The Montelukast Therapy in Asthmatic Children with and without Food Allergy: Does It Make Any Difference?

Introduction: Children with food allergy are at increased risk for asthma and asthma morbidity. Since leukotrienes are implicated in the pathogenesis of both asthma and probably in food allergies, we hypothesized that asthmatic children with concomitant food allergy may have a favorable response to antileukotriene treatment. Methods: Asthmatic children aged 6–18 years with and without food allergy were treated with montelukast and placebo in a double-blind, placebo-controlled cross-over parallel-group study. The primary outcome of the study was improvement in FEV1%. Asthma control tests, spirometry and methacholine challenges were performed as well as Fractional Exhaled Nitric Oxide (FeNO) levels. PGD2, CystLT, and lipoxin levels were measured in exhaled breath condensate (EBC). Results: A total of 113 children were enrolled and 87 completed the study in accordance with the protocol. At baseline, children with food allergy and asthma (FAA) had higher levels of PGD2 and CysLT levels in the EBC than children with asthma alone (AA) (p < 0.001 for each). In the montelukast arm, although FEV1% was significantly higher in the FAA group compared to AA (p = 0.005), this effect was linked to the baseline difference of FEV1% between both arms. Montelukast treatment failed to improve FEV1% in both groups compared to the placebo. No effect of montelukast was observed in the remaining study parameters. Conclusion: Although children with FAA do not show a more favorable response to montelukast treatment compared to AA, a significant difference between baseline PGD2 and CystLT levels between FAA and AA groups may point to a different endotype of childhood asthma.

Download Full-text

Exhaled 15-HETE and thromboxin-B2 are associated with the therapeutic outcome in childhood asthma

10.22541/au.161727578.88968481/v1 ◽

2021 ◽

Author(s):

Li-Chen Chen ◽

Hsu-Min Tseng ◽

Ming-Ling Kuo ◽

Chih-Yung Chiu ◽

Sui-Ling Liao ◽

...

Keyword(s):

Childhood Asthma ◽

Metabolic Pathways ◽

Operating Characteristic ◽

Exhaled Breath ◽

Asthmatic Children ◽

Therapeutic Outcomes ◽

Significant Difference ◽

Children With Asthma ◽

Severe Group ◽

Steroid Responsiveness

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). Analysis of asthmatics (N=75) during exacerbation and convalescence showed significant improvement in lung function (FEV1; p<0.001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p<0.001) and reduced levels of TXB2 (p<0.05) after therapy, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and LXA4 at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent after treatment.

Download Full-text

Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens

Frontiers in Immunology ◽

10.3389/fimmu.2018.02689 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 9

Author(s):

Sayantani Sindher ◽

Andrew J. Long ◽

Natasha Purington ◽

Madeleine Chollet ◽

Sara Slatkin ◽

...

Keyword(s):

Food Allergy ◽

Food Challenge ◽

Diagnostic Methods ◽

Population Characteristics ◽

Food Allergies ◽

Double Blind ◽

Data Set ◽

Prick Test ◽

Increased Risk ◽

Food Challenges

Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy.Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts.Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges.Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

Download Full-text

Correlation between vitamin D serum level and total IgE in asthmatic children

Archives of Public Health ◽

10.3889/aph.2020.4069 ◽

2020 ◽

Vol 12 (2) ◽

pp. 37-45

Author(s):

Vesna Micevska ◽

Tatjana Jakovska Mareti ◽

Ilija Kirovski ◽

Olivera Jordanova

Keyword(s):

Vitamin D ◽

Serum Level ◽

P Value ◽

Healthy Children ◽

Total Ige ◽

Asthmatic Children ◽

Significant Difference ◽

Children With Asthma ◽

The Mean ◽

Chronical Disease

Asthma is a chronical disease of the airways characterized by reversible obstruction of the bronchi and airway inflammation. In recent decades, the scientific interest of the vitamin D system and its role in development of asthma and other alergic diseases has been increased. Aims of this study are to mesure and compare the serum level of 25 OHD in asthmatic and healthy children and corelate the level of 25OHD and total IgE in asthmatic children. This prospective study includes 70 children at age 2 to 14, of which 32 are children with diagnosed asthma and 38 healthy children. In both of the groups the serum level of 25 OHD was measured and by the results 18 % of the healthy children (C) and 28% of the asthma children (E) had 25OHD deficiency, 45% of C and 50% of E were insufficient and 37 % of C / 22% of E were with normal 25 OHD serum level. The mean level of 25OHD in C was 27,83 +/- 10,24 and in E 20,9 ng/ml +/- 10,72. The mean levels in both groups had statistic significant difference with p-value < 0,05. According to age no statistic significant difference was found in both of the groups. There was a statisticaly significant decreased serum level of 25 OHD in asthmatic females.In the examined group (children with asthma) there was a negative linear correlation (association) of the level of 25OHD and total IgE serum level with r=- 0,55 Vitamin D serum level measurements in asthma patients gives the possibility for discovering the connection between its deficiency and development of asthma symptoms.

Download Full-text

Metabolites of L-ARG in Exhaled Breath Condensate and Serum Are Not Biomarkers of Bronchial Asthma in Children

Journal of Clinical Medicine ◽

10.3390/jcm11010252 ◽

2022 ◽

Vol 11 (1) ◽

pp. 252

Author(s):

Joanna Połomska ◽

Barbara Sozańska

Keyword(s):

Bronchial Asthma ◽

Pediatric Patients ◽

Exhaled Breath Condensate ◽

Mass Spectrometric ◽

Mass Spectrometric Analysis ◽

Spectrometric Analysis ◽

Exhaled Breath ◽

Asthmatic Children ◽

Healthy Control ◽

Breath Condensate

(1) Background: L-arginine (L-ARG) and its metabolites are involved in some aspects of asthma pathogenesis (airway inflammation, oxidative stress, bronchial responsiveness, collagen deposition). Published data indicate that lungs are a critical organ for the regulation of L-ARG metabolism and that alterations in L-ARG metabolism may be significant for asthma. The aim of this study was to assess the levels of L-ARG and its metabolites in pediatric patients with asthma in serum and exhaled breath condensate (EBC) by mass spectrometric analysis and compare them with non-asthmatic children. (2) Methods: Sixty-five children (37 pediatric patients with bronchial asthma and 28 healthy control subjects) aged 6–17 participated in the study. All participants underwent a clinical visit, lung tests, allergy tests with common aeroallergens, and serum and EBC collection. The levels of biomarkers were determined in both serum and EBC. Analytical chromatography was conducted using an Acquity UPLC system equipped with a cooled autosampler and an Acquity HSS T3 column. Mass spectrometric analysis was conducted using the Xevo G2 QTOF MS with electrospray ionization (ESI) in positive ion mode. (3) Results: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels in serum and EBC did not differ significantly in asthmatic children and healthy control subjects. We found no correlation between forced expiratory volume in one second (FEV1) and L-ARG and its metabolites, as well as between interleukin-4 (IL-4) serum level and L-ARG and its metabolites. Concentrations of ADMA, SDMA, citrulline (CIT), and ornithine (ORN) were higher in serum than EBC in asthmatics and non-asthmatics. By contrast, concentrations of dimethylarginine (DMA) were higher in EBC than serum. ADMA/L-ARG, SDMA/L-ARG, and DMA/L-ARG ratios were significantly higher in EBC than in serum in asthmatics and in non-asthmatics. (4) Conclusions: Serum and EBC concentrations of L-ARG and its metabolites were not an indicator of pediatric bronchial asthma in our study.

Download Full-text

A double-blind randomized placebo-controlled study of low dose mirtazapine once daily in patients of major depressive disorders on escitalopram

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20191602 ◽

2019 ◽

Vol 8 (5) ◽

pp. 1067

Author(s):

Mallikarjuna Rao I. ◽

Usha Kiran Prayaga ◽

Dharma Rao Uppada ◽

Ramachandra Rao E. ◽

B. L. Kudagi

Keyword(s):

Depressive Disorders ◽

Low Dose ◽

Rating Scale ◽

Controlled Study ◽

P Value ◽

Chi Square ◽

Double Blind ◽

Increased Risk ◽

Significant Difference ◽

Chi Square Test

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.

Download Full-text

Behavior Abnormalities and Poor School Performance Due to Oral Theophylline Use

PEDIATRICS ◽

10.1542/peds.78.6.1133 ◽

1986 ◽

Vol 78 (6) ◽

pp. 1133-1138 ◽

Cited By ~ 1

Author(s):

Gary S. Rachelefsky ◽

Julie Wo ◽

Judith Adelson ◽

M. Ray Mickey ◽

Sheldon L. Spector ◽

...

Keyword(s):

School Performance ◽

Serum Levels ◽

Treatment Modalities ◽

School Behavior ◽

Double Blind ◽

Asthmatic Children ◽

Oral Theophylline ◽

Standardized Report ◽

Children With Asthma ◽

And Behavior

Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 µg/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.

Download Full-text