The need for inhaled phosphodiesterase inhibitors in chronic obstructive pulmonary disease.

Introduction: The therapeutic implications of phosphodiesterase (PDE) inhibitors have attracted interest because PDEs are regarded as an intracellular target to be exploited for therapeutic advancements in the treatment of COPD. At present, the only approved approach for the treatment of COPD with PDE inhibitors is the use of an oral PDE4 inhibitor. However, this treatment is not widely employed, primarily due to the narrow therapeutic index associated with oral PDE4 inhibitors, which significantly limits the tolerable dose. The inhalation route represents a viable alternative to the oral route for improving the therapeutic index of PDE4 inhibitors.

Areas covered: The development of inhaled PDE4 inhibitors, with a focus on tanimilast and ensifentrine, the latter of which is a dual PDE3/PDE4 inhibitor.

Expert opinion: The inhalation route offers several advantages regarding the delivery of PDE inhibitors for the management of COPD. Tanimilast and ensifentrine have been shown to improve lung function, reduce exacerbations and enhance quality of life in COPD patients. However, it has not yet been determined which type of COPD patient might benefit more from inhaled PDE4 inhibitors, and it remains unclear whether concomitant inhibition of PDE3 and PDE4 confers a significant benefit compared to blocking PDE4 alone in COPD.