Asthma diagnosis and treatment - 1012. The efficacy of budesonide in the treatmetn of acute asthma in children: a double-blind, randomized, controlled trial.

Background Current evidence suggests that inhaled glucocorticoids (IGC) have a more profound topical none genomic effect on bronchial airways as compared to systemic glucocorticoids. The value of adding IGC to current therapy of acute asthma is not well established. Methods We conducted a double-blind, randomized, two-arm, parallel groups, controlled clinical trial to compare the addition of budesonide 1500 mcg or placebo (normal saline) to standard acute asthma treatment (albuterol and ipratropium bromide) administered in 3 divided mixed doses within 1 hour in the emergency department (ED). Children 2-12 years of age with moderate or severe acute asthma, scoring 8-15/15 on a well-validated scoring system were included. Both groups received a single dose of prednisone 2 mg/kg/day (max. 60 mg) at the beginning of therapy. The primary outcome was admission rate within 2-4 hours from starting therapy. Results A total of 723 children were enrolled in the study over 17 months duration, of whom 139 were allowed to re-enroll and be randomized to constitute 906 randomization assignments (458 on the treatment group and 448 on the control group); with baseline mean + SD asthma score of 10.63 + 1.73; age 5.52 + 2.76 years; 35% girls; 30.8% (16.5%) with baseline severe asthma score of ≥12 (≥ 13). Statistical Analysis plan allowed for the potential dependency in response due to reenrollments of a subset of children, using Generalized Linear Mixed Modeling (GLMM) techniques. Baseline demographic and clinical characteristics were not significantly different between the two randomized groups. Seventy-five out of 458 (16.4%) of the treatment group vs. 82/448 (18.3%) of the control group were admitted, (OR 0.85, CI: 0.59-1.23, p-value=0.39). Among the severe asthmatics with baseline score ≥13, treatment vs. placebo group, GLMM adjusted admission rate was 30% vs. 47%, indicating a 17% difference in admission rate in favor of the treatment group (adjusted OR of 0.49, CI: 0.25-0.95; p-value= 0.035) that indicated a 51% reduction in the risk of admission for the treatment vs. control group. Conclusions Children with baseline severe asthma score ≥13 who were treated with budesonide had a significant reduction in their admission rate

A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression

<p>Abstract</p> <p>Background</p> <p>"Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation.</p> <p>Methods</p> <p>OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation <it>in vitro</it>. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone.</p> <p>Results</p> <p>PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT) by anacardic acid attenuated dexamethasone-induced PTEN expression.</p> <p>Conclusions</p> <p>Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The <it>in vitro </it>studies also suggest that the PTEN pathway may be involved in human asthma.</p

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

BACKGROUND AND OBJECTIVES: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. METHODS AND PRINCIPAL FINDINGS: We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. SIGNIFICANCE: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity

The effect of sand storms on acute asthma in Riyadh, Saudi Arabia.

OBJECTIVE: Major sand storms are frequent in the Middle East. This study aims to investigate the role of air particulate matter (PM) level in acute asthma in children in Riyadh, Saudi Arabia. METHODS: An aerosol spectrometer was used to evaluate PM < 10μm in diameter (PM10) and PM < 2.5 μm in diameter (PM2.5) concentrations in the air every 30 minutes throughout February and March 2012 in Riyadh. Data on children 2-12 years of age presenting to the emergency department of a major children's hospital with acute asthma during the same period were collected including their acute asthma severity score. RESULTS: The median with interquartile range (IQR) levels of PM10 and PM2.5 were 454 μg/m3 (309,864) and 108 μg/m3 (72,192) respectively. There was no correlation between the average daily PM10 levels and the average number of children presenting with acute asthma per day (r = -0.14, P = 0.45), their daily asthma score (r = 0.014, P = 0.94), or admission rate ( r= -0.08, P = 0.65). This was also true for average daily PM2.5 levels. In addition, there was no difference in these variables between days with PM10 >1000 μg/m3, representing major sand storms, plus the following 5 days and other days with PM10< 1000 μg/m3. CONCLUSION: Sand storms, even major ones, had no significant impact on acute asthma exacerbations in children in Riyadh, Saudi Arabia. The very high levels of PM, however, deserve further studying especially of their long-term effects

Budesonide nebulization added to systemic prednisolone in the treatment of acute asthma in children: a double-blind, randomized, controlled trial.

Background Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. Methods A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. Results A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P = .38). However, among cases with high baseline clinical score (≥ 13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P = .03). Conclusions The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma

Anaphylaxis in atypical cold urticaria: case report and review of literature

Abstract Background Cold-induced urticaria is a kind of physical urticaria characterized by the appearance of wheals after exposure to cold. The atypical form is a rare sub-type characterized by appearance of hives even in areas not directly exposed to the cold and by a negative cold stimulation test. Its diagnosis is often challenging because of the lack of specific tests and it is usually based on the patient’s clinical history. Hypotension due to generalized exposure to the cold is described both in the typical and the atypical forms. Case presentation We describe a 9-year-old boy who, at the beginning of the summer after the first swim in the sea, developed generalized urticaria, dyspnea, conjunctival hyperemia, blurred vision and loss of strength. The child was treated with intramuscular steroid and intravenous antihistamine, and the symptoms quickly resolved. Insect bite, contact with fish and drug ingestion were denied, and no unusual food had been eaten before the swim. A tentative diagnosis was made of either aquagenic urticaria or cold urticaria, but the specific tests were negative. Although the cause was unknown, prophylactic treatment with antihistamines was prescribed but in spite of this, wheals developed all over the body, after every swim in the sea. The child then came to our attention and relying on clinical history a diagnosis of atypical cold urticaria was made: development of hives even in areas not directly exposed to cold and a negative response to the cold stimulation test, are the characteristic features of this rare form of cold urticaria. Conclusion Atypical cold urticaria should be suspected in all cases of anaphylaxis related to cold exposure (i.e. contact with water) with a negative cold stimulation test