Randomised, double-blind, placebo-controlled pilot trial of omeprazole in idiopathic pulmonary fibrosis.

BACKGROUND: Cough is a common, disabling symptom of idiopathic pulmonary fibrosis (IPF), which may be exacerbated by acid reflux. Inhibiting gastric acid secretion could potentially reduce cough. This study aimed to determine the feasibility of a larger, multicentre trial of omeprazole for cough in IPF, to assess safety and to quantify cough. METHODS: Single-centre, double-blind, randomised, placebo-controlled pilot trial of the proton pump inhibitor (PPI) omeprazole (20 mg twice daily for 3 months) in patients with IPF. Primary objectives were to assess feasibility and acceptability of trial procedures. The primary clinical outcome was cough frequency. RESULTS: Forty-five participants were randomised (23 to omeprazole, 22 to placebo), with 40 (20 in each group) having cough monitoring before and after treatment. 280 patients were screened to yield these numbers, with barriers to discontinuing antacids the single biggest reason for non-recruitment. Recruitment averaged 1.5 participants per month. Geometric mean cough frequency at the end of treatment, adjusted for baseline, was 39.1% lower (95% CI 66.0% lower to 9.3% higher) in the omeprazole group compared with placebo. Omeprazole was well tolerated and adverse event profiles were similar in both groups, although there was a small excess of lower respiratory tract infection and a small fall in forced expiratory volume and forced vital capacity associated with omeprazole. CONCLUSIONS: A large randomised controlled trial of PPIs for cough in IPF appears feasible and justified but should address barriers to randomisation and incorporate safety assessments in relation to respiratory infection and changes in lung function.

Optimized and accelerated 19 F-MRI of inhaled perfluoropropane to assess regional pulmonary ventilation.

PURPOSE: To accelerate 19 F-MR imaging of inhaled perfluoropropane using compressed sensing methods, and to optimize critical scan acquisition parameters for assessment of lung ventilation properties. METHODS: Simulations were performed to determine optimal acquisition parameters for maximal perfluoropropane signal-to-noise ratio (SNR) in human lungs for a spoiled gradient echo sequence. Optimized parameters were subsequently employed for 19 F-MRI of inhaled perfluoropropane in a cohort of 11 healthy participants using a 3.0 T scanner. The impact of 1.8×, 2.4×, and 3.0× undersampling ratios on 19 F-MRI acquisitions was evaluated, using both retrospective and prospective compressed sensing methods. RESULTS: 3D spoiled gradient echo 19 F-MR ventilation images were acquired at 1-cm isotropic resolution within a single breath hold. Mean SNR was 11.7 ± 4.1 for scans acquired within a single breath hold (duration = 18 s). Acquisition of 19 F-MRI scans at shorter scan durations (4.5 s) was also demonstrated as feasible. Application of both retrospective (n = 8) and prospective (n = 3) compressed sensing methods demonstrated that 1.8× acceleration had negligible impact on qualitative image appearance, with no statistically significant change in measured lung ventilated volume. Acceleration factors of 2.4× and 3.0× resulted in increasing differences between fully sampled and undersampled datasets. CONCLUSION: This study demonstrates methods for determining optimal acquisition parameters for 19 F-MRI of inhaled perfluoropropane and shows significant reduction in scan acquisition times (and thus participant breath hold duration) by use of compressed sensing.