Workman and Cohen (2014) examined 229 substances based on their effects on CBF. Among PDE4 inhibitors, roflumilast, roflumilast-N-oxide, and ibudilast increased CBF, whereas theophylline as a non-selective PDE inhibitor decreased it, probably due to antagonistic action on adenosine A2B receptors (Allen-Gipson et al., 2011). Furthermore, most of tested glucocorticosteroids and anticholinergics led to decrease of CBF, suggesting a benefit of co-administration of PDE4 inhibitors with these groups of drugs to prevent worsening of expectoration in COPD patients (Workman and Cohen, 2014). The gene discussed is PDE4A; the disease is chronic obstructive pulmonary disease.