Researchers at the University of Iowa have uncovered a link between the dysfunction of cystic fibrosis protein CFTR and airway smooth muscle (ASM) abnormalities — two common pathologies of the chronic lung disorder cystic fibrosis (CF).
The study, “Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities,” confirmed that restoring the function of CFTR (cystic fibrosis transmembrane conductance regulator) in certain CF patients can rapidly reduce ASM abnormalities, suggesting they are an early consequence of CFTR dysfunction that may potentially drive disease progression.
Cystic fibrosis is a genetic disorder that primarily affects the lungs and is characterized by the chronic production of thickened mucus, causing frequent, persistent lung infections. It is estimated that cystic fibrosis affects 30,000 Americans and 70,000 people worldwide.
Disease progression in cystic fibrosis has been attributed to a variety of genetic mutations that disrupt the function of CFTR, a component that plays a critical role in the transport of fluids in the lungs. Additionally, airflow obstruction, caused by airway hyper-responsiveness of smooth muscle, is a common outcome of cystic fibrosis, but it remains unclear if this is a primary or secondary cause of the disease.
Cell culture and animal studies have suggested that loss of CFTR, which is present in the ASM, may increase smooth muscle abnormalities and promote cystic fibrosis.
By studying patients harboring the G551D-CFTR mutation, a common mutation in CFTR that results in cystic fibrosis, researchers aimed to uncover whether CFTR function impacts ASM and whether this is a primary or secondary outcome of cystic fibrosis.
Ivacaftor enhances the activity of CFTR and is a common drug used to treat CF. In this study, researchers promoted proper CFTR function in patients with the G551D-CFTR mutation by administering ivacaftor and subsequently assessed the effect on ASM physiology.
The researchers found that treatment of G551D-CFTR cystic fibrosis patients with ivacaftor rapidly improved their CFTR function and ASM physiology, as measured by airflow obstruction and vascular tone.
These results suggest that abnormalities in ASM are likely primary outcomes of cystic fibrosis and are directly caused by CFTR dysfunction. Additionally, treatment with ivacaftor may serve to reduce ASM abnormalities in such patients, alleviating some symptoms of disease.