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.
[Show abstract][Hide abstract] ABSTRACT: Asthma is a chronic inflammatory disease of the airways, resulting in bronchial hyperresponsiveness with every allergen exposure. It is now clear that asthma is not a single disease, but rather a multifaceted syndrome that results from a variety of biologic mechanisms. Asthma is further problematic given that the disease consists of many variants, each with its own etiologic and pathophysiologic factors, including different cellular responses and inflammatory phenotypes. These facets make the rapid and accurate diagnosis (not to mention treatments) of asthma extremely difficult. Protein biomarkers can serve as powerful detection tools in both clinical and basic research applications. Recent endeavors from biomedical researchers have developed technical platforms, such as cytokine antibody arrays, that have been employed and used to further the global analysis of asthma biomarker studies. In this review, we discuss potential asthma biomarkers involved in the pathophysiologic process and eventual pathogenesis of asthma, how these biomarkers are being utilized, and how further testing methods might help improve the diagnosis and treatment strain that current asthma patients suffer.
"Several studies have evaluated whether the presence of inflammatory soluble mediators such as chemokines and cytokines were applicable as biomarkers for type and extent of asthma phenotypes.47 Recent studies utilized multiplex analysis, allowing the parallel analysis of multiple cytokines within one serum/plasma sample.48,49 Unfortunately, these studies have led to neither a clinically useful diagnostic tool to identify distinct disease phenotypes, nor to a tool to assess disease severity. "
[Show abstract][Hide abstract] ABSTRACT: Asthma is a chronic disease characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. The disease is very heterogeneous in onset, course, and response to treatment, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted clinical biomarkers to assess the nature and severity of the disease. Currently available biomarkers for clinical practice - for example markers in bronchial lavage, bronchial biopsies, sputum, or fraction of exhaled nitric oxide (FeNO) - are limited due to invasiveness or lack of specificity. The assessment of markers in peripheral blood might be a good alternative to study airway inflammation more specifically, compared to FeNO, and in a less invasive manner, compared to bronchoalveolar lavage, biopsies, or sputum induction. In addition, promising novel biomarkers are discovered in the field of breath metabolomics (eg, volatile organic compounds) and (pharmaco)genomics. Biomarker research in asthma is increasingly shifting from the assessment of the value of single biomarkers to multidimensional approaches in which the clinical value of a combination of various markers is studied. This could eventually lead to the development of a clinically applicable algorithm composed of various markers and clinical features to phenotype asthma and improve diagnosis and asthma management.
"If the chymase mechanism of action is inhibited, there should be detectable levels of IL-18 in the biological sample . Significantly higher interleukin-18 levels were found in poorly controlled rather than well controlled asthma . "
[Show abstract][Hide abstract] ABSTRACT: This review informs on current literature on patents for biomarkers for asthma from 2009 to 2011. Variable airflow obstruction in asthma is generally triggered by gene-environment interactions that can lead to key symptoms of cough, shortness of breath, chest tightness, and wheezing. The episodic and variable degrees of airway hyperresponsiveness arise from a variety of inflammatory pathways that can make diagnosis and management difficult. Standard pulmonary function tests used for the diagnosis of asthma may fail to predict individual responses to the standard bronchodilator and corticosteroid therapies. Phenotypic predispositions can alter the severity of the asthmatic condition and treatment response. Biomarkers from sputum, exhaled gases, exhaled breath condensates, urine, serum, and broncheolaveolar fluid lavage proteins are currently explored to provide objective metrics for identifying individuals at risk, provide therapy guidance, monitor disease progression and evaluate response to therapy, as a supplement to standard pulmonary function tests. Updates on the refinement of technologies, inherent limitations and benefits of these biomarkers are discussed to provide insights on how current understanding of pathologic mechanisms has been applied to provide information for addressing gaps in the diagnosis and management of asthma.
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