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PURPOSE: 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.

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The 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.

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PURPOSE:Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early onset atopic, obese non eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a longterm follow up period, but the exacerbation prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. METHODS:A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow up were compared among the clusters. RESULTS:Four sub phenotypes were identified: cluster 1 was comprised of patients with early onset atopic asthma with preserved lung function, cluster 2 late onset non atopic asthma with impaired lung function, cluster 3 early onset atopic asthma with severely impaired lung function, and cluster 4 late onset non atopic asthma with well preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation prone asthmatics, showing a higher risk of asthma exacerbation.CONCLUSIONS: Two different phenotypes of exacerbation prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

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Glycolysis 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.

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Despite 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.

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PURPOSE: 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.

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PURPOSE: Chinese herbal medicine (CHM) has been widely used in China to treat allergic rhinitis (AR). However, several studies have produced conflicting data with regard to the efficacy of the medicine. Our aim was to perform a meta-analysis of randomized clinical trials (RCTs) to evaluate the relative efficacy of CHM. METHODS: We systematically searched the PubMed, Medline, and Springer electronic databases up to March 2017 for RCTs comparing the efficacy of CHM versus placebo for the treatment of patients with AR. Total nasal symptoms and quality of life were assessed through pooling mean difference (MD) with its 95% confidence interval (CI). Moreover, sensitivity and subgroup analyses according to control design and quality of life assessment were performed to evaluate the source of heterogeneity. RESULTS: Eleven RCTs were enrolled in the meta-analysis. Assessment of overall heterogeneity indicated significant heterogeneity among the individual studies (I²=100%, P<0.00001), and thus ransomed effects model was used to pool data. CHM was found to significantly enhance quality of life compared with placebo (MD=-0.88, (95% CI: -1.55, -0.21); P=0.01). The symptom of itchy nose, sneezing or total nasal symptoms scores were not significantly improved after CHM treatment, although the improvement in itchy nose just failed to reach significance (MD=0.09, (95% CI: 0.00, 0.18); P=0.06). CONCLUSIONS: This study suggests that CHM appears to improve the quality of life of AR patients. However, these findings, as well as the findings for the effect of CHM on sneezing, total nasal symptoms, and the symptom of itchy nose, need to be substantiated in larger cohorts of AR patients by further well-designed studies.

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PURPOSE: 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.

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BACKGROUND: Black tiger shrimp Penaeus monodon is one of the common causes of shellfish allergy that is increasing worldwide. One of the important problems in the management of shellfish allergy is the lack of accurate diagnostic assay because the biological and immunological properties of allergens in black tiger shrimp have not been well characterized. This study aims to detect proteins with the ability to bind and cross-link immunoglobulin E (IgE) from black tiger shrimp by enzyme-linked immunosorbent assay (ELISA), Western blot, and a humanized rat basophilic leukemia reporter cell line RS-ATL8. METHODS: Sera from shrimp allergic subjects were subjected to ELISA and Western blots using raw or cooked shrimp extract as antigens. Pooled sera were used to sensitize the RS-ATL8 reporter cell line and cells were activated by shrimp extract. Eluted protein extracts separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were tested on the RS-ATL8 cell line and subjected to mass spectrometry to identify potential candidate allergens. RESULTS: Allergic sera reacted stronger to raw shrimp extract than cooked shrimp extract (P=0.009). Western blot demonstrated that major IgE reactivity protein bands were at 32-39 kDa and 91-230 kDa in both raw and cooked shrimp extracts. The eluted protein bands at the molecular weight of 38 and 115 kDa from raw shrimp extract induced IgE cross-linking as assayed by the RS-ATL8 cell line. These protein bands were subjected to mass spectrometry for analysis. Ubiquitin-activating enzyme and crustacyanin were identified as potential candidate novel shrimp allergens. CONCLUSIONS: The RS-ATL8 reporter cell line can be used to identify potential new shrimp allergens that can functionally cross-link IgE and induce mast cell degranulation.