PDE4A and airway hyperresponsiveness: Among various issues raised by the present observations, the finding that asthmatic HASM cells exhibit constitutively increased PDE activity was not unexpected, given recent independent evidence demonstrating intrinsically heightened PDE4 activity in cultured asthmatic vs. normal HASM cells [27], and that treatment of asthmatic individuals with the PDE4 inhibitor, roflumilast, decreases airway hyperresponsiveness following allergen challenge [19,21] and improves lung function [20].