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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.

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Citations
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Journal ArticleDOI

T-helper Type 2–driven Inflammation Defines Major Subphenotypes of Asthma

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

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.

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

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

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.
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