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"AbstrakPURPOSE:Claudin-4 has been reported to function as a paracellular sodium barrier and is one of the 3 major claudins expressed in lung alveolar epithelial cells. However, the possible role of claudin-4 in bronchial asthma has not yet been fully studied. In this study, we aimed to elucidate the role of claudin-4 in the pathogenesis of bronchial asthma.METHODS:We determined claudin-4 levels in blood from asthmatic patients. Moreover, using mice sensitized and challenged with OVA, as well as sensitized and challenged with saline, we investigated whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1 induced the inflammatory cytokines in NHBE cells.RESULTS:We found that claudin-4 in blood from asthmatic patients was increased compared with that from healthy control subjects. Plasma claudin-4 levels were significantly higher in exacerbated patients than in control patients with bronchial asthma. The plasma claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant increases in transcripts and proteins of claudin-4 as well as in TJ breaks and the densities of claudin-4 staining. When claudin-4 was knocked down by transfecting its siRNA, inflammatory cytokine expressions, which were induced by Der p1 treatment, were significantly increased.CONCLUSIONS:These findings thus raise the possibility that regulation of lung epithelial barrier proteins may constitute a therapeutic approach for asthma."

"AbstrakGlycolysis is a process that rapidly converts glucose to lactate to produce adenosine triphosphate (ATP) under anaerobic conditions and occurs in all eukaryotic and prokaryotic cells. On the other hand, the hexosamine biosynthetic pathway (HBP) converts glucose to intermediate products like UDP-N-acetylglucosamine, which is critical for post-translational modifications of proteins, such as protein glycosylation. These 2 pathways are well known to contribute to glucose metabolism, but recent studies indicate modulation of these pathways can alter immune system function. In this review article, the authors present results suggesting how cellular metabolism, including glycolysis and the HBP, occurs in immune cells, and the immunologic significances of such activities. In addition, they provide a review of the literature on the effects of glycolysis and the HBP on various autoimmune, immunologic, and allergic diseases. Finally, the authors briefly introduce the results of their research on the immunologic effects of HBP supplementation (glucosamine) in animal models of allergic disease."

"AbstrakDespite asthma being the most common chronic childhood ailment, there is still much to learn about the disease. Early childhood infections with well-known or emerging viruses can lay the pathophysiologic framework for asthma development and exacerbation later in life, which may be due partly to alteration of the airway microbiome. Once asthma is established, acute exacerbations are usually associated with infections with respiratory viruses, such as rhinoviruses (RVs). Once again, there are bidirectional interactions between viruses and airway bacteria that appear to influence the severity of illness and the likelihood of exacerbation. Studies employing recent advances in viral and bacterial identification analytic techniques will clarify these new concepts and may provide the basis for new treatments or prevention or respiratory infection-associated exacerbation. This paper is a review of the associations among respiratory viruses, bacteria, inflammatory mechanisms, and asthma exacerbation."

"AbstrakEosinophilic inflammation in combination with immunoglobulin E (IgE) production is a characteristic feature of atopic dermatitis. Although activated T-helper type (Th) 2 cells play critical roles in the local accumulation and activation of eosinophils, whether they induce eosinophilic skin inflammation, independent of the IgE-mediated pathway has been unclear. To address the functional role of T cells in allergic skin diseases, we herein transferred Th1/Th2-differentiated or naive DO11.10 T cells into unprimed BALB/c mice. Ovalbumin-specific Th2 cells, as well as eosinophils, accumulated in the skin upon antigen challenge, despite the absence of antigen-specific IgE. Neither antigen-specific Th1 nor naive T cells induced eosinophil accumulation, although Th1 cells by themselves migrated into the skin. Interleukin (IL)-4, IL-5, and eotaxin were specifically produced in the skin of antigen-challenged, Th2 cell-transferred mice, whereas interferon (IFN)-γ and regulated on activation, normal T cell expressed and secreted (RANTES) were preferentially produced in Th1 cells-transferred mice. Production of monocyte chemoattractant protein (MCP)-1 and MCP-3 was enhanced by both Th1 and Th2 cells. The accumulation of eosinophils and Th2 cells in the skin was suppressed by both dexamethasone and FK506, indicating an essential role of Th2 cells in eosinophil recruitment. We conclude that Th2 cells can induce eosinophilic infiltration into the skin in the absence of antigen-specific IgE."

"AbstrakPURPOSE:House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM.METHODS:We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. 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. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes.RESULTS:The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed.CONCLUSIONS:SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients."

"ABSTRACTThe treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁receptor blockers are typically employed up to 4 times a day. Firstgeneration antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine refractory patients. H₂receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%-70% of patients; however, care is needed regarding possible side effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3 to 10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine."

"AbstrakPURPOSE:Cold weather exercise is common in many regions of the world; however, it is unclear whether respiratory function and symptom worsen progressively with colder air temperatures. Furthermore, it is unclear whether high-ventilation sport background exacerbates dysfunction and symptoms.METHODS:Seventeen active females (measure of the maximum volume of oxygen [VO(2max)]: 49.6±6.6 mL·kg⁻¹·min⁻¹) completed on different days in random order 5 blinded running trials at 0°C, -5°C, -10°C, -15°C, and -20°C (humidity 40%) in an environmental chamber. Distance, heart rate, and rating of perceived exertion (RPE) were measured within each trial; forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%-75% (FEF₂₅₋₇₅), and forced expiratory flow at 50% (FEF₅₀) were measured pre- and post-test (3, 6, 10, 15, and 20 minutes). Respiratory symptoms and global effort were measured post-test spirometry.RESULTS:Mean decreases were found in FEV1 (4%-5% at 0°C, -5°C, -10°C, and -15°C; 7% at -20°C). FEF₂₅₋₇₅ and FEF₅₀ decreased 7% and 11% at -15°C and -20°C, respectively. Post-exertion spirometry results were decreased most at 3 to 6 minutes, recovering back to baseline at 20 minutes. Respiratory symptoms and global effort significantly increased at -15°C and -20°C with decreased heart rate. High-ventilation sports decreased function more than low-ventilation participants but had fewer symptoms.CONCLUSIONS:These results indicate that intense exercise at cold air temperatures up to -20°C is achievable; however, greater effort along with transient acute bronchoconstriction and symptoms of cough after exercising in temperatures colder than -15°C are likely. It is recommended that individuals cover their mouth and reduce exercise intensity to ameliorate the effects of cold weather exercise."

"AbstrakThe aim of this study was to examine the daily practice patterns of Symbicort Maintenance and Reliever Therapy (SMART) in Korean asthmatic patients and to analyze clinical signs related to overuse. This study used an observational, multicenter, noninterventional, prospective, uncontrolled design for examining asthmatic patients prescribed SMART to assess the frequency and pattern of Symbicort® usage as a maintenance and reliever medication. The characteristics of patients showing signs of overuse (frequency of inhalation: 8 or more times per day) were also analyzed. Among the 1,518 patients analyzed, 1,292 (85.1%) completed the trial. The number of mean inhalations per day was 2.14±1.15; the number of patients who had at least 1 as needed usage (PRN) inhalation per day was 843 (55.5%); the mean frequency of PRN use was 0.25±0.67 inhalations per day. The number of patients who overused for at least 1 day was 260 (17.1%). In particular, young patients, patients with limited physical activity, and patients with nocturnal symptoms demonstrated high frequency of overuse. The frequency of overuse during SMART was not high in Korean asthmatic patients and the asthma status of follow-up outpatients improved overall. However, there is a need for careful education targeted toward younger patients, patients with limited physical activity, and patients with nocturnal symptoms owing to their tendency to frequently overuse."

"AbstrakThe aim of this study was to examine the daily practice patterns of Symbicort Maintenance and Reliever Therapy (SMART) in Korean asthmatic patients and to analyze clinical signs related to overuse. This study used an observational, multicenter, noninterventional, prospective, uncontrolled design for examining asthmatic patients prescribed SMART to assess the frequency and pattern of Symbicort® usage as a maintenance and reliever medication. The characteristics of patients showing signs of overuse (frequency of inhalation: 8 or more times per day) were also analyzed. Among the 1,518 patients analyzed, 1,292 (85.1%) completed the trial. The number of mean inhalations per day was 2.14±1.15; the number of patients who had at least 1 as needed usage (PRN) inhalation per day was 843 (55.5%); the mean frequency of PRN use was 0.25±0.67 inhalations per day. The number of patients who overused for at least 1 day was 260 (17.1%). In particular, young patients, patients with limited physical activity, and patients with nocturnal symptoms demonstrated high frequency of overuse. The frequency of overuse during SMART was not high in Korean asthmatic patients and the asthma status of follow-up outpatients improved overall. However, there is a need for careful education targeted toward younger patients, patients with limited physical activity, and patients with nocturnal symptoms owing to their tendency to frequently overuse."