-
1.
Montelukast and Nasal Corticosteroids to Treat Pediatric Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.
Liming, BJ, Ryan, M, Mack, D, Ahmad, I, Camacho, M
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2019;(4):594-602
Abstract
OBJECTIVE To systematically review the literature on anti-inflammatory medications for treating pediatric obstructive sleep apnea and perform meta-analysis of the available data. DATA SOURCES PubMed/MEDLINE and 4 additional databases. REVIEW METHODS Three authors independently and systematically searched through June 28, 2018, for studies that assessed anti-inflammatory therapy for treatment of pediatric obstructive sleep apnea (OSA). Data were compiled and analyzed using Review Manager 5.3 (Nordic Cochrane Centre). RESULTS After screening 135 studies, 32 were selected for review with 6 meeting inclusion criteria. In total, 668 patients aged 2 to 5 years met inclusion criteria for meta-analysis. Of these, 5 studies (166 children) that evaluated montelukast alone as treatment for pediatric OSA found a 55% improvement in the apnea-hypopnea index (AHI) (mean [SD] 6.2 [3.1] events/h pretreatment and 2.8 [2.7] events/h posttreatment; mean difference [MD] of -2.7 events/h; 95% confidence interval [CI], -5.6 to 0.3) with improvement in lowest oxygen saturation (LSAT) from 89.5 (6.9) to 92.1 (3.6) (MD, 2.2; 95% CI, 0.5-4.0). Two studies (502 children) observing the effects of montelukast with intranasal corticosteroids on pediatric OSA found a 70% improvement in AHI (4.7 [2.1] events/h pretreatment and 1.4 [1.0] events/h posttreatment; MD of -4.2 events/h; 95% CI, -6.3 to -2.0), with an improvement in LSAT from 87.8 (3.1) to 92.6 (2.2) (MD, 4.8; 95% CI, 4.5-5.1). CONCLUSIONS Treatment with montelukast and intranasal steroids or montelukast alone is potentially beneficial for short-term management of mild pediatric OSA.
-
2.
DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics.
Wang, AL, Gruzieva, O, Qiu, W, Kebede Merid, S, Celedón, JC, Raby, BA, Söderhäll, C, DeMeo, DL, Weiss, ST, Melén, E, et al
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(9):1225-1234
-
-
Free full text
-
Abstract
BACKGROUND Response to inhaled corticosteroids is highly variable, and the association between DNA methylation and treatment response is not known. OBJECTIVE To examine the association between peripheral blood DNA methylation and inhaled corticosteroid response in children with persistent asthma. METHODS Epigenome-wide DNA methylation was analysed in individuals on inhaled corticosteroids in three independent and ethnically diverse cohorts-Childhood Asthma Management Program (CAMP); Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE); and Genetic Epidemiology of Asthma in Costa Rica Study (GACRS). Treatment response was evaluated using two definitions, the absence of emergency department visits and/or hospitalizations and the absence oral corticosteroid use while on inhaled corticosteroid therapy. CpG sites meeting nominal significance (P < 0.05) for each outcome were combined in a three-cohort meta-analysis with adjustment for multiple testing. DNA methylation was correlated with gene expression using Pearson and partial correlations. RESULTS In 154 subjects from CAMP, 72 from BAMSE, and 168 from GACRS, relative hypomethylation of cg00066816 (171 bases upstream of IL12B) was associated with the absence of emergency department visits and/or hospitalizations (Q = 0.03) in all cohorts and lower IL12B expression (ρ = 0.34, P = 0.01) in BAMSE. Relative hypermethylation of cg04256470 (688 bases upstream of CORT) was associated with the absence of oral corticosteroid use (Q = 0.04) in all cohorts and higher CORT expression (ρ = 0.20, P = 0.045) in CAMP. CONCLUSION AND CLINICAL RELEVANCE Differential DNA methylation of IL12B and CORT are associated with inhaled corticosteroid treatment response in persistent childhood asthmatics. Pharmaco-methylation can identify novel markers of treatment sensitivity in asthma.
-
3.
Growth failure in Crohn's disease children: may the first treatment have a role?
Capriati, T, Bizzarri, C, Dilillo, A, Nobili, V, Oliva, S, Diamanti, A
Expert review of clinical immunology. 2019;(1):97-104
Abstract
Introduction: Growth failure in children is a frequent feature of childhood-onset Crohn's disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth. Areas covered: We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course. We conducted a systematic literature search to identify relevant studies published on the PubMed database from January 2002 up to now. We found only six surveys that documented mid-term growth course in newly diagnosed CD patients. Expert commentary: In the last years there have been relevant advances in the clinical management of CD children; however, there is a lack of knowledge about the best strategy to reverse growth failure. Children treated with enteral nutrition have appropriate height and weight gain but do not reverse the growth course. Further surveys are required to better explore not only clinical outcomes but also long-term growth course following each therapeutic strategy.
-
4.
Preoperative Considerations in Inflammatory Bowel Disease.
McKenna, NP, Lightner, AL
The Surgical clinics of North America. 2019;(6):1083-1094
Abstract
Patients with ulcerative colitis and Crohn's disease often present to surgery malnourished and on combination immunosuppression. These factors affect operation selection and postoperative outcomes. Corticosteroids have a well-established detrimental effect on postoperative outcomes, whereas the impact of biologic agents is more controversial. In a patient exposed to these medications, and in the presence of other risk factors, temporary intestinal diversion is likely the best choice. Enteral nutrition may help optimize malnourished patients at high risk of adverse postoperative outcomes.
-
5.
Steroidogenic Acute Regulatory Protein: Structure, Functioning, and Regulation.
Tugaeva, KV, Sluchanko, NN
Biochemistry. Biokhimiia. 2019;(Suppl 1):S233-S253
Abstract
Steroidogenesis takes place mainly in adrenal and gonadal cells that produce a variety of structurally similar hormones regulating numerous body functions. The rate-limiting stage of steroidogenesis is cholesterol delivery to the inner mitochondrial membrane, where it is converted by cytochrome P450scc into pregnenolone, a common precursor of all steroid hormones. The major role of supplying mitochondria with cholesterol belongs to steroidogenic acute regulatory protein (STARD1). STARD1, which is synthesized de novo as a precursor containing mitochondrial localization sequence and sterol-binding domain, significantly accelerates cholesterol transport and production of pregnenolone. Despite a tremendous interest in STARD1 fueled by its involvement in hereditary diseases and extensive efforts of numerous laboratories worldwide, many aspects of STARD1 structure, functioning, and regulation remain obscure and debatable. This review presents current concepts on the structure of STARD1 and other lipid transfer proteins, the role of STARD1 in steroidogenesis, and the mechanism of its functioning, as well as identifies the most controversial and least studied questions related to the activity of this protein.
-
6.
Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis.
Zhong, YY, Li, JC, Liu, YL, Zhao, XB, Male, M, Song, DK, Bai, Y
Current medical science. 2019;(3):493-499
Abstract
There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67; 95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56; 95% CI: 0.45-0.69, and RR: 0.35; 95% CI: 0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI: 0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.
-
7.
Copeptin levels upon corticosteroid treatment in acute community-acquired pneumonia.
Popovic, M, Blum, CA, Christ-Crain, M
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2019;(2):e1
-
8.
Comparison between montelukast and tiotropium as add-on therapy to inhaled corticosteroids plus a long-acting β2-agonist in for patients with asthma.
Hoshino, M, Akitsu, K, Ohtawa, J
The Journal of asthma : official journal of the Association for the Care of Asthma. 2019;(9):995-1003
Abstract
Objective: Asthma often remains uncontrolled despite treatment with inhaled corticosteroids (ICS) alone or with ICS plus a long-acting β2-agonist (LABA). The recommended alternative is the addition of either montelukast or tiotropium. The aim of this study was to compare the effects of montelukast and tiotropium on airway inflammation and remodeling in persistent asthma. Methods: Eighty-seven patients with asthma were treated with budesonide and formoterol (640/18 μg); then, the patients were randomly allocated to three groups to receive oral montelukast (10 mg/day), inhaled tiotropium (5 μg/day), or no add-on to the maintenance therapy for 48 weeks. Fractional exhaled nitric oxide (FeNO) and pulmonary function were measured, and quantitative computed tomography was performed. Results: Compared to the maintenance therapy, add-on montelukast significantly decreased FeNO (p < 0.05) and improved airflow obstruction (p < 0.05), whereas airway dimensions remained unchanged. Changes in FeNO were significantly correlated with changes in FEV1 (r = -0.71, p < 0.001). In contrast, the addition of tiotropium significantly decreased airway wall area corrected for body surface area (WA/BSA) (p < 0.05), decreased wall thickness (T/√BSA) (p < 0.05) and improved airflow obstruction (p < 0.05) with no change in FeNO. Changes in WA/BSA and T/√BSA were significantly correlated with the change in percentage predicted FEV1 (r = -0.84, p < 0.001 and r = -0.59, p < 0.01, respectively). Conclusions:Adding either montelukast or tiotropium to ICS/LABA may provide additive benefits with respect to the pulmonary function and airway inflammation or remodeling in patients with asthma.
-
9.
Randomized, Open-Label, Phase IV, Korean Study of Kidney Transplant Patients Converting From Cyclosporine to Prolonged-Release Tacrolimus Plus Standard- or Reduced-Dose Corticosteroids.
Baek, CH, Kim, CD, Lee, DR, Kim, YH, Yang, J, Kim, BS, Lee, JS, Han, SY, Kim, SW, Lee, S, et al
Transplantation proceedings. 2019;(3):749-760
Abstract
BACKGROUND This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.
-
10.
Obesity prevention in corticosteroid-treated patients: Use and effectiveness of strategies for weight management.
Conklin, AI, Hong, J
Clinical obesity. 2019;(4):e12312
Abstract
We conducted a systematic review to identify the use and effectiveness of clinical interventions to prevent or mitigate weight gain in patients using systemic corticosteroids. We independently searched nine bibliometric databases for reviews and longitudinal studies published up to 26 October 2018, and assessed the quality of studies meeting inclusion criteria. We identified 3893 records and screened 3037 eligible studies, read four full-texts and extracted data from three randomized control trials. Two studies examined a diet-only intervention for weight management, while one study examined a mixed intervention for diet and exercise. Overall, existing evidence is of poor quality and based on small feasibility studies of either paediatric leukaemia or female lupus patients, which suggested divergent effects of lifestyle interventions on weight, body mass index or waist circumference. Current evidence suggests a state of clinical equipoise that deserves greater research attention given the prevalent use of corticosteroids for treating a variety of chronic conditions. Robust high-quality longitudinal studies to decipher preventive strategies of steroid-induced weight gain must be prioritized in research and policy to improve patient care and prevent further obesity-related disease burden.