Recent advances in asthma biomarker research

Abstract

Asthma is characterized by recurrent and reversible airflow obstruction, which is routinely monitored by history and physical examination, spirometry and home peak flow diaries. As airway inflammation is central to asthma pathogenesis, its monitoring should be part of patient management plans. Fractional exhaled nitric oxide level (FeNO) is the most extensively studied biomarker of airway inflammation, and FeNO references were higher in Chinese (Asians) than Whites. Published evidence was inconclusive as to whether FeNO is a useful management strategy for asthma. Other biomarkers include direct (histamine, methacholine) and indirect (adenosine, hypertonic saline) challenges of bronchial hyperresponsiveness (BHR), induced sputum and exhaled breath condensate (EBC). A management strategy that normalized sputum eosinophils among adult patients resulted in reductions of BHR and asthma exacerbations. However, subsequent adult and pediatric studies failed to replicate these benefits. Asthma phenotypes as defined by inflammatory cell populations in sputum were also not stable over a 12-month period. A recent meta-analysis concluded that induced sputum is not accurate enough to be applied in routine monitoring of childhood asthma. There is poor correlation between biomarkers that reflect different asthma dimensions: spirometry (airway caliber), BHR (airway reactivity) and FeNO or induced sputum (airway inflammation). Lastly, EBC is easily obtained noninvasively by cooling expired air. Many biomarkers ranging from acidity (pH), leukotrienes, aldehydes, cytokines to growth factors have been described. However, significant overlap between groups and technical difficulty in measuring low levels of inflammatory molecules are the major obstacles for EBC research. Metabolomics is an emerging analytical method for EBC biomarkers. In conclusion, both FeNO and induced sputum are useful asthma biomarkers. However, they will only form part of the clinical picture. Longitudinal studies with focused hypotheses and well-designed protocols are needed to establish the roles of these biomarkers in asthma management. The measurement of biomarkers in EBC remains a research tool.