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Jiang WY, Jiao RH, Ma SL, Dai JS, Zhu HF, Wu MY, Che YR, Zhang L, Ding XY. Serum inflammatory factors, vitamin D levels, and asthma severity in children with comorbid asthma and obesity/overweight: a comparative study. Front Pediatr 2025; 13:1439841. [PMID: 40083433 PMCID: PMC11903463 DOI: 10.3389/fped.2025.1439841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 02/17/2025] [Indexed: 03/16/2025] Open
Abstract
Objective To investigate serum inflammatory factors, vitamin D levels, and asthma severity in children with comorbid asthma and obesity/overweight, compared with those with asthma or obesity/overweight alone. Methods This retrospective comparative study included children suffering from asthma alone, asthma combined with obesity/overweight, or obesity/overweight alone at Shanghai Pudong New Area People's Hospital between January 2020 and December 2021. Results A total of 168 children (mean age: 4.32 ± 1.64 years; 117 males) were included. Compared with children with asthma alone (n = 56), those with comorbid asthma and obesity/overweight (n = 56) exhibited higher levels of serum levels of interleukin 6 (IL-6) (35.75 ± 24.56 vs. 15.40 ± 19.67), TNF-α (15.44 ± 7.35 vs. 12.16 ± 7.24), and leptin (3.89 ± 3.81 vs. 1.27 ± 2.31), and lower levels of 25-hydroxycholecalciferol (25-(OH) D3) (26.03 ± 10.77 vs. 37.15 ± 13.35), IL-10 (8.69 ± 2.76 vs. 15.32 ± 6.28), and IL-13 (449.40 ± 315.37 vs. 605.27 ± 351.02) (all P < 0.05). Compared with children with obese/overweight alone (n = 56), those with comorbid asthma and obesity/overweight had lower IL-10 (8.69 ± 2.76 vs. 12.29 ± 6.61) and higher IL-6 (35.75 ± 24.56 vs. 20.53 ± 17.07), IL-13 (449.40 ± 315.37 vs. 309.47 ± 257.45), and leptin (3.89 ± 3.81 vs. 2.48 ± 3.52) (all P < 0.05). Children with comorbid asthma and obesity/overweight showed higher Preschool Respiratory Assessment Measure (PRAM) scores (3.14 ± 2.40 vs. 1.93 ± 1.02, P = 0.008) and longer hospital stays (5.96 ± 1.25 vs. 5.29 ± 1.36 days, P = 0.007) compared to those with asthma alone. Conclusions Significant differences were observed in IL-6, IL-10, IL-13, 25-(OH) D3 levels, and leptin among children with asthma combined with obesity/overweight and those with asthma or obesity/overweight alone. Children with obesity/overweight alone displayed more severe clinical manifestations and longer hospital stays compared with those with asthma alone.
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Affiliation(s)
- Wan-yu Jiang
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Rong-hong Jiao
- Department of Clinical Laboratory, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Su-li Ma
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Jin-sheng Dai
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Hai-feng Zhu
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Meng-ya Wu
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Yan-ran Che
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Lei Zhang
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Xiao-yuan Ding
- Pediatrics Department, Shanghai Pudong New Area People’s Hospital, Shanghai, China
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El Abd A, Dasari H, Dodin P, Trottier H, Ducharme FM. Associations between vitamin D status and biomarkers linked with inflammation in patients with asthma: a systematic review and meta-analysis of interventional and observational studies. Respir Res 2024; 25:344. [PMID: 39322954 PMCID: PMC11423515 DOI: 10.1186/s12931-024-02967-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/03/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Numerous studies indicate an association between vitamin D status and inflammatory biomarkers in patients with asthma, but findings are inconsistent. This review aims to summarize the relationship between serum vitamin D status, assessed by 25-hydroxyvitamin D (25(OH)D) level, and inflammatory biomarkers in children and adults with asthma. METHODS A literature search of interventional and observational studies on 25(OH)D up to November 2022 was conducted across six electronic databases. Outcomes of interest included a range of inflammatory biomarkers classified in four categories: T helper 2 (Th2) pro-inflammatory, non-Th2 pro-inflammatory, anti-inflammatory, and non-specific biomarkers. Study characteristics were extracted and risk of bias was evaluated using the American Academy of Nutrition and Dietetics tool. Meta-analysis was conducted on studies with a low risk of bias, while narrative reporting was used to present the direction of associations (positive, no association, or negative) for each biomarker, overall and within the low-risk studies. RESULTS We included 71 studies (3 interventional, 68 observational) involving asthma patients. These studies investigated the association between serum 25(OH)D and Th2 pro-inflammatory biomarkers (N = 58), non-Th2 pro-inflammatory biomarkers (N = 18), anti-inflammatory biomarkers (N = 16), and non-specific biomarkers (N = 10). Thirteen (18.3%) studies, 50 (70.4%), and 8 (11.3%) were at high, moderate, and low risk of bias, respectively. In all studies, irrespective of risk of bias, the most frequently reported finding was no significant association, followed by a negative association between 25(OH)D and pro-inflammatory biomarkers and a positive association with anti-inflammatory biomarkers. In low-risk studies, one biomarker could be meta-analysed. The pooled estimate for 25(OH)D and serum IgE showed a negative association (β (95% CI)= - 0.33 (-0.65 to - 0.01); I2 = 88%; N = 4 studies). A negative association between 25(OH)D and blood eosinophils was also observed in the largest of three studies, as well as with cathelicidin (LL-37) in the only study reporting it. For other biomarkers, most low-risk studies revealed no significant association with 25(OH)D. CONCLUSION Serum 25(OH)D is negatively associated with serum IgE and possibly with blood eosinophils and LL-37, supporting an in vivo immunomodulatory effect of 25(OH)D. Future research should employ rigorous methodologies and standardized reporting for meta-analysis aggregation to further elucidate these associations.
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Affiliation(s)
- Asmae El Abd
- Sainte-Justine University Health Center, Research Center, Montreal, Quebec, Canada.
- Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, Quebec, Canada.
| | - Harika Dasari
- Sainte-Justine University Health Center, Research Center, Montreal, Quebec, Canada
| | - Philippe Dodin
- Sainte-Justine University Health Center, Research Center, Montreal, Quebec, Canada
| | - Helen Trottier
- Sainte-Justine University Health Center, Research Center, Montreal, Quebec, Canada
- Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, Quebec, Canada
| | - Francine M Ducharme
- Sainte-Justine University Health Center, Research Center, Montreal, Quebec, Canada
- Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, Quebec, Canada
- Department of Pediatrics, Faculty of Medicine, University of Montreal, Sainte-Justine Hospital, Montreal, Quebec, Canada
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Arkenberg P, Dittmar M. The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults. GeroScience 2024; 46:2489-2502. [PMID: 37991642 PMCID: PMC10828295 DOI: 10.1007/s11357-023-01012-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 11/07/2023] [Indexed: 11/23/2023] Open
Abstract
It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, in particular to inflammaging, that is associated with increased levels of TNF-α. This study aimed (1) to investigate how 24-h profiles for OGG1 change during healthy aging and (2) to analyze the relationship of OGG1 with TNF-α, central body fat, cortisol and oxidative DNA/RNA damage. In a cross-sectional study in 20 healthy older and 20 young women, salivary levels of OGG1, TNF-α, cortisol and oxidative DNA/RNA damage were quantified by ELISAs every 4 h for a 24-h period. Trunk circumferences were taken as measures of central body fat. Older women, compared to young women, exhibited significantly lower protein levels of OGG1 throughout the whole 24-h period, a 2.5 times lower 24-h mean level for OGG1 (P < 0.00001) and loss of 24-h variation of OGG1. Both age groups demonstrated significant 24-h variation for TNF-alpha, cortisol and oxidative damage. The 24-h mean level for TNF-α was more than twice as high in older compared to young women (P = 0.011). Regression analysis detected that age, TNF-α and waist circumference were negative significant predictors of OGG1, explaining 56% of variance of OGG1 (P < 0.00001), while levels of cortisol and oxidative damage were no predictors of OGG1. Results indicate a strong decrease of protein levels of OGG1 and a loss of 24-h variation during natural cellular aging. The negative relationship, found between OGG1 and TNF-α and between OGG1 and waist circumference, suggests involvement of proinflammatory processes in DNA repair.
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Affiliation(s)
- Per Arkenberg
- Department of Human Biology, Zoological Institute, Christian-Albrechts-University, Am Botanischen Garten 9, 24118 Kiel, Germany
| | - Manuela Dittmar
- Department of Human Biology, Zoological Institute, Christian-Albrechts-University, Am Botanischen Garten 9, 24118 Kiel, Germany.
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Jamshidian-Ghalehsefidi N, Rabiee F, Tavalaee M, Kiani S, Pouriayevali F, Razi M, Dattilo M, Nasr-Esfahani MH. The role of the transsulfuration pathway in spermatogenesis of vitamin D deficient mice. Sci Rep 2023; 13:19173. [PMID: 37932339 PMCID: PMC10628119 DOI: 10.1038/s41598-023-45986-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 10/26/2023] [Indexed: 11/08/2023] Open
Abstract
Vitamin D deficiency is a global health problem and has been linked to defective spermatogenesis and male infertility. In this study, we aimed to investigate the main enzymes involved in the transsulfuration pathway of 1-carbon metabolism, and spermatogenesis function. Therefore, sixteen male C57 mice were addressed to a control (standard diet) or vitamin D deficient (VDD) diet for 14 weeks. The results show that compared to the standard diet, VDD increased final body weight and reduced sperm quality, caused damage to the testicular structure, and decreased the serum levels of testosterone. In addition, serum concentrations of homocysteine, vitamin B12, and sperm oxidative stress markers increased. In testicular tissues, the CBS and CSE protein levels were down-regulated whereas HO-1 was up-regulated at both mRNA and protein expression levels. Within a mice deprivation model, VDD deeply suppressed testosterone and impaired spermatogenesis with oxidative stress-mediated mechanisms. The effects of the deprivation appeared to be at least in part independent of genomic and receptor-mediated vitamin D actions and suggest a specific impairment of the alternative transsulfuration pathway.
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Affiliation(s)
- Narges Jamshidian-Ghalehsefidi
- ACECR Institute of Higher Education, Isfahan Branch, Isfahan, Iran
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Farzaneh Rabiee
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Marziyeh Tavalaee
- ACECR Institute of Higher Education, Isfahan Branch, Isfahan, Iran.
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
| | - Shaghayegh Kiani
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Farnaz Pouriayevali
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mazdak Razi
- Division of Histology and Embryology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | | | - Mohammad Hossein Nasr-Esfahani
- ACECR Institute of Higher Education, Isfahan Branch, Isfahan, Iran.
- Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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Antonio Buendía J, Patiño DG, Lindarte EF. Vitamin D supplementation for children with mild to moderate asthma: an economic evaluation. J Asthma 2023; 60:1668-1676. [PMID: 36755388 DOI: 10.1080/02770903.2023.2178007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/29/2023] [Accepted: 02/05/2023] [Indexed: 02/10/2023]
Abstract
INTRODUCTION A large proportion of asthma patients remain uncontrolled despite using inhaled corticosteroids. Some add-on therapies such as vitamin D supplements have been recommended for this subgroup of patients. The purpose of this study was to assess the cost-utility of vitamin D supplementation in children with mild to moderate persistent asthma in Colombia. METHODS A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. The model was analyzed probabilistically, and a value of information (VOI) analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS The mean incremental cost of vitamin D supplementation versus no supplementation is USD $44.60. The mean incremental benefit of vitamin D supplementation versus no supplementation is 0.05 QALY. This position of absolute dominance (vitamin D supplementation has lower costs and higher QALYs than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. Our base-case results were robust to variations in all assumptions and parameters. CONCLUSION Add-on therapy with vitamin D supplementation is a cost-effective strategy for patients between 6 and 17 years of age with mild to moderate asthma in Colombia.
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Affiliation(s)
- Jefferson Antonio Buendía
- Research Group in Pharmacology and Toxicology "INFARTO", Department of Pharmacology and Toxicology, University of Antioquia, Medellín, Colombia
| | - Diana Guerrero Patiño
- Research Group in Pharmacology and Toxicology "INFARTO", Department of Pharmacology and Toxicology, University of Antioquia, Medellín, Colombia
| | - Erika Fernanda Lindarte
- Research Group in Pharmacology and Toxicology "INFARTO", Department of Pharmacology and Toxicology, University of Antioquia, Medellín, Colombia
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Zajac D, Wojciechowski P. The Role of Vitamins in the Pathogenesis of Asthma. Int J Mol Sci 2023; 24:ijms24108574. [PMID: 37239921 DOI: 10.3390/ijms24108574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/27/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
Vitamins play a crucial role in the proper functioning of organisms. Disturbances of their levels, seen as deficiency or excess, enhance the development of various diseases, including those of the cardiovascular, immune, or respiratory systems. The present paper aims to summarize the role of vitamins in one of the most common diseases of the respiratory system, asthma. This narrative review describes the influence of vitamins on asthma and its main symptoms such as bronchial hyperreactivity, airway inflammation, oxidative stress, and airway remodeling, as well as the correlation between vitamin intake and levels and the risk of asthma in both pre- and postnatal life.
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Affiliation(s)
- Dominika Zajac
- Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warszawa, Poland
| | - Piotr Wojciechowski
- Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warszawa, Poland
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8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer. Int J Mol Sci 2023; 24:ijms24065488. [PMID: 36982562 PMCID: PMC10052644 DOI: 10.3390/ijms24065488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/10/2023] [Accepted: 03/12/2023] [Indexed: 03/15/2023] Open
Abstract
DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)—a DNA repair enzyme—may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.
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Abstract
BACKGROUND Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and improving asthma control. We therefore conducted an updated meta-analysis to include data from new trials completed since this date. OBJECTIVES To evaluate the effectiveness and safety of administration of vitamin D or its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control. SEARCH METHODS We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search: 8 September 2022. SELECTION CRITERIA We included double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control, or both. DATA COLLECTION AND ANALYSIS Four review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). The primary outcome was the incidence of severe asthma exacerbations requiring treatment with systemic corticosteroids. Secondary outcomes included the incidence of asthma exacerbations precipitating an emergency department visit or requiring hospital admission, or both, end-study childhood Asthma Control Test (cACT) or Asthma Control Test (ACT) scores, and end-study % predicted forced expiratory volume in one second (FEV1). We performed subgroup analyses to determine whether the effect of vitamin D on risk of asthma exacerbation was modified by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, form of vitamin D given, and age of participants. MAIN RESULTS We included 20 studies in this review; 15 trials involving a total of 1155 children and five trials involving a total of 1070 adults contributed data to analyses. Participant ages ranged from 1 to 84 years, with two trials providing data specific to participants under five years (n = 69) and eight trials providing data specific to participants aged 5 to 16 (n = 766). Across the trials, 1245 participants were male and 1229 were female, with two studies not reporting sex distribution. Fifteen trials contributed to the primary outcome analysis of exacerbations requiring systemic corticosteroids. The duration of trials ranged from three to 40 months; all but two investigated effects of administering cholecalciferol (vitamin D3). As in the previous Cochrane Review, the majority of participants had mild to moderate asthma, and profound vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25 nmol/L) at baseline was rare. Administration of vitamin D or its hydroxylated metabolites did not reduce or increase the proportion of participants experiencing one or more asthma exacerbations treated with systemic corticosteroids (odds ratio (OR) 1.04, 95% CI 0.81 to 1.34; I2 = 0%; 14 studies, 1778 participants; high-quality evidence). This equates to an absolute risk of 226 per 1000 (95% CI 185 to 273) in the pooled vitamin D group, compared to a baseline risk of 219 participants per 1000 in the pooled placebo group. We also found no effect of vitamin D supplementation on the rate of exacerbations requiring systemic corticosteroids (rate ratio 0.86, 95% CI 0.62 to 1.19; I2 = 60%; 10 studies, 1599 participants; high-quality evidence), or the time to first exacerbation (hazard ratio 0.82, 95% CI 0.59 to 1.15; I2 = 22%; 3 studies, 850 participants; high-quality evidence). Subgroup analysis did not reveal any evidence of effect modification by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, or age. A single trial investigating administration of calcidiol reported a benefit of the intervention for the primary outcome of asthma control. Vitamin D supplementation did not influence any secondary efficacy outcome meta-analysed, which were all based on moderate- or high-quality evidence. We observed no effect on the incidence of serious adverse events (OR 0.89, 95% CI 0.56 to 1.41; I2 = 0%; 12 studies, 1556 participants; high-quality evidence). The effect of vitamin D on fatal asthma exacerbations was not estimable, as no such events occurred in any trial. Six studies reported adverse reactions potentially attributable to vitamin D. These occurred across treatment and control arms and included hypercalciuria, hypervitaminosis D, kidney stones, gastrointestinal symptoms and mild itch. In one trial, we could not ascertain the total number of participants with hypercalciuria from the trial report. We assessed three trials as being at high risk of bias in at least one domain; none of these contributed data to the analysis of the outcomes reported above. Sensitivity analyses that excluded these trials from each outcome to which they contributed did not change the null findings. AUTHORS' CONCLUSIONS In contrast to findings of our previous Cochrane Review on this topic, this updated review does not find evidence to support a role for vitamin D supplementation or its hydroxylated metabolites to reduce risk of asthma exacerbations or improve asthma control. Participants with severe asthma and those with baseline 25(OH)D concentrations < 25 nmol/L were poorly represented, so further research is warranted here. A single study investigating effects of calcidiol yielded positive results, so further studies investigating effects of this metabolite are needed.
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Affiliation(s)
- Anne Williamson
- Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Adrian R Martineau
- Asthma UK Centre for Applied Research, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Aziz Sheikh
- Asthma UK Centre for Applied Research, Usher Institute, The University of Edinburgh, Edinburgh, UK
| | - David Jolliffe
- Asthma UK Centre for Applied Research, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Chris J Griffiths
- Asthma UK Centre for Applied Research, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
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25-hydroxyvitamin D3 inhibits oxidative stress and ferroptosis in retinal microvascular endothelial cells induced by high glucose through down-regulation of miR-93. BMC Ophthalmol 2023; 23:22. [PMID: 36639741 PMCID: PMC9840274 DOI: 10.1186/s12886-022-02762-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 12/28/2022] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND The decrease of vitamin D plays a critical role in diabetes mellitus (DM)-induced oxidative stress and vascular endothelial injury. Therefore, we investigated the effect and mechanism of 25-hydroxyvitamin D3 (25 (OH) D3) on oxidative stress and ferroptosis induced by high glucose in human retinal microvascular endothelial cells (hRMVECs). And the objective of this paper was to propose a new strategy for the prevention and treatment of diabetic retinopathy (DR). METHODS First, hRMVECs were transfected with mimics NC or miR-93. After that, cells were treated with 100 nM / 500 nM 25 (OH) D3 and then cultured in a high glucose (30 mM) environment. Subsequently, qRT-PCR was employed to detect the expression level of miR-93; CCK-8 for the proliferation of cells in each group; biochemical tests for the level of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and ferrous ion (Fe2+); and Western blot for the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and SLC7A11). RESULTS Under a high glucose environment, 25 (OH) D3 at 100 nM/500 nM could significantly promote the proliferation of hRMVECs, remarkably decrease the level of intracellular ROS/MDA, and up-regulate the level of GSH. Besides, 25 (OH) D3 greatly reduced Fe2+ level in the cells while increased protein level of GPX4 and SLC7A11. Subsequently, we found that high glucose induced miR-93 expression, while 25 (OH) D3 markedly decreased high glucose-induced miR-93 overexpression. Furthermore, overexpression of miR-93 inhibited the functions of 25 (OH) D3 by activating ROS (ROS and MDA were up-regulated while GSH was down-regulated) and inducing Fe2+ (Fe2+ level was up-regulated while GPX4 and SLC7A11 level was down-regulated) in cells. CONCLUSION 25 (OH) D3 may inhibit oxidative stress and ferroptosis in hRMVECs induced by high glucose via down-regulation of miR-93.
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Grandinetti R, Fainardi V, Caffarelli C, Capoferri G, Lazzara A, Tornesello M, Meoli A, Bergamini BM, Bertelli L, Biserna L, Bottau P, Corinaldesi E, De Paulis N, Dondi A, Guidi B, Lombardi F, Magistrali MS, Marastoni E, Pastorelli S, Piccorossi A, Poloni M, Tagliati S, Vaienti F, Gregori G, Sacchetti R, Mari S, Musetti M, Antodaro F, Bergomi A, Reggiani L, Caramelli F, De Fanti A, Marchetti F, Ricci G, Esposito S. Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group. J Clin Med 2022; 11:6558. [PMID: 36362786 PMCID: PMC9655250 DOI: 10.3390/jcm11216558] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/01/2022] [Accepted: 11/02/2022] [Indexed: 07/30/2023] Open
Abstract
Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health.
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Affiliation(s)
- Roberto Grandinetti
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Valentina Fainardi
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Carlo Caffarelli
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Gaia Capoferri
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Angela Lazzara
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Marco Tornesello
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Aniello Meoli
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
| | - Barbara Maria Bergamini
- Paediatric Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy
| | - Luca Bertelli
- Pediatric Clinic, Scientific Institute for Research and Healthcare (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Loretta Biserna
- Paediatrics and Neonatology Unit, Ravenna Hospital, AUSL Romagna, 48121 Ravenna, Italy
| | - Paolo Bottau
- Paediatrics Unit, Imola Hospital, 40026 Imola, Italy
| | | | - Nicoletta De Paulis
- Paediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
| | - Arianna Dondi
- Pediatric Clinic, Scientific Institute for Research and Healthcare (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Battista Guidi
- Hospital and Territorial Paediatrics Unit, Pavullo, 41026 Pavullo Nel Frignano, Italy
| | | | - Maria Sole Magistrali
- Paediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy
| | - Elisabetta Marastoni
- Paediatrics Unit, Santa Maria Nuova Hospital, AUSL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy
| | | | - Alessandra Piccorossi
- Paediatrics and Paediatric Intensive Care Unit, Cesena Hospital, AUSL Romagna, 47521 Cesena, Italy
| | - Maurizio Poloni
- Paediatrics Unit, Rimini Hospital, AUSL Romagna, 47921 Rimini, Italy
| | | | - Francesca Vaienti
- Paediatrics Unit, G.B. Morgagni—L. Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy
| | - Giuseppe Gregori
- Primary Care Pediatricians, AUSL Piacenza, 29121 Piacenza, Italy
| | | | - Sandra Mari
- Primary Care Pediatricians, AUSL Parma, 43126 Parma, Italy
| | | | | | - Andrea Bergomi
- Primary Care Pediatricians, AUSL Modena, 41125 Modena, Italy
| | | | - Fabio Caramelli
- Pediatric Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alessandro De Fanti
- Paediatrics Unit, Santa Maria Nuova Hospital, AUSL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Federico Marchetti
- Paediatrics and Neonatology Unit, Ravenna Hospital, AUSL Romagna, 48121 Ravenna, Italy
| | - Giampaolo Ricci
- Pediatric Clinic, Scientific Institute for Research and Healthcare (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Susanna Esposito
- Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
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11
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Antonio Buendía J, Rodriguez-Martinez CE, Sossa-Briceño MP. Cost utility of Vitamin D supplementation in adults with mild to moderate asthma. J Asthma 2022; 60:951-959. [PMID: 35920247 DOI: 10.1080/02770903.2022.2110113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
IntroductionUncontrolled asthma significantly impairs health-related quality of life and work productivity. Some add-on therapies, such as vitamin D supplements, safely reduce the rate of asthma exacerbation. The purpose of this study was to assess the cost-utility of vitamin D supplementation in adults with mild to moderate persistent asthma in Colombia.MethodsA Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYs of two therapy strategies, vitamin D supplementation plus ICS versus ICS alone, were calculated over a one-year time horizon. Deterministic and probability sensitivity analyses were conducted, and cost-effectiveness was evaluated at a willingness-to-pay value of $5,180 per QALY gained.ResultsThe base-case analysis showed that compared with no supplementation, vitamin D supplementation was associated with higher costs and higher QALYs. The expected annual cost per patient with vitamin D supplementation was US$1338 and without this supplementation it was US$1095. The QALYs per person estimated with vitamin D supplementation was 0,80, and without this supplementation it was 0,63. The estimated incremental cost-effectiveness ratio (ICER) was US$1583 per QALY.ConclusionAdd-on vitamin D supplement was cost-effective when added to the usual care in patients with mild to moderate persistent asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines.
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Affiliation(s)
- Jefferson Antonio Buendía
- Research group in Pharmacology and Toxicology" INFARTO". Department of Pharmacology and Toxicology. University of Antioquia, Medellín, Colombia
| | - Carlos E Rodriguez-Martinez
- Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia.,Department of Pediatric Pulmonology, School of Medicine, Universidad El Bosque, Bogota, Colombia
| | - Monica P Sossa-Briceño
- Department of Internal Medicine, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia
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12
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Rehman R, Azhar A, Naseem Z, Haider G, Farooqui N, Farhat S. PCOS model: Apoptotic changes and role of vitamin D. ELECTRONIC JOURNAL OF GENERAL MEDICINE 2022. [DOI: 10.29333/ejgm/12275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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13
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Liu M, Wang J, Sun X. A Meta-Analysis on Vitamin D Supplementation and Asthma Treatment. Front Nutr 2022; 9:860628. [PMID: 35873428 PMCID: PMC9300755 DOI: 10.3389/fnut.2022.860628] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 05/25/2022] [Indexed: 12/23/2022] Open
Abstract
Background Vitamin D, as an immunomodulator, may be related to the therapeutic effect of asthma patients, but the research in this area is still controversial. The aim of this meta-analysis was to analyze the role of vitamin D supplementation in the treatment of asthma patients. Materials and Methods Randomized Controlled Trials (RCTs) of vitamin D supplementation in asthma were searched in PubMed, EMBASE, and the Cochrane library. Primary outcomes were forced expiratory volume in one second (FEV1), asthma exacerbations, Asthma Control Test scores (ACT scores), and fractional exhaled nitric oxide (FENO). Results A total of 10 RCTs were included, including 1,349 patients. Vitamin D supplementation didn't affect the ACT scores (SMD = 0.04, 95% CI = -0.13 to 0.21, P = 0.87), FEV1 (SMD = 0.04, 95% CI = -0.35 to 0.43, P < 0.01) and FENO (SMD = -0.01, 95% CI = -0.22 to 0.20, P = 0.27), but reduced the rate of asthma exacerbations (RR = 0.69, 95% CI = 0.41 to 0.88, P < 0.01), especially in subgroups of children (RR = 0.46, 95% CI = 0.30 to 0.70, P = 0.83) and follow up time less than 6 months (RR = 0.45, 95% CI = 0.32 to 0.63, P = 0.95). Additionally, though there was only one study included in the subgroup, it significantly enhanced FEV1 at the last visit for patients whose FEV1 baseline value was less than 70% (SMD = 0.94, 95% CI = 0.47 to 1.41). Conclusion Vitamin D supplementation can reduce asthma exacerbations, especially in children, and within 6 months of follow up time. In addition, vitamin D has a positive effect on improving FEV1 of patients whose FEV1 baseline value is less than 70%, but more RCTs are still needed to support this conclusion. Systematic Review Registration [https://inplasy.com], identifier [10.37766/inplasy20 22.6.0049].
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Affiliation(s)
- Meiqi Liu
- Department of Respiratory Medicine, Xi’an Children’s Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Jun Wang
- Department and Institute of Infectious Disease, Xi’an Children’s Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Xinrong Sun
- Department of Respiratory Medicine, Xi’an Children’s Hospital, Xi’an Jiaotong University, Xi’an, China
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14
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Piazza M, Di Cicco M, Pecoraro L, Ghezzi M, Peroni D, Comberiati P. Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome. Biomolecules 2022; 12:556. [PMID: 35454144 PMCID: PMC9024951 DOI: 10.3390/biom12040556] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/29/2022] [Accepted: 03/31/2022] [Indexed: 02/04/2023] Open
Abstract
Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences.
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Affiliation(s)
- Michele Piazza
- Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37126 Verona, Italy; (M.P.); (L.P.)
| | - Maria Di Cicco
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
| | - Luca Pecoraro
- Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37126 Verona, Italy; (M.P.); (L.P.)
| | - Michele Ghezzi
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy;
| | - Diego Peroni
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
| | - Pasquale Comberiati
- Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, 56126 Pisa, Italy; (M.D.C.); (P.C.)
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15
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Gayan‐Ramirez G, Janssens W. Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho. JBMR Plus 2021; 5:e10569. [PMID: 34950829 PMCID: PMC8674778 DOI: 10.1002/jbm4.10569] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 09/29/2021] [Accepted: 10/09/2021] [Indexed: 11/16/2022] Open
Abstract
Vitamin D is well known for its role as a calcium regulator and in maintenance of phosphate homeostasis in musculoskeletal health, and fibroblast growth factor 23 (FGF23) and its coreceptor α-klotho are known for their roles as regulators of serum phosphate levels. However, apart from these classical actions, recent data point out a relevant role of vitamin D and FGF23/klotho in lung health. The expression of the vitamin D receptor by different cell types in the lung and the fact that those cells respond to vitamin D or can locally produce vitamin D indicate that the lung represents a target for vitamin D actions. Similarly, the presence of the four FGF receptor isoforms in the lung and the ability of FGF23 to stimulate pulmonary cells support the concept that the lung is a target for FGF23 actions, whereas the contribution of klotho is still undetermined. This review will give an overview on how vitamin D or FGF23/klotho may act on the lung and interfere positively or negatively with lung health. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Ghislaine Gayan‐Ramirez
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETAKU LeuvenLeuvenBelgium
| | - Wim Janssens
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETAKU LeuvenLeuvenBelgium
- Clinical Department of Respiratory DiseasesUZ LeuvenLeuvenBelgium
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16
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Chan Y, Raju Allam VSR, Paudel KR, Singh SK, Gulati M, Dhanasekaran M, Gupta PK, Jha NK, Devkota HP, Gupta G, Hansbro PM, Oliver BGG, Chellappan DK, Dua K. Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases. Crit Rev Food Sci Nutr 2021:1-31. [PMID: 34613853 DOI: 10.1080/10408398.2021.1986467] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.
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Affiliation(s)
- Yinghan Chan
- School of Pharmacy, International Medical University (IMU), Kuala Lumpur, Malaysia
| | | | - Keshav Raj Paudel
- Centre for Inflammation, Centenary Institute, Sydney, NSW, Australia.,School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
| | - Sachin K Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Muralikrishnan Dhanasekaran
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA
| | - Piyush Kumar Gupta
- Department of Life Sciences, School of Basic Sciences and Research (SBSR), Sharda University, Greater Noida, Uttar Pradesh, India
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, India
| | - Hari Prasad Devkota
- Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India
| | - Philip M Hansbro
- Centre for Inflammation, Centenary Institute, Sydney, NSW, Australia.,School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia
| | - Brian Gregory George Oliver
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia.,Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Kamal Dua
- Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, India.,Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, Australia.,Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, Australia
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17
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Ng CY, Amini F, Ahmad Bustami N, Tan ESS, Tan PY, Mitra SR. Association of DNA damage with vitamin D and hair heavy metals of obese women. Mol Cell Toxicol 2021. [DOI: 10.1007/s13273-021-00149-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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18
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Vaghari-Tabari M, Mohammadzadeh I, Qujeq D, Majidinia M, Alemi F, Younesi S, Mahmoodpoor A, Maleki M, Yousefi B, Asemi Z. Vitamin D in respiratory viral infections: a key immune modulator? Crit Rev Food Sci Nutr 2021; 63:2231-2246. [PMID: 34470511 DOI: 10.1080/10408398.2021.1972407] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Iraj Mohammadzadeh
- Non-Communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Durdi Qujeq
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran.,Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Maryam Majidinia
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Forough Alemi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Simin Younesi
- Schoole of Health and Biomedical Sciences, RMIT University, Melborne, VIC, Australia
| | - Ata Mahmoodpoor
- Department of Anesthesiology and Intensive Care, School of Medicine, Tabriz University of Medical Science and Health Services, Tabriz, Iran
| | - Masomeh Maleki
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahman Yousefi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.,Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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19
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Adam-Bonci TI, Bonci EA, Pârvu AE, Herdean AI, Moț A, Taulescu M, Ungur A, Pop RM, Bocșan C, Irimie A. Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation. Int J Mol Sci 2021; 22:7089. [PMID: 34209324 PMCID: PMC8268667 DOI: 10.3390/ijms22137089] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/27/2021] [Accepted: 06/28/2021] [Indexed: 01/15/2023] Open
Abstract
Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation.
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Affiliation(s)
- Teodora-Irina Adam-Bonci
- Department of Pathophysiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (T.-I.A.-B.); (A.-E.P.)
| | - Eduard-Alexandru Bonci
- Department of Oncological Surgery and Gynecologic Oncology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;
| | - Alina-Elena Pârvu
- Department of Pathophysiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (T.-I.A.-B.); (A.-E.P.)
| | - Andrei-Ioan Herdean
- Department of Anatomy and Embryology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Augustin Moț
- Department of Chemistry, Faculty of Chemistry and Chemical Engineering, “Babeș-Bolyai” University, 400028 Cluj-Napoca, Romania;
| | - Marian Taulescu
- Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania; (M.T.); (A.U.)
- Synevovet Laboratory, 81 Pache Protopopescu, 021408 Bucharest, Romania
| | - Andrei Ungur
- Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania; (M.T.); (A.U.)
| | - Raluca-Maria Pop
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (R.-M.P.); (C.B.)
| | - Corina Bocșan
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (R.-M.P.); (C.B.)
| | - Alexandru Irimie
- Department of Oncological Surgery and Gynecologic Oncology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;
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20
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Cereta AD, Oliveira VR, Costa IP, Guimarães LL, Afonso JPR, Fonseca AL, de Sousa ART, Silva GAM, Mello DACPG, de Oliveira LVF, da Palma RK. Early Life Microbial Exposure and Immunity Training Effects on Asthma Development and Progression. Front Med (Lausanne) 2021; 8:662262. [PMID: 34222279 PMCID: PMC8241902 DOI: 10.3389/fmed.2021.662262] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022] Open
Abstract
Asthma is the most common inflammatory disease affecting the lungs, which can be caused by intrauterine or postnatal insults depending on the exposure to environmental factors. During early life, the exposure to different risk factors can influence the microbiome leading to undesired changes to the immune system. The modulations of the immunity, caused by dysbiosis during development, can increase the susceptibility to allergic diseases. On the other hand, immune training approaches during pregnancy can prevent allergic inflammatory diseases of the airways. In this review, we focus on evidence of risk factors in early life that can alter the development of lung immunity associated with dysbiosis, that leads to asthma and affect childhood and adult life. Furthermore, we discuss new ideas for potential prevention strategies that can be applied during pregnancy and postnatal period.
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Affiliation(s)
- Andressa Daronco Cereta
- School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - Vinícius Rosa Oliveira
- Department of Physical Therapy, EUSES University School, University of Barcelona-University of Girona (UB-UdG), Barcelona, Spain.,Research Group on Methodology, Methods, Models and Outcomes of Health and Social Sciences (M3O), University of VIC-Central University of Catalonia, Vic, Spain
| | - Ivan Peres Costa
- Master's and Doctoral Programs in Rehabilitation Sciences, Nove de Julho University, São Paulo, Brazil
| | - Letícia Lopes Guimarães
- School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
| | - João Pedro Ribeiro Afonso
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Adriano Luís Fonseca
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Alan Robson Trigueiro de Sousa
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Guilherme Augusto Moreira Silva
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Diego A C P G Mello
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Luis Vicente Franco de Oliveira
- Human Movement and Rehabilitation, Post Graduation Program Medical School, University Center of Anápolis-UniEVANGELICA, Anápolis, Brazil
| | - Renata Kelly da Palma
- School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil.,Department of Physical Therapy, EUSES University School, University of Barcelona-University of Girona (UB-UdG), Barcelona, Spain.,Institute for Bioengineering of Catalonia, Barcelona, Spain
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21
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Vitamin D can safely reduce asthma exacerbations among corticosteroid-using children and adults with asthma: a systematic review and meta-analysis of randomized controlled trials. Nutr Res 2021; 92:49-61. [PMID: 34274554 DOI: 10.1016/j.nutres.2021.05.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 05/14/2021] [Accepted: 05/23/2021] [Indexed: 12/16/2022]
Abstract
Previous studies have failed to draw a consistent conclusion over the effect of vitamin D administration on asthma. We hypothesized that vitamin D supplementation could improve the clinical efficacy of corticosteroids in patients with asthma as measured by exacerbations, Asthma Control Test (ACT) score, and lung function in order to maintain asthma control. We searched Web of Science, PubMed, the Cochrane Library, and ScienceDirect up through January 20, 2021 for randomized controlled trials analyzing the effect of vitamin D supplementation on asthma exacerbation. Studies were limited to patients with moderate to severe asthma who were treated with corticosteroids. We identified 12 studies involving 1,543 participants in this meta-analysis. Vitamin D supplementation significantly reduced the risk of asthma exacerbation (pooled risk ratio (RR) 0.70, 95% confidence interval (CI), 0.59, 0.83; P < .05). The pooled RR of the ACT score was 0.04 (95% CI, -0.19, 0.27; P > .05). The pooled standardized mean difference in vitamin D levels was 1.07 (95% CI, 0.77, 1.38; P < .05), and in the percentage of forced expiratory volume in one second was -0.02 (95% CI, -0.13, 0.09; P > .05). The pooled RR of adverse events was 1.06 (95% CI, 0.89, 1.25; P > .05). We performed subgroup analysis and meta-regression of serum vitamin D levels but found no source of heterogeneity. Vitamin D supplementation safely reduced the rate of asthma exacerbation but did not improve ACT score or lung function among patients with asthma treated with corticosteroids.
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Effect of age and body mass index on vitamin D level in children with asthma in Riyadh. Sci Rep 2021; 11:11522. [PMID: 34075181 PMCID: PMC8169780 DOI: 10.1038/s41598-021-91108-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 05/20/2021] [Indexed: 12/20/2022] Open
Abstract
Vitamin D deficiency prevalence in children has been rising. Low 25-hydroxyvitamin D3 (25(OH)D3) levels contribute to poor asthma control in children. This study assessed 25(OH)D3 levels in children with asthma from Riyadh with respect to anthropometrics, dietary, and lifestyle variables. Children with asthma (n, 60; 2–17 years) were assessed for serum 25-hydroxy vitamin D3 (25(OH)D3) level and body anthropometrics (weight, height, and body mass index [BMI]). Vitamin D dietary intake, sun exposure, and sociodemographic data were collected using a structured questionnaire. Thirty-one children (52%) had a 25(OH)D3 level < 50 nmol/L, 15 of whom (25%) had a level < 30 nmol/L. 25(OH)D3 level was significantly negatively correlated with age (P < 0.05), weight (P < 0.02), and height (P < 0.05). Children with a 25(OH)D3 level < 30 nmol/L had a significantly higher BMI than children with insufficient and sufficient vitamin D levels (P < 0.01). There was no significant effect of sex on 25(OH)D3 level. Higher 25(OH)D3 level was associated with a greater body area exposure to the sun. This study found that > 50% of the children with asthma had below sufficiency vitamin D levels. The vitamin D screening and supplementation of older and overweight children with asthma is recommended.
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Yousuf S, Atif F, Espinosa-Garcia C, Harris W, Turan N, Stein DG. Stroke-Induced Peripheral Immune Dysfunction in Vitamin D-Deficient Conditions: Modulation by Progesterone and Vitamin D. Mol Neurobiol 2021; 58:950-963. [PMID: 33063282 DOI: 10.1007/s12035-020-02129-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/09/2020] [Indexed: 12/15/2022]
Abstract
Vitamin D deficiency (Ddef) alters morphology and outcomes after a stroke. We investigated the interaction of Ddef following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. Ddef rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were measured along with immune cell populations from the spleen, thymus, and blood. Severely altered outcomes were observed in the Ddef group compared to the D-sufficient (Dsuf) group. Stroke caused peripheral immune dysfunction in the Dsuf group which was worse in the Ddef group. Systemic inflammation exacerbated injury outcomes in the Dsuf group and these were worse in the Ddef group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. Ddef as a comorbid condition with stroke worsens stroke outcomes and can delay functional recovery. Combination treatment with P and D might be promising for future stroke therapeutics in Ddef.
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Affiliation(s)
- Seema Yousuf
- Department of Emergency Medicine, Brain Research Laboratory, Emory University, 615 Michael Street, Room 655A, Atlanta, GA, 30322, USA.
| | - Fahim Atif
- Department of Emergency Medicine, Brain Research Laboratory, Emory University, 615 Michael Street, Room 655A, Atlanta, GA, 30322, USA
| | | | - Wayne Harris
- School of Medicine, Department of Hematology-Oncology, Emory University, Atlanta, GA, 30322, USA
| | - Nefize Turan
- Department of Neurology, School of Medicine, Tufts University, Boston, MA, 0211, USA
| | - Donald G Stein
- Department of Emergency Medicine, Brain Research Laboratory, Emory University, 615 Michael Street, Room 655A, Atlanta, GA, 30322, USA
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Checa J, Aran JM. Airway Redox Homeostasis and Inflammation Gone Awry: From Molecular Pathogenesis to Emerging Therapeutics in Respiratory Pathology. Int J Mol Sci 2020; 21:E9317. [PMID: 33297418 PMCID: PMC7731288 DOI: 10.3390/ijms21239317] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/05/2020] [Indexed: 02/06/2023] Open
Abstract
As aerobic organisms, we are continuously and throughout our lifetime subjected to an oxidizing atmosphere and, most often, to environmental threats. The lung is the internal organ most highly exposed to this milieu. Therefore, it has evolved to confront both oxidative stress induced by reactive oxygen species (ROS) and a variety of pollutants, pathogens, and allergens that promote inflammation and can harm the airways to different degrees. Indeed, an excess of ROS, generated intrinsically or from external sources, can imprint direct damage to key structural cell components (nucleic acids, sugars, lipids, and proteins) and indirectly perturb ROS-mediated signaling in lung epithelia, impairing its homeostasis. These early events complemented with efficient recognition of pathogen- or damage-associated recognition patterns by the airway resident cells alert the immune system, which mounts an inflammatory response to remove the hazards, including collateral dead cells and cellular debris, in an attempt to return to homeostatic conditions. Thus, any major or chronic dysregulation of the redox balance, the air-liquid interface, or defects in epithelial proteins impairing mucociliary clearance or other defense systems may lead to airway damage. Here, we review our understanding of the key role of oxidative stress and inflammation in respiratory pathology, and extensively report current and future trends in antioxidant and anti-inflammatory treatments focusing on the following major acute and chronic lung diseases: acute lung injury/respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and cystic fibrosis.
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Affiliation(s)
| | - Josep M. Aran
- Immune-Inflammatory Processes and Gene Therapeutics Group, IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Spain;
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Schrumpf JA, van der Does AM, Hiemstra PS. Impact of the Local Inflammatory Environment on Mucosal Vitamin D Metabolism and Signaling in Chronic Inflammatory Lung Diseases. Front Immunol 2020; 11:1433. [PMID: 32754156 PMCID: PMC7366846 DOI: 10.3389/fimmu.2020.01433] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023] Open
Abstract
Vitamin D plays an active role in the modulation of innate and adaptive immune responses as well as in the protection against respiratory pathogens. Evidence for this immunomodulatory and protective role is derived from observational studies showing an association between vitamin D deficiency, chronic airway diseases and respiratory infections, and is supported by a range of experimental studies using cell culture and animal models. Furthermore, recent intervention studies have now shown that vitamin D supplementation reduces exacerbation rates in vitamin D-deficient patients with chronic obstructive pulmonary disease (COPD) or asthma and decreases the incidence of acute respiratory tract infections. The active vitamin D metabolite, 1,25-dihydroxy-vitamin D (1,25(OH)2D), is known to contribute to the integrity of the mucosal barrier, promote killing of pathogens (via the induction of antimicrobial peptides), and to modulate inflammation and immune responses. These mechanisms may partly explain its protective role against infections and exacerbations in COPD and asthma patients. The respiratory mucosa is an important site of local 1,25(OH)2D synthesis, degradation and signaling, a process that can be affected by exposure to inflammatory mediators. As a consequence, mucosal inflammation and other disease-associated factors, as observed in e.g., COPD and asthma, may modulate the protective actions of 1,25(OH)2D. Here, we discuss the potential consequences of various disease-associated processes such as inflammation and exposure to pathogens and inhaled toxicants on vitamin D metabolism and local responses to 1,25(OH)2D in both immune- and epithelial cells. We furthermore discuss potential consequences of disturbed local levels of 25(OH)D and 1,25(OH)2D for chronic lung diseases. Additional insight into the relationship between disease-associated mechanisms and local effects of 1,25(OH)2D is expected to contribute to the design of future strategies aimed at improving local levels of 1,25(OH)2D and signaling in chronic inflammatory lung diseases.
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Affiliation(s)
- Jasmijn A Schrumpf
- Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands
| | - Anne M van der Does
- Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands
| | - Pieter S Hiemstra
- Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands
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Kumarathas I, Harsløf T, Andersen CU, Langdahl B, Hilberg O, Bjermer L, Løkke A. The risk of osteoporosis in patients with asthma. Eur Clin Respir J 2020; 7:1763612. [PMID: 32595917 PMCID: PMC7301699 DOI: 10.1080/20018525.2020.1763612] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 04/24/2020] [Indexed: 12/16/2022] Open
Abstract
It is well-known that use of continuous systemic corticosteroids (SG) affects bone metabolism, bone mineral density (BMD), and ultimately increases the risk of osteoporosis. In patients with asthma, on the other hand, the effects of long-term high-dose inhaled corticosteroids (ICS) on BMD and risk of osteoporotic fractures is controversial. The reasons for this inconsistency could be explained by the fact that only few long-term studies investigating the effect of ICS in patients with asthma exist. The studies are characterized by different study designs and duration of ICS exposure, small study populations, and differences between the used ICS. The aim of this article is to unravel which factors, if any, that contribute to an increased risk of osteoporosis in patients with asthma and to summarize the evidence regarding adverse effects of ICS on bone metabolism, BMD and osteoporotic fractures in patients with asthma.
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Affiliation(s)
| | - Torben Harsløf
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Charlotte Uggerhøj Andersen
- Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.,Institute for Biomedicine, Aarhus University, Aarhus, Denmark
| | - Bente Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Ole Hilberg
- Department of Medicine, Vejle Hospital, Vejle, Denmark
| | - Leif Bjermer
- Department of Respiratory Medicine and Allergology, Skaane University Hospital, Lund, Sweden
| | - Anders Løkke
- Department of Medicine, Vejle Hospital, Vejle, Denmark
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Forno E, Litonjua AA. Pollution, Obesity, Vitamin D, or Why Is Asthma So Complicated-and Interesting. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 7:1823-1824. [PMID: 31279465 DOI: 10.1016/j.jaip.2019.04.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 04/01/2019] [Indexed: 10/26/2022]
Affiliation(s)
- Erick Forno
- Division of Pulmonary Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa
| | - Augusto A Litonjua
- Division of Pulmonology, Department of Pediatrics, University of Rochester and Golisano Children's Hospital, Rochester, NY.
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Juergens LJ, Worth H, Juergens UR. New Perspectives for Mucolytic, Anti-inflammatory and Adjunctive Therapy with 1,8-Cineole in COPD and Asthma: Review on the New Therapeutic Approach. Adv Ther 2020; 37:1737-1753. [PMID: 32200535 PMCID: PMC7467491 DOI: 10.1007/s12325-020-01279-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Indexed: 12/30/2022]
Abstract
The mucolytic monoterpene 1,8-cineole (eucalyptol), the major constituent of eucalyptus species, is well known for its anti-inflammatory, antioxidant, bronchodilatory, antiviral and antimicrobial effects. The main protective antiviral, anti-inflammatory and mucolytic mechanisms of 1,8-cineole are the induction of interferon regulatory factor 3 (IRF3), the control of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) along with decreasing mucin genes (MUC2, MUC19). In normal human monocytes direct inhibition was shown of reactive oxygen species (ROS)-mediated mucus hypersecretion and of steroid resistence inducing superoxides (O2·-) and pro-inflammatory hydrogen peroxides (H2O2) with partial control of superoxide dismutase (SOD), which enzymatically metabolizes O2·- into H2O2. By inhibition of NF-κB, 1,8-cineole, at relevant plasma concentrations (1.5 µg/ml), strongly and significantly inhibited in normal human monocyte lipopolysaccharide (LPS)-stimulated cytokines relevant for exacerbation (tumour necrosis factor alpha (TNFα), interleukin (IL)-1β and systemic inflammation (IL-6, IL-8). Infectious agents and environmental noxa have access via TNFα and IL-1β to the immune system with induction of bronchitis complaints and exacerbations of chronic obstructive pulmonary disease (COPD), asthma and asthma-COPD overlap. In lymphocytes from healthy human donors 1,8-cineole inhibited TNFα, IL-1β, IL-4 and IL-5 and demonstrated for the first time control of Th1/2-type inflammation. 1,8-Cineole at relevant plasma levels increased additively in vitro the efficacy of inhaled guideline medications of budesonide (BUD) and budesonide + formoterol ,and preliminary data also showed increased efficacy of long-acting muscarinic receptor antagonist (LAMA)-mediated cytokine inhibition in vitro. On the basis of the preclinical data, earlier randomised controlled studies with adjunctive therapy of 1,8-cineole (3 × 200 mg/day) for 6 months showed improvement of uncontrolled asthma by significant improvement of lung function, nocturnal asthma and quality of life scores and in COPD decrease of exacerbations (- 38.5%) (during wintertime). This review reports an update with reference to the literature of 1,8-cineole, also as adjunctive therapy, as a therapeutic agent for the protection and control of inflammatory airway diseases.
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Affiliation(s)
- Lisa Joy Juergens
- Medical University of Tübingen, Medical School, 72070 Tübingen, Germany
| | | | - Uwe R. Juergens
- Department of Pulmonary Rehabilitation, Asklepios Nordseeklinik Westerland, Norderstraße 81, 25980 Sylt, Germany
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Wang Y, Chen YJ, Xiang C, Jiang GW, Xu YD, Yin LM, Zhou DD, Liu YY, Yang YQ. Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas. JOURNAL OF ETHNOPHARMACOLOGY 2020; 252:112635. [PMID: 32004629 DOI: 10.1016/j.jep.2020.112635] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 01/23/2020] [Accepted: 01/24/2020] [Indexed: 06/10/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments. AIM OF THE STUDY Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy. MATERIALS AND METHODS A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated. RESULTS The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10-2 mM) and ginkgolide A (1 × 10-5 mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 μg/kg) and ginkgolide A (205 μg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6). CONCLUSION Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy.
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Affiliation(s)
- Yu Wang
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yan-Jiao Chen
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Cheng Xiang
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Guang-Wei Jiang
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yu-Dong Xu
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Lei-Miao Yin
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Dong-Dong Zhou
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yan-Yan Liu
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yong-Qing Yang
- International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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Vitamin D and childhood asthma: causation and contribution to disease activity. Curr Opin Allergy Clin Immunol 2020; 19:126-131. [PMID: 30608234 DOI: 10.1097/aci.0000000000000509] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
PURPOSE OF REVIEW To review the literature of the past 18 months (April 2017 through September, 2018) relating to vitamin D and childhood asthma. RECENT FINDINGS A combined analysis of two clinical trials of maternal vitamin D supplementation trials showed a significant protective effect of vitamin D supplementation trials in the primary prevention of asthma and recurrent wheeze up to age 3 years. Secondary analyses from these trials have also suggested that initial maternal vitamin D status could affect the response to supplementation during pregnancy, with the biggest protective effect in children born to mothers with initial 25hydroxyvitamin D (25OHD) levels of at least 30 ng/ml. A postnatal, 6-month vitamin D supplementation trial in black, premature babies showed a 34% decreased risk of recurrent wheezing at 1 year among the infants who received supplementation. An individual patient data meta-analysis of published clinical trials concluded that vitamin D supplementation decreased the risk of asthma exacerbations in those with 25OHD levels less than 10 ng/ml. Results of observational analyses on primary prevention of asthma and in prevention of exacerbations remain mixed, with the bulk of the evidence suggesting that there is a protective effect of higher vitamin D levels. SUMMARY Evidence continues to accumulate that vitamin D supplementation helps to prevent the development of asthma and recurrent wheeze in early life, and may also help in the management of asthma. The level(s) of circulating vitamin D that maximizes these effects remains to be identified.
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Malliaraki N, Lakiotaki K, Vamvoukaki R, Notas G, Tsamardinos I, Kampa M, Castanas E. Translating vitamin D transcriptomics to clinical evidence: Analysis of data in asthma and chronic obstructive pulmonary disease, followed by clinical data meta-analysis. J Steroid Biochem Mol Biol 2020; 197:105505. [PMID: 31669573 DOI: 10.1016/j.jsbmb.2019.105505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 09/29/2019] [Accepted: 10/22/2019] [Indexed: 12/29/2022]
Abstract
Vitamin D (VitD) continues to trigger intense scientific controversy, regarding both its bi ological targets and its supplementation doses and regimens. In an effort to resolve this dispute, we mapped VitD transcriptome-wide events in humans, in order to unveil shared patterns or mechanisms with diverse pathologies/tissue profiles and reveal causal effects between VitD actions and specific human diseases, using a recently developed bioinformatics methodology. Using the similarities in analyzed transcriptome data (c-SKL method), we validated our methodology with osteoporosis as an example and further analyzed two other strong hits, specifically chronic obstructive pulmonary disease (COPD) and asthma. The latter revealed no impact of VitD on known molecular pathways. In accordance to this finding, review and meta-analysis of published data, based on an objective measure (Forced Expiratory Volume at one second, FEV1%) did not further reveal any significant effect of VitD on the objective amelioration of either condition. This study may, therefore, be regarded as the first one to explore, in an objective, unbiased and unsupervised manner, the impact of VitD levels and/or interventions in a number of human pathologies.
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Affiliation(s)
- Niki Malliaraki
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece; Laboratory of Clinical Chemistry/Biochemistry, University Hospital, Heraklion, Greece
| | - Kleanthi Lakiotaki
- Department of Computer Science, University of Crete, School of Sciences, Heraklion, Greece
| | - Rodanthi Vamvoukaki
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece
| | - George Notas
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece
| | - Ioannis Tsamardinos
- Department of Computer Science, University of Crete, School of Sciences, Heraklion, Greece; Gnosis Data Analysis PC, Heraklion, Greece
| | - Marilena Kampa
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece
| | - Elias Castanas
- Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
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Abstract
PURPOSE OF REVIEW Asthma is a common chronic disease of the airways characterized by recurrent respiratory symptoms, bronchoreactivity, and airway inflammation. The high toll on quality of life has led to sustained efforts to understand the factors leading to asthma inception and poor disease control. Obesity is another increasingly common pediatric disease, which appears to increase the risk for incident asthma and worsened disease severity. Currently, our understanding of how obesity affects asthma risk and affects its phenotypic characteristics remains incomplete. The current review describes our current understanding of the epidemiology, clinical characteristics, and management considerations of obesity-related asthma in children. RECENT FINDINGS The epidemiologic relationship between obesity in children and incident asthma remains confusing despite numerous longitudinal cohort studies, and appears to be influenced by early life exposures, patterns of somatic growth and underlying familial risks of allergic disease. Children with comorbid obesity and asthma demonstrate diverse phenotypic characteristics which are still becoming clear. SUMMARY Like any child with asthma, a child with comorbid obesity requires an individualized approach adhering to current best-practice guidelines and an understanding of how obesity and asthma may interact.
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Maes K, Serré J, Mathyssen C, Janssens W, Gayan-Ramirez G. Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential? Calcif Tissue Int 2020; 106:76-87. [PMID: 31350569 DOI: 10.1007/s00223-019-00591-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 07/18/2019] [Indexed: 12/16/2022]
Abstract
Patients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency is a worldwide problem and is extremely prevalent in these patients. Vitamin D, known for its calcemic effects, also has immunomodulatory and anti-infectious actions and can therefore be a possible agent to treat or prevent exacerbations. This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in CF, COPD, and asthma.
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Oxidative Stress and Vitamin D as Predictors in Multiple Sclerosis. CURRENT HEALTH SCIENCES JOURNAL 2020; 46:371-378. [PMID: 33717511 PMCID: PMC7948027 DOI: 10.12865/chsj.46.04.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Accepted: 12/18/2020] [Indexed: 11/08/2022]
Abstract
Multiple Sclerosis (MS) is a multifactorial demyelinating diseases that affect mostly the young and active people. Here, is crucial to identify new strategies in order to slow down the diseases progression and maintain a good functional outcome. Our hypothesis was that the interconnection between anti-oxidant molecules and anti-inflammatory or neuroprotective molecules can act as predictors of diseases progression. In the study were included 36 patients with MS. Inclusion criteria were the following: patients over 18 years old were divided in three groups, 16 relapsing-remitting MS (RRMS) group, 10 secondary progressive MS (SPMS) group and 10 healthy control group. We showed that the vitamin D sufficiency did not improve de EDSS score in the later stage of diseases. Also, we showed that in the early stage (RRMS) the vitamin D status can significantly improve the EDSS and IADL score and may slow down the diseases progression. started with the early stage of diseases (RRMS) we found that catalase activity, an enzyme that act as anti-oxidant, is significantly decreased compare with healthy people, and can be associated with a low level of vitamin D. we concluded that a pro-oxidative and anti-oxidative balance is an important player in the multifactorial mechanism of MS diseases progression and additional prospective studies are needed to determine optimal vitamin D levels that lead to clinical and immunological benefits for patients with MS. Long-term follow-up studies using high-dose vitamin D supplementation are needed to confirm the preliminary results of the studies.
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Liu X, Zhang Y, Jiang H, Jiang N, Gao J. Integrative analysis of the contribution of mRNAs and long non‑coding RNAs to the pathogenesis of asthma. Mol Med Rep 2019; 20:2617-2624. [PMID: 31524265 PMCID: PMC6691207 DOI: 10.3892/mmr.2019.10511] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Accepted: 05/23/2019] [Indexed: 12/27/2022] Open
Abstract
Asthma, a common but poorly controlled disease, is one of the most serious health problems worldwide; however, the mechanisms underlying the development of asthma remain unknown. Long non-coding RNAs (lncRNAs) and mRNAs serve important roles in the initiation and progression of various diseases. The present study aimed to investigate the role of differentially expressed lncRNAs and mRNAs associated with asthma. Differentially expressed lncRNAs and mRNAs were screened between the expression data of 62 patients with asthma and 43 healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the biological functions and pathways associated with the lncRNAs and mRNAs identified. Protein-protein interaction (PPI) networks were subsequently generated. In addition, lncRNA-mRNA weighted co-expression networks were obtained. In total, 159 differentially expressed lncRNAs and 1,261 mRNAs were identified. GO and KEGG analyses revealed that differentially expressed mRNAs regulated asthma by participating in the ‘vascular endothelial (VEGF) signaling pathway’, ‘oxidative phosphorylation’, ‘Fc ε RI signaling pathway’, ‘amino sugar and nucleotide sugar metabolism’, ‘histidine metabolism’, ‘β-alanine metabolism’ and ‘extracellular matrix-receptor interaction’ (P<0.05). Furthermore, protein kinase B 1 had the highest connectivity degree in the PPI network, and was significantly enriched in the ‘VEGF signaling pathway’ and ‘Fc ε RI signaling pathway’. A total of 8 lncRNAs in the lncRNA-mRNA co-expression network were reported to interact with 52 differentially expressed genes, which were enriched in asthma-associated GO and KEGG pathways. The results obtained in the present study may provide insight into the profile of differentially expressed lncRNAs associated with asthma. The identification of a cluster of dysregulated lncRNAs and mRNAs may serve as a potential therapeutic strategy to reverse the progression of asthma.
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Affiliation(s)
- Xiaochuang Liu
- Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China
| | - Yanyan Zhang
- Department of Pharmacy, Anhui Medical College, Hefei, Anhui 230601, P.R. China
| | - Hui Jiang
- Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China
| | - Nannan Jiang
- Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China
| | - Jiarong Gao
- Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, P.R. China
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Yan YX, Li YN. [Pathogenesis of steroid-resistant asthma and the influence of vitamin D]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21:724-729. [PMID: 31315776 PMCID: PMC7389094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/22/2019] [Indexed: 11/04/2023]
Abstract
Glucocorticoid (GC) is currently the most effective drug for controlling persistent asthma; however, there is a significant difference in the response to GC among patients with asthma. Steroid-resistant asthma is one of the subtypes of asthma and has poor response to high-dose GC treatment. It may affect the quality of life of patients and even threaten their lives. Therefore, it is of great significance to explore the pathogenesis of steroid-resistant asthma and related targeted treatment strategy. In recent years, a variety of pathogeneses have been found to participate in the development and progression of steroid-resistant asthma, including the reduction in the binding between GC receptor and GC, the increase in the expression of GC receptor β, over-activation of nuclear transcription factor activating protein 1 and nuclear factor-κB, abnormality in histone acetylation, and immune-mediated cytokine dysregulation. In addition, many studies have shown that vitamin D can improve the sensitivity to GC among patients with steroid-resistant asthma. This article reviews the pathogenesis of steroid-resistant asthma and the influence of vitamin D.
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Affiliation(s)
- Yu-Xiao Yan
- First Clinical Medical College of Lanzhou University, Lanzhou 730000, China.
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Yan YX, Li YN. [Pathogenesis of steroid-resistant asthma and the influence of vitamin D]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21:724-729. [PMID: 31315776 PMCID: PMC7389094 DOI: 10.7499/j.issn.1008-8830.2019.07.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/22/2019] [Indexed: 06/10/2023]
Abstract
Glucocorticoid (GC) is currently the most effective drug for controlling persistent asthma; however, there is a significant difference in the response to GC among patients with asthma. Steroid-resistant asthma is one of the subtypes of asthma and has poor response to high-dose GC treatment. It may affect the quality of life of patients and even threaten their lives. Therefore, it is of great significance to explore the pathogenesis of steroid-resistant asthma and related targeted treatment strategy. In recent years, a variety of pathogeneses have been found to participate in the development and progression of steroid-resistant asthma, including the reduction in the binding between GC receptor and GC, the increase in the expression of GC receptor β, over-activation of nuclear transcription factor activating protein 1 and nuclear factor-κB, abnormality in histone acetylation, and immune-mediated cytokine dysregulation. In addition, many studies have shown that vitamin D can improve the sensitivity to GC among patients with steroid-resistant asthma. This article reviews the pathogenesis of steroid-resistant asthma and the influence of vitamin D.
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Affiliation(s)
- Yu-Xiao Yan
- First Clinical Medical College of Lanzhou University, Lanzhou 730000, China.
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38
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Vitamin D Supplementation Reduces Both Oxidative DNA Damage and Insulin Resistance in the Elderly with Metabolic Disorders. Int J Mol Sci 2019; 20:ijms20122891. [PMID: 31200560 PMCID: PMC6628266 DOI: 10.3390/ijms20122891] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 05/31/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023] Open
Abstract
Background: Research evidence indicates that vitamin D deficiency is involved in the pathogenesis of insulin resistance (IR) and associated metabolic disorders including hyperglycemia and dyslipidemia. It also suggested that vitamin D deficiency is associated with elevated levels of oxidative stress and its complications. Therefore, the aim of our study was to determine the effect of vitamin D supplementation on DNA damage and metabolic parameters in vitamin D deficient individuals aged >45 with metabolic disorders. Material and Methods: Of 98 initially screened participants, 92 subjects deficient in vitamin D were included in the study. They were randomly assigned to the following group: with vitamin D supplementation (intervention group, n = 48) and without supplementation (comparative group, n = 44). The patients from both groups were divided into two subgroups according to the presence or absence of type 2 diabetes (T2DM). The intervention group was treated with 2000 International Unit (IU) cholecalciferol/day between October and March for three months. At baseline and after three-month supplementation vitamin D concentration (25-OH)D3 and endogenous and oxidative DNA damage were determined. In addition, fast plasma glucose (FPG), fasting insulin, HbA1c and lipid fraction (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglyceride (TG)), as well as anthropometric measurements (weight, height) were gathered. The following IR-related parameters were calculated Homeostatic Model Assesment – Insulin Resistance (HOMA-IR) and TG/HDL ratio. Results: Three-month vitamin D supplementation increased the mean vitamin D concentration to generally accepted physiological level independently of T2DM presence. Importantly, vitamin D exposure decreased the level of oxidative DNA damage in lymphocytes of patients of intervention group. Among studied metabolic parameters, vitamin D markedly increased HDL level, decreased HOMA-IR, TG/HDL ratio. Furthermore, we found that HbA1c percentage diminished about 0.5% in T2DM patients supplemented with vitamin D. Conclusion: The current study demonstrated that daily 2000I U intake of vitamin D for three months decreased the level of oxidative DNA damage, a marker of oxidative stress, independently on T2DM presence. Furthermore, vitamin D reduced metabolic parameters connected with IR and improved glucose and lipid metabolism. Therefore, our results support the assertion that vitamin D, by reducing oxidative stress and improving of metabolic profile, may decrease IR and related diseases.
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Ramadan A, Sallam SF, Elsheikh MS, Ishak SR, Abdelsayed MG, Salah M, Nazih R, Khairat R, Ibrahim OM. VDR gene expression in asthmatic children patients in relation to vitamin D status and supplementation. GENE REPORTS 2019. [DOI: 10.1016/j.genrep.2019.100387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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de Groot LES, van der Veen TA, Martinez FO, Hamann J, Lutter R, Melgert BN. Oxidative stress and macrophages: driving forces behind exacerbations of asthma and chronic obstructive pulmonary disease? Am J Physiol Lung Cell Mol Physiol 2018; 316:L369-L384. [PMID: 30520687 DOI: 10.1152/ajplung.00456.2018] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Oxidative stress is a common feature of obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Lung macrophages are key innate immune cells that can generate oxidants and are known to display aberrant polarization patterns and defective phagocytic responses in these diseases. Whether these characteristics are linked in one way or another and whether they contribute to the onset and severity of exacerbations in asthma and COPD remain poorly understood. Insight into oxidative stress, macrophages, and their interactions may be important in fully understanding acute worsening of lung disease. This review therefore highlights the current state of the art regarding the role of oxidative stress and macrophages in exacerbations of asthma and COPD. It shows that oxidative stress can attenuate macrophage function, which may result in impaired responses toward exacerbating triggers and may contribute to exaggerated inflammation in the airways.
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Affiliation(s)
- Linsey E S de Groot
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.,Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands
| | - T Anienke van der Veen
- Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen , Groningen , The Netherlands.,Groningen Research Institute for Asthma and Chronic Obstructive Pulmonary Disease, University Medical Center Groningen, University of Groningen , Groningen , The Netherlands
| | - Fernando O Martinez
- Department of Biochemical Sciences, University of Surrey , Guildford , United Kingdom
| | - Jörg Hamann
- Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands
| | - René Lutter
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.,Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands
| | - Barbro N Melgert
- Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen , Groningen , The Netherlands.,Groningen Research Institute for Asthma and Chronic Obstructive Pulmonary Disease, University Medical Center Groningen, University of Groningen , Groningen , The Netherlands
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41
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Chaoyang Y, Qingfeng B, Jinxing F. MiR-216a-5p protects 16HBE cells from H 2O 2-induced oxidative stress through targeting HMGB1/NF-kB pathway. Biochem Biophys Res Commun 2018; 508:416-420. [PMID: 30502088 DOI: 10.1016/j.bbrc.2018.11.060] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Accepted: 11/11/2018] [Indexed: 02/06/2023]
Abstract
Asthma is a complex, chronic inflammatory disorder of the bronchial tree, and can affect patients of all ages including children. High mobility group box 1 (HMGB1) has been proved as a therapeutic target in children with asthma, and was predicted to be the target gene of microRNA-216a-5p (miR-216a-5p). The present study aimed to investigate the function of miR-216a-5p in asthma by creating a human bronchial epithelial cell (16HBE) injury model using H₂O₂. A significantly elevation of HMGB1 protein expression and a reduction of miR-216a-5p expression were observed in children with asthma as well as in H₂O₂ stimulated 16HBE cells. Dual luciferase reporter assays confirmed the target reaction between HMGB1 and miR-216a-5p. MiR-216a-5p repressed HMGB1 protein expression in H₂O₂ induced 16HBE cells. Moreover, miR-216a-5p inhibited H₂O₂ induced cell injury by elevating cell proliferation and decreasing cell apoptosis in 16HBE cells. Furthermore, miR-216a-5p repressed NF-kB pathway activation in H₂O₂ induced 16HBE cells. In conclusion, these results suggested that miR-216a-5p functions as a negative regulator of H₂O₂ induced 16HBE cell injury through targeting HMGB1/NF-kB pathway, provided a potential therapeutic target for asthma.
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Affiliation(s)
- Yin Chaoyang
- Department of Paediatrics, Shangluo Central Hospital, Shangluo, 726000, Shaanxi, China
| | - Bai Qingfeng
- Department of Paediatrics, Shangluo Central Hospital, Shangluo, 726000, Shaanxi, China.
| | - Feng Jinxing
- Department of Paediatrics, Shenzhen Children's Hospital, Shenzhen, 518026, Guangdong, China
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42
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Prenatal 25-hydroxyvitamin D deficiency affects development of atopic dermatitis via DNA methylation. J Allergy Clin Immunol 2018; 143:1215-1218. [PMID: 30352202 DOI: 10.1016/j.jaci.2018.10.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 09/28/2018] [Accepted: 10/11/2018] [Indexed: 11/21/2022]
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Pfeffer PE, Lu H, Mann EH, Chen YH, Ho TR, Cousins DJ, Corrigan C, Kelly FJ, Mudway IS, Hawrylowicz CM. Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter. PLoS One 2018; 13:e0200040. [PMID: 30157189 PMCID: PMC6114286 DOI: 10.1371/journal.pone.0200040] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 08/16/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma. OBJECTIVES Mechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways. METHODS Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D. RESULTS Transcriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D. CONCLUSIONS In a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.
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Affiliation(s)
- Paul E. Pfeffer
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom
| | - Haw Lu
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
| | - Elizabeth H. Mann
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
| | - Yin-Huai Chen
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
| | - Tzer-Ren Ho
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
| | - David J. Cousins
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
- Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester and NIHR Leicester Biomedical Research Centre–Respiratory, Glenfield Hospital, Leicester, United Kingdom
| | - Chris Corrigan
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
| | - Frank J. Kelly
- MRC-PHE Centre for Environment and Health and NIHR HPRU in Health Impact of Environmental Hazards, King’s College London, Franklin Wilkins Building, London, United Kingdom
| | - Ian S. Mudway
- MRC-PHE Centre for Environment and Health and NIHR HPRU in Health Impact of Environmental Hazards, King’s College London, Franklin Wilkins Building, London, United Kingdom
| | - Catherine M. Hawrylowicz
- MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, Guy’s Hospital, London, United Kingdom
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Taylor RJ, Schlosser RJ, Soler ZM, Mattos JL, Mulligan JK. Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis. Int Forum Allergy Rhinol 2018; 8:10.1002/alr.22120. [PMID: 29719127 PMCID: PMC6214788 DOI: 10.1002/alr.22120] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 02/22/2018] [Accepted: 03/01/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS). METHODS PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non-atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients. Demographics, atopic status, asthmatic status, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, Lund-Kennedy nasal endoscopy scores, Lund-Mackay sinus computed tomography (CT) scores, Kennedy Osteitis scores, and GC utilization 6 months postoperatively were collected. Intracellular immunostaining was then performed for functional GC receptor α (GCRα) and nonfunctional GC receptor β (GCRβ), followed by flow cytometry analysis of geometric mean fluorescent intensity (MFI) and the percentage of cells expressing each GC receptor isoform. RESULTS Compared to controls, each CRS subtype had decreased PBML GCRα and GCRα:GCRβ MFI expression, but no difference in GCRβ expression. Decreasing PBML GCRα in AFRS was associated with increasing Lund-Mackay sinus CT scores (r = -0.880, p =0.004). No significant associations were found between GC receptor isoform expression and other clinical measures. CONCLUSION CRS patients have reduced functional PBML GCRα expression and decreased GCRα:GCRβ compared to controls. Reductions in GCRα in AFRS are associated with worsening Lund-Mackay sinus CT scores. The clinical implications of decreased functional GC receptor expression merits further investigation.
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Affiliation(s)
- Robert J. Taylor
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, SC
| | - Rodney J. Schlosser
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, SC
- Ralph H. Johnson VA Medical Center, Charleston, SC
| | - Zachary M. Soler
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, SC
| | - Jose L. Mattos
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, SC
| | - Jennifer K. Mulligan
- Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, SC
- Ralph H. Johnson VA Medical Center, Charleston, SC
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC
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Asthma and Allergy "Epidemic" and the Role of Vitamin D Deficiency. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 996:169-183. [PMID: 29124699 DOI: 10.1007/978-3-319-56017-5_14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The increase in asthma and allergies prevalence that has been recorded in many countries during the last decades, and the reemergence of vitamin D (VD) deficiency in many populations worldwide, renders fairly plausible the assumption of an underlying association between these two conditions and justifies the research effort invented in this issue. Indeed, there is growing body of evidence from epidemiological, laboratory, and clinical studies, suggesting that such an association does exist. The hypothesis of low levels of VD leading to compromised fetal programming and impairment of various immune functions involved in asthma and allergic disorders, stands as the most credible explanation of this presumed association. However, the evidence is not yet definite and there are some conflicting results among studies. As a consequence, no safe conclusions can be drawn yet, and more research is required in order to fully clarify the involvement of VD deficiency in the pathogenesis of asthma and allergies, and decide if VD has a role to play in the prevention and therapy of these disorders.
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Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol 2018; 141:1169-1179. [PMID: 29627041 PMCID: PMC5973542 DOI: 10.1016/j.jaci.2018.02.004] [Citation(s) in RCA: 545] [Impact Index Per Article: 77.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 12/14/2017] [Accepted: 02/09/2018] [Indexed: 12/14/2022]
Abstract
Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.
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Affiliation(s)
- Ubong Peters
- Pulmonary and Critical Care Medicine, University of Vermont, Burlington, Vt
| | - Anne E Dixon
- Pulmonary and Critical Care Medicine, University of Vermont, Burlington, Vt
| | - Erick Forno
- Pediatric Pulmonary Medicine, Allergy, and Immunology, University of Pittsburgh, Pittsburgh, Pa.
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Investigation of the uterine structural changes in the experimental model with polycystic ovary syndrome and effects of vitamin D treatment: An ultrastructural and immunohistochemical study. Reprod Biol 2018; 18:53-59. [DOI: 10.1016/j.repbio.2018.01.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/17/2017] [Accepted: 01/02/2018] [Indexed: 01/26/2023]
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Bai YJ, Dai RJ. Serum levels of vitamin A and 25-hydroxyvitamin D3 (25OHD3) as reflectors of pulmonary function and quality of life (QOL) in children with stable asthma: A case-control study. Medicine (Baltimore) 2018; 97:e9830. [PMID: 29443744 PMCID: PMC5839812 DOI: 10.1097/md.0000000000009830] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND This study aims to explore the relationship between serum vitamin A and 25-hydroxyvitamin D3 (25OHD3) levels with pulmonary function and quality of life (QOL) in children with stable asthma. METHODS A total of 117 cases of children with stable asthma were assigned into the case group and 129 healthy children underwent physical examination during the same period into the control group. Electrochemiluminescence was employed to determine serum vitamin A and 25OHD3 levels. The children with stable asthma were further divided into the mild, moderate, and severe groups according to their degree of asthma. A pulmonary function meter was used to assess the pulmonary function indexes: percentage of forced expiratory volume in 1 sec/predictive value (FEV1%pred), forced vital capacity (FVC), forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), and maximal voluntary ventilation (MVV). The children's quality (QOL) of life with asthma was evaluated by their activities of daily living (ADLs) and Medical Research Council (MRC) scores. Pearson correlation analysis was applied to analyze the correlations of serum vitamin A and 25OHD3 levels with FEV1%pred, FVC, FEV1/FVC, PEF, MVV, ADL, and MRC. RESULTS Serum vitamin A and 25OHD3 levels were lower in children with stable asthma than those who were in the control group (P < .05). The severe group showed the lowest FEV1%pred, FVC, FEV1/FVC, PEF, MVV, and ADL scores, and the highest MRC score compared to the mild and moderate groups (all P < .05). Serum vitamin A and 25OHD3 levels were positively correlated with pulmonary function and ADL score in children with stable asthma, while serum vitamin A and 25OHD3 levels were negatively correlated with MRC score (all P < .05). In the case group, serum vitamin A and 25OHD3 levels were positively correlated with serum calcium and phosphorus levels (all P < .05). CONCLUSION These findings indicate that increased serum vitamin A and 25OHD3 levels reflect good pulmonary function and good QOL in children with stable asthma.
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Affiliation(s)
| | - Ru-Jun Dai
- 2nd Department of Pediatric, Cangzhou Central Hospital, Cangzhou, P.R. China
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Asthmatic Patients with Vitamin D Deficiency have Decreased Exacerbations after Vitamin Replacement. Nutrients 2017; 9:nu9111234. [PMID: 29137124 PMCID: PMC5707706 DOI: 10.3390/nu9111234] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 11/07/2017] [Accepted: 11/08/2017] [Indexed: 12/24/2022] Open
Abstract
Background: Intervention studies with vitamin D in asthma are inconclusive for several reasons, such as inadequate dosing or duration of supplementation or uncontrolled baseline vitamin D status. Our aim was to evaluate the benefit of long term vitamin D add-on in asthmatic patients with actual vitamin D deficiency, that is a serum 25-hydroxy vitamin D (25-OHD ) below 20 ng/mL. Methods: Serum 25-OHD, asthma exacerbations, spirometry and inhaled corticosteroids (CS) dose were evaluated in a cohort of 119 asthmatic patients. Patients with deficiency were evaluated again after one year vitamin supplementation. Results: 25-OHD was low in 111 patients and was negatively related to exacerbations (p < 0.001), inhaled CS dose (p = 0.008) and asthma severity (p = 0.001). Deficiency was found in 90 patients, 55 of whom took the supplement regularly for one year, while 24 discontinued the study and 11 were not adherent. Patients with vitamin D deficiency after 12 months supplementation showed significant decrease of exacerbations (from 2.6 ± 1.2 to 1.6 ± 1.1, p < 0.001), circulating eosinophils (from 395 ± 330 to 272 ± 212 106/L, p < 0.001), and need of oral CS courses (from 35 to 20, p = 0.007) and improvement of airway obstruction. Conclusions: Asthma exacerbations are favored by vitamin D deficiency and decrease after long-term vitamin D replacement. Patients who are vitamin D deficient benefit from vitamin D supplementation.
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Pfeffer PE, Hawrylowicz CM. Vitamin D in Asthma: Mechanisms of Action and Considerations for Clinical Trials. Chest 2017; 153:1229-1239. [PMID: 28923762 DOI: 10.1016/j.chest.2017.09.005] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 08/15/2017] [Accepted: 09/06/2017] [Indexed: 12/17/2022] Open
Abstract
There is increasing interest in the therapeutic utility of vitamin D in asthma, which is supported by a significant body of evidence on epidemiologic associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunologic pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells, and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterized by a failure of immune tolerance and the development of pathologic responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation. Alarmin cytokines are increasingly implicated in nonallergic eosinophilic inflammation, which vitamin D also regulates. Steroid resistance and pathologic interleukin (IL)-17 responses are features of severe asthma, and vitamin D beneficially enhances the response to steroids in these individuals. Additionally, vitamin D enhances antimicrobial pathways, which is of relevance to infection-precipitated asthma exacerbations. These mechanisms support a role for vitamin D as secondary prevention to reduce exacerbations and inflammation in asthma. Similar mechanisms, and effects on fetal lung development, likely underlie a primary prevention therapeutic role in pregnancy for vitamin D to reduce the development of asthma in children. However, randomized controlled trials of variable design show inconsistent positive outcomes for vitamin D interventions in asthma. Increased understanding of the biological characteristics of vitamin D reveals methodological issues that might explain certain negative outcomes. Importantly, on systematic review of the trials to date, vitamin D is shown to be beneficial in asthma. The evidence discussed in this review supports the importance of optimizing vitamin D in holistic asthma care.
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Affiliation(s)
- Paul E Pfeffer
- William Harvey Research Institute, Queen Mary University of London, London, England; MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, England
| | - Catherine M Hawrylowicz
- MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, Guy's Hospital, London, England.
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