Increased levels of osteopontin in sputum supernatant in severe refractory asthma

Delimpoura, Vasiliki; Bakakos, Petros; Tseliou, Eleni; Bessa, Vasiliki; Hillas, Georgios; Simoes, Davina Camargo Madeira; Papiris, Spyros; Loukides, Stelios

doi:10.1136/thx.2010.138552

Cited by 47 publications

(42 citation statements)

References 36 publications

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“…Furthermore, periostin is a wellinvestigated, systemic biomarker of eosinophilic inflammation in asthmatic patients that is superior to blood eosinophil counts (111). In contrast, minimally invasive sputum fluids show better amplitude and facilitate the discrimination of the osteopontin levels between mild, moderate and severe/refractory asthma (112). In addition, theses studies showed a highly significant correlation with smoke-induced neutrophilic infiltration, but not with bronchial hyper-responsiveness (113).…”

Section: Biomarkers Of Airway Remodellingmentioning

confidence: 99%

Current and future biomarkers in allergic asthma

Zissler

Bieren

Jakwerth

et al. 2016

Allergy

105

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Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-typespecific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value.

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Section: Biomarkers Of Airway Remodellingmentioning

confidence: 99%

Current and future biomarkers in allergic asthma

Zissler

Bieren

Jakwerth

et al. 2016

Allergy

105

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“…In fact, TH2 high inflammation is characterized by high levels of expression of Il-13 and IL-4 inducible genes, including periostin [58]. Osteopontin and periostin sputum and serum concentration are associated with refractory eosinophilic airway inflammation and an accelerated decline in pulmonary function in patients undergoing inhaled corticosteroid (ICS) therapy [59,60,61]. Thus, they might be predictive of the response to anti-IL-13 therapy in ICS-insensitive patients, helping to stratify patients in which a relevant improvement of lung function is expected.…”

Section: Biomarkersmentioning

confidence: 99%

A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma

Bagnasco

Ferrando

Varricchi

et al. 2016

Int Arch Allergy Immunol

185

126

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Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma. IL-13 and IL-4 partly share the same receptor and signaling pathways and both are deeply involved in immunoglobulin E (IgE) synthesis, eosinophil activation, mucus secretion and airways remodeling. Several anti-IL-13 strategies have been proposed (anrukinzumab, lebrikizunab and tralokinumab), with relevant clinical results reported with lebrikizumab. Such studies facilitate better definition of the possible predictive markers of response to a specific treatment (e.g. eosinophils, total IgE, fraction of exhaled nitric oxide and periostin). In parallel, anti-IL-4 strategies have been attempted (pascolizumab, pitakinra and dupilumab). So far, dupilumab was reported capable of reducing the severity of asthma and the rate of exacerbations. IL-13 and IL-4 are crucial in TH2-mediated inflammation in asthma, but it remains clear that only specific endotypes respond to these treatments. Although the use of anti-IL-14 and anti-IL-13 strategies is promising, the search for appropriate predictive biomarkers is urgently needed to better apply biological treatments.

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“…dexamethasone and A3R activation might underlie the resistance to corticosteroids that is experienced in severe refractory asthma. Consistent with this notion is the tight association between severe refractory asthma and intense inflammatory fibrosis that is linked with increased levels of angiopoietin, VEGF, IL8 and SPP1 in the sputum supernatant (Simpson et al, 2008;Delimpoura et al, 2010;Tseliou et al, 2012;Hantera et al, 2014).…”

Section: Discussionmentioning

confidence: 58%