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Dave Singh,1 Leonardo M Fabbri,2,3 Stefano Vezzoli,4 Stefano Petruzzelli,4 Alberto Papi2 1Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 2Section of Cardiorespiratory and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 3COPD Center, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; 4Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy Background: Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations. Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed. We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies. Methods: The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE). All studies recruited patients with symptomatic COPD, FEV1

Dave Singh,1 Stefano Vezzoli,2 Stefano Petruzzelli,2 Alberto Papi3 1Medicines Evaluation Unit, University of Manchester, Manchester, UK; 2Chiesi Farmaceutici SpA, Parma, 3Section of Respiratory Diseases, University of Ferrara, Ferrara, Italy Abstract: The GOLD 2017 strategy document recommends that the pharmacological management of COPD patients be based on the risk of future exacerbations and the severity of symptoms. A threshold of two moderate exacerbations or one hospitalization is used to define high-risk patients. The FORWARD study was a randomized, double-blind, parallel-group trial that compared 48 weeks’ treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP-FF) versus FF in severe COPD patients with a history of one or more exacerbations in the previous year. The new GOLD 2017 recommendations mean that many patients in the FORWARD study are now reclassified as GOLD B. We conducted a post hoc analysis of the FORWARD study, in order to investigate the effects of extrafine BDP/FF in patients with one exacerbation in the previous year, focusing on those categorized as group B using the GOLD 2017 definition. The analysis showed a 35% reduction in exacerbation rate with an inhaled corticosteroid (ICS) + long-acting β-agonist (LABA) versus LABA. We propose that ICS-LABA treatment is a therapeutic option for COPD patients with one exacerbation in the previous year. Keywords: COPD, GOLD B, GOLD 2017, exacerbations, corticosteroid

Dave Singh,1 Mario Scuri,2 Sara Collarini,2 Stefano Vezzoli,2 Fabrizia Mariotti,2 Annamaria Muraro,2 Daniela Acerbi2 1Medicines Evaluation, University Of Manchester, University Hospital of South Manchester, Manchester, UK; 2Global Clinical Development, Chiesi Farmaceutici SpA, Parma, Italy Abstract: An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium bromide (GB) is in development for chronic obstructive pulmonary disease (COPD), in combination with beclometasone dipropionate and formoterol fumarate – a “fixed triple”. This two-part study was randomized, double blind, placebo controlled in patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5, 25, 50, 100 or 200 µg versus placebo; Part 2: repeat-dose (7-day), four-period crossover, GB 12.5, 25 or 50 µg twice daily (BID) versus placebo, with an open-label extension in which all patients received tiotropium 18 µg once daily. On the morning of Day 8 in all five periods, patients also received formoterol 12 µg. In study Part 1, 27 patients were recruited. All GB doses significantly increased from baseline forced expiratory volume in 1 second (FEV1) area under the curve (AUC0–12h) and peak FEV1, with a trend toward greater efficacy with higher GB dose. All adverse events were mild–moderate in severity, with a lower incidence with GB than placebo and no evidence of a dose–response relationship. In study Part 2, of 38 patients recruited, 34 completed the study. Adjusted mean differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and 136 mL for GB 12.5, 25 and 50 µg BID, respectively (all P

The photon statistics of CdSe/CdS dot-in-rods nanocrystals is studied with a method involving postselection of the photon detection events based on the photoluminescence count rate. We show that flickering between two states needs to be taken into account to interpret the single-photon emission properties. With postselection we are able to identify two emitting states: the exciton and the charged exciton (trion), characterized by different lifetimes and different second-order correlation functions. Measurements of the second-order autocorrelation function at zero delay with postselection shows a degradation of the single-photon emission for CdSe/CdS dot-in-rods in a charged state that we explain by deriving the neutral and charged biexciton quantum yields. [ABSTRACT FROM AUTHOR]

Quantum field theory predicts that a spatially homogeneous but temporally varying medium will excite photon pairs out of the vacuum state. However, this important theoretical prediction lacks experimental verification due to the difficulty in attaining the required nonadiabatic and large amplitude changes in the medium. Recent work has shown that in epsilon-near-zero (ENZ) materials it is possible to optically induce changes of the refractive index of the order of unity, in femtosecond time scales. By studying the quantum field theory of a spatially homogeneous, time-varying ENZ medium, we theoretically predict photon-pair production that is up to several orders of magnitude larger than in non-ENZ time-varying materials. We also find that while in standard materials the emission spectrum depends on the time scale of the perturbation, in ENZ materials the emission is always peaked at the ENZ wavelength. These studies pave the way to technologically feasible observation of photon-pair emission from a time-varying background with implications for quantum field theories beyond condensed matter systems and with potential applications as a new source of entangled light. [ABSTRACT FROM AUTHOR]

Time-varying metasurfaces are emerging as a powerful instrument for the dynamical control of the electromagnetic properties of a propagating wave. Here we demonstrate an efficient time-varying metasurface based on plasmonic nano-antennas strongly coupled to an epsilon-near-zero (ENZ) deeply subwavelength film. The plasmonic resonance of the metal resonators strongly interacts with the optical ENZ modes, providing a Rabi level spitting of ∼30%. Optical pumping at frequency ω induces a nonlinear polarization oscillating at 2ω responsible for an efficient generation of a phase conjugate and a negative refracted beam with a conversion efficiency that is more than 4 orders of magnitude greater compared to the bare ENZ film. The introduction of a strongly coupled plasmonic system therefore provides a simple and effective route towards the implementation of ENZ physics at the nanoscale. [ABSTRACT FROM AUTHOR]