Search

Yoshihisa Ishiura, Shosaku Nomura, Yuka Ishii, Kai Imai, Yusuke Sawai, Takeshi Tamaki, Toshiki Shimizu, Naoyuki Miyashita, Tomoki Ito First Department of Internal Medicine, Kansai Medical University, Osaka, JapanCorrespondence: Yoshihisa Ishiura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan, Tel +81-6-6992-1001, Fax +81-6-6993-9837, Email ishiuray@takii.kmu.ac.jpAbstract: Cough, a frequent symptom encountered in clinical practice, often has a considerable impact on patients’ lives. There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, particularly atopic cough, which is a major cause of chronic refractory cough in Japan. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity to sensory nerve C-fibers is the pathophysiology of atopic cough. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. A 64-year-old female non-smoker presented to our hospital with a complaint of chronic intractable cough due to atopic cough. Addition of gefapixant (90 mg/day) to her previous treatment improved her distressing cough, despite the partial efficacy of many other drugs. The findings of this case demonstrate that P2X3 inhibition is a viable therapeutic option for patients with chronic refractory cough caused by atopic cough. This case report offers valuable information regarding currently available treatment options for refractory chronic refractory cough caused by atopic cough. There remains an urgent need to clarify the disease entities presenting with chronic cough that can be effectively treated by inhibiting P2X3.Plain Language Summary: There is an urgent need to investigate more potent antitussive treatments for chronic refractory cough, because cough has a considerable impact on patients’ lives. Previous studies have shown that eosinophilic tracheobronchitis with hypersensitivity of sensory nerve C-fibers is the pathophysiology of atopic cough, which is a major cause of chronic cough in Japan. Gefapixant is a first-in-class P2X3 antagonist that has recently become available for clinical use in patients with refractory coughs. Herein, we present the case of a 64-year-old female with a refractory atopic cough. The gefapixant add-on improved her distressing cough, indicating that P2X3 inhibition could be a viable therapeutic option for patients with chronic refractory cough caused by atopic cough.Keywords: chronic cough, atopic cough, gefapixant, P2X3

Yoshihisa Ishiura,1 Masaki Fujimura,2 Noriyuki Ohkura,3 Johsuke Hara,3 Kahori Nakahama,1 Yusuke Sawai,1 Takeshi Tamaki,1 Ryuta Murai,1 Toshiki Shimizu,1 Naoyuki Miyashita,1 Shosaku Nomura1 1First Department of Internal Medicine, Kansai Medical University, Osaka, Japan; 2Respiratory Medicine, National Hospital Organization Nanao Hospital, Nanao, Japan; 3Respiratory Medicine, Kanazawa University Hospital, Kanazawa, JapanCorrespondence: Yoshihisa Ishiura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan, Tel +81-6-6992-1001, Fax +81-6-6993-9837, Email ishiura-@p2322.nsk.ne.jp; ishiuray@takii.kmu.ac.jpPurpose: The ‘treatable traits’ strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting β2 agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a ‘treatable traits’ approach suitable for ACO remains obscure.Methods: A 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 μg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 μg/day compared with FP/FM 500/20 μg/day alone. A 4-week run-in period and two 4-week treatment periods were included.Results: A total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV1) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV1 values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01).Conclusion: TIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a “treatable traits” option for standard treatment for ACO.Keywords: treatable trait, asthma-COPD overlap, tiotropium, fluticasone, formoterol, triple therapy

Rolling friction is of great importance for many applications, such as tires and conveyor belts. We study the rolling friction for hard cylinders rolling on flat rubber sheets. The rolling friction depends on the number of rolling cycles, the rolling speed, and the temperature. We show that when the rubber is cooled down below the glass transition temperature, the deformations of the rubber surface are frozen-in, resulting in a non-flat rolling track where uphill and downhill rolling movements strongly affect the rolling force. The experimental data are analyzed using the Persson rolling friction theory; good agreement with the experiments is obtained when the non-linear (strain-softening) properties of the viscoelastic modulus are taken into account. [ABSTRACT FROM AUTHOR]

We study the friction when rectangular blocks made from rubber, polyethylene, and silica glass are sliding on ice surfaces at different temperatures ranging from −40 to 0 °C, and sliding speeds ranging from 3 μm/s to 1 cm s−1. We consider a winter tire rubber compound both in the form of a compact block and as a foam with ∼ 10 % void volume. We find that both rubber compounds exhibit a similar friction on ice for all studied temperatures. As in a previous study at low temperatures and low sliding speeds, we propose that an important contribution to the friction force is due to slip between the ice surface and ice fragments attached to the rubber surface. At temperatures around 0 °C (or for high enough sliding speeds), a thin pre-melted water film will occur at the rubber–ice interface, and the contribution to the friction from shearing the area of real contact is small. In this case, the dominant contribution to the friction force is due to viscoelastic deformations of the rubber by the ice asperities. The sliding friction for polyethylene (PE) and silica glass (SG) blocks on ice differs strongly from that of rubber. The friction coefficient for PE is ∼ 0.04 − 0.15 and is relatively weakly velocity dependent except close to the ice melting temperature where the friction coefficient increases toward low sliding speeds. Silica glass exhibits a similarly low friction as PE for T > −10 °C but very large friction coefficients (of order unity) at low temperatures. For both PE and SG, unless the ice track is very smooth, the friction force depends on the position x along the sliding track. This is due to bumps on the ice surface, which are sheared off by the elastically stiff PE and SG blocks, resulting in a plowing-type of contribution to the friction force. This results in friction coefficients, which locally can be very large ∼ 1 , and visual inspection of the ice surface after the sliding acts show ice wear particles (white powder) in regions where ice bumps occur. Similar effects can be expected for rubber blocks below the rubber glass transition temperature, and the rubber is in the (elastically stiff) glassy state. [ABSTRACT FROM AUTHOR]

There are two contributions to the friction force when a rubber block is sliding on a hard and rough substrate surface, namely, a contribution Fad = τfA from the area of real contact A and a viscoelastic contribution Fvisc from the pulsating forces exerted by the substrate asperities on the rubber block. Here we present experimental results obtained at different sliding speeds and temperatures, and we show that the temperature dependency of the shear stress τf, for temperatures above the rubber glass transition temperature Tg, is weaker than that of the bulk viscoelastic modulus. The physical origin of τf for T > Tg is discussed, and we propose that its temperature dependency is determined by the rubber molecule segment mobility at the sliding interface, which is higher than in the bulk because of increased free-volume effect due to the short-wavelength surface roughness. This is consistent with the often observed reduction in the glass transition temperature in nanometer-thick surface layers of glassy polymers. For temperatures T < Tg, the shear stress τf is nearly velocity independent and of similar magnitude as observed for glassy polymers such as PMMA or polyethylene. In this case, the rubber undergoes plastic deformations in the asperity contact regions and the contact area is determined by the rubber penetration hardness. For this case, we propose that the frictional shear stress is due to slip at the interface between the rubber and a transfer film adsorbed on the concrete surface. [ABSTRACT FROM AUTHOR]