Role of phosphodiesterase-4 inhibitors in chronic obstructive pulmonary disease

Abstract

Phosphodiesterase-4 inhibitors (PDE4Is) are potent anti-inf lammatory agents and roflumilast has been used to prevent acute exacerbation of chronic obstructive pulmonary disease (COPD). Roflumilast decreases neutrophil migration, restores cystic fibrosis transmembrane conductance regulator activity, and recovers glucocorticoid effects. A forced expiratory volume in 1 second of < 50%, a chronic bronchitis phenotype, high blood eosinophil levels, and a history of hospitalization are biomarkers for predicting responses to roflumilast. Adverse effects are common in clinical practice. An inhaled PDE4I has recently been developed and is under clinical trial. CHF6001 and RPL554 exhibit promise and may be future treatment options for COPD.

The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications

“…Roflumilast is a phosphodiesterase 4 inhibitor (PDE4i) used as add-on therapy to suppress inflammation for a subgroup of patients with severe COPD and persistent symptoms or exacerbations, despite optimal management [ 57 ]. Roflumilast reduces the number of neutrophils and eosinophils in induced sputum of patients with COPD [ 58 ]. Also, the levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein, and α2-macroglobulin are significantly reduced with roflumilast [ 59 ].…”

“…However, most enzymes have several substrates, and inhibitors may block the other substrates too. It is encouraging that the available PDE4 inhibitors also lower POP activity and generally appear to be well tolerated; some of them have been tested in humans and one (roflumilast) is included in the guidelines for the anti-inflammatory treatment of COPD [ 58 , 77 ].…”

New putative insights into Neprilysin (NEP)-dependent pharmacotherapeutic role of Roflumilast in treating COVID-19

“…Thus, for improving patient tolerability, a study in the allergen-challenged Brown Norway rats, has been performed to evaluate the efficacy of inhaled roflumilast given either intratracheally or by nasal inhalation. As concluded, the inhaled form showed a powerful effect on improving the lung function (Chapman et al, 2007), supporting the therapeutic importance of using inhaled PDE4i against inflammatory lung diseases, which may be then more efficacious and less adverse effects than its oral forms, however it is still under clinical trial (Rhee and Kim, 2020).…”

New putative insights into neprilysin (NEP)-dependent pharmacotherapeutic role of roflumilast in treating COVID-19

“…Thus, for improving patient tolerability, a study in the allergen-challenged Brown Norway rats, has been performed to evaluate the efficacy of inhaled roflumilast given either intratracheally or by nasal inhalation. As concluded, the inhaled form showed a powerful effect on improving the lung function ( Chapman et al, 2007 ), supporting the therapeutic importance of using inhaled PDE4i against inflammatory lung diseases, which may be then more efficacious with fewer adverse effects than its oral forms, however it is still under clinical trial ( Rhee and Kim, 2020 ).…”