Lebrikizumab Treatment in Adults with Asthma

Corren, Jonathan; Lemanske, Robert F.; Hanania, Nicola A.; Korenblat, Phillip E.; Parsey, Merdad V.; Arron, Joseph R.; Harris, Jeffrey M.; Scheerens, Heleen; Wu, Lawren C.; Su, Zheng; Mosesova, Sofia; Eisner, Mark D.; Bohen, Sean P.; Matthews, John G.

doi:10.1056/nejmoa1106469

Cited by 1,402 publications

(1,106 citation statements)

References 28 publications

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“…Furthermore, high serum periostin levels have been shown to predict therapy response to anti‐IL‐13 treatment (Corren et al. 2011; Hanania et al. 2013; Brightling et al.…”

Section: Discussionmentioning

confidence: 99%

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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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“…Furthermore, high serum periostin levels have been shown to predict therapy response to anti‐IL‐13 treatment (Corren et al. 2011; Hanania et al. 2013; Brightling et al.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, there is evidence suggesting that circulating periostin levels may help in the identification of asthma patients that benefit from anti‐IL‐13 treatment (Corren et al. 2011; Noonan et al. 2013; Brightling 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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“…Дальнейшие исследования по-казали, что у пациентов с высоким сывороточным перио-стином по сравнению с больными, у которых его уровень был низким, применение лебрикизумаба сопровожда-лось выраженным улучшением функции легких (определя-ли ОФВ 1 ) [51]. Такая же закономерность наблюдалась при включении в терапию БА меполизумаба (моноклональные анти-IL5 антитела).…”

Section: периостин как потенциальный маркер эозинофильного воспаленияunclassified

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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“…Ces cellules sont également présentes au niveau de polypes prélevés chez des patients atteints de rhinosinusite chronique, une pathologie qui se caractérise par une inflammation induite par les cytokines de type 2 [17]. En outre, des essais cliniques de blocage de l'IL-13 par un anticorps monoclonal, menés chez des patients asthmatiques, ont montré une efficacité relative [18]. Les ILC1 (NK) et les ILC2 pourraient également intervenir dans l'asthme via l'induction de l'apoptose des éosinophiles par les NK et la production d'IL-13 par les ILC2, ces deux mécanismes étant régulés par la lipoxine A4 [19].…”

Section: Les Ilc2 Chez L'hommeunclassified

Les cellules lymphoïdes innées

Cherrier

2014

Med Sci (Paris)

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Lebrikizumab Treatment in Adults with Asthma

Cited by 1,402 publications

References 28 publications

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

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

Les cellules lymphoïdes innées

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