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Association of RAGE gene multiple variants with the risk for COPD and asthma in northern Han Chinese.
Niu, H, Niu, W, Yu, T, Dong, F, Huang, K, Duan, R, Qumu, S, Lu, M, Li, Y, Yang, T, et al
Aging. 2019;(10):3220-3237
Abstract
Clinical and experimental data have shown that the receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of respiratory disorders. In this study, we genotyped five widely-evaluated variants in RAGE gene, aiming to assess their association with the risk for chronic obstructive pulmonary disease (COPD) and asthma in northern Han Chinese. Genotypes were determined in 105 COPD patients, 242 asthma patients and 527 controls. In single-locus analysis, there was significant difference in the genotype distributions of rs1800624 between COPD patients and controls (p=0.022), and the genotype and allele distributions of rs1800625 differed significantly (p=0.040 and 0.016) between asthma patients and controls. Haplotype analysis revealed that haplotype T-A-G-T (allele order: rs1800625, rs1800624, rs2070600, rs184003) was significantly associated with a reduced COPD risk (OR=0.32, 95% CI: 0.06-0.60), and haplotype T-A-A-G was significantly associated with a reduced asthma risk (OR=0.19, 95% CI: 0.04-0.96). Further haplotype-phenotype analysis showed that high- and low-density lipoprotein cholesterol and blood urea nitrogen were significant mediators for COPD (psim=0.041, 0.043 and 0.030, respectively), and total cholesterol was a significant mediator for asthma (psim=0.009). Taken together, our findings indicate that RAGE gene is a promising candidate for COPD and asthma, and importantly both disorders are genetically heterogeneous.
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Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial.
Jensen, ME, Ducharme, FM, Alos, N, Mailhot, G, Mâsse, B, White, JH, Sadatsafavi, M, Khamessan, A, Tse, SM, Alizadehfar, R, et al
BMJ open. 2019;(12):e033075
Abstract
INTRODUCTION Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D3 supplementation on exacerbations requiring OCS, in preschoolers with recurrent URTI-induced asthma exacerbations. METHODS AND ANALYSIS This is a phase III, randomised, triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D3 supplementation in children aged 1-5 years, with asthma triggered by URTIs and a recent history of frequent URTIs and OCS use. Children (n=865) will be recruited in the fall and early winter and followed for 7 months. They will be randomised to either the (1) intervention: two oral boluses of 100 000 international unit (IU) vitamin D3 (3.5 months apart) with 400 IU vitamin D3 daily; or (2) control: identical placebo boluses with daily placebo. The primary outcome is the number of exacerbations requiring OCS per child, documented by medical and pharmacy records. Secondary outcomes include number of laboratory-confirmed viral URTIs, exacerbation duration and severity, parent functional status, healthcare use, treatment deintensification, cost and safety. ETHICS AND DISSEMINATION This study has received ethical approval from all sites. Results will be disseminated via international conferences and manuscripts targeting paediatricians and respirologists, and to families of asthmatic children via our Quebec parents-partners outreach programme. If proven effective, findings may markedly influence the management of URTI-induced asthma in high-morbidity preschoolers and could be directly implemented into practice with an update to clinical guidelines. TRIAL REGISTRATION NUMBER NCT03365687.
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Meta-analysis of vitamin D and lung function in patients with asthma.
Liu, J, Dong, YQ, Yin, J, Yao, J, Shen, J, Sheng, GJ, Li, K, Lv, HF, Fang, X, Wu, WF
Respiratory research. 2019;(1):161
Abstract
BACKGROUND There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients. METHODS Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5. RESULTS This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = - 0.1, 95% CI = - 0.11 to - 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = - 10.02, 95% CI = - 11 to - 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults. CONCLUSIONS Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.
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Pediatric asthma: An unmet need for more effective, focused treatments.
Papadopoulos, NG, Čustović, A, Cabana, MD, Dell, SD, Deschildre, A, Hedlin, G, Hossny, E, Le Souëf, P, Matricardi, PM, Nieto, A, et al
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019;(1):7-16
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Abstract
BACKGROUND Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.
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Fatty acids in pregnancy and risk of allergic sensitization and respiratory outcomes in childhood.
Maslova, E, Rifas-Shiman, SL, Oken, E, Platts-Mills, TAE, Gold, DR
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2019;(1):120-122.e3
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Anti-IgE Significantly Changes Circulating Interleukin-25, Vitamin-D and Interleukin-33 Levels in Patients with Allergic Asthma.
Yalcin, AD, Uzun, R
Current pharmaceutical design. 2019;(35):3784-3795
Abstract
BACKGROUND Multi-center, randomized-controlled trials and observational studies have demonstrated that, in severe asthmatic patients receiving omalizumab treatment, the frequency of exacerbations, the number of urgent adverse events, and the need for oral steroids tend to decrease. MATERIALS AND METHODS This study included a total of 32 patients. The patients were divided into two groups as Group IA (pre-omalizumab) and Group IB (post-omalizumab). Serum IL-25 and IL-33 levels were measured and the number of emergency admissions, length of hospitalization (day), Asthma Control Test (ACT) scores, eosinophil cationic protein (ECP), and fractional exhaled nitric oxide (FeNO) value were analyzed. RESULTS ACT and FeNO values increased after omalizumab treatment, while IL-33, IL-25 levels decreased after the completion of omalizumab treatment. Furthermore, there was a weak, positive, and significant relationship between the changes in the ECP levels and IL-33 levels (r=0.38, p=0.03). CONCLUSION To the best of our knowledge, this is the first study to compare circulating IL-25 and IL-33 levels with specific IgE synthesis in the literature. Multivariate correlation analysis showed that the changes in serum IL-33 levels were significantly correlated with the changes in the mite sIgE levels and length of hospital stay (Fmodel=11.2, p=0.01, r2=0.45). On the other hand, there was no significant relationship between the other variables and changes in the IL-25 levels.
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Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.
Manarin, G, Anderson, D, Silva, JME, Coppede, JDS, Roxo-Junior, P, Pereira, AMS, Carmona, F
Journal of ethnopharmacology. 2019;:111882
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment. AIM OF THE STUDY We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. PATIENTS AND METHODS We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. RESULTS Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months. CONCLUSION The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.
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Associations between physical activity and asthma, eczema and obesity in children aged 12-16: an observational cohort study.
Jago, R, Salway, RE, Ness, AR, Shield, JPH, Ridd, MJ, Henderson, AJ
BMJ open. 2019;(1):e024858
Abstract
OBJECTIVES To compare the physical activity of adolescents with three common long-term conditions (asthma, eczema and obesity) with adolescents without these conditions. DESIGN Cross-sectional and longitudinal analyses of adolescents at ages 12, 14 and 16 in a large UK cohort study. SETTING The Avon Longitudinal Study of Parents and Children. PARTICIPANTS 6473 adolescents with complete accelerometer data at at least one time point. METHODS Mean minutes of moderate to vigorous intensity physical activity (MVPA) and sedentary time per day were derived from accelerometer-based measurements at ages 12, 14 and 16. Obesity was defined at each time point from height and weight measurements. Parents reported doctor-assessed asthma or eczema. Cross-sectional and longitudinal regression models examined any differences in MVPA or sedentary time for adolescents with asthma, eczema or obesity compared with those without. RESULTS In longitudinal models, boys engaged in an average of 69.7 (95% CI 67.6 to 71.7) min MVPA at age 12, declining by 3.1 (95% CI 2.6 to 3.6) min/year while girls' average MVPA was 47.5 (95% CI 46.1 to 48.9) min at age 12, declining by 1.8 (95% CI 1.5 to 2.1) min/year. There was no strong evidence of differences in physical activity patterns of those with and without asthma or eczema. Obese boys engaged in 11.1 (95% CI 8.7 to 13.6) fewer minutes of MVPA, and obese girls in 5.0 (95% CI 3.3 to 6.8) fewer minutes than their non-obese counterparts. Cross-sectional models showed comparable findings. CONCLUSIONS Mean minutes of MVPA per day did not differ between adolescents with asthma or eczema and those without, but obese adolescents engaged in fewer minutes of MVPA. Findings reinforce the need for strategies to help obese adolescents be more active but suggest no need to develop bespoke physical activity strategies for adolescents with mild asthma or eczema.
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A review on the management of asthma in the Avicenna's Canon of Medicine.
Amini, F, Jaladat, AM, Atarzadeh, F, Mosavat, SH, Parvizi, MM, Zamani, N
Journal of complementary & integrative medicine. 2019;(4)
Abstract
Introduction In this study, we attempted to identify medicinal plants for treating asthma by investigating Persian Medicine (PM) sources. Methods In the present review study, materials concerning asthma were assessed by the (most) reliable source of PM (Canon of Medicine) written by Avicenna. Recommended medicinal plants for treating asthma were extracted from this book. Likewise, the electronic databases were used for investigating the pharmacological properties of offered herbs. Results The signs and symptoms of "Rabv" discussed by Avicenna are very similar to the asthma in modern medicine. Avicenna dichotomized asthma causing into pulmonary and non-pulmonary ones, including asthma with the heart, liver, or stomach origin. Overall, 14 medicinal plants were mentioned for the treatment of asthma presented in Canon of Medicine, including celery, juniper, dodder, chamomile, fennel, quince seed, black caraway, lavender, hyssop, squill, anise, absinthe, asafoetida, and common polypody. Conclusions PM prescribes medicinal plants for treating asthma, based on each patient's symptoms and trigger factors.
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Monoclonal antibodies for severe asthma: Pharmacokinetic profiles.
Matera, MG, Calzetta, L, Rogliani, P, Cazzola, M
Respiratory medicine. 2019;:3-13
Abstract
Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.