Biomarkers for the Phenotyping and Monitoring of Asthma in Children

An 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.