Biomarkers for the Phenotyping and Monitoring of Asthma in Children

Abstract

Opinion statementAn important issue in relation to the utility and reliability of biomarkers for asthma monitoring is how asthma is defined and characterized. What kind of asthma, or at what stage of the disease is a particular biomarker supposed to add information? Often, the purpose, or usefulness of a biomarker is not made clear. Diagnosis, severity evaluation, and monitoring are all different clinical uses for a biomarker, and confusion may arise when a biomarker is suitable for one of these but not another. When the utility of available biomarkers are discussed, these different roles need to be clarified. Our opinion is that there are four aspects of relevance to asthma, for which biomarkers are required: to diagnose allergies, to evaluate inflammation in the airways, to evaluate hyper-responsiveness, and for certain measures of lung function, such as lung clearance index. These types of biomarkers are needed for the phenotyping and monitoring of asthma. Another important role for biomarkers is, as mentioned above, to monitor asthma in order to follow treatment effects on inflammation and hyper-responsiveness as objective adjuncts to the patients’ own symptom reports and lung function. This review will mainly focus on biomarkers that reflect airway inflammation. In spite of the numerous studies that have been conducted, we still have to remember that the value of biomarkers available for routine use, such as eosinophil counts in blood and sputum and exhaled nitric oxide, have to be interpreted in relation to reported symptoms and lung function. Measures of bronchial hyper-responsiveness, performed either by direct (methacholine challenge) or indirect (exercise or mannitol challenge) methods, could be considered biomarkers but will not be included in this review. On the other hand, diagnosing allergy is not usually useful for monitoring asthma although it is of fundamental importance for the interpretation of most biomarkers that are suitable for monitoring. We have therefore included the different approaches for diagnosing and evaluating allergic sensitization in this review.

<p>Confounding Patient Factors Affecting the Proper Interpretation of the Periostin Level as a Biomarker in Asthma Development</p>

“…There is an imminent need to discover new biomarkers that can discriminate and classify different asthmatic phenotypes, predict the clinical behavior and therapeutic response as well as aid in the identification of new therapeutic targets. 8,9 Those markers need to be less invasive and more technically convenient in comparison to the currently available ones. 10 Despite that necessity, only a few markers were shown to have potential roles in the clinical practice.…”

“…29 For instance, baseline POSTN levels were high in children and hence might mask any changes due to its local release within the airways leading to inconsistent findings in children. 9 Therefore, we explored publicly available datasets to identify possible confounders affecting POSTN gene expression and hence may limit the interpretation of its level in the clinical settings. Our analysis showed that POSTN gene mRNA expression was upregulated in the asthmatic, smoker COPD and IPF bronchial epithelium when compared to matching healthy controls (Figure 4).…”

“…Hamoudi et al found that the best strategy for generating variant probes that are differentially expressed between the groups was using a combination of gcRMA and MAS5 normalization followed by cross-referencing the probes that passed through non-specific filtering based on the coefficient of variation and absolute value thresholding. 9 After the removal of the non-variant probes, the resultant filtered ones were the only variant probes. Also, the housekeeping probes and those that are not assigned to a gene were excluded.…”

“…8 The proper use of POSTN as a biomarker is hindered by many limitations as relatively few numbers of proper studies showed conflicting results in different settings. 9 Since POSTN is one of the very few biomarkers available to reflect refractory Th2/eosinophilic inflammation; therefore, understanding the factors that may affect its expression is essential for managing the patients and understanding the disease. 10 Here we used bioinformatics analysis of publicly available transcriptomics data to confirm that POSTN is an asthma specific gene and participate in different pathways in asthmatic patients' bronchial epithelium.…”

Diagnosis of Bronchial Asthma in Children 3–6 Years Old by Using Serum Periostin and Surrogate Markers of Eosinophilic Inflammation (Blood Eosinophils and Total IgE): a Cross-Sectional Study

“…Поиску маркеров БА в образцах крови в настоящее время уделяется большое внимание [4]. В числе потенциальных диагностических маркеров рассматривается периостин -протеин, экспрессируемый преимущественно эпителиальными клетками, а также фибробластами и гладкомышечными клетками бронхов [5,6].…”