A recent clinical study of the treatment of severe COPD patients with an inhaled PDE4 inhibitor (CHF6001) as an add-on to triple inhaled therapy (formoterol combined with a long-acting muscarinic antagonist and a corticoid) showed a reduction in the levels of expression of genes associated with the pathophysiology of COPD (e.g. TNF- α, CCL2,3,4,5 and CXCL9) (Govoni et al., 2020) and in the sputum concentrations of TNF-α, CCL2, CCL4 and CXCL8 but did not evidence a reduction in the neutrophil count (Singh et al., 2019). This evidence concerns the gene TNF and chronic obstructive pulmonary disease.