ECLIPSE Investigators, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Elizabeth A. Regan, Stephanie Santorico, Edwin K. Silverman, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, Elizabeth A. Regan, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, Carla G. Wilson, John E. Hokanson, John Hughes, Gregory Kinney, Sharon M. Lutz, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Dawn L. DeMeo, Craig Hersh, Francine L. Jacobson, George Washko, R. Graham Barr, John Austin, Belinda D'Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Marilyn G. Foreman, Eugene Berkowitz, Gloria Westney, Russell Bowler, David A. Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, MeiLan K. Han, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina Kiev, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, D. Lomas, W. MacNee, E. Silverman, R. Tal Singer, J. Vestbo, J. Yates, A. Agusti, P. Calverley, B. Celli, C. Crim, B. Miller, W. MacNee, S. Rennard, R. Tal-Singer, E. Wouters, J. Yates
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?