Emerging molecular phenotypes of asthma

Abstract

Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease.

Keywords: Type 2; asthma; endotypes; molecular; phenotypes.

Fig. 1.

Definitions for the transition from clinical phenotypes to molecular phenotypes to endotypes.

Fig. 2.

A: traditional view of Type 2/Th2 inflammation in early-onset, allergic asthma. iNOS, inducible nitric oxide synthase; PGD, prostaglandin D; TSLP, thymic stromal lymphopoieten; CCR, CC chemokine receptor; MUC5AC, mucin 5AC. B: possible underlying pathobiology in patients with nontraditional Type 2 inflammation associated with adult-onset, eosinophilic disease. ILC2, innate lymphoid cells. C: possible underlying pathobiology in complicated/mixed Type 2 severe asthma. APC, antigen-presenting cell; GCSF, granuloyte colony-stimulating factor; DUOX2, dual oxidase 2.

Fig. 3.

The increasingly granular umbrella for Type 2 cytokine-associated asthma molecular phenotypes, all of which encompass some Type 2 inflammatory biomarkers. CS, corticosteroid; FeNo, fractional exhaled NO.