Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur, Gyu Young; Broide, David H.

Environmental factors that can contribute to decline in lung function in asthma include virus-triggered asthma exacerbations and tobacco smoke. In terms of genetic factors contributing to decline in lung function in asthma, several genes have been linked to decline in lung function, but these studies require replication to determine if any of these genes is important for lung function decline in asthma as well as the magnitude of the effect. As rhinoviral infections are an important trigger of asthma exacerbations which are associated with decline in lung function in asthma, it is of interest that children harboring chromosome 17q21 variants (linked to the genes ORMDL3 and GSDMB) were predisposed to develop rhinovirus wheezing illnesses in early life, but not RSV wheezing illnesses. In addition to studying genes and environmental factors, studies of asthmatic airway biopsies have also identified mediators, cytokines, and pathways associated with airway remodeling. Ultimately, intervention studies in asthmatics inhibiting a specific mediator, cytokine, or pathway associated with airway remodeling will need to be performed to determine the importance of each intervention. Although at present there is insufficient evidence for targeting a specific molecular pathway to reduce airway remodeling or decline in lung function in asthma, continued research will help identify the most promising targets to be considered in the subset asthmatics with the greatest decline in lung function.