RT Journal Article
SR Electronic
T1 Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis
JF European Respiratory Review
JO EUROPEAN RESPIRATORY REVIEW
FD European Respiratory Society
SP 220206
DO 10.1183/16000617.0206-2022
VO 32
IS 167
A1 Kolb, Martin
A1 Crestani, Bruno
A1 Maher, Toby M.
YR 2023
UL http://err.ersjournals.com/content/32/167/220206.abstract
AB Patients with interstitial lung disease can develop a progressive fibrosing phenotype characterised by an irreversible, progressive decline in lung function despite treatment. Current therapies slow, but do not reverse or stop, disease progression and are associated with side-effects that can cause treatment delay or discontinuation. Most crucially, mortality remains high. There is an unmet need for more efficacious and better-tolerated and -targeted treatments for pulmonary fibrosis. Pan-phosphodiesterase 4 (PDE4) inhibitors have been investigated in respiratory conditions. However, the use of oral inhibitors can be complicated due to class-related systemic adverse events, including diarrhoea and headaches. The PDE4B subtype, which has an important role in inflammation and fibrosis, has been identified in the lungs. Preferentially targeting PDE4B has the potential to drive anti-inflammatory and antifibrotic effects via a subsequent increase in cAMP, but with improved tolerability. Phase I and II trials of a novel PDE4B inhibitor in patients with idiopathic pulmonary fibrosis have shown promising results, stabilising pulmonary function measured by change in forced vital capacity from baseline, while maintaining an acceptable safety profile. Further research into the efficacy and safety of PDE4B inhibitors in larger patient populations and for a longer treatment period is needed.Preferential inhibition of phosphodiesterase 4 (PDE4) B in patients with pulmonary fibrosis could provide anti-inflammatory and antifibrotic effects with improved safety compared with pan-PDE4 inhibitors. https://bit.ly/3UE0CdU