COPD: Drug Can Partly Reverse Mucolciliary Dysfunction from Smoking

Researchers have shown that roflumilast can help lungs damaged by smoking work better. Matthias Salathe, MD, of the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, at the University of Miami Miller School of Medicine, and colleagues evaluated the effect of roflumilast on normal human bronchial epithelial cells (NHBE) that were exposed to cigarette smoke. The results of their investigation were included in a paper published in Respiratory Research.

One of the most important ways that the airways protect themselves from dust and other irritants is through the process of mucociliary clearance (MCC). There are two processes that are major factors in effective MCC, and both are regulated by cAMP. One is ciliary beat frequency (CBF) and the other is the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

Phosphodiesterases (PDEs) are enzymes that can make cAMP inactive, making MCC less effective. PDE inhibitors could be useful in treating patients with chronic obstructive pulmonary disease (COPD). Roflumilast, which is a PDE inhibitor, “has been approved in the United States and Europe to reduce the risk of COPD exacerbations in patients with sever COPD associated with chronic bronchitis and a history of exacerbations.”

The researchers set out to examine “the role of roflumilast on parameters of MCC in normal human bronchial epithelial (NHBE) cells.” They began by culturing NHBE cells from non-smokers, then exposed those cells to cigarette smoke with a “Vitrocell VC-10 smoking robot.” Several tests were performed to measure the effect of roflumilast on CBF and CFTR function in both cells that had and had not been exposed to smoke.

“Our results show that inhibition of PDE4 with roflumilast improves parameters of mucociliary clearance in NHBE cells,” the researchers state. The results provide some information “on basic non-inflammatory related mechanisms as to why roflumilast positively influences COPD in patients.” In fact, this study showed that “CBF increases more than 50% in smoke-exposed cells in the presence of roflumilast.”