A Randomized, Noninferiority Trial Comparing ICS + LABA with ICS + LABA + LAMA in Asthma-COPD Overlap (ACO) Treatment: The ACO Treatment with Optimal Medications (ATOMIC) Study.

BACKGROUND: Current guidelines for the treatment of asthma and chronic obstructive pulmonary disease overlap (ACO) recommend initial treatment using inhaled corticosteroids (ICSs) plus 1 or more bronchodilators. OBJECTIVE: To clarify which therapeutic effect is better between the ICS + long-acting ß2 agonist (LABA) and ICS + LABA + long-acting muscarinic antagonist (LAMA) treatment in patients with ACO. METHODS: We conducted a multicenter, 48-week, randomized, noninferiority trial. Patients with ACO were enrolled if they were treated with a moderate to high dose of ICS + LABA. In total, 303 patients were involved in the present trial, with 149 receiving ICS + LABA + LAMA. The primary end point was the time to first exacerbation. Secondary outcomes included changes in FEV1, forced vital capacity, FEV1/forced vital capacity ratio, asthma control, blood eosinophil count, and fractional exhaled nitric oxide. RESULTS: In the ICS + LABA treatment group, 29 of 154 patients (18.83%) experienced exacerbation, whereas 28 of 149 patients (18.79%) experienced exacerbation in the ICS + LABA + LAMA treatment group. The results of this noninferiority study were ultimately inconclusive (hazard ratio, 1.1; 95% CI, 0.66-1.84). However, the patients treated with the addition of LAMA showed significant improvements in FEV1 and forced vital capacity (P < .001). Asthma control did not improve in either group. CONCLUSIONS: Although this study was unable to conclude that ICS + LABA treatment is not inferior to ICS + LABA + LAMA in terms of exacerbation, it is obvious that the ICS + LABA + LAMA treatment group had improved lung function in ACO.

Subcutaneous Immunotherapy for Allergic Asthma in a Single Center of Korea: Efficacy, Safety, and Clinical Response Predictors.

Allergen-specific immunotherapy is the only causal treatment for allergic diseases. However, the efficacy of immunotherapy may vary around the world due to differences in climate, the nature of aero-allergens and their distribution. The aim of this study was to describe the effects of subcutaneous immunotherapy (SCIT) in Korean adults with allergic asthma (AA). As a retrospective cohort study, we reviewed medical records for 627 patients with AA in Korea who were sensitized to house dust mite (HDM) and/or pollens and who underwent SCIT with aluminum hydroxide adsorbed allergen extract from 2000 to 2012. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Herein, 627 asthmatic patients achieved remission within a mean of 4.7 ± 0.2 years. The cumulative incidence rates of remission from AA were 86.9% upon treatment with SCIT. Baseline forced expiratory volume in the first second (FEV1) ≥ 80% (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.79-5.39; P < 0.001), and maintenance of immunotherapy for more than 3 years (HR, 1.82; 95% CI, 1.21-2.72; P = 0.004) were significant predictors of asthma remission during SCIT. In 284 patients on SCIT with HDM alone, initial specific immunoglobulin E (IgE) levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae did not show significant difference between remission and non-remission group after adjusting demographic variables. In conclusion, SCIT was effective and safe treatment modality for patients with AA. Initial FEV1 ≥ 80% and immunotherapy more than 3 years were found to be associated with favorable clinical responses to SCIT.

Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of ß-catenin.

BACKGROUND AND PURPOSE: Aberrant expression of ß-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of ß-catenin. METHODS: In vitro effects of EGCG on the transcription, translation, or degradation of ß-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and ß-catenin expression was checked in HNC patients' samples. RESULTS: ß-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of ß-catenin signaling. Knockdown of ß-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of ß-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of ß-catenin. The suppression of ß-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits ß-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation. CONCLUSION: This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs.

Protective effect of Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract against cisplatin-induced apoptosis of human HaCaT keratinocytes: Involvement of NF-kappa B- and Bcl-2-controlled mitochondrial signaling.

BACKGROUND: Oral mucositis is a common adverse effect of antineoplastic chemotherapy limiting sufficient dose of chemoregimen. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. HYPOTHESIS: We hypothesize that Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract (Aa-EE) would mitigate cisplatin-induced cytotoxicity to oral mucosal epithelial cells. STUDY DESIGN: In vitro experimental study. METHODS: Cell viability and wound healing assay were performed. Apoptosis, mitochondrial membrane potential (MMP) change, and changes in apoptosis-related signaling were demonstrated in human primary keratinocyte (HaCaT). RESULTS: Cisplatin inhibited HaCaT cell proliferation and migration. Aa-EE protected against these effects. Cisplatin treatment of HaCaT cells caused apoptosis and changes in MMP. Aa-EE inhibited cisplatin-induced apoptosis, and stabilized the cisplatin-induced loss of MMP. Western blots revealed that Aa-EE reduced the expression of cytochrome c and cleaved caspase-3 and inhibited nuclear translocation of nuclear factor-kappa B (NF-κB), compared with the levels observed after cisplatin treatment, whereas Bcl-2 expression was increased by Aa-EE. CONCLUSION: Collectively, our results suggest that Aa-EE protects HaCaT cells by inhibiting cisplatin-induced mitochondrial damage associated with Bcl-2 activity and by inhibiting nuclear translocation of NF-κB.

Paradoxical increase of IgE binding components during allergen-specific immunotherapy in pollinosis patients.

Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens.

Protective effects of Korean red ginseng on radiation-induced oral mucositis in a preclinical rat model.

Numerous studies' attempts to improve radiation-induced oral mucositis have not produced a qualified treatment yet. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in an in vivo rat model. After 20 Gy of irradiation, rats were divided randomly into the following 4 groups: control, KRG only, radiotherapy (RT) only, and RT + KRG group. The rats were monitored in terms of survival rate, activity, mucositis grade, oral intake, and body weight. The tongue, buccal mucosa, and submandibular gland (SMG) were harvested, and the weight of the SMG was analyzed. The samples then underwent hematoxylin and eosin, TUNEL, and immunohistochemical staining. Radiation-induced severe oral mucositis and SMG injury led to poor oral intake and delayed healing, resulting in the death of some rats. We found that survival rate, oral intake, and body weight increased. Moreover, rats treated with KRG showed less severe mucositis and decreased histologic changes of the oral mucosa and SMG. Furthermore, we showed that the protective effects of KRG were caused by inhibition of the apoptotic signal transduction pathway linked to caspase-3. In conclusion, KRG protects the oral mucosa and SMG from radiation-induced damage by inhibiting caspase-mediated apoptosis in rats.

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes.

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.

Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

Current status of Oriental medicine in treating Korean allergy patients.

PURPOSE: To evaluate the prevalence, compliance, pattern of use, and economic cost of OM in Korean allergy patients. METHODS: A total of 647 allergy patients were enrolled from 10 general hospitals, and were surveyed by the questionnaire. It consisted of 12 items and regarded the prescription rates, reasons for referring, their opinions for the efficacy of OM, and economic costs. RESULTS: A total of 259 (40.5%) patients had used OM, and 35.5% of these patients experienced two or more kinds of these practices. A patients' income or education level did not affect the prescription rates of OM. Of the patients that used OM, 34.6% of them were satisfied with the effect of OM treatment, and 40.9% of them were inclined to continue with their OM treatments. The most frequent reasons for choosing OM were the patient's belief that OM can predispose 'allergic constitution to normal' (30.2%), worries about the possible adverse reactions of the long-term administration of the proven drugs (20.2%), and the safety of OM (15.6%). However, 18.9% of these patients experienced perceived adverse events to their OM treatment such as skin rashes, gastrointestinal discomfort, and hepatitis. The patients that have used OM spent on average $915 US dollars annually for OM treatment. CONCLUSIONS: Many Korean allergy patients are cliental to OM. Some patients experienced a satisfactory treatment effect from OM, however, others had no treatment effect, even adverse event. Therefore, it is important to educate people to use OM appropriately to make harmony with modern medicine.

Optimal conditions for the removal of house dust mite, dog dander, and pollen allergens using mechanical laundry.

BACKGROUND: Mechanical laundry is an effective tool for the environmental control of allergens, but the optimal conditions for removing allergens are not yet clear. OBJECTIVE: To evaluate the optimal conditions of mechanical laundry for the removal of house dust mite (HDM), dog dander, and pollen allergens. METHODS: The 4 washing modes of 30 degrees C (86 degrees F), 40 degrees C (104 degrees F), 60 degrees C (140 degrees F), and steam water (SW) with detergent were evaluated. Allergen removal performance was assayed using a 2-site enzyme-linked immunosorbent assay (ELISA) or an ELISA inhibition test. RESULTS: Using the 30 degrees C and 40 degrees C washing modes, only 6.5% and 9.6% of Dermatophagoides farinae, respectively, were killed. However, using the 60 degrees C and SW washing modes, all HDMs were killed. The amounts of Der f 1 remaining after the 30 degrees C, 40 degrees C, 60 degrees C, and SW washing modes were 26.8%, 2.4%, 1.3%, and 0.6%, respectively, with unmanipulated contaminated sheets. The effects of rinse on Der f 1 levels after the 30 degrees C washing were greater compared with those after the 40 degrees C, 60 degrees C, and SW modes. The amounts of Can f 1 in the extractions after washing were 0.3% to 1.3% for all modes, and all extracts, even without a rinse, did not inhibit specific IgE binding to dog allergens according to ELISA. The remaining pollen allergen levels after washing were lower in the 60 degrees C and SW modes than in the lower temperature modes. However, the levels did not differ among the various washing modes after rinsing once. CONCLUSION: Water temperature and number of rinses are critical factors for the removal of HDM, dog dander, and pollen allergens.