Identification of innate immune response endotypes in asthma: implications for personalized medicine

Abstract

Asthma is an idiopathic disease characterized by episodic inflammation and reversible airway obstruction triggered by exposure to environmental agents. Because this disease is heterogeneous in onset, exacerbations, inflammatory states, and response to therapy, there is intense interest in developing personalized approaches to its management. Of focus in this review, the recognition that a component of the pathophysiology of asthma is mediated by inflammation has implications for understanding its etiology and individualizing its therapy. Despite understanding how Th2 polarization mediates asthma exacerbations by aeroallergen exposure, we do not yet fully understand how RNA virus infections produce asthmatic exacerbations. This review will summarize the explosion of information that has revealed how patterns produced by RNA virus infection trigger the innate immune response (IIR) in sentinel airway cells. When the IIR is triggered, these cells elaborate inflammatory cytokines and protective mucosal interferons whose actions activate long-lived adaptive immunity and limit organismal replication. Recent work has shown the multifaceted way that dysregulation of the IIR is linked to viral-induced exacerbation, steroid insensitivity, and T helper polarization of adaptive immunity. New developments in quantitative proteomics now enable accurate identification of subgroups of individuals that demonstrate activation of IIR ("innate endotype"). Potential applications to clinical research are proposed. Together, these developments open realistic prospects for how identification of the IIR endotype may inform asthma therapy in the future.

Figure 1

Personalized medicine for innate endotypes in asthma. A schematic view of a sampling strategy, inflammatory measurement, and potential targets for developing actionable individual interventions in asthma. CDKi cyclin-dependent kinase inhibitor, ICS inhaled corticosteroids, SID stable-isotope dilution, SRM-MS selective reaction monitoring mass spectrometry