Randomized, Double-Blind, Placebo-Controlled Trial of Vitamin D Supplementation in the Build-up Phase of House Dust Mite-Specific Immunotherapy.

PURPOSE: Vitamin D (VitD) is an immunomodulatory molecule capable of alleviating allergic symptoms. However, the effectiveness of allergen-specific immunotherapy (AIT) is not commonly evidenced in the early build-up phase. The aim of the study was to determine the potential of VitD supplementation in this treatment phase. METHODS: Thirty-four house dust mite (HDM)-allergic adult patients treated with subcutaneous AIT were randomized to receive VitD2 60,000 IU/week or placebo for 10 weeks and followed up for 10 weeks. The primary endpoints were the symptom-medication score (SMS) and the treatment response rate. The secondary endpoints were eosinophil count and levels of plasma IL-10, Der p 2-specific IgG4, and dysfunctional regulatory T (CRTH2+ Treg) cells. RESULTS: Of 34 patients, 15 in each group completed the study. Patients with VitD deficiency receiving a VitD supplement showed significantly lower mean change SMS than the placebo group in weeks 10 (mean difference -54.54%, P = 0.007) and 20 (mean difference -42.69%, P = 0.04). The percentage of treatment responders reached 78% and 50% in the VitD and placebo groups, respectively, and the effect remained in week 20 (89% and 60%). No significant difference was observed for the tested immunological read-outs, with the exception of the frequency of CRTH2+ Treg cells, which was remarkably reduced in the VitD-treated patients. Moreover, improvement in SMS was correlated to the number of CRTH2+ Treg cells. Our in vitro experiment indicated that VitD downregulated activation markers, whereas it improved the function of CRTH2+ Treg cells. CONCLUSIONS: VitD supplementation in the build-up phase of AIT could relieve symptoms and decrease Treg cell dysfunction, especially in patients with VitD deficiency.

Successful treatment of atopic dermatitis with house dust mite sublingual immunotherapy tablets.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Allergen-specific immunotherapy is a treatment option for selected patients with severe AD sensitization to house dust mites (HDM). OBJECTIVE: To report the first case of successful treatment with HDM sublingual immunotherapy (SLIT) tablets in patients with severe AD. METHODS: A Thai male patient with HDM sensitization and severe AD who had not responded to topical corticosteroids and calcineurin inhibitors underwent 1 month of HDM subcutaneous immunotherapy (SCIT), after which his skin symptoms were minimally improved. He lost follow-up SCIT and the symptoms worsened, with large wheal lesions appearing at the SCIT injection site, so we decided to switch from SCIT to HDM SLIT tablets. RESULTS: After the SLIT treatment, the AD and skin lesions improved and the medication could be stopped. CONCLUSIONS: HDM SLIT might be an alternative treatment in patients with HDM sensitization and severe AD who are refractory to conventional treatment.

Features and outcomes of immunoglobulin therapy in patients with Good syndrome at Thailand's largest tertiary referral hospital.

BACKGROUND: Good syndrome (GS) is an adult-onset immunodeficiency characterized by coexisting thymoma and hypogammaglobulinemia. Clinical course after treatment with intravenous immunoglobulin (IVIg) has rarely been reported. OBJECTIVE: To investigate and report the clinical course and outcomes of GS patients after treatment with IVIg at Thailand's largest national tertiary referral hospital METHODS: This retrospective chart review included patients diagnosed with GS and treated with IVIg during the 1 January 2005 to 31 December 2015 study period. RESULTS: Nine GS patients with a median age at diagnosis of 53 years were included. Pneumonia and sepsis were the most common clinical manifestations. Six infectious organisms suggestive of cell-mediated immunity defect occurred in six patients, including cytomegalovirus (CMV), Mycobacterium tuberculosis, Mycobacterium abscessus, Herpes simplex virus (HSV), Pneumocystis jirovecii, and Aspergillus. Mean serum IgG level was 317 mg/dL. Eight patients had very low to undetectable B-cells. Five patients had either low CD4 number or impaired T-cell function, and one patient had both. All patients received IVIg replacement therapy monthly at a dose of 0.4 g/kg. The mean trough IgG level was 881 mg/dL. After treatment with IVIg replacement, seven patients had favorable clinical outcomes. However, two patients expired due to septicemia. CONCLUSION: Clinical outcomes of patients with GS are more dependent on the severity of infections and associated hematologic and autoimmune diseases than on the severity of thymoma itself. Therefore, early recognition and prompt IVIg replacement may change the natural course of this condition and may be successful in keeping the patient infections free.

Der p 1-specific regulatory T-cell response during house dust mite allergen immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells. METHODS: We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30 weeks, and 3 years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramer-positive cells and correlated with nasal symptom score. RESULTS: Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3+ Helios+ CD25+ CD127- Treg cells after 30 weeks was observed, which slightly decreased after 3 years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3)+ CD25+ Treg cells decreased substantially from baseline after 3 years of AIT. ILT3+ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30 weeks, but only IL-10+ Der p 1-specific Treg cells remained present at high frequency after 3 years of AIT. Increased number of FOXP3+ Helios+ and IL-10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms. CONCLUSION: The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.

Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy.

BACKGROUND: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. OBJECTIVE: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. METHODS: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG1- and IgG4-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. RESULTS: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 ± 0.28 to 2.45 ± 0.24 (P = .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 ± 1.3 to 2.7 ± 0.5 mm (P = .001). IgG4+ and IgA+ Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG4+ but not the IgA+ fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4+ B cells, plasmablasts, and IL-10+ and dual-positive IL-10+IL-1RA+ Breg cells significantly correlated with improved clinical symptoms over the course of AIT. CONCLUSION: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG4-expressing Der p 1-specific B cells, plasmablasts, and IL-10+ and/or IL-1RA+ Breg cells.

Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy.

PURPOSE: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. METHODS: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). RESULTS: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)⁺ and NCR⁻ in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. CONCLUSIONS: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Serum Vitamin D Levels and Vitamin D Supplement in Adult Patients with Asthma Exacerbation.

Introduction. Vitamin D deficiency has been linked to an increased risk of asthma exacerbations. Objective. This study aimed to compare vitamin D status during the period of severe asthma exacerbations and investigate if vitamin D supplementation improves asthma control. Methods. A total of 47 asthmatic patients and 40 healthy subjects participated in this study. Serum 25-hydroxyvitamin D (25(OH)D), asthma control test (ACT) score, and % predicted peak expiratory flow rate were evaluated in the period with and without severe asthma exacerbations. After that, we provided vitamin D2 supplements to the patients with low vitamin D levels for 3 months. Results. At the period of asthma exacerbation, the prevalence of vitamin D deficiency and insufficiency was 38.29% and 34.04%. There was no significant difference in the levels of serum 25(OH)D with and without asthma exacerbations but the levels were significantly higher in the healthy group. Serum 25(OH)D levels significantly correlated with ACT score. Moreover, vitamin D2 supplementation improved asthma control in uncontrolled asthma group. Conclusions. Hypovitaminosis D was common in asthmatic patients but was not the leading cause of asthma exacerbations. Serum 25(OH)D levels correlated with the ability to control asthma. Improving vitamin D status might be a benefit in uncontrolled asthmatic patients.

The effectiveness of oxymetazoline plus intranasal steroid in the treatment of chronic rhinitis: A randomised controlled trial.

BACKGROUND: The recommended drug for moderate to severe chronic rhinitis is intranasal steroids (INS). However, nasal congestion could be refractory and need additional treatments. OBJECTIVE: We sought to explore the benefit of oxymetazoline (Oxymet) plus INS on nasal congestion without inducing rhinitis medicamentosa. METHODS: We performed a 60-week, randomised, double-blind clinical trial in 50 patients, 18 years of age or greater, with chronic rhinitis who had used INS and cetirizine and still had nasal congestion. Subjects were randomised to receive 2 sprays of 0.05% Oxymet in each nostril twice daily or placebo for 4 weeks. All patients received 2 sprays of budesonide (100 µg/spray) in each nostril twice daily and 10 mg cetirizine once daily from entry throughout the study. Nasal symptom scores, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life (Rcq) scores were measured. RESULTS: Oxymet significantly reduced nasal congestion in subjects with chronic rhinitis compared with placebo on the day of 15-28 and 29-42. In subjects with allergic rhinitis, nasal congestion scores in the Oxymet group were significantly reduced compared with those in the placebo group on days 4-7, days 8-14, days 15-28 and days 29-42. In the Oxymet group, post hoc analysis showed that subjects with allergic rhinitis significantly improved their nasal congestion scores compared to non-allergic individuals (N, allergic/non-allergic = 18/7, p < 0.05). The combination of INS and Oxymet was not associated with rhinitis medicamentosa. CONCLUSIONS: The combination of INS and Oxymet provides additional benefit compared to INS monotherapy in relieving nasal congestion in subjects with chronic rhinitis and allergic rhinitis without developing rhinitis medicamentosa.

Vitamin D supplements improve urticaria symptoms and quality of life in chronic spontaneous urticaria patients: A prospective case-control study.

Vitamin D plays an important role in the immune system; decreased serum vitamin D concentrations have been linked to dysregulated immune function. Low vitamin D status is probably associated with chronic spontaneous urticaria (CSU). We evaluated the prevalence of low vitamin D status, and the clinical response and quality of life following vitamin D supplementation, in a prospective case-control study with 60 CSU patients and 40 healthy individuals. Serum 25-hydroxy vitamin D (25(OH)D) concentrations were measured at baseline and after 6 weeks. For patients with 25(OH)D concentrations < 30 ng/ml, treatment included 20,000 IU/day of ergocalciferol (vitamin D2) and non-sedative antihistamine drugs for 6 weeks. Urticaria symptom severity and quality of life were assessed based on the Urticaria Activity Score over 7 days (UAS7) and the Dermatology Life Quality Index (DLQI). Of the 100 participants, 73% were female; the mean age was 39 ± 16 years. Vitamin D deficiency (measured as 25(OH)D < 20 ng/ml) was significantly higher in the CSU group than the control group. The median 25(OH)D concentration for the CSU group, 15 (7 - 52) ng/ml was significantly lower than for control group, 30 (25 - 46) ng/ml. Overall, 83% (50/60) of CSU patients (25(OH)D < 30 ng/ml) were treated with ergocalciferol (vitamin D2) supplementation; after 6 weeks, these patients showed significant improvements in UAS7 and DLQI scores compared with the non-vitamin D supplement group. This study revealed a significant association of lower serum 25(OH)D concentrations with CSU. Vitamin D supplements might improve symptoms and quality of life in CSU patients.

Vitamin d supplements improve urticaria symptoms and quality of life in chronic spontaneous urticaria patients: a prospective case-control study.

Vitamin D plays an important role in the immune system; decreased serum vitamin D concentrations have been linked to dysregulated immune function. Low vitamin D status is probably associated with chronic spontaneous urticaria (CSU). We evaluated the prevalence of low vitamin D status, and the clinical response and quality of life following vitamin D supplementation, in a prospective case-control study with 60 CSU patients and 40 healthy individuals. Serum 25-hydroxy vitamin D (25(OH)D) concentrations were measured at baseline and after 6 weeks. For patients with 25(OH)D concentrations < 30 ng/ml, treatment included 20,000 IU/day of ergocalciferol (vitamin D2) and non-sedative antihistamine drugs for 6 weeks. Urticaria symptom severity and quality of life were assessed based on the Urticaria Activity Score over 7 days (UAS7) and the Dermatology Life Quality Index (DLQI). Of the 100 participants, 73% were female; the mean age was 39 ± 16 years. Vitamin D deficiency (measured as 25(OH)D < 20 ng/ml) was significantly higher in the CSU group than the control group. The median 25(OH)D concentration for the CSU group, 15 (7 - 52) ng/ml was significantly lower than for control group, 30 (25 - 46) ng/ml. Overall, 83% (50/60) of CSU patients (25(OH)D < 30 ng/ml) were treated with ergocalciferol (vitamin D2) supplementation; after 6 weeks, these patients showed significant improvements in UAS7 and DLQI scores compared with the non-vitamin D supplement group. This study revealed a significant association of lower serum 25(OH)D concentrations with CSU. Vitamin D supplements might improve symptoms and quality of life in CSU patients.

Adverse reactions to iodinated contrast media: prevalence, risk factors and outcome-the results of a 3-year period.

BACKGROUND: Iodinated contrast media (CM) are commonly used. Hypersensitivity reactions to CM occasionally result in morbidity. Risk factors and the role of premedication remain to be investigated. OBJECTIVE: We sought to explore the prevalence, risk factors and outcome of CM reactions. METHODS: The retrospective case-control study was conducted between 2008 and 2010. In total, 55,286 subjects who were exposed to iodinated CM were enrolled to determine the prevalence of CM reactions. The case-control statistical method was applied to determine the risk factors of CM reactions. 579 subjects who had CM reactions were categorised in the case group and 1,175 of the 55,286 subjects who had tolerated CM exposure were randomised for the control group. RESULTS: The overall prevalence of CM reactions was 1.05%. In a multivariate analysis, the history of previous CM reactions, female gender and the history of seafood allergy were significant risk factors for CM reactions. The significant risk factors for the first episode of CM reactions were female gender, the history of seafood allergy and asthma. We found sixteen serious reactions in the immediate reaction group: ten fully recovered after hospitalisation, five fully recovered after out-patient treatment and one died after the administration of CM via an intra-arterial route during coronary angiogram. The most significant risk factor associated with serious reactions was asthma, whereas comorbid cardiovascular disease, male gender, history of seafood allergy and history of previous CM reactions were significant risk factors for mild reactions. CONCLUSIONS: The prevalence of CM adverse reactions was as low as 1.05%. Risk factors consist of a history of previous CM reactions, female gender and seafood allergy. Nevertheless, serious immediate reactions could occur particularly in patients with asthma.

How we teach military medicine to medical cadets at Phramongkutklao College of Medicine.

Phramongkutklao College of Medicine has a unique curriculum for "Military Medicine." Military Medicine involves prevention, threat assessment, evacuations and clinical management of diseases and injuries resulting from military occupational exposures. The Military Medicine curriculum covers all the entities of knowledge of Military Sciences, Combat Medical Skills, Military Preventive Medicine, Military Applied Physiology and Military Contingency Medicine. The highlight of the curriculum is "Operation Petcharavut" that represents simulated battlefield operations, involving multidisciplinary clinical integration and military regulation. In this course, medical cadets review all the knowledge that they have learnt and in addition, Medical Platoon leader strategies, Advanced Cardiac Life support and Phramongkutklao Traumatic Life support, crucial medical practices. Medical cadets would experience simulated patients with minimal injuries to critical wounds and complications including combat stress syndromes in various situations, from advancing to retreating units and from Battalion Aid Station to Division Medical Operations Center, whether during day or night. Since the medical cadets experience all Military Medicine courses from the second to the sixth year class and pass all medical knowledge-based examinations, Phramongkutklao College of Medicine expects all graduates to be excellent in not only all standard requirements of the medical professional set forth by the Medical Council of Thailand but also ready to serve the nation effectively in the Royal Thai Armed Forces.