Asthma phenotypes: the evolution from clinical to molecular approaches

Wenzel, Sally E.

doi:10.1038/nm.2678

Cited by 2,063 publications

(1,903 citation statements)

References 133 publications

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“…However, as the biological treatments target very specific pathways in the immune system, they are only effective in specific phenotypes of severe asthma [7]. Accordingly, phenotyping of severe asthma patients has become increasingly important, in order to target novel treatments tailored to the appropriate patient.…”

Section: Introductionmentioning

confidence: 99%

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Porsbjerg

Ulrik

Skjold

et al. 2018

European Clinical Respiratory Journal

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Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma (‘difficult asthma’) should undergo systematic assessment, in order to differentiate between true severe asthma, and ‘difficult-to-treat’ patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.

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Section: Introductionmentioning

confidence: 99%

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Porsbjerg

Ulrik

Skjold

et al. 2018

European Clinical Respiratory Journal

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“…Historically asthma, and particularly allergic asthma, has been considered to be mainly driven by a T helper 2 (Th2)‐mediated immune response. However, it is now well recognized that asthma is a heterogeneous disease with different pathophysiological pathways underlying airway inflammation (Wenzel 2012). Molecular phenotyping of diseased airway tissue has the potential to unravel the multiple phenotypes of asthma.…”

Section: Introductionmentioning

confidence: 99%

“…2009; Wenzel 2012). A Th2‐high subtype of asthma has been described and is associated with increased bronchial epithelial expression of periostin ( POSTN ), serpin B2 ( SERPINB2 ), and chloride channel regulator 1 ( CLCA1 ), and predicts a beneficial therapeutic response to corticosteroids (Woodruff et al.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

et al. 2017

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Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN,CLCA1, and SERPINB2. This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2‐high and Th2‐low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL‐13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin‐related genes MUC5AC and SPDEF in air–liquid interface differentiated human bronchial (ALI‐PBEC) and tracheal epithelial cells (ALI‐PTEC). Cultures were exposed to IL‐13 for 14 days followed by 5 days of IL‐13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14 days, followed by 5 days CS with IL‐13. POSTN,SERPINB2, and CLCA1 expression were measured 24 h after the last exposure to CS and IL‐13. In both models POSTN,SERPINB2, and CLCA1 expression were increased by IL‐13. CS markedly affected the IL‐13‐induced Th2 gene signature as indicated by a reduced POSTN,CLCA1, and MUC5AC expression in both models. In contrast, IL‐13‐induced SERPINB2 expression remained unaffected by CS, whereas SPDEF expression was additively increased. Importantly, cessation of CS exposure failed to restore IL‐13‐induced POSTN and CLCA1 expression. We show for the first time that CS differentially affects the IL‐13‐induced gene signature for Th2‐high asthma. These findings provide novel insights into the interaction between Th2 inflammation and cigarette smoke that is important for asthma pathogenesis and biomarker‐guided therapy in asthma.

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“…СОВРЕМЕННЫЙ ВЗГЛЯД НА МЕХАНИЗМЫ РАЗВИТИЯ БРОНХИАЛЬНОЙ АСТМЫ С момента создания концепции о том, что иммунный ответ организма определяется Th1-и Th2-типами лим-фоцитов, развитие бронхиальной астмы ассоциировали с активацией Th2 лимфоцитов, которая тесно связана с развитием реакции гиперчувствительности 1-го типа и эозинофильным воспалением [9]. При аллергической БА пролиферация Th2 лимфоцитов и синтез интерлейки-на (Interleukin, IL) 4 активированными тучными клетка-ми способствует переключению изотипа В лимфоцитов на синтез иммуноглобулина (Immunoglobulin, Ig) E. С пози-ций современных данных, активация тучных клеток анти-телами IgE не ограничивается реакцией немедленного типа при встрече с установленным аллергеном.…”

Section: актуальностьunclassified

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

Sobotyuk¹,

Gaponenko²,

Бочанцев³

et al. 2016

Vopr. sovr. pediatr.

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АКТУАЛЬНОСТЬНи значительные достижения в диагностике бронхи-альной астмы (БА), ни внедрение в практику современных методов контроля и профилактики бронхиальной обструк-ции так и не привели к снижению заболеваемости, осо-бенно среди детского населения. B наши дни БА -наи-более распространенная хроническая форма патологии дыхательных путей в младшей возрастной группе [1,2].В конце XX -начале XXI века исследователи на экс-периментальных моделях убедительно показали, что Т хел перы второго типа (Th2) играют важнейшую роль в развитии аллергической БА, и с их активацией связаны

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Asthma phenotypes: the evolution from clinical to molecular approaches

Cited by 2,063 publications

References 133 publications

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

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