A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

HD 2685 b: A hot Jupiter orbiting an early F-type star detected by TESS

We report on the confirmation of a transiting giant planet around the relatively hot (Teff = 6801 ± 76 K) star HD 2685, whose transit signal was detected in Sector 1 data of NASA's TESS mission. We confirmed the planetary nature of the transit signal using Doppler velocimetric measurements with CHIRON, CORALIE, and FEROS, as well as using photometric data obtained with the Chilean-Hungarian Automated Telescope and the Las Cumbres Observatory. From the joint analysis of photometry and radial velocities, we derived the following parameters for HD 2685 b: P = 4.12688-0.00004+0.00005 days, e = 0.091-0.047+0.039, MP = 1.17 ± 0.12 MJ, and RP =1.44 ± 0.05 RJ. This system is a typical example of an inflated transiting hot Jupiter in a low-eccentricity orbit. Based on the apparent visual magnitude (V = 9.6 mag) of the host star, this is one of the brightest known stars hosting a transiting hot Jupiter, and it is a good example of the upcoming systems that will be detected by TESS during the two-year primary mission. This is also an excellent target for future ground- and space-based atmospheric characterization as well as a good candidate for measuring the projected spin-orbit misalignment angle through the Rossiter-McLaughlin effect

A universal power-law prescription for variability from synthetic images of black hole accretion flows

Instrumentatio

First sagittarius A* Event Horizon Telescope results. VI. Testing the black hole metric

Galaxie

Millimeter light curves of sagittarius A* observed during the 2017 Event Horizon Telescope campaign

Galaxie

First sagittarius A* Event Horizon Telescope results. IV. Variability, morphology, and black hole mass

Galaxie

First M87 Event Horizon Telescope results. IX.: detection of near-horizon circular polarization

Galaxie

Characterizing and mitigating intraday variability: reconstructing source structure in accreting black holes with mm-VLBI

Instrumentatio