In this study, we report a facile and effective production process of palladium nanoparticles supported on polypyrrole/reduced graphene oxide (rGO/Pd@PPy NPs). A novel electrochemical sensor was fabricated by incorporation of the prepared NPs onto glassy carbon electrode (GCE) for the simultaneous detection of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The electrodes modified with rGO/Pd@PPy NPs were well decorated on the GCE and exhibited superior catalytic activity and conductivity for the detection of these molecules with higher current and oxidation peak intensities. Simultaneous detection of these molecules was achieved due to the high selectivity and sensitivity of rGO/Pd@PPy NPs. For each biomolecule, well-separated voltammetric peaks were obtained at the modified electrode in cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements. Additionally, the detection of these molecules was performed in blood serum samples with satisfying results. The detection limits and calibration curves for AA, DA, and UA were found to be 4.9 × 10^-8, 5.6 × 10^-8, 4.7 × 10^-8 M (S/N = 3) and ranging from 1 × 10^-3 to 1.5 × 10^-2 M (in 0.1 M PBS, pH 3.0), respectively. Hereby, the fabricated rGO/Pd@PPy NPs can be used with high reproducibility, selectivity, and catalytic activity for the development of electrochemical applications for the simultaneous detection of these biomolecules.

Effects of some MPTP or MPP+ analogues on mouse body temperature were studied. Of the analogues tested, 4-phenylpyridine (PPY) and 4-phenyl-1,2,3,6-tetrahydropyridine (PTP) given in single i.p. doses to mice caused marked hypothermia. Intracerebroventricular (i.c.v.) injection of PPY or PTP caused similar hypothermia. Pretreatment with clorgyline or (-)-deprenyl greatly prevented hypothermia induced by i.c.v. PPY, but hypothermia by i.c.v. PTP was prevented only by (-)-deprenyl. These results indicate that, in order to cause central hypothermia, PTP does not seem to require metabolism to PPY and both analogues per se may cause hypothermia.

A photo-redox-catalyzed procedure for the one-step formation of sultones from α,ω-alkenols and trifluoromethylsulfonyl chloride is described. Using [Cu(dap)2]Cl (1 mol %), a wide range of substrates can be cleanly converted to the target compounds, while commonly employed photoelectron transfer catalysts such as [Ru(bpy)3]Cl2 or fac-Ir(ppy)3 fail in this transformation. The obtained fluorinated sultones are attractive as potential electrolyte additives or as structural motifs in drug synthesis, with the latter being demonstrated with the synthesis of a trifluoroethyl-substituted analogue of a benzoxathiin that has high anti-arrhythmic activity.

Single crystalline nanoneedles of polyaniline (PANI) and polypyrrole (PPY) were synthesized using an interfacial polymerization for the first time. The interfacial crystallization of conductive polymers at the liquid/liquid interface allowed PANI and PPY polymers to form single crystalline nanocrystals in a rice-like shape in the dimensions of 63 nm x 12 nm for PANI and 70 nm x 20 nm for PPY. Those crystalline nanoneedles displayed a fast conductance switching in the time scale of milliseconds. An important growth condition necessary to yield highly crystalline conductive polymers was the extended crystallization time at the liquid/liquid interfaces to increase the degree of crystallization. As compared to other interfacial polymerization methods, lower concentrations of monomer and oxidant solutions were employed to further extend the crystallization time. While other interfacial growth of conducting polymers yielded noncrystalline polymer fibers, our interfacial method produced single crystalline nanocrystals of conductive polymers. We recently reported the liquid/liquid interfacial synthesis of conducting PEDOT nanocrystals; however, this liquid/liquid interfacial method needs to be extended to other conductive polymer nanocrystal syntheses in order to demonstrate that our technique could be applied as the general fabrication procedure for the single crystalline conducting polymer growth. In this report, we showed that the liquid/liquid interfacial crystallization could yield PANI nanocrystals and PPY nanocrystals, other important conductive polymers, in addition to PEDOT nanocrystals. The resulting crystalline polymers have a fast conductance switching time between the insulating and conducting states on the order of milliseconds. This technique will be useful to synthesize conducting polymers via oxidative coupling processes in a single crystal state, which is extremely difficult to achieve by other synthetic methods.

Simple or even rapid bioanalytical methods are rare, since they generally involve complicated, time-consuming sample preparation from the biological matrices like LLE or SPE. SPME provides a promising approach to overcome these limitations. The full potential of this innovative technique for medical diagnostics, pharmacotherapy or biochemistry has not been tapped yet. In-house manufactured SPME probes with polypyrrole (PPy) coating were evaluated using three antibiotics of high clinical relevance - linezolid, daptomycin, and moxifloxacin - from PBS, plasma, and whole blood. The PPy coating was characterised by scanning electron microscopy. Influences of pH, inorganic salt, and blood anticoagulants were studied for optimum performance. Extraction yields were determined from stagnant media as well as re-circulating human blood using the heart-and-lung machine model system. The PPy-SPME fibres showed high extraction yields, particularly regarding linezolid. The reproducibility of the method was optimised to achieve RSDs of 9% or 17% and 7% for SPME from stagnant or re-circulating blood using fresh and re-used fibres, respectively. The PPy-SPME approach was demonstrated to meet the requirements of therapeutic monitoring of the drugs tested, even from re-circulating blood at physiological flow rates. SPME represents a rapid and simple dual-step procedure with potency to significantly reduce the effort and expenditure of complicated sample preparations in biomedical analysis.

Polypyrrole (PPy) nanotubes with different diameters were readily fabricated using cylindrical micelle templates in sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse microemulsions. Interestingly, Raman spectroscopy and ultraviolet (UV)-visible spectroscopy revealed that the PPy nanotubes with smaller diameters had a more extended conjugation length as well as a higher oxidation level. The PPy nanotubes were deposited onto a microelectrode array and were exposed to chemical vapor and electromagnetic radiation: typically, NH(3) vapor and UV light were chosen. The electrical response of PPy nanotubes to two different kinds of analytes was strongly dependent on their diameters. Moreover, since the small dimensions of PPy nanotubes facilitated the interaction between nanotubes and analytes, the PPy nanotube sensors showed conspicuously enhanced responses compared with conventional PPy.

High-performance theranostic nanoagents, which integrate multimodal imaging and photothermal therapy for clinical anticancer treatment, are highly desired. Herein, we report the synthesis and bioapplication of a multifunctional theranostic nanoagent based on polyethylene glycol (PEG)-modified polypyrrole (PPy)-coated bismuth (Bi) nanohybrids (referred to as Bi@PPy-PEG NHs) for X-ray computed tomography/photoacoustic (CT/PA) dual-modal imaging and photothermal therapy (PTT). The obtained Bi@PPy-PEG NHs have a distinct core-shell structure with the metallic Bi nanoparticle as the inner core and the PPy-PEG layer as the shell. The Bi@PPy-PEG NHs show excellent physiological stability and compatibility, without noticeable cytotoxicity. Importantly, the NHs exhibit strong NIR absorbance and remarkable photothermal conversion capability and conversion stability, with the photothermal conversion efficiency as high as ∼46.3%. Thanks to the strong PTT effect, highly effective photothermal ablation on cancer cells has been achieved both in vitro and in vivo. Furthermore, a high-contrast in vitro and in vivo CT/PA dual-modal imaging has been realized, showing great potential to provide comprehensive diagnosis information for antitumor treatment. In particular, the CT enhancement efficiency of the NHs is of ∼14.4 HU mM-1, which is ∼3.7-fold that of clinically used iohexol. Therefore, our work highlights the potential of using such core-shell Bi@PPy-PEG NHs as a versatile theranostic nanoplatform for cancer imaging and therapy.

With tunability and porosity, nanoscale metal-organic frameworks (nMOFs) can incorporate multiple components to realize complex functions for biomedical applications. Here we report the synthesis of W₁₈@Hf₁₂-DBB-Ir, a new nMOF assembly hierarchically incorporating three high-Z components-Hf-based metal-oxo clusters, Ir-based bridging ligands, and W-based polyoxometalates (POMs)-as a multifarious radioenhancer. Cationic Hf₁₂-DBB-Ir was built from Hf₁₂ secondary building units (SBUs) and [Ir(bpy)₂(ppy)]⁺ (bpy = 2,2'-bipyridine, ppy = 2-phenylpyridine) derived dicarboxylate ligands (DBB-Ir) and then loaded with Wells-Dawson-type [P₂W₁₈O₆₂]^6- (W₁₈) POMs to afford W₁₈@Hf₁₂-DBB-Ir. Upon X-ray irradiation, W₁₈@Hf₁₂-DBB-Ir significantly enhances hydroxyl radical generation from Hf₁₂ SBUs, singlet oxygen generation from DBB-Ir ligands, and superoxide generation from W₁₈ POMs, respectively. Through synergistic cell killing by these distinct reactive oxygen species, W₁₈@Hf₁₂-DBB-Ir elicited superb anticancer efficacy with >98% tumor regression at a low X-ray dose of 5 × 1 Gy.

Multidimensional FeOOH nanoneedle-decorated hybrid polypyrrole nanoparticles (PFFs) were fabricated using dual-nozzle electrospray and heat stirring process. To decorate metal oxide nanoneedles on the polypyrrole (PPy) surface, metal oxide particle-decorated PPys (E_PPy) were fabricated as starting materials. The E_PPy particles were prepared by dual-nozzle electrospray because ferric ions (Fe(3+)) dispersed on the surface reacted with hydroxide (OH(-)) ions in the collector solution without aggregation of each particles. Multidimensional hybrid PFFs with maximized surface area were then formed by heat stirring reaction in the aqueous metal precursor contained solutions. The decoration morphology of the metal oxide nanoneedles could be controlled by precursor concentration in the aqueous solution. These multidimensional hybrid PPFs were applied to nerve gas agent (DMMP) chemical sensor at room temperature with excellent sensitivity. The minimum detectable level (MDL) of PFFs was as low as 0.1 ppb, which is higher than that for a chemical sensor based on hybrid materials. This is because the metal oxide nanoneedles increase surface area and affinity to DMMP vapor.

A facilely prepared fluorescent sensor was developed for dopamine (DA) detection with high sensitivity and selectivity based on polypyrrole/graphene quantum dots (PPy/GQDs) core/shell hybrids. The composites exhibit strong fluorescence emission, which is dramatically enhanced as high as three times than pristine GQDs. The prepared sensor allows a highly sensitive determination of DA by fluorescent intensity decreasing with the addition of DA and presents a good linearity in range of 5-8000 nM with the detection limit of 10 pM (S/N = 3). Furthermore, the application of the proposed approach have been demonstrated in real samples and showed promise in diagnostic purposes.

A novel controlled drug delivery system in which drug release is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs has been developed. The valves are bilayer structures, made in shape of a flap hinged on one side to a valve seat, consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). Drugs (dry or wet) were pre-stored in an array of these reservoirs and their release is accomplished by bending the bilayer flaps away from the substrate with a small applied bias. In vitro color dye release experiment has been conducted. Seventy-five percent less energy consumption was achieved with this bilayer polymer valve design to open a same size reservoir compared to metal-corrosion based valves. Complex release patterns such as multiple drug pulsatile release and continuous linear release have been successfully implemented through flexible control of valve actuation sequence. These valves can be actuated under closed-loop-control of sensors responding to a specific biological or environmental stimulus, leading to potential applications in advanced responsive drug delivery systems.

Combining different therapeutic functions within single tumor-targeted nanoscale delivery systems is promising to overcome the limitations of conventional cancer therapies. Herein, transferrin that recognizes transferrin receptors up-regulated on tumor cells is pre-labeled with iodine-131 (131I) and then utilized as the stabilizer in the fabrication of polypyrrole (PPy) nanoparticles. The obtained transferrin-capped PPy@Tf-131I nanoparticles could be used for tumor-targeted radioisotope therapy (RIT) and photothermal therapy (PTT), by employing beta-emission from 131I and the intrinsic high near-infrared (NIR) absorbance of PPy, respectively. Owing to the transferrin-mediated tumor targeting, PPy@Tf-131I nanoparticles exhibit obviously enhanced in vitro cancer cell binding and in vivo tumor uptake compared to its non-targeting counterpart. The combined RIT and PTT based on PPy@Tf-131I nanoparticles is then conducted, achieving a remarkable synergistic therapeutic effect. This work thus demonstrates a rather simple one-step approach to fabricate tumor-targeting nanoparticles based on protein-capped conjugated polymers, promising for combination cancer therapy with great efficacy and high safety.

The influence of the composition and electropolymerization conditions upon the propulsion of new template-prepared polymer-based bilayer microtubular microbots is described. The effects of different electropolymerized outer layers, including polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT), polyaniline (PANI), and of various inner catalytic metal surfaces (Ag, Pt, Au, Ni-Pt alloy), upon the movement of such bilayer microtubes are evaluated and compared. Electropolymerization conditions, such as the monomer concentration and medium (e.g. surfactant, electrolyte), have a profound effect upon the morphology and locomotion of the resulting microtubes. The most efficient propulsion is observed using PEDOT/Pt microbots that offer a record-breaking speed of over 1400 body lengths s(-1) at physiological temperature, which is the fastest relative speed reported to date for all artificial micro/nanomotors. An inner Pt-Ni alloy surface is shown useful for combining magnetic control and catalytic fuel decomposition within one layer, thus greatly simplifying the preparation of magnetically-guided microbots. Polymer-based microbots with an inner gold layer offer efficient biocatalytic propulsion in low peroxide level in connection to an immobilized catalase enzyme. Metallic Au/Pt bilayer microbots can also be prepared electrochemically to offer high speed propulsion towards potential biomedical applications through functionalization of the outer gold surface. Such rational template preparation and systematic optimization of highly efficient microbots hold considerable promise for diverse practical applications.

Previously, we discovered a new compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), from Vitex rotundifolia L. and evaluated its anti-inflammatory and anti-asthmatic effects. In this study, we synthesized a new, modified compound 4-acetyl-3-methyl-6-(2-bromophenyl)pyrano[3,4-c]pyran-1,8-dione (PPY-Br) based on the PPY skeleton and evaluated its anti-inflammatory effects in lipopolysaccharide (LPS)-activated microglia. PPY-Br suppresses nitric oxide production, inducible nitric oxide synthase expression, and tumor necrosis factor-α and interleukin-6 production in LPS-activated BV-2 microglial cell line and mouse primary microglia. The effect of PPY-Br on the activation of nuclear factor (NF)-kappaB was examined to identify the mechanism involved. The LPS-induced translocation of NF-κB to the nucleus and phosphorylation of inhibitory-kappaB were almost completely blocked by PPY-Br. This study indicates that PPY-Br significantly attenuates the level of neurotoxic, proinflammatory mediators and proinflammatory cytokines via inhibition of the NF-κB signaling pathway. We suggest that PPY-Br presents a new candidate treatment for various neuro-inflammatory diseases.

This study examined how PPY, a peptide from Porphyra yezoensis, regulates multiple cell growth-related signaling pathways in MCF-7 cells. This study determined that PPY induces cell cycle arrest and inhibits the IGF-IR signaling pathway. Cell proliferation studies revealed that PPY induced cell death in a dose-dependent manner. Expression levels of IGF-IR were decreased in MCF-7 cells by PPY in a dose‑dependent manner. These results indicate that inhibition of the IGF-IR pathway is also involved in PPY induced proliferation of MCF-7 cells. In addition, these data demonstrated that PPY induces cell cycle arrest and activates apoptosis.

Monodispersed polypyrrole (PPy) nanospheres were physically incorporated as guest species into stacked graphene layers without significant property degradation, thereby facilitating the formation of unique three-dimensional hybrid nanoarchitecture. The electrochemical properties of the graphene/particulate PPy (GPPy) nanohybrids were dependent on the sizes and contents of the PPy nanospheres. The nanohybrids exhibited optimum electrochemical performance in terms of redox activity, charge-transfer resistance, and specific capacitance at an 8:1 PPy/graphite (graphene precursor) weight ratio. The packing density of the alternately stacked nanohybrid structure varied with the nanosphere content, indicating the potential for high volumetric capacitance. The nanohybrids also exhibited good long-term cycling stability because of a structural synergy effect. Finally, fabricated nanohybrid-based flexible all-solid state capacitor cells exhibited good electrochemical performance in an acidic electrolyte with a maximum energy density of 8.4 Wh kg(-1) or 1.9 Wh L(-1) at a maximum power density of 3.2 kW kg(-1) or 0.7 kW L(-1); these performances were based on the mass or packing density of the electrode materials.

Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species.

The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes.

Herein, we report a new method of generation of TiO(2) nanoparticles (NPs) incorporated thin films of polypyrrole (PPy) at the air-water interface. Aqueous TiO(2) NPs when treated with H(2)O(2) and left in a chamber of pyrrole vapor resulted in the formation of a film at the interface, in addition to bulk precipitate. Spectroscopic, X-ray diffraction, and electron microscopic measurements establish the formation of a thin film of PPy with the incorporation of TiO(2) NPs. The TiO(2)-containing PPy films when transferred onto glass substrates were able to photo catalyze the decomposition of aqueous organic dyes: methyl orange and methylene blue. Further, these films could also photo catalyze the oxidation of iodide to triiodide ions in aqueous potassium iodide solution. We find that the PPy-TiO(2) composite films catalyze the reactions in the presence of light more efficiently than a suspension of TiO(2) NPs.

Flexible membrane consisting of ultralong V2O5@conducting polypyrrole (V2O5@PPy) core-shell nanowires is prepared by a facile in situ interfacial synthesis approach. The V2O5 is for the first time demonstrated to show versatile function of reactive template to initiate the uniform and conformal polymerization of PPy nanocoating without the need for extra oxidants. The freestanding PPy-encapsulated V2O5 nanowire membrane is of great benefit in achieving strong electrochemical harvest by increasing electrical conductivity, shortening ion/electron transport distance, and enlarging electrode/electrolyte contact area. When evaluated as binder- and additive-free supercapacitor electrodes, the V2O5@PPy core-shell hybrid delivers a significantly enhanced specific capacitance of 334 F g-1 along with superior rate capability and improved cycling stability. The present work would provide a simple yet powerful interfacial strategy for elaborate constructing V2O5/conducting polymers toward various energy-storage technologies.

Highly aligned nanoarchitecture arrays directly grown on conducting substrates open up a new direction to accelerate Faradaic reactions for charge storage as well as address "dead volume" limitations for high-performance pseudocapacitor electrodes. Here we reported the electrochemical fabrication of well-ordered polypyrrole (PPy) nanowire arrays (NWAs) on surfaces of carbon fibers in an untreated carbon cloth to construct hierarchical structures constituted by the three-dimensional conductive carbon fiber skeleton and the atop well-ordered electroactive polymer nanowires. The morphologies, wetting behaviors, and charge-storage performances of the polymer were investigated by scanning electron microscopy, transmission electron microscopy, contact-angle measurement, cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy. The well-ordered PPy NWA electrode exhibited a high specific capacitance of 699 F/g at 1 A/g with excellent rate capability, and 92.4% and 81.5% of its capacitance could be retained at 10 and 20 A/g, respectively. An extremely high energy density of 164.07 Wh/kg could be achieved by the PPy NWAs at a power density of 0.65 kW/kg. It also displayed a quite high energy density of 133.79 Wh/kg at a high power density of 13 kW/kg. The assembled symmetric supercapacitor of PPy NWAs//PPy NWAs also exhibited excellent rate capability, and only 19% of its energy density decreased when the power density increased 20 times from 0.65 to 13 kW/kg.

A cyclometallated rhodium(III) complex [Rh(ppy)(2)(dppz)](+) (1) (where ppy=2-phenylpyridine and dppz=dipyrido[3,2-a:2',3'-c]phenazine dipyridophenazine) has been prepared and identified as an inhibitor of NEDD8-activating enzyme (NAE). The complex inhibited NAE activity in cell-free and cell-based assays, and suppressed the CRL-regulated substrate degradation and NF-κB activation in human cancer cells with potency comparable to known NAE inhibitor MLN4924. Molecular modeling analysis suggested that the overall binding mode of 1 within the binding pocket of the APPBP1/UBA3 heterodimer resembled that for MLN4924. Complex 1 is the first metal complex reported to suppress the NEDDylation pathway via inhibition of the NEDD8-activating enzyme.

A novel design and fabrication method of glucose sensors based on high aspect ratio carbon post-microarrays is reported in this paper. Apart from the fact that carbon has a wide electrochemical stability window, a major advantage of using carbon post-microarrays as working electrodes for an amperometric glucose sensor is the large reactive surface per unit footprint substrate area, improving sensitivity of the glucose sensor. The carbon post-microarrays were fabricated by carbon-microelectromechanical systems (C-MEMS) technology. Immobilization of enzyme onto the carbon post-electrodes was carried out through co-deposition of glucose oxidase (GOx) and electrochemically polymerized polypyrrole (PPy). Sensing performance of the glucose sensors with different post-heights and various post-densities was tested and compared. The carbon post-glucose sensors show a linear range from 0.5mM to 20mM and a response time of about 20s, which are comparable to the simulation result. Sensitivity per unit footprint substrate area as large as 2.02mA/(mMcm(2)) is achieved with the 140microm high (aspect ratio around 5:1) carbon post-samples, which is two times the sensitivity per unit footprint substrate area of the flat carbon films. This result is consistent with the hypothesis that the number of reaction sites scales with the reactive surface area of the sensor. Numerical simulation based on enzymatic reaction and glucose diffusion kinetics gives the optimum geometric design rules for the carbon post-glucose sensor. Glucose sensors with even higher sensitivity can be achieved utilizing higher carbon post-microarrays when technology evolution will permit it.

UNASSIGNED

There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time. Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.

UNASSIGNED

The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention. The evolution of the CAT was analyzed using linear regression. The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen-Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.

UNASSIGNED

The median CAT at inclusion was 17 (interquartile range 13-22) points. During the study, 25% of patients had a significant negative slope (median -7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy). The median slope of the CAT in the overall cohort was +1 (interquartile range -3 to +6) ppy. A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03-1.13; p<0.001). There was an 8% increase of the risk of exacerbation per unit increase in CAT. We detected a significant learning effect in filling out the CAT in 18.4% of patients with a median learning phase of five filled questionnaires.

UNASSIGNED

Sixty-three percent of the COPD patients monitored by THC experienced a stable or improved CAT during 1-year follow-up. We found a significant positive association between the evolution of the CAT over time and the risk of exacerbations. In about one-fifth of patients, there was a significant learning effect in filling out the CAT, before reliable results could be obtained. The evolution of the CAT could help to assess the risk for future exacerbations.