Journal ArticleDOI
Inflammatory subtypes in asthma: assessment and identification using induced sputum.
TLDR
The authors sought to investigate the detection of non‐eosinophilic asthma using induced sputum because this is an important subtype of clinical asthma, but its recognition is not standardized.Abstract:
Objective: The authors sought to investigate the detection of non-eosinophilic asthma using induced sputum. Although this is an important subtype of clinical asthma, its recognition is not standardized.
Methods: Adult non-smokers with asthma and healthy controls underwent sputum induction and hypertonic saline challenge. Non-eosinophilic asthma was defined as symptomatic asthma with normal sputum eosinophil counts. The normal range for sputum eosinophil count was determined using the 95th percentile from the healthy control group as a cut-off point.
Results: The recognition of non-eosinophilic asthma using eosinophil proportion was in agreement with a definition based on absolute eosinophil count (kappa 0.67). Non-eosinophilic asthma was a stable subtype over both the short term (4 weeks) and longer term (5 years, kappa 0.77). Airway inflammation in asthma could be categorized into four inflammatory subtypes based on sputum eosinophil and neutrophil proportions. These subtypes were neutrophilic asthma, eosinophilic asthma, mixed granulocytic asthma and paucigranulocytic asthma. Subjects with increased neutrophils (neutrophilic asthma and mixed granulocytic asthma) were older and had an increased total cell count and cell viability compared with other subtypes.
Conclusion: Induced sputum eosinophil proportion is a good discriminator for eosinophilic asthma, providing a reproducible definition of a homogenous group. The remaining non-eosinophilic subjects are heterogeneous and can be further classified based on the presence of neutrophils. These inflammatory subtypes have important implications for the investigation and characterization of airway inflammation in asthma.read more
Citations
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Journal ArticleDOI
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Kian Fan Chung,Sally E. Wenzel,Jan Brozek,Andrew Bush,Mario Castro,Peter J. Sterk,Ian M. Adcock,Eric D. Bateman,Elisabeth H. Bel,Eugene R. Bleecker,Louis-Philippe Boulet,Christopher E. Brightling,Pascal Chanez,Sven-Erik Dahlén,Ratko Djukanovic,Urs Frey,Mina Gaga,Peter G. Gibson,Qutayba Hamid,Nizar N. Jajour,Thais Mauad,Ronald L. Sorkness,W. Gerald Teague +22 more
TL;DR: Recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults and coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy are provided.
Journal ArticleDOI
T-helper Type 2–driven Inflammation Defines Major Subphenotypes of Asthma
Prescott G. Woodruff,Barmak Modrek,David F. Choy,Guiquan Jia,Alexander R. Abbas,Almut Ellwanger,Joseph R. Arron,Laura L. Koth,John V. Fahy +8 more
TL;DR: Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation, and Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma.
Journal ArticleDOI
Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease
TL;DR: This approach is already suggesting entirely novel pathways to disease-eg, alternative macrophage specification, steroid refractory innate immunity, the interleukin-17-regulatory T-cell axis, epidermal growth factor receptor co-amplification, and Th2-mimicking but non-T-cell,interleukins 18 and 33 dependent processes that can offer unexpected therapeutic opportunities for specific patient endotypes.
Journal ArticleDOI
Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.
Guiquan Jia,Richard W. Erickson,David F. Choy,Sofia Mosesova,Lawren C. Wu,Owen D. Solberg,Aarti Shikotra,Richard Carter,Severine Audusseau,Qutayba Hamid,Peter Bradding,Peter Bradding,John V. Fahy,Prescott G. Woodruff,Jeffrey M. Harris,Joseph R. Arron +15 more
TL;DR: Periostin is a systemic biomarker of airway eosinophilia in asthmatic patients and has potential utility in patient selection for emerging asthma therapeutics targeting T(H)2 inflammation.
Journal ArticleDOI
Clarithromycin targets neutrophilic airway inflammation in refractory asthma.
TL;DR: Clarithromycin therapy can modulate IL-8 levels and neutrophil accumulation and activation in the airways of patients with refractory asthma and may be an important additional therapy that could be used to reduce noneosinophilic airway inflammation, particularly neutrophilic inflammation, in asthma.
References
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Journal ArticleDOI
Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial.
Ruth H. Green,Christopher E. Brightling,S McKenna,Beverley Hargadon,Debbie Parker,Peter Bradding,Andrew J. Wardlaw,Ian D. Pavord +7 more
TL;DR: A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.
Journal ArticleDOI
Evidence That Severe Asthma Can Be Divided Pathologically into Two Inflammatory Subtypes with Distinct Physiologic and Clinical Characteristics
Sally E. Wenzel,Lawrence B. Schwartz,Esther L. Langmack,Janet L. Halliday,John B. Trudeau,Robyn L. Gibbs,Hong Wei Chu +6 more
TL;DR: The results suggest that two distinct pathologic, physiologic, and clinical subtypes of severe asthma exist, with implications for further research and treatment.
Journal ArticleDOI
Neutrophilic inflammation in severe persistent asthma.
TL;DR: The role of eosinophils in asthma is confirmed but a potential role of neutrophils in more severe asthma is suggested, as well as the role of interleukin-8 and neutrophil myeloperoxidase levels, with the highest levels in severe asthma.
Journal ArticleDOI
Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids
Ruth H. Green,Christopher E. Brightling,Gerrit Woltmann,Debbie Parker,Andrew J. Wardlaw,Ian D. Pavord +5 more
TL;DR: The results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids.
Journal ArticleDOI
Non-eosinophilic asthma: importance and possible mechanisms
TL;DR: If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and Prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eos inophilic asthma and allergen avoidance measures, respectively.