Research in context
Evidence before this study
Clinical trials in patients with chronic fibrosing interstitial lung diseases (ILDs) have led to the development of two antifibrotic agents, nintedanib and pirfenidone. These therapies have been shown to reduce the rate of decline in lung function and are now recommended in clinical practice guidelines for patients with idiopathic pulmonary fibrosis. The INCREASE study was a randomised clinical trial of patients with ILD and pulmonary hypertension that evaluated the safety and efficacy of inhaled treprostinil. The study met its primary endpoint of change in the peak 6-min walk distance at week 16. Pulmonary function testing was obtained as a safety parameter in this study. Somewhat unexpectedly, this study also showed that inhaled treprostinil was associated with improvements in forced vital capacity (FVC) over a 16-week period. We searched PubMed on June 9, 2021, using the search terms “treprostinil” and “lung function” for all articles published from database inception up to June 9, 2021, with no language restrictions. One retrospective study of 22 patients with interstitial lung disease and associated pulmonary hypertension treated with inhaled treprostinil assessed lung function. No significant changes were observed in percentage predicted FVC but this study was limited by its observational, uncontrolled design. The effects of inhaled treprostinil on lung function in this disease population have otherwise not been studied.
Added value of this study
In this post-hoc analysis of the INCREASE trial, inhaled treprostinil was associated with significant improvements in the percentage of predicted FVC at week 8 and week 16. Improvement in FVC was greatest among patients with idiopathic interstitial pneumonia, particularly those with idiopathic pulmonary fibrosis. These results suggest that inhaled treprostinil might have independent antifibrotic properties beyond traditional vasodilatory effects. Whether this will be substantiated in a study of patients with interstitial lung disease, with or without pulmonary hypertension, remains to be determined.
Implications of all the available evidence
The present study serves as proof of concept that inhaled treprostinil can have a beneficial effect on the loss of lung function in patients with ILDs and associated pulmonary hypertension. These findings were most pronounced in patients with idiopathic pulmonary fibrosis. Further studies are needed to investigate the clinical benefits of inhaled treprostinil in this patient population, with or without associated pulmonary hypertension, and to explore potential mechanisms of action.