Journal ArticleDOI
Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Identification of Biologic Clusters and Their Biomarkers
Mona Bafadhel,S McKenna,Sarah Terry,Vijay Mistry,C Reid,Pranabashis Haldar,M McCormick,Koirobi Haldar,Tatiana Kebadze,Annelyse Duvoix,Kerstin Lindblad,Hemu Patel,Paul Rugman,Paul Dodson,Martin Jenkins,Michael A. Saunders,Paul Newbold,Ruth H. Green,Per Venge,David A. Lomas,Michael R. Barer,Sebastian L. Johnston,Ian D. Pavord,Christopher E. Brightling +23 more
TLDR
In this paper, the authors investigated biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.Abstract:
Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.read more
Citations
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Journal ArticleDOI
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary
Claus Vogelmeier,Gerard J. Criner,Fernando J. Martinez,Antonio Anzueto,Peter J. Barnes,Jean Bourbeau,Bartolome R. Celli,Rongchang Chen,Marc Decramer,Leonardo M. Fabbri,Peter Frith,David M.G. Halpin,M. Victorina López Varela,Masaharu Nishimura,Nicolas Roche,Roberto Rodriguez-Roisin,Don D. Sin,Dave Singh,Robert Stockley,Jørgen Vestbo,Jadwiga A. Wedzicha,Alvar Agusti +21 more
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of deescalation of therapy is introduced in the treatment assessment scheme.
Journal ArticleDOI
Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.
Ian D. Pavord,Stephanie Korn,Peter H. Howarth,Eugene R. Bleecker,Roland Buhl,Oliver N. Keene,Hector Ortega,Pascal Chanez +7 more
TL;DR: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.
Journal ArticleDOI
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary
Claus Vogelmeier,Gerard J. Criner,Fernando J. Martinez,Antonio Anzueto,Peter J. Barnes,Jean Bourbeau,Bartolome R. Celli,Rongchang Chen,Marc Decramer,Leonardo M. Fabbri,Peter Frith,David M.G. Halpin,M. Victorina López Varela,Masaharu Nishimura,Nicolas Roche,Roberto Rodriguez-Roisin,Don D. Sin,Dave Singh,Robert Stockley,Jørgen Vestbo,Jadwiga A. Wedzicha,Alvar Agusti +21 more
TL;DR: The assessment of COPD has been refined to separate the spirometric assessment from symptom evaluation, and the concept of de-escalation of therapy is introduced in the treatment assessment scheme.
Journal ArticleDOI
After asthma: redefining airways diseases
Ian D. Pavord,Richard Beasley,Alvar Agusti,Gary P. Anderson,Elisabeth H. Bel,Guy Brusselle,Guy Brusselle,Paul Cullinan,Adnan Custovic,Francine M. Ducharme,John V. Fahy,Urs Frey,Peter G. Gibson,Peter G. Gibson,Liam G Heaney,Patrick G. Holt,Marc Humbert,Marc Humbert,Clare M. Lloyd,Guy B. Marks,Fernando D. Martinez,Peter D. Sly,Erika von Mutius,Sally E. Wenzel,Heather J. Zar,Andrew Bush +25 more
TL;DR: The only way to make progress in the future is to be much more clear about the meaning of the labels used for asthma and to acknowledge the assumptions associated with them, which are believed to be the most important causes of the stagnation in key clinical outcomes observed in the past 10 years.
Journal ArticleDOI
Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary
Claus Vogelmeier,Gerard J. Criner,Fernando J. Martinez,Antonio Anzueto,Peter J. Barnes,Jean Bourbeau,Bartolome R. Celli,Rongchang Chen,Marc Decramer,Leonardo M. Fabbri,Peter Frith,David M.G. Halpin,M. Victorina López Varela,Masaharu Nishimura,Nicolas Roche,Roberto Rodriguez-Roisin,Don D. Sin,Dave Singh,Robert Stockley,Jørgen Vestbo,Jadwiga A. Wedzicha,Alvar Agusti +21 more
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of de‐escalation of therapy is introduced in the treatment assessment scheme.
References
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Antibiotic Therapy in Exacerbations of Chronic Obstructive Pulmonary Disease
Nicholas R. Anthonisen,Jure Manfreda,C. P. W. Warren,Earl Hershfield,G. K. M. Harding,N. A. Nelson +5 more
TL;DR: There was a significant benefit associated with antibiotic and Peak flow recovered more rapidly with antibiotic treatment than with placebo, and side effects were uncommon and did not differ between antibiotic and placebo.
Journal ArticleDOI
Disordered Microbial Communities in Asthmatic Airways
Markus Hilty,Conor Burke,Helder Pedro,Helder Pedro,Paul Cardenas,Andrew Bush,Cara Bossley,Jane C. Davies,Aaron Ervine,Len Poulter,Lior Pachter,Miriam F. Moffatt,William O.C.M. Cookson +12 more
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Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease
Sanjay Sethi,Timothy F. Murphy +1 more
TL;DR: New molecular, cellular, and immunologic techniques used to study host–pathogen interactions have led to a reexamination of the role of infection in chronic obstructive pulmonary disease.