The association of PAH with increased mortality in IPF patients has raised the possibility that therapy directed against PAH may be of benefit in IPF patients. The endothelin signaling pathway and nitric oxide/cyclic guanosine monophosphate pathways are both important in the development of PAH. Sildenafil is an oral agent that preferentially blocks phosphodiesterase-5 in well-ventilated areas of the lung.13When compared to therapy with inhaled nitric oxide and IV prostacyclin, sildenafil was found to preferentially lower pulmonary vascular resistance and improve gas exchange in a mixed group of patients with severe pulmonary fibrosis.14In this issue of CHEST (see page 897), Collard et al15 report the findings of an open-label, 3-month study of sildenafil in patients with IPF and PAH. Fourteen patients were followed up, and 11 patients completed serial 6-min walk studies. There was an overall improvement in the walk distance of 49.0 m (90% confidence interval, 17.5 to 84.0). The authors arbitrarily defined a ≥ 20% improvement in their 6-min walk distance as being clinically significant; 57% of patients exceeded this threshold. These preliminary data provide an intriguing suggestion that the modulation of PAP in IPF patients may provide a functional benefit. They should, however, be interpreted with caution as the sample size was small, 3 of 14 patients were not able to provide data to assess the primary end point, and the treatment duration was short. Furthermore, the mean 49.0-m improvement seen in this study falls short of the widely accepted clinically significant 54.0-m improvement in 6-min walk distance, which is the shortest distance that correlates with subjective improvement in patients with COPD.16 These limitations, in addition to the lack of a control group, limit our ability to arrive at definitive conclusions about the role of sildenafil in the treatment of IPF complicated by PAH. Nevertheless, these authors provide preliminary data that can be used to design future, placebo-controlled studies examining the long-term effects of modulating PAH in IPF. In fact, further investigation of sildenafil in the treatment of PAH complicating IPF is ongoing with two phase 2 trials underway (NCT00352482 and NCT00359736 [www.clinicaltrials.gov]).