Heterogeneity in Asthma

Abstract

Asthma is a chronic relapsing airways disease that represents one of the most com- mon chronic diseases worldwide (Busse et al. 2001; Masoli et al. 2004). Currently it is estimated that over 300 M people suffer from asthma, and its prevalence is increasing in both adult and pediatric populations. Asthma therefore represents a major public health problem and is worthy of attention to develop cost-effective prevention and management approaches. Clinically asthma is a syndrome characterized by episodic, reversible obstructive airways obstruction that variably presents as a myriad of symptoms from cough to wheezing, shortness of breath, or chest tightness. The presence of bronchial muscu- lar hypertrophy, mucous hypersecretion, tissue remodeling, and a T-lymphocyte predominant infl ammation are pathogenic signatures of this disease (Busse et al. 2001; Lemanske et al. 2010). Asthma is a disease signifi cantly modifi ed by environ- mental interactions. Characteristic of asthma is intermittent exacerbations provoked by airway mucosal exposure to proinfl ammatory stimuli. Here, common cold (RNA viral infections) or inhaled allergens are two of the most common precipitants (Lemanske et al. 2010; Montalbano et al. 2002). It is widely appreciated that asthma is different from one individual to the next; this heterogeneity is manifested in onset, exacerbating stimuli, severity, and treat- ment response. Presently, asthma classifi cation methods are largely descriptive, focus on a single aspect or dimension of the disease, and do not lead to actionable intervention. Specifi cally, the current standard of care treatment for asthma is a stepped-care model; for those with persistent symptoms, anti-infl ammatory treat- ment with inhaled corticosteroids (ICS) remains the fi rst-line treatment. Yet effi cacy studies indicate up to 30 % of subjects do not have a response to ICS. Currently, no reliable biomarker has been validated that identify an ICS response (Szefl er 2002). v vi Preface A robust, objective method for diagnosis and measurement of the effi cacy for treat- ment interventions is, therefore, sorely needed