Detection of immunological biomarkers correlated with asthma control and quality of life measurements in sera from chronic asthmatic patients.
ABSTRACT Clinical outcomes of patients with asthma are highly variable. Immunological biomarkers associated with asthma control have not been elucidated.
To identify the association between clinical control of asthma and serum immunological profiles of asthmatics and compare these profiles with those of healthy controls by using a multiplex assay.
Sera were obtained from 28 nonsmokers 18 to 55 years of age with moderate and severe persistent asthma. Patients were classified as having well-controlled (WC, n = 14) or poorly controlled (PC, n = 14) asthma based on their responses to the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire. Sera from nonasthmatic control individuals (NAC, n = 14) were used for comparison. Levels of 50 analytes, including cytokines, chemokines, angiogenic, and growth factors, were determined, using a multiplex assay.
Twelve of the 29 cytokines levels were significantly higher in patients with asthma than in NACs, but only interferon gamma levels were significantly lower in patients with asthma than in the NAC group. Among these, interleukin (IL)-3 and IL-18 levels were significantly higher in the PC group than the WC group. Five of the 12 tested chemokine levels were significantly higher in patients with asthma than in NACs. Five of six growth factor levels were significantly higher in patients with asthma than in NACs, and 3 were higher in PC than WC. Interleukin-18, fibroblast growth factor, hepatocyte growth factor, and stem cell growth factor-beta were positively correlated with poor asthma control and negatively with quality of life scores.
Increased serum levels of fibroblast growth factor, hepatocyte growth factor, and stem cell growth factor-beta might be useful biomarkers of asthma control status and targets of future asthma therapy.
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ABSTRACT: Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.Asia Pacific allergy. 10/2014; 4(4):187-96.
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ABSTRACT: Asthma is a chronic and heterogeneous inflammatory disorder with several different phenotypes. Whereas clinical features of asthma are non-specific and pulmonary function tests are often insensitive, further development is needed for efficient treatment or even early diagnosis. Recently, several airway inflammatory biomarkers have emerged as valuable tools in diagnosis and management of asthma. The analysis of molecular markers of airways inflammation has provided promising and non-invasive techniques that facilitate the detection of disease phenotypes as well as measurement of therapeutic efficacy. Although conventional treatments remain the preferred therapy, they do not adequately control some severe cases of asthma. Novel therapeutic agents have been developed to target various biomarkers involved in the inflammatory responses and have been investigated in patients with asthma. In this article, we summarized the most studied asthma biomarkers, derived from a variety of biological sources including exhaled gases, induced sputum, serum and urine. Likewise, the effects of current anti-inflammatory asthma treatments on inflammatory biomarkers and some promising biomarkers for developing new targeted therapies are also discussed.Respirology 04/2014; · 3.50 Impact Factor
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ABSTRACT: Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or "primed", or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. This article is protected by copyright. All rights reserved.Clinical & Experimental Allergy 02/2014; · 4.32 Impact Factor