Type-2 innate immune responses that occur in airways and are accompanied by goblet-cell hyperplasia and mucus production are largely driven by interleukin-33 (IL-33) and natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2s) and the major target of IL-33. Here we report that the corticosteroid resistance observed as a result of airway inflammation triggered by sensitization and exposure to allergen is induced via the IL-33/NHcell axis. Thymic stromal lymphopoietin (TSLP) synthesized during airway inflammation plays a pivotal role in the induction of NH-cell corticosteroid resistance in vitro and in vivo, by controlling phosphorylation of STAT5 and expression of Bcl-xL in NH cells. Blockade of TSLP with a neutralizing antibody or blocking the TSLP/STAT5 signalling pathway with low molecular-weight STAT5 inhibitors such as pimozide restores corticosteroid sensitivity. Thus, the TSLP-STAT5 pathway could be a new therapeutic target in severe, corticosteroid-resistant asthma.

Evidence of the long-term efficacy of digital therapies for smoking cessation that include a smartphone application (app) is limited. In this multi-center randomized controlled trial, we tested the efficacy of a novel digital therapy for smoking cessation: the "CureApp Smoking Cessation (CASC)" system, including a CASC smartphone app, a web-based patient management PC software for primary physicians, and a mobile exhaled carbon monoxide (CO) checker. A total of 584 participants with nicotine dependence were recruited from October 2017 to January 2018, and allocated 1:1 to the CASC intervention group or the control group. Both groups received a standard smoking cessation treatment with pharmacotherapy and counseling for 12 weeks. Meanwhile, the intervention group used the CASC system, and the control group used a control-app without a mobile CO checker, each for 24 weeks. The primary outcome was the biochemically validated continuous abstinence rate (CAR) from weeks 9 to 24. The main secondary outcome was an extended CAR from weeks 9 to 52. Except for 12 participants who did not download or use the apps, 285 participants were assigned to the intervention group, and 287, to the control. CAR from weeks 9 to 24 in the intervention group was significantly higher than that in the control group (63.9% vs. 50.5%; odds ratio [OR], 1.73; 95% confidence interval [CI], 1.24 to 2.42; P = 0.001). The CAR from weeks 9 to 52 was also higher in the intervention group than that in the control group (52.3% vs. 41.5%; OR, 1.55; 95% CI, 1.11 to 2.16; P = 0.010). No specific adverse events caused by the CASC system were reported. Augmenting standard face-to-face counseling and pharmacotherapy with a novel smartphone app, the CASC system significantly improved long-term CARs compared to standard treatment and a minimally supportive control app.

Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.

Background Mobile apps have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone app improves long-term abstinence rates in nicotine-dependent patients. Objective This study aimed to evaluate the long-term abstinence effect of a novel smartphone app, CureApp Smoking Cessation (CASC), in patients with nicotine dependence. Methods In this prospective, interventional, multicenter, single-arm study, we provided the CASC app to all the participants, who used it daily for 24 weeks. The CASC app includes features to maximize the therapeutic effect of pharmacological therapies and counseling at outpatient clinics for smoking cessation. The primary endpoint was a continuous abstinence rate (CAR) from weeks 9 to 24, whereas secondary endpoints were CARs from weeks 9 to 12 and 9 to 52. Results Of the 56 adult smokers recruited, 1 did not download the app; therefore, 55 participants constituted the full analysis sample. The CAR from weeks 9 to 24 was 64% (35/55, 95% CI 51%-76%), whereas the CARs from weeks 9 to 12 and 9 to 52 were 76% (42/55, 95% CI 65%-88%) and 58% (32/55, 95% CI 46%-71%), respectively. These CARs were better than the results of the national survey on outpatient clinics with regard to smoking cessation under the National Health Insurance Program and that of the varenicline phase 3 trial in Japan and the United States. There was only 1 participant who dropped out during the 12 weeks of the treatment period. This treatment decreased the scores related to withdrawal and craving symptoms. Conclusions The addition of CASC to usual smoking cessation therapies resulted in high CARs, high patient retention rates, and improvement of cessation-related symptoms. The smartphone app CASC is a feasible and useful tool to help long-term continuous abstinence that can be combined with a standard smoking cessation treatment program.

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