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Khalil B, Sharif-Askari NS, Selvakumar B, Mdkhana B, Hachim I, Zakri A, Hundt J, Hamid Q, Halwani R. Vitamin D3 suppresses NLRP3 inflammasome pathway and enhances steroid sensitivity in a neutrophilic steroid hyporesponsive asthma mouse model. Inflamm Res 2025; 74:51. [PMID: 40082319 DOI: 10.1007/s00011-025-02009-4] [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: 10/24/2024] [Revised: 01/29/2025] [Accepted: 02/10/2025] [Indexed: 03/16/2025] Open
Abstract
OBJECTIVE Severe steroid hyporesponsive asthma is a heterogeneous group of chronic inflammatory diseases characterized by irreversible airflow limitation, hyperresponsiveness, inflammation, and remodelling of the airways. Severe asthmatics account for more than 60% of asthma-related healthcare cost worldwide given they are hyporesponsive to corticosteroids and due to the absence of targeted treatment specifically for the T helper-17 (Th-17) high endotype. Hence, there is a clear unmet need to investigate other treatment options to control patients' symptoms. The role of the NLRP3 inflammasome pathway has been highlighted in the literature to contribute to disease pathogenesis and severity. Interestingly, vitamin D3 is an important regulator of the NLRP3 inflammasome pathway. METHODS Using house dust mite (HDM) and lipopolysaccharide (LPS), we induced a neutrophilic steroid hyporesponsive asthma mouse model to investigate the effect of vitamin D3 on downregulating the NLRP3 inflammasome pathway and enhancing steroid sensitivity. RESULTS We showed that calcitriol, the active form of vitamin D3, could downregulate the NLRP3 inflammasome pathway. This was associated with a significant reduction in airway hyperresponsiveness, IL-17 release, neutrophil infiltration, and mucus secretion. Further, calcitriol enhanced steroid sensitivity by inhibiting the expression of GR-β. Mechanistically, calcitriol targeted the NLRP3 inflammasome to ubiquitination. CONCLUSIONS Our research highlights the potential use of calcitriol as a low cost and accessible supplement to ameliorate airway inflammation during severe steroid hyporesponsive asthma.
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Affiliation(s)
- Bariaa Khalil
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Narjes Saheb Sharif-Askari
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Balachandar Selvakumar
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Bushra Mdkhana
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Ibrahim Hachim
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Adel Zakri
- Department of Plant Production, Faculty of Agriculture and Food Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Jennifer Hundt
- Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany
| | - Qutayba Hamid
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, QC, Canada
| | - Rabih Halwani
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
- Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
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Li T, Wang Q, Li Y, Zhang W, Chen M, Deng B, Liang L, Lin W, Lin Y, Meng Y. Predictive effects of advanced lung cancer inflammation index and serum vitamin D on mortality in patients with asthma. Nutr J 2025; 24:26. [PMID: 39955522 PMCID: PMC11829343 DOI: 10.1186/s12937-024-01065-6] [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: 09/27/2024] [Accepted: 12/22/2024] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Changes in systemic inflammation, nutritional status and serum vitamin D level are important characteristics of asthma. However, role and importance of nutritional inflammatory indicators or serum vitamin D concentrations in predicting the prognosis of asthma remain unclear. The advanced lung cancer inflammation index (ALI), based on body mass index (BMI), serum albumin and neutrophil-lymphocyte ratio (NLR), is a comprehensive index to assess systemic inflammation and nutrition. This study aimed to evaluate their independent and combined predictive value of mortality in asthma patients. METHODS This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Cox regression analysis was used to assess the independent or joint effect of ALI and serum vitamin D on mortality risks of asthma. Receiver operator characteristic curve analysis was used to compare the prognostic ability of ALI with its component factors, including NLR, albumin, neutrophil, lymphocyte and BMI. RESULTS A total of 2870 eligible asthma patients were included. After adjustment, higher ALI correlated significantly with reduced all-cause and respiratory disease mortality (adjusted hazard ratio [aHR] = 0.64 and 0.34; P < 0.05). Meanwhile, vitamin D deficiency correlated significantly with increased all-cause and respiratory disease mortality (aHR = 2.06 and 2.73; P < 0.05). The area under the curve of ALI in predicting 1-year, 5-year or 10-year all-cause mortality surpassed that of its five component indices. Joint analyses showed that individuals with higher levels of ALI and vitamin D had the lowest risks of all-cause and respiratory disease mortality (aHR = 0.31 and 0.17; P < 0.05). CONCLUSIONS ALI and serum vitamin D are robust independent and combined predictors of mortality in asthma patients. ALI offers superior predictive capability over its components, and sufficient vitamin D levels are beneficial for survival outcomes. The synergistic effect of high ALI and adequate vitamin D highlights the benefit of integrating both metrics into clinical practice for enhanced prognostic accuracy.
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Affiliation(s)
- Ting Li
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
- Department of Respiratory and Critical Care Medicine, Ganzhou Hospital-Nanfang Hospital, Ganzhou, 341000, China
| | - Qi Wang
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Yuhan Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China
| | - Wenyong Zhang
- Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Manyu Chen
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Bihua Deng
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Lin Liang
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Weixian Lin
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Yuying Lin
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China
| | - Ying Meng
- Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou North Road, Guangzhou, 510515, China.
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Lin B, Liu W, Wang HH, Qian H, Zhu X, Xu M, Zheng Y, Alhazmi N, Bai Y. Associations of co-exposure to polycyclic aromatic hydrocarbons and vitamin D with early lung dysfunction: Mediating roles of metabolic score-visceral adiposity index. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 289:117496. [PMID: 39657380 DOI: 10.1016/j.ecoenv.2024.117496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 12/04/2024] [Accepted: 12/04/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Preserved ratio impaired spirometry (PRISm) and airflow obstruction are recognized as critical early signs of chronic obstructive pulmonary disease (COPD). While these conditions arise from concurrent exposure to toxicants and essential nutrients, how vitamin D modifies the pulmonary toxicity induced by polycyclic aromatic hydrocarbons (PAHs) and the metabolic mechanisms involved is still unclear. METHODS Based on the National Health and Nutrition Examination Survey (NHANES) 2007-2012, data on urinary PAH metabolites (ΣOH-PAHs), serum vitamin D metabolite levels [Σ25(OH)D], and pulmonary function tests [forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC] from 2189 participants, including 369 subjects with early lung dysfunction, defined as PRISm or airflow obstruction. Multiple metabolic disorder indicators were calculated using biochemical markers. The interaction effects between vitamin D and PAHs were evaluated using multiple linear and logistic regression models. Causal mediation analyses and structural equation modeling were employed to investigate the mediating roles of metabolic indicators. RESULTS PAHs and vitamin D had opposite effects on lung function parameters [FEV1: β (95 CIs) = -0.01 (-0.02, -0.01) vs. 0.01 (0.01, 0.04); FVC: β (95 CIs) = -0.01 (-0.02, 0.01) vs. 0.04 (0.01, 0.06)] and risk of early lung dysfunction [OR (95 CIs) = 1.22 (1.06, 1.40) vs. 0.52 (0.37, 0.73)]. Decreased associations of ΣOH-PAHs with FEV1, FVC, and early lung dysfunction, as well as with metabolic score-visceral adiposity index (MSV) were visualized with increased Σ25(OH)D among subjects with body mass index (BMI) < 28 kg/m2. Furthermore, 2.18 %, 18.20 %, 5.70 %, and 4.70 % of the associations of co-exposure to ΣOH-PAHs and Σ25(OH)D with FEV1, FVC, FEV1/FVC, and early lung dysfunction disease were mediated by MSV. CONCLUSIONS Our findings indicated that vitamin D antagonizes the hazardous effects of PAHs on early lung dysfunction by metabolic alteration, providing new insight into the identification of the underlying high-risk populations and accessible prevention and intervention measures for attenuating PAH-induced lung dysfunction.
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Affiliation(s)
- Baihao Lin
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China
| | - Wanlu Liu
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China
| | - Hank-Han Wang
- Departments of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Haixia Qian
- Wuchang District Center for Disease Control and Prevention, Wuhan, Hubei, China
| | - Xinyu Zhu
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China
| | - Mengya Xu
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China
| | - Yuyu Zheng
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China
| | - Nada Alhazmi
- Department of Basic Sciences, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Yansen Bai
- School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, China.
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Fedora K, Setyoningrum RA, Aina Q, Rosyidah LN, Ni’mah NL, Titiharja FF. Vitamin D supplementation decrease asthma exacerbations in children: a systematic review and meta-analysis of randomized controlled trials. Ann Med 2024; 56:2400313. [PMID: 39421966 PMCID: PMC11492411 DOI: 10.1080/07853890.2024.2400313] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 11/04/2023] [Accepted: 07/03/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Observational studies have linked low vitamin D (VD) levels to increased asthma attacks in children. Subsequent meta-analyses of adults and children revealed that VD treatment might benefit asthmatic patients by reducing the incidence of exacerbations. Therefore, this review aims to analyze the effects of VD supplementation in reducing asthma exacerbations in children. METHODS Published reports from PubMed, Cochrane, and Google Scholar were systematically searched until April 2023. The study protocol was registered in the PROSPERO database CRD42023411796. Randomized controlled trial studies were included in this review. Meta-analysis was performed using Cochrane RevMan 5.1 and presented with 95% confidence intervals (CIs). RESULTS Ten relevant studies enrolled 1243 asthmatic children (631 children receiving vitamin D3 supplementation, 612 children receiving placebo) were included in this review. Our pooled analysis found that VD supplementation had a significant effect on lowering the total number of asthma exacerbations (RR 0.62; 95% CI: 0.44, 0.87; p = 0.01). Subgroup analysis revealed that a daily dose of VD given based on standard daily dose recommendation had a significant improvement on asthma exacerbations [(RR 0.41; 95% CI: 0,18, 0,92; p = 0.03). CONCLUSIONS Vitamin D supplementation can lower the occurrence of exacerbations in children with asthma, along with the improvement of FEV1.
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Affiliation(s)
- Katherine Fedora
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
- Department of Child Health, Dr. Soetomo General Hospital, Surabaya, East Java, Indonesia
| | - Retno Asih Setyoningrum
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
- Department of Child Health, Dr. Soetomo General Hospital, Surabaya, East Java, Indonesia
| | - Qorri’ Aina
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
| | - Laili Nur Rosyidah
- Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
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Bellavia D, Costa V, De Luca A, Maglio M, Pagani S, Fini M, Giavaresi G. Vitamin D Level Between Calcium-Phosphorus Homeostasis and Immune System: New Perspective in Osteoporosis. Curr Osteoporos Rep 2024; 22:599-610. [PMID: 27734322 DOI: 10.1007/s11914-016-0331-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Vitamin D is a key molecule in calcium and phosphate homeostasis; however, increasing evidence has recently shown that it also plays a crucial role in the immune system, both innate and adaptive. A deregulation of vitamin D levels, due also to mutations and polymorphisms in the genes of the vitamin D pathway, determines severe alterations in the homeostasis of the organism, resulting in a higher risk of onset of some diseases, including osteoporosis. This review gives an overview of the influence of vitamin D levels on the pathogenesis of osteoporosis, between bone homeostasis and immune system.
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Affiliation(s)
- Daniele Bellavia
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Viviana Costa
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Angela De Luca
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy
| | - Melania Maglio
- Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Stefania Pagani
- Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Milena Fini
- Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Gianluca Giavaresi
- Innovative Technology Platforms for Tissue Engineering, Theranostics and Oncology, Rizzoli Orthopaedic Institute, Via Divisi, 83, 90100, Palermo, Italy.
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Mainguy-Seers S, Holcombe SJ, Lavoie JP. Serum Vitamin D Level Is Unchanged in Equine Asthma. Animals (Basel) 2024; 14:3310. [PMID: 39595361 PMCID: PMC11591496 DOI: 10.3390/ani14223310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/09/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
Vitamin D deficiency is associated with asthma development and severity of symptoms in humans, but whether the same occurs in horses is unknown. We aimed to determine whether the serum vitamin D levels differ in horses with asthma compared to control animals and, secondarily, to explore clinical, respiratory, and environmental parameters associated with its concentration in equids in a retrospective cross-sectional study. The total serum vitamin D (25(OH)D) was measured by radioimmunoassay in 45 serum samples from the Equine Respiratory Tissue Biobank (15 control animals, 14 horses with mild or moderate asthma (MEA), and 16 horses with severe asthma (SEA)). Descriptive clinical and environmental parameters, bronchoalveolar lavage fluid cytology, and lung function data were extracted. There was no difference in serum 25(OH)D levels between healthy controls, horses with MEA, and horses with SEA (respectively, means of 57.9 ± 11.6, 55.6 ± 20.0, and 64.6 ± 14.5 nmol/L; p = 0.3), suggesting that this micronutrient does not play a major role in equine asthma pathophysiology.
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Affiliation(s)
- Sophie Mainguy-Seers
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada;
| | - Susan J. Holcombe
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48823, USA
| | - Jean-Pierre Lavoie
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada;
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Ki MS, Kim NE, Woo A, Kim SY, Kim YS, Kim HE, Lee JG, Paik HC, Park MS. Post-Transplant Vitamin D Deficiency in Lung Transplant Recipients: Impact on Outcomes and Prognosis. Transpl Int 2024; 37:13313. [PMID: 39524045 PMCID: PMC11543412 DOI: 10.3389/ti.2024.13313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/15/2024] [Indexed: 11/16/2024]
Abstract
Despite the recognized clinical significance of vitamin D deficiency in other solid organ transplant recipients, its specific relevance in lung transplantation remains to be fully understood. In this study, we performed a retrospective observational study on the impact of vitamin D deficiency on clinical outcomes and prognosis in 125 lung transplant recipients (LTRs) from October 2014 to March 2020 at a university hospital in Seoul, South Korea. Among 125 LTRs, 51 patients (40.8%) were vitamin D deficient. LTRs in the vitamin D-deficient group exhibited a higher incidence of post-transplant pneumonia and overall mortality than those with normal vitamin D levels during the follow-up period. This trend persisted when subjects were stratified into vitamin D tertiles. Furthermore, post-transplant vitamin D levels and C-reactive protein (CRP) significantly impacted pneumonia incidence and survival outcomes. Prognosis also varied based on cumulative vitamin D supplementation after transplantation, with patients receiving higher cumulative supplementation demonstrating improved prognosis. Our findings underscore the importance of assessing and maintaining optimal vitamin D levels post-transplantation, suggesting a potential avenue for improving outcomes in lung transplant recipients, especially in mitigating infection risk and enhancing long-term survival. Further research into optimal vitamin D levels and supplementation strategies in this population is warranted.
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Affiliation(s)
- Min Seo Ki
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Division of Pulmonology and Allergy, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Nam Eun Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University College of Medicine, Ewha Womans Seoul Hospital, Seoul, Republic of Korea
| | - Ala Woo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Song Yee Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Sam Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ha Eun Kim
- Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Gu Lee
- Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyo Chae Paik
- Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Thoracic and Cardiovascular Surgery, Myongji Hospital, Goyang, Republic of Korea
| | - Moo Suk Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Paramonova N, Trapina I, Gradauskiene (Sitkauskiene) B, Plavina S, Tamasauskiene L, Bastyte D, Rumba-Rozenfelde I, Tapina S, Stakaitiene I, Ugenskiene R, Shih-Hsin Wu L, Wang JY, Hsieh MH, Chen PC, Sjakste N. Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts. Int J Mol Sci 2024; 25:1943. [PMID: 38339221 PMCID: PMC10856277 DOI: 10.3390/ijms25031943] [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: 12/18/2023] [Revised: 01/18/2024] [Accepted: 01/28/2024] [Indexed: 02/12/2024] Open
Abstract
Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.
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Affiliation(s)
- Natalia Paramonova
- Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, LV-1004 Riga, Latvia; (N.P.); (S.P.); (N.S.)
| | - Ilva Trapina
- Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, LV-1004 Riga, Latvia; (N.P.); (S.P.); (N.S.)
| | | | - Samanta Plavina
- Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, LV-1004 Riga, Latvia; (N.P.); (S.P.); (N.S.)
| | - Laura Tamasauskiene
- Department of Immunology and Allergology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania (L.T.); (D.B.)
| | - Daina Bastyte
- Department of Immunology and Allergology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania (L.T.); (D.B.)
| | | | - Sandra Tapina
- Faculty of Medicine, University of Latvia, LV-1586 Riga, Latvia; (I.R.-R.); (S.T.)
| | - Ieva Stakaitiene
- Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania; (I.S.); (R.U.)
| | - Rasa Ugenskiene
- Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania; (I.S.); (R.U.)
| | - Lawrence Shih-Hsin Wu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan;
- Research Center of Allergy, Immunology, and Microbiome (AIM), China Medical University Hospital, Taichung 404327, Taiwan; (J.-Y.W.); (M.-H.H.); (P.-C.C.)
| | - Jiu-Yao Wang
- Research Center of Allergy, Immunology, and Microbiome (AIM), China Medical University Hospital, Taichung 404327, Taiwan; (J.-Y.W.); (M.-H.H.); (P.-C.C.)
- Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung 404327, Taiwan
| | - Miao-Hsi Hsieh
- Research Center of Allergy, Immunology, and Microbiome (AIM), China Medical University Hospital, Taichung 404327, Taiwan; (J.-Y.W.); (M.-H.H.); (P.-C.C.)
| | - Pei-Chi Chen
- Research Center of Allergy, Immunology, and Microbiome (AIM), China Medical University Hospital, Taichung 404327, Taiwan; (J.-Y.W.); (M.-H.H.); (P.-C.C.)
| | - Nikolajs Sjakste
- Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, LV-1004 Riga, Latvia; (N.P.); (S.P.); (N.S.)
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Dong H, Lv X, Gao P, Hao Y. Potential role of irisin in lung diseases and advances in research. Front Pharmacol 2023; 14:1307651. [PMID: 38143500 PMCID: PMC10746167 DOI: 10.3389/fphar.2023.1307651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 11/27/2023] [Indexed: 12/26/2023] Open
Abstract
Irisin, a myokine, is secreted by the movement of skeletal muscles. It plays an important role in metabolic homeostasis, insulin resistance, anti-inflammation, oxidative stress, and bone metabolism. Several studies have reported that irisin-related signaling pathways play a critical role in the treatment of various diseases, including obesity, cardiovascular disease, diabetes, and neurodegenerative disorders. Recently, the potential role of irisin in lung diseases, including chronic obstructive pulmonary disease, acute lung injury, lung cancer, and their associated complications, has received increasing attention. This article aims to explore the role of irisin in lung diseases, primarily focusing on the underlying molecular mechanisms, which may serve as a marker for the diagnosis as well as a potential target for the treatment of lung diseases, thus providing new strategies for their treatment.
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Affiliation(s)
| | | | - Peng Gao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Yuqiu Hao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
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Reyes Noriega N, Del-Río-Navarro BE, Berber A, de Jesús Romero Tapia S, Molina Díaz DJM. Effect of Obesity on Lung Function in the Pediatric and Adult Populations with Asthma: A Review. J Clin Med 2023; 12:5385. [PMID: 37629427 PMCID: PMC10456025 DOI: 10.3390/jcm12165385] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
Obesity and asthma are major global health concerns, particularly in industrialized nations. Obesity has been shown to have detrimental effects on the respiratory system and lung function owing to metabolic issues and immunological consequences. Research has indicated that obese patients with asthma (atopic or T2-high and non-atopic or T2-low) have diminished lung function in terms of functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV), the FEV1/FVC ratio, and FEF 25-75% due to mechanical fat loading on the diaphragm and central adiposity when compared to non-obese asthmatic patients. Therefore, it is plausible that changes in lung function are the result of a combination of mechanical (fat loading on the diaphragm, central adiposity, bronchial hyper-reactivity, and an increase in cholinergic tone), environmental (diet and exercise), and inflammatory factors (local and systemic), which can lead to the obesity-related asthma phenotype characterized by severe asthma symptoms, poor response to corticosteroid treatment, loss of lung function, and poor quality of life from an early age.
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Affiliation(s)
- Nayely Reyes Noriega
- Allergy and Immunology Pediatric Department, Hospital Infantil de México Federico Gómez, Ciudad de México 06720, Mexico; (N.R.N.); (A.B.)
| | - Blanca E. Del-Río-Navarro
- Allergy and Immunology Pediatric Department, Hospital Infantil de México Federico Gómez, Ciudad de México 06720, Mexico; (N.R.N.); (A.B.)
| | - Arturo Berber
- Allergy and Immunology Pediatric Department, Hospital Infantil de México Federico Gómez, Ciudad de México 06720, Mexico; (N.R.N.); (A.B.)
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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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Lin Z, Huang J, Xie S, Zheng Z, Tang K, Li S, Chen R. The Association Between Insulin Use and Asthma: An Epidemiological Observational Analysis and Mendelian Randomization Study. Lung 2023; 201:189-199. [PMID: 36971839 DOI: 10.1007/s00408-023-00611-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 03/09/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Asthma is a common respiratory disease caused by genetic and environmental factors, but the contribution of insulin use to the risk of asthma remains unclear. This study aimed to investigate the association between insulin use and asthma in a large population-based cohort, and further explore their causal relationship by Mendelian randomization (MR) analysis. METHODS An epidemiological study including 85,887 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 was performed to evaluate the association between insulin use and asthma. Based on the inverse-variance weighted approach, MR analysis were conducted to estimate the causal effect of insulin use on asthma from the UKB and FinnGen datasets, respectively. RESULTS In the NHANES cohort, we found that insulin use was associated with an increased risk of asthma [odd ratio (OR) 1.38; 95% CI 1.16-1.64; p < 0.001]. For the MR analysis, we found a causal relationship between insulin use and a higher risk of asthma in both Finn (OR 1.10; p < 0.001) and UK Biobank cohorts (OR 1.18; p < 0.001). Meanwhile, there was no causal association between diabetes and asthma. After multivariable adjustment for diabetes in UKB cohort, the insulin use remained significantly associated with an increased risk of asthma (OR 1.17, p < 0.001). CONCLUSIONS An association between insulin use and an increased risk of asthma was found via the real-world data from the NHANES. In addition, the current study identified a causal effect and provided a genetic evidence of insulin use and asthma. More studies are needed to elucidate the mechanisms underlying the association between insulin use and asthma.
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Affiliation(s)
- Zikai Lin
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
- Nanshan School of Medical, Guangzhou Medical University, Guangzhou, China
| | - Junfeng Huang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
| | - Shuojia Xie
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
- Nanshan School of Medical, Guangzhou Medical University, Guangzhou, China
| | - Ziwen Zheng
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
| | - Kailun Tang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China
- Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Clinical Medical College of Henan University, Kaifeng, China
| | - Shiyue Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
| | - Ruchong Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
- Department of Allergy and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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Dong H, Yang W, Li W, Zhu S, Zhu L, Gao P, Hao Y. New insights into autophagy in inflammatory subtypes of asthma. Front Immunol 2023; 14:1156086. [PMID: 37090692 PMCID: PMC10117973 DOI: 10.3389/fimmu.2023.1156086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/27/2023] [Indexed: 04/25/2023] Open
Abstract
Asthma is a heterogeneous airway disease characterized by airway inflammation and hyperresponsiveness. Autophagy is a self-degrading process that helps maintain cellular homeostasis. Dysregulation of autophagy is involved in the pathogenesis of many diseases. In the context of asthma, autophagy has been shown to be associated with inflammation, airway remodeling, and responsiveness to drug therapy. In-depth characterization of the role of autophagy in asthma can enhance the understanding of the pathogenesis, and provide a theoretical basis for the development of new biomarkers and targeted therapy for asthma. In this article, we focus on the relationship of autophagy and asthma, and discuss its implications for asthma pathogenesis and treatment.
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Affiliation(s)
- Hongna Dong
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Wei Yang
- Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Wei Li
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Simin Zhu
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Ling Zhu
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Peng Gao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
- *Correspondence: Peng Gao, ; Yuqiu Hao,
| | - Yuqiu Hao
- Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
- *Correspondence: Peng Gao, ; Yuqiu Hao,
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Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency. INFORMATICS IN MEDICINE UNLOCKED 2022; 34:101116. [PMID: 36338941 PMCID: PMC9616486 DOI: 10.1016/j.imu.2022.101116] [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: 08/28/2022] [Revised: 10/21/2022] [Accepted: 10/22/2022] [Indexed: 11/06/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein–Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug–target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.
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Sobczak M, Pawliczak R. Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling? Int J Mol Sci 2022; 23:12798. [PMID: 36361588 PMCID: PMC9656909 DOI: 10.3390/ijms232112798] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/19/2022] [Accepted: 10/21/2022] [Indexed: 12/25/2023] Open
Abstract
Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student's t-test or Welch's t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)2D3 had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.
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Affiliation(s)
| | - Rafał Pawliczak
- Department of Immunopathology, Division of Biomedical Science, Faculty of Medicine, Medical University of Lodz, 90-752 Lodz, Poland
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Zhu Y, Jing D, Liang H, Li D, Chang Q, Shen M, Pan P, Liu H, Zhang Y. Vitamin D status and asthma, lung function, and hospitalization among British adults. Front Nutr 2022; 9:954768. [PMID: 36034921 PMCID: PMC9399919 DOI: 10.3389/fnut.2022.954768] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/19/2022] [Indexed: 11/23/2022] Open
Abstract
Background Vitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear. Objective To investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults. Methods Multivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37-73 years old from the UK Biobank. Results Compared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio (aOR) = 0.936; 95% CI: 0.911-0.962; p < 0.001] and 9.8% (aOR = 0. 0.902; 95% CI: 0.877-0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (β = 1.328 ml, 95% CI = 0.575-2.080), FVC (β = 2.018 ml, 95% CI = 1.127-2.908), and FEV1/FVC (β = 0.006%, 95% CI = 0.002-0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3-19.9% higher odds of current wheeze than insufficient categories (aOR = 0.907; 95% CI: 0.861-0.957; p < 0.001) and optimal categories (aOR = 0.801; 95% CI: 0.759-0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant. Conclusion Vitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.
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Affiliation(s)
- Yiqun Zhu
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
| | - Danrong Jing
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Huaying Liang
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
| | - Dianwu Li
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
| | - Qinyu Chang
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
| | - Minxue Shen
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Pinhua Pan
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
- National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Hong Liu
- National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Zhang
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
- National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
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Entrenas-Castillo M, Salinero-González L, Entrenas-Costa LM, Andújar-Espinosa R. Calcifediol for Use in Treatment of Respiratory Disease. Nutrients 2022; 14:2447. [PMID: 35745177 PMCID: PMC9231174 DOI: 10.3390/nu14122447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/10/2022] [Accepted: 06/10/2022] [Indexed: 02/01/2023] Open
Abstract
Calcifediol is the prohormone of the vitamin D endocrine system (VDES). It requires hydroxylation to move to 1,25(OH)2D3 or calcitriol, the active form that exerts its functions by activating the vitamin D receptor (VDR) that is expressed in many organs, including the lungs. Due to its rapid oral absorption and because it does not require first hepatic hydroxylation, it is a good option to replace the prevalent deficiency of vitamin D (25 hydroxyvitamin D; 25OHD), to which patients with respiratory pathologies are no strangers. Correcting 25OHD deficiency can decrease the risk of upper respiratory infections and thus improve asthma and COPD control. The same happens with other respiratory pathologies and, in particular, COVID-19. Calcifediol may be a good option for raising 25OHD serum levels quickly because the profile of inflammatory cytokines exhibited by patients with inflammatory respiratory diseases, such as asthma, COPD or COVID-19, can increase the degradation of the active metabolites of the VDES. The aim of this narrative revision is to report the current evidence on the role of calcifediol in main respiratory diseases. In conclusion, good 25OHD status may have beneficial effects on the clinical course of respiratory diseases, including COVID-19. This hypothesis should be confirmed in large, randomized trials. Otherwise, a rapid correction of 25(OH)D deficiency can be useful for patients with respiratory disease.
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Affiliation(s)
- Marta Entrenas-Castillo
- Pneumology Department, Hospital QuironSalud, 14004 Cordoba, Spain; (M.E.-C.); (L.M.E.-C.)
- School of Medicine, University of Córdoba, 14071 Cordoba, Spain
| | | | - Luis M. Entrenas-Costa
- Pneumology Department, Hospital QuironSalud, 14004 Cordoba, Spain; (M.E.-C.); (L.M.E.-C.)
- School of Medicine, University of Córdoba, 14071 Cordoba, Spain
- Pneumology Department, Hospital Universitario Reina Sofía, 14004 Cordoba, Spain
| | - Rubén Andújar-Espinosa
- Pneumology Department, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain
- Medicine Department, University of Murcia, 30120 Murcia, Spain
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Gao Z, Xie J, Li C, Liu L, Yang Y. High Dose Vitamin D3 Supplementation Is Not Associated With Lower Mortality in Critically Ill Patients: A Meta-Analysis of Randomized Control Trials. Front Nutr 2022; 9:762316. [PMID: 35600814 PMCID: PMC9116294 DOI: 10.3389/fnut.2022.762316] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 03/28/2022] [Indexed: 11/24/2022] Open
Abstract
Background Vitamin D deficiency is a common condition in critically ill patients. A high dose of vitamin D3 can rapidly restore vitamin D levels. The aim of this meta-analysis was to synthesize the results from up-to-date randomized control trials (RCT) and validate the effect of vitamin D3 in critically ill patients. Study Methods Several databases, including PubMed, Web of Science, EMBASE, and the Cochrane Central database, were searched up to December 4th, 2020. All RCTs that investigated the use of a high dose of vitamin D3 in critically ill patients and reported mortality data were included in the meta-analysis. The primary outcome was the mortality truncated to day 28 and day 90. Results A total of 10 RCTs enrolling 2058 patients were finally included. The use of a high dose of vitamin D3 in critically ill patients could not decrease the mortality truncated to day 28 (RR 0.93, 95% CI 0.78–1.11, P = 0.43) or day 90 (RR 0.91, 95% CI 0.79–1.05, P = 0.21). A high dose of vitamin D3 could significantly reduce the ventilator days (MD −9.38, 95%CI −13.44 to −5.31, P < 0.001), but there were no statistic difference in length of ICU stay (MD −2.76, 95% CI −6.27 to 0.74, P = 0.12) and hospital stay (MD −2.42, 95% CI −6.21 to 1.36, P = 0.21). No significant difference was observed in adverse events between the vitamin D3 group and the placebo group. Conclusion The use of high dose vitamin D3 was not associated with decreased mortality in critically ill patients, but could significantly reduce the ventilator days. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier: CRD42020179195.
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Affiliation(s)
- Zhiwei Gao
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine Southeast University, Zhongda Hospital, Nanjing, China
- Department of Emergency Intensive Care Unit, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Jianfeng Xie
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine Southeast University, Zhongda Hospital, Nanjing, China
| | - Cong Li
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine Southeast University, Zhongda Hospital, Nanjing, China
| | - Ling Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine Southeast University, Zhongda Hospital, Nanjing, China
| | - Yi Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, School of Medicine Southeast University, Zhongda Hospital, Nanjing, China
- *Correspondence: Yi Yang
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Bantulà M, Arismendi E, Picado C, Mullol J, Roca-Ferrer J, Tubita V. Reference Gene Validation for RT-qPCR in PBMCs from Asthmatic Patients with or without Obesity. Methods Protoc 2022; 5:35. [PMID: 35645343 PMCID: PMC9149987 DOI: 10.3390/mps5030035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/10/2022] [Accepted: 04/19/2022] [Indexed: 01/26/2023] Open
Abstract
Obesity is known to impair the efficacy of glucocorticoid medications for asthma control. Glucocorticoid-induced gene expression studies may be useful to discriminate those obese asthmatic patients who present a poor response to glucocorticoids. The expression of genes of interest is normalized with respect to reference genes (RGs). Ideally, RGs have a stable expression in different samples and are not affected by experimental conditions. The objective of this work was to analyze suitable RGs to study the role of glucocorticoid-induced genes in obese asthmatic patients in further research. The gene expression of eight potential RGs (GUSB, B2M, POLR2A, PPIA, ACTB, GAPDH, HPRT1, and TBP) was assessed with reverse transcription-quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from asthmatic, obese asthmatic, and healthy individuals. Their stability was analyzed using four different algorithms-BestKeeper, ΔCt, geNorm, and NormFinder. geNorm analysis recommended the use of a minimum of three genes for normalization. Moreover, intergroup variation due to the treatment was calculated by NormFinder, which found that B2M was the gene that was least affected by different treatments. Comprehensive rankings indicated GUSB and HPRT1 as the best RGs for qPCR in PBMCs from healthy and asthmatic subjects, while B2M and PPIA were the best for obese asthmatic subjects. Finally, our results demonstrated that B2M and HPRT1 were the most stable RGs among all groups, whereas ACTB, TBP, and GAPDH were the worst shared ones.
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Affiliation(s)
- Marina Bantulà
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
| | - Ebymar Arismendi
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
- Department of Pneumology, Hospital Clinic, 08036 Barcelona, Spain
- Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), 08036 Barcelona, Spain
| | - César Picado
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
- Department of Pneumology, Hospital Clinic, 08036 Barcelona, Spain
- Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), 08036 Barcelona, Spain
| | - Joaquim Mullol
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
- Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), 08036 Barcelona, Spain
- Rhinology Unit and Smell Clinic, ENT Department, Hospital Clinic, 08036 Barcelona, Spain
| | - Jordi Roca-Ferrer
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
- Centre for Biomedical Investigation in Respiratory Diseases (CIBERES), 08036 Barcelona, Spain
| | - Valeria Tubita
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain; (E.A.); (C.P.); (J.M.); (J.R.-F.); (V.T.)
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Association Between Serum 25-Hydroxy Vitamin D Levels and Severity of Asthma. Clin Nutr ESPEN 2022; 49:197-200. [DOI: 10.1016/j.clnesp.2022.04.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 11/19/2022]
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Farrell SW, Meyer KJ, Leonard D, Shuval K, Barlow CE, Pavlovic A, DeFina L, Haskell WL. Physical Activity, Adiposity, and Serum Vitamin D Levels in Healthy Women: The Cooper Center Longitudinal Study. J Womens Health (Larchmt) 2022; 31:957-964. [PMID: 35352989 DOI: 10.1089/jwh.2021.0402] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Although physical inactivity, obesity, and low serum vitamin D [25-hydroxyvitamin D, 25(OH)D] are common among women, joint associations among these biomarkers are not well-described. Materials and Methods: A total of 7553 healthy women received a comprehensive examination (2006-2018), including self-reported physical activity (PA), body mass index (BMI), waist circumference (WC), waist:height ratio (W:HT), percent body fat (%Fat), and 25(OH)D. Participants were divided into four categories of PA based on current guidelines: <500 (not meeting guidelines), 500-1000 (meeting guidelines), 1001-2500 (>1-2.5 times guidelines), and >2500 (>2.5 times guidelines) metabolic equivalent-minutes/week (MET-Min/wk), and were also classified by clinical cut points for adiposity measures and 25(OH)D. We examined trends of 25(OH)D and adiposity exposures across PA categories and calculated odds ratios (ORs) of vitamin D deficiency across categories of each adiposity exposure. We examined joint associations among PA and adiposity with 25(OH)D. Results: A positive trend was observed for 25(OH)D across PA categories (p < 0.001). Compared with normal weight status, the odds for 25(OH)D deficiency were significantly higher for overweight women within adiposity exposures (p for all <0.001). When examining joint associations, 25(OH)D was higher across PA categories within each stratum of BMI, WC, W:HT, and %Fat (p trend <0.007 for all). When examining PA and BMI as continuous variables, OR for vitamin D deficiency were 0.95 (95% confidence interval [CI]: 0.93-0.96) per 250 MET-minutes/week increment in PA, and 1.20 (95% CI: 1.17-1.23) per 2 kg/m2 increment in BMI. Conclusions: 25(OH)D levels are positively associated with PA and negatively associated with different measures of adiposity. Higher levels of PA attenuate the association between adiposity and 25(OH)D.
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Affiliation(s)
| | | | | | | | | | | | | | - William L Haskell
- Department of Medicine, Stanford University, Palo Alto, California, USA
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Gaffin JM, Castro M, Bacharier LB, Fuhlbrigge AL. The Role of Comorbidities in Difficult-to-Control Asthma in Adults and Children. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:397-408. [PMID: 34863928 PMCID: PMC8837696 DOI: 10.1016/j.jaip.2021.11.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/29/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023]
Abstract
Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps, may improve asthma control and reduce exacerbations. In addition, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities.
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Affiliation(s)
- Jonathan M. Gaffin
- Division of Pulmonary Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston MA, USA
| | - Mario Castro
- Division of Pulmonary, Critical Care Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
| | - Leonard B. Bacharier
- Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA
| | - Anne L. Fuhlbrigge
- Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA
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Abdul Ridha Al-Awade H, Shakir Abed Almjalawi B. Effects of Vitamin D on Risks and Severity of COVID-19 Infection. ARCHIVES OF RAZI INSTITUTE 2022; 77:163-168. [PMID: 35891758 PMCID: PMC9288609 DOI: 10.22092/ari.2021.356807.1914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 12/04/2021] [Indexed: 05/25/2023]
Abstract
In the last two decades, numerous studies have been carried out to find correlations between vitamin D and the efficiency of the lungs and respiratory system. This study aimed to find the relationship of taking vitamin D with the risks of the severity of infection with coronavirus disease 2019 (COVID-19) and the risk of infection of patients with chronic diseases. A total of 100 COVID-19 patients (61 males and 39 females) were included in the study and divided into groups, namely never taken vitamin D and taken a dose of 50 and 1,000 IU. The effects of gender, chronic diseases (i.e., hypertension and diabetes), and requiring intensive care unit (ICU) were evaluated. The results showed that females were at lower risks of infection with COVID-19 than males and taking 50 IU of vitamin D could lower the severe cases by 33%. It was also revealed that patients with chronic disease were more sensitive to COVID-19 and administering 50 units of vitamin D in these patients decreased the need for ICU from 49% to 9%. Given that vitamin D enhances the immune system and respiratory function, the findings of this research indicated that vitamin D reduced the risk of COVID-19; however, it was not able to prevent it.
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Affiliation(s)
- H Abdul Ridha Al-Awade
- Department of Biology, College of Education for Pure Sciences, University of Kerbala, Kerbala, Iraq
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Abstract
Asthma is chronic eosinophilic bronchitis with the dominancy of T helper 2 (Th2) inflammation. However, patients with asthma and metabolic dysfunction have pathogenic and pathological differences from those with Th2 inflammation. Metabolic dysfunction, typically presented as metabolic syndrome, has several important clinical components including central obesity, insulin resistance or glucose intolerance, dyslipidemia, and vitamin D deficiency. Data from large epidemiological studies support the significance of these components in the control of asthma and their contribution to airway remodeling, suggesting the presence of an asthma phenotype with metabolic dysfunction. These components are quite interactive with each other, so it is difficult to reveal the individual role of each. It is well known that asthma is difficult to treat in patients with obesity, due in part to inadequate response to inhaled corticosteroids. Additionally, vitamin D deficiency and insulin resistance have been regarded as aggravating factors of asthma control and airway remodeling. Recent clinical and in vivo studies have revealed the specific mechanisms of these components, which may aggravate asthma control and airway remodeling. In this review article, I summarize the recent studies and unmet needs for patients with asthma and metabolic dysfunction.
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Affiliation(s)
- Jung-Won Park
- Institute for Allergy & Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
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Afzal M, Kazmi I, Al-Abbasi FA, Alshehri S, Ghoneim MM, Imam SS, Nadeem MS, Al-Zahrani MH, Alzarea SI, Alquraini A. Current Overview on Therapeutic Potential of Vitamin D in Inflammatory Lung Diseases. Biomedicines 2021; 9:1843. [PMID: 34944659 PMCID: PMC8698997 DOI: 10.3390/biomedicines9121843] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 11/24/2021] [Accepted: 12/01/2021] [Indexed: 11/16/2022] Open
Abstract
Inflammatory lung disorders (ILDs) are one of the world's major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses.
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Affiliation(s)
- Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia; (M.A.); (S.I.A.)
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (F.A.A.-A.); (M.S.N.); (M.H.A.-Z.)
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (F.A.A.-A.); (M.S.N.); (M.H.A.-Z.)
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.A.); (S.S.I.)
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia;
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (S.A.); (S.S.I.)
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (F.A.A.-A.); (M.S.N.); (M.H.A.-Z.)
| | - Maryam Hassan Al-Zahrani
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (F.A.A.-A.); (M.S.N.); (M.H.A.-Z.)
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia; (M.A.); (S.I.A.)
| | - Ali Alquraini
- Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia;
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Einisadr A, Rajabi M, Moezzi H, Bakhshandeh H. Impact of rapid correction of vitamin D deficiency in asthmatic patients. Wien Klin Wochenschr 2021; 134:18-23. [PMID: 34817666 DOI: 10.1007/s00508-021-01975-z] [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: 02/04/2020] [Accepted: 10/18/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Asthma is one of the most common chronic diseases, which is a growing public health concern worldwide. In recent years, there has been an increasing number of interests in the relationship between vitamin D level and asthma control. Hence, the objective of this study was to assess the effect of high doses of vitamin D3 injection on asthmatic patient's respiratory condition and quality of life. METHODS This was a single arm, before and after interventional study involving 18 patients with moderate to severe asthma. Spirometry test, St George's respiratory questionnaire (SGRQ) and serum vitamin D assay were performed. Subjects with 25-hydroxyvitamin D3 (25-(OH) D3) < 20 ng/ml were deemed deficient (n = 18) and received 2 intramuscular injections of vitamin D3 300,000 IU at monthly intervals consecutively. RESULTS The mean changes of forced expiratory volume in the first second (FEV1) were significantly different in subjects who received vitamin D3 injections (p = 0.008). Also, the mean changes in FEV1/forced vital capacity ratio (FEV1/FVC) were significant (p < 0.001) as well as maximum expiratory flow between 25% and 75% of FVC (MEF25-75) (p = 0.001). Interestingly, improvement in clinical parameters of SGRQ was also observed with significant differences in total score (p = 0.001). Naturally, serum vitamin D levels were increased in our patients following the injections (p < 0.001). CONCLUSIONS Our findings suggest that screening for serum 25-(OH) D3 deficiency is important in asthmatic patients and correction of this deficiency with high doses of vitamin D3 injection may lead to improvement in pulmonary function, symptoms and quality of life (QOL).
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Affiliation(s)
- Ariandokht Einisadr
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Yasaman Alley, Yakhchal Street, Gholhak Street, Shariati Avenue, Tehran, Iran
| | - Mehdi Rajabi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Yasaman Alley, Yakhchal Street, Gholhak Street, Shariati Avenue, Tehran, Iran. .,Department of Clinical Pharmacy, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, ST4 6QG, UK.
| | - Hamidreza Moezzi
- Department of Respiratory Medicine, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hooman Bakhshandeh
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
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The Effects of Climate Therapy on Cardiorespiratory Fitness and Exercise-Induced Bronchoconstriction in Children with Asthma. ATMOSPHERE 2021. [DOI: 10.3390/atmos12111486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
We investigated whether a 1-week stay in the mountains may have a positive impact on Exercise-Induced Bronchoconstriction (EIB) and cardiorespiratory endurance in asthmatic children from an urban area. Spirometry was performed before and 10 min after a 20 m shuttle run test (20mSRT) on the first and seventh day of a summer asthma camp in the Italian Alps at 900 m of altitude. Spirometry z-scores were derived from the Global Lung Initiative 2012 prediction equations, and percentiles of the 20mSRT performance were assigned according to De Miguel-Etayo’s and Tomkinson’s predictive equations. A FEV1 decrease ≥10% after the exercise was defined as EIB. Particulate matter pollution was monitored during the camp and in the urban area of provenience. Twenty-four subjects (age range 7–16 years) were included. Frequency of EIB decreased from 58% (14/24) at day-1 to 33% (8/24) at the end of the camp (p = 0.08). Most subjects with a 20mSRT in the lowest quartile at day 1 had EIB (9/11). The proportion of children with a 20mSRT <25° percentile decreased from 45% (11/24) at day-1 to 16% (4/24) at day-7 (p = 0.02). Conclusion: One-week climate therapy in the mountains improved both bronchial hyperreactivity and cardiorespiratory endurance in our cohort of asthmatic children.
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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: 17] [Impact Index Per Article: 4.3] [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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Han H, Chung SI, Park HJ, Oh EY, Kim SR, Park KH, Lee JH, Park JW. Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness. Am J Respir Cell Mol Biol 2021; 64:357-367. [PMID: 33296297 DOI: 10.1165/rcmb.2020-0086oc] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023] Open
Abstract
Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effects of VitD supplementation were analyzed using high-fat diet (HFD)-induced obese mice and TGF-β1 (transforming growth factor-β1) triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mice had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-β1, IL-1β, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-β1-overexpressing transgenic mice enhanced macrophages in BAL fluid, lung expression of RAS, epithelial-mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-β1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro-stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-β1 expression, supporting the suppressive effect of VitD for TGF-β1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-β1, and proinflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity.
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Affiliation(s)
| | | | - Hye Jung Park
- Department of Internal Medicine and Gangnam Severance Hospital, and
| | | | - Sung-Ryeol Kim
- Institute for Allergy
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Hee Park
- Institute for Allergy
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae-Hyun Lee
- Institute for Allergy
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jung-Won Park
- Institute for Allergy
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Corlateanu A, Stratan I, Covantev S, Botnaru V, Corlateanu O, Siafakas N. Asthma and stroke: a narrative review. Asthma Res Pract 2021; 7:3. [PMID: 33608061 PMCID: PMC7896413 DOI: 10.1186/s40733-021-00069-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 02/04/2021] [Indexed: 02/08/2023] Open
Abstract
Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation, bronchial reversible obstruction and hyperresponsiveness to direct or indirect stimuli. It is a severe disease causing approximately half a million deaths every year and thus possessing a significant public health burden. Stroke is the second leading cause of death and a major cause of disability worldwide. Asthma and asthma medications may be a risk factors for developing stroke. Nevertheless, since asthma is associated with a variety of comorbidities, such as cardiovascular, metabolic and respiratory, the increased incidence of stroke in asthma patients may be due to a confounding effect. The purpose of this review is to analyze the complex relationship between asthma and stroke.
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Affiliation(s)
- A. Corlateanu
- Department of Internal Medicine, Division of Pneumology and Allergology, Nicolae Testemitanu State University of Medicine and Pharmacy, Stefan cel Mare street 165, 2004 Chisinau, Republic of Moldova
| | - Iu Stratan
- Department of Internal Medicine, Division of Pneumology and Allergology, Nicolae Testemitanu State University of Medicine and Pharmacy, Stefan cel Mare street 165, 2004 Chisinau, Republic of Moldova
| | - S. Covantev
- Department of Internal Medicine, Division of Pneumology and Allergology, Nicolae Testemitanu State University of Medicine and Pharmacy, Stefan cel Mare street 165, 2004 Chisinau, Republic of Moldova
| | - V. Botnaru
- Department of Internal Medicine, Division of Pneumology and Allergology, Nicolae Testemitanu State University of Medicine and Pharmacy, Stefan cel Mare street 165, 2004 Chisinau, Republic of Moldova
| | - O. Corlateanu
- Department of Internal Medicine, Nicolae Testemitanu State University of Medicine and Pharmacy, Stefan cel Mare street 165, 2004 Chisinau, Republic of Moldova
| | - N. Siafakas
- Department of Thoracic Medicine, University General Hospital, Stavrakia, 71110 Heraklion, Crete, Greece
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Spiers JG, Steiger N, Khadka A, Juliani J, Hill AF, Lavidis NA, Anderson ST, Cortina Chen HJ. Repeated acute stress modulates hepatic inflammation and markers of macrophage polarisation in the rat. Biochimie 2021; 180:30-42. [PMID: 33122103 DOI: 10.1016/j.biochi.2020.10.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 09/29/2020] [Accepted: 10/24/2020] [Indexed: 12/24/2022]
Abstract
Bidirectional communication between the neuroendocrine stress and immune systems permits classically anti-inflammatory glucocorticoids to exert pro-inflammatory effects in specific cells and tissues. Liver macrophages/Kupffer cells play a crucial role in initiating inflammatory cascades mediated by the release of pro-inflammatory cytokines following tissue injury. However, the effects of repeated acute psychological stress on hepatic inflammatory phenotype and macrophage activation state remains poorly understood. We have utilised a model of repeated acute stress in rodents to observe the changes in hepatic inflammatory phenotype, including anti-inflammatory vitamin D status, in addition to examining markers of classically and alternatively-activated macrophages. Male Wistar rats were subjected to control conditions or 6 h of restraint stress applied for 1 or 3 days (n = 8 per group) after which plasma concentrations of stress hormone, enzymes associated with liver damage, and vitamin D status were examined, in addition to hepatic expression of pro- and anti-inflammatory markers. Stress increased glucocorticoids and active vitamin D levels in addition to expression of glucocorticoid alpha/beta receptor, whilst changes in circulating hepatic enzymes indicated sustained liver damage. A pro-inflammatory response was observed in liver tissues following stress, and inducible nitric oxide synthase being observed within hepatic macrophage/Kupffer cells. Together, this suggests that stress preferentially induces a pro-inflammatory response in the liver.
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Affiliation(s)
- Jereme G Spiers
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3083, Australia.
| | - Natasha Steiger
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia
| | - Arun Khadka
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Juliani Juliani
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Andrew F Hill
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Nickolas A Lavidis
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia
| | - Stephen T Anderson
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia
| | - Hsiao-Jou Cortina Chen
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom.
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Papathanasiou IV, Kotsopoulos A, Kotsiou O, Daniil Z, Fradelos ΕC, Papagiannis D, Gourgoulianis KI, Malli F. Compliance of Bronchial Asthma Patients’ with the Mediterranean Diet. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1337:117-125. [DOI: 10.1007/978-3-030-78771-4_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Emami Ardestani M, Movahedi A. Effect of Vitamin D Supplementation on Improvement of Symptoms in Mild-to-Moderate Asthma Patients with Vitamin D Insufficiency and Deficiency. TANAFFOS 2020; 19:322-329. [PMID: 33959169 PMCID: PMC8088147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND In the current study, we assessed the effect of vitamin D supplementation on improvement of symptoms in mild-to-moderate asthma patients with vitamin D insufficiency and deficiency. MATERIALS AND METHODS This randomized, controlled clinical trial included 132 mild-to-moderate asthma patients with vitamin D insufficiency (n=66) and those with vitamin D deficiency (n=66). They were assigned randomly to two groups of cases (with two subgroups) and controls (with two subgroups). In the case subgroups, for patients with vitamin D deficiency, a dose of 50,000 U vitamin D supplementation was administered orally on a weekly basis and for six weeks followed by a maintenance dose of 1000 U daily. For patients with vitamin D insufficiency, a dose of 1000 U vitamin D supplementation was prescribed daily. In control group, we administered placebo. The information including asthma symptoms, parameters measured by spirometer (Forced Vital Capacity-FVC, Forced Expiratory Volume in one second-FEV1) and 25-hydroxyvitamin D [25(OH)D] concentration was collected at baseline and three months later and analyzed using SPSS, Version 20. RESULTS Improvement of FEV1/FVC ratios were found in both groups but this improvement in both case subgroups of patients with vitamin D insufficiency and deficiency suggested more appropriate results compared to control group (P-value=0.022). Moreover, the correlation between changes in 25(OH)D level and changes in FEV1 was positive and significant in patients receiving vitamin D supplementation within a three-month follow up (r=0.202, P-value=0.042). CONCLUSION According to the results, vitamin D supplementation can be associated with the improvement of asthma symptoms and lung function in mild-to-moderate asthma patients with vitamin D insufficiency and deficiency.
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Affiliation(s)
| | - Azam Movahedi
- Correspondence to: Movahedi A Address: Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Email address:
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Kalmarzi RN, Ahmadi S, Rahehagh R, Fathallahpour A, Khalafi B, Kashefi H, Roshani D, Zaryan RN, Mohamadi S, Kooti W. The Effect of Vitamin D Supplementation on Clinical Outcomes of Asthmatic Children with Vitamin D Insufficiency. Endocr Metab Immune Disord Drug Targets 2020; 20:149-155. [PMID: 31942850 DOI: 10.2174/1871530319666190426161809] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 03/01/2019] [Accepted: 03/04/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND The extensive impacts of vitamin D on the immune system has gathered the attention of scholars in last years. In this regard, studies about vitamin D and incidence of asthma have showed various results. The aim of this study was to evaluate the effect of vitamin D supplements on clinical outcomes in asthmatic children with vitamin D insufficiency. MATERIALS & METHODS This before-after interventional study was conducted on all asthmatic children who attended the Be'sat Hospital, Iran. Serum levels of 25(OH)D, asthma severity and pulmonary function tests before and after therapeutic prescription of vitamin D were evaluated. Serum levels of 25(OH)D were measured by enzyme-linked immunosorbent assay. RESULTS The mean age of the samples was 10.69±9.78 years and 39 subjects (57.4%) were male. The primary mean level of serum 25(OH)D (18.21±8.22, ng/mL) has significantly (p<0.05) increased after treatment (35.45±9.35, ng/mL). Also, asthma severity, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC indicators were significantly (p<0.05) increased after treatment. CONCLUSION We can conclude that therapeutic prescription of vitamin D is very effective in improving the clinical status of asthmatic children.
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Affiliation(s)
- Rasoul N Kalmarzi
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Sivan Ahmadi
- Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Asadollah Fathallahpour
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Behzad Khalafi
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Hajar Kashefi
- Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Daem Roshani
- Social Determinants of Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Rama N Zaryan
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Shilan Mohamadi
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Wesam Kooti
- Lung Diseases and Allergy Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Andújar-Espinosa R, Salinero-González L, Illán-Gómez F, Castilla-Martínez M, Hu-Yang C, Ruiz-López FJ. Effect of vitamin D supplementation on asthma control in patients with vitamin D deficiency: the ACVID randomised clinical trial. Thorax 2020; 76:126-133. [PMID: 33154023 DOI: 10.1136/thoraxjnl-2019-213936] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 10/06/2020] [Accepted: 10/10/2020] [Indexed: 01/25/2023]
Abstract
BACKGROUND The relationship between asthma and vitamin D deficiency has been known for some time. However, interventional studies conducted in this regard have shown conflicting results. OBJECTIVE To evaluate the efficacy of vitamin D supplementation in asthmatic patients in improving the degree of control of asthma. METHODS Randomised, triple-blind, placebo-controlled, parallel-group study in adult asthmatic patients with serum 25-hydroxyvitamin-D3 <30 ng/mL. The intervention group received oral supplementation with 16 000 IU of calcifediol per week, and the control group had placebo added to their usual asthma treatment. The study period was 6 months. The primary endpoint was the degree of asthma control as determined by the asthma control test (ACT). Secondary endpoints included quality of life measured using the mini Asthma Quality of Life Questionnaire, the number of asthma attacks, oral corticosteroid cycles, the dose of inhaled corticosteroids, number of emergency visits, unscheduled consultations with the primary care physician and hospitalisations for asthma. RESULTS One hundred and twelve patients were randomised (mean age 55 years, with 87 (78%) being women). Of the 112 patients, 106 (95%) completed the trial. Half the patients (56) were assigned to the intervention group and the other half to the control group. A statistically significant clinical improvement was observed in the intervention group (+3.09) compared with the control group (-0.57) (difference 3.66 (95% CI 0.89 to 5.43); p<0.001) as measured using ACT scores. Among the secondary endpoints, a significant improvement in the quality of life was found in the intervention group (5.34), compared with the control group (4.64) (difference 0.7 (95% CI 0.15 to 1.25); p=0.01). CONCLUSION Among adults with asthma and vitamin D deficiency, supplementation with weekly oral calcifediol compared with placebo improved asthma control over 6 months. Further research is needed to assess long-term efficacy and safety. TRIAL REGISTRATION NUMBER NCT02805907.
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Affiliation(s)
- Rubén Andújar-Espinosa
- Pulmonology, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | | | - Fátima Illán-Gómez
- Endocrinology and Nutrition, Hospital Morales Meseguer, Murcia, Murcia, Spain
| | - Manuel Castilla-Martínez
- Pulmonology, Hospital General Universitario Los Arcos del Mar Menor, Pozo Aledo-San Javier, Murcia, Spain
| | - Chunshao Hu-Yang
- Pulmonology, Hospital General Universitario Los Arcos del Mar Menor, Pozo Aledo-San Javier, Murcia, Spain
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Sarhan TS, Elrifai A. Serum level of vitamin D as a predictor for severity and outcome of pneumonia. Clin Nutr 2020; 40:2389-2393. [PMID: 33158588 DOI: 10.1016/j.clnu.2020.10.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 09/05/2020] [Accepted: 10/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM of the study: Pneumonia is the most common medical illness causing hospital admissions and the most common cause of sepsis and septic shock. Vitamin D deficiency is a global health problem that affects several populations worldwide. Unfortunately, data regarding the relationship between vitamin D concentrations and outcomes of pneumonia in adult patients are sparse. Thus, we aimed to assess the prevalence of vitamin D deficiency among pneumonia patients and to correlate its levels with patients' outcomes. PATIENTS AND METHODS This is a prospective study of 100 patients with pneumonia admitted to Al-Azhar University hospital at New Damietta City. Data from history, Physical examination and biochemical analyses were collected. Grouping was based on vitamin D status. A comparison was made between groups regarding pneumonia severity and outcome. Also, correlation between Vit D level and outcome was studied. RESULTS Our study showed that 63% of patients had vitamin D level below 12 ng/mL, and patients with vitamin D level below 20 was 84%. We found an association between vitamin D deficiency and pneumonia severity. The severity of pneumonia was significantly higher among the deficient group. We also found that there was statistically significant increase of complications in deficient group. The patients improved without complications had the highest levels of vitamin D, while ARDS and septicemia complicated patients had the lowest levels of vitamin D. In addition, there was a difference between the two groups regarding to mortality. The mortality rate was higher in the deficient group as compared to non-deficient group. CONCLUSION Vitamin D deficiency is a common problem among critically ill patients. Its status affects pneumonia severity and outcome.
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Affiliation(s)
- Tarik Saber Sarhan
- Anesthesiology and Intensive Care Department, Faculty of Medicine, Damietta, Al-Azhar University, Egypt.
| | - Atef Elrifai
- Chest Department, Faculty of Medicine, Damietta, Al-Azhar University, Egypt
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Saad K, Abdelmoghny A, Aboul-Khair MD, Abdel-Raheem YF, Gad EF, Hammour AES, Hawary B, Zahran AM, Alblihed MA, Elhoufey A. Vitamin D Status in Egyptian Children With Allergic Rhinitis. EAR, NOSE & THROAT JOURNAL 2020; 99:508-512. [PMID: 31088298 DOI: 10.1177/0145561319850814] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective: This study aimed to assess the serum levels of vitamin D in an Egyptian cohort of children with allergic rhinitis (AR) and to evaluate any correlation of vitamin D status with the disease severity. Patient and methods: One hundred twenty children with AR and 100 healthy children were included in our study. We studied the serum levels of vitamin D 25(OH)D and 1,25(OH)2D in all participants. The associations between vitamin D levels and clinical characteristics of AR were examined. Results: In AR group, the serum levels of calcium, (25(OH)D and 1,25(OH)2D levels were significantly lower (p < .0001, p < .001, and p < .0001, respectively) in AR children than in controls. Furthermore, the mean 25-OHD3 levels in patients with moderate/severe AR were significantly lower than those with mild AR (p < .001). We found significant negative correlations between mean 25(OH)D levels and total nasal symptom score (r = -.62, p = .002) and total immunoglobulin E levels (r = -.27, p = .013) in AR group. Conclusions: Vitamin D deficiency is a frequent finding among Egyptian children with AR when compared to the healthy group. A significant inverse association was observed between vitamin D levels and AR disease severity.
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Affiliation(s)
- Khaled Saad
- Faculty of Medicine, Department of Pediatrics, 68796Assiut University, Assiut, Egypt
| | - Abobakr Abdelmoghny
- Faculty of Medicine, Department of ENT, 68820Al-Azhar University, Assiut, Egypt
| | | | | | - Eman Fathalla Gad
- Faculty of Medicine, Department of Pediatrics, 68796Assiut University, Assiut, Egypt
| | | | - Bahaa Hawary
- Faculty of Medicine, Department of Pediatrics, 435387Aswan University, Aswan, Egypt
| | - Asmaa M Zahran
- Department of Clinical Pathology, 165177South Egypt Cancer Institute, Assiut, Egypt
| | - Mohamd A Alblihed
- Department of Medical Biochemistry, 158240School of Medicine Taif University, Taif, Saudi Arabia
| | - Amira Elhoufey
- 113315Faculty of Nursing, Department of Community Health Nursing, Assiut University, Assiut, Egypt
- Department of Community Health Nursing, Sabia University College, Jazan University, Kingdom of Saudi Arabia
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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: 17] [Impact Index Per Article: 3.4] [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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The Role of Vitamin D in Respiratory Allergies Prevention. Why the Effect Is so Difficult to Disentangle? Nutrients 2020; 12:nu12061801. [PMID: 32560403 PMCID: PMC7353247 DOI: 10.3390/nu12061801] [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: 05/21/2020] [Revised: 06/15/2020] [Accepted: 06/16/2020] [Indexed: 11/17/2022] Open
Abstract
Asthma and allergic rhinitis are the most common chronic childhood diseases with an increasing prevalence worldwide. There is an urgent need to look for methods of preventing allergic diseases from an early age. The relationship between vitamin D status and allergic diseases has been discussed in several studies recently. 25-hydroxyvitamin D (25(OH)D) is suggested to affect the development and/or severity of asthma and allergic rhinitis. Observational studies have seemed to confirm that vitamin D deficiency may contribute to an increase in allergy and asthma. Following interventional studies, however, have yielded ambiguous results. In this review, we describe recent findings regarding 25(OH)D impact on allergic diseases and provide a systematic analysis of the causes of great variability of the achieved results in different studies.
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Asthma rehabilitation at high vs. low altitude and its impact on exhaled nitric oxide and sensitization patterns: Randomized parallel-group trial. Respir Med 2020; 170:106040. [PMID: 32843171 DOI: 10.1016/j.rmed.2020.106040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 05/19/2020] [Accepted: 05/20/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Allergens and pollution are reduced at high altitude. We investigated the effect of asthma rehabilitation at high altitude (HA, 3100 m) compared to low altitude (LA, 760 m) on exhaled nitric oxide (FeNO) and on specific IgE levels for house dust mites (HDM,d1) and common pollen (sx1). METHODS For this randomized controlled trial adult asthmatics living <1000 m were randomly assigned to a 3-week in-hospital-rehabilitation (education, physical- and breathing-exercises) at either LA or HA. Changes in FeNO, d1 and sx1 from baseline to end-rehabilitation were measured. RESULTS 50 asthmatics (34 females) were randomized [mean ± standard deviation LA: n = 25, 44 ± 11 years, total IgE 267 ± 365kU/l; HA: n = 25, 43 ± 13 years, total IgE 350 ± 445kU/l]. FeNO significantly improved at HA from 69 ± 56 ppb at baseline to the first day at altitude 23 ± 19 ppb and remained decreased until end-rehabilitation with 37 ± 23 ppb, mean difference 95%CI -31(-50 to -13, p = 0.001) whereas at LA FeNO did not change. A significant decrease in d1 and sx1 at end-rehabilitation was observed in the LA-group [mean difference 95%CI -10.2 kUA/l (-18.9 to -1.4) for d1 and -4.95 kUA/l(-9.69 to -0.21) for sx1] but not in the HA-group. No significant difference between groups [d1 5.9 kUA/l(-4.2 to 16.2) and sx1 4.4 kUA/l(-3.5 to 12.4)] was found. CONCLUSION Rehabilitation at HA led to significant FeNO reduction starting from the first day until end-rehabilitation despite unchanged levels of specific IgE. The significant decrease in d1 and sx1 at end-rehabilitation in the LA group might be explained by less HDM in the hospital and/or reduced seasonal pollen, as this decrease was not observed at HA.
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Palumbo ML, Prochnik A, Wald MR, Genaro AM. Chronic Stress and Glucocorticoid Receptor Resistance in Asthma. Clin Ther 2020; 42:993-1006. [PMID: 32224031 DOI: 10.1016/j.clinthera.2020.03.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/04/2020] [Accepted: 03/04/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Chronic and persistent exposure to negative stress can lead to adverse consequences on health. Particularly, psychosocial factors were found to increase the risk and outcome of respiratory diseases like asthma. Glucocorticoids (GCs) are the most efficient anti-inflammatory therapy for asthma. However, a significant proportion of patients don't respond adequately to GC administration. GC sensitivity is modulated by genetic and acquired disease-related factors. Additionally, it was proposed that endogenous corticosteroids may limit certain actions of synthetic GCs, contributing to insensitivity. Psychological and physiological stresses activate the hypothalamic-pituitary-adrenal axis, increasing cortisol levels. Here, we review the mechanism involved in altered GC sensitivity in asthmatic patients under stressful situations. Strategies for modulation GC sensitivity and improving GC therapy are discussed. METHODS PubMed was searched for publications on psychological chronic stress and asthma, GC resistance in asthma, biological mechanisms for GC resistance, and drugs for steroid-resistant asthma, including highly potent GCs. FINDINGS GC resistance in patients with severe disease remains a major clinical problem. In asthma, experimental and clinical evidence suggests that chronic stress induces inflammatory changes, contributing to a worse GC response. GC resistant patients can be treated with other broad-spectrum anti-inflammatory drugs, but these generally have major side effects. Different mechanisms of GC resistance have been described and might be useful for developing new therapeutic strategies against it. Novel drugs, such as highly potent GCs, phosphoinositide 3-kinase-delta inhibitors that reestablish histone deacetylase-2 function, decrease of GC receptor phosphorylation by p38 mitogen-activated protein kinase inhibitors, or phosphatase activators, are currently in clinical development and might be combined with GC therapy in the future. Furthermore, microRNAs (small noncoding RNA molecules) operate as posttranscriptional regulators, providing another level of control of GC receptor levels. Empirical results allow postulating that the detection and study of microRNAs might be a promising approach to better characterize and treat asthmatic patients. IMPLICATIONS Many molecular and cellular pathobiological mechanisms are responsible of GC resistance. Therefore detecting specific biomarkers to help identify patients who would benefit from new therapies is crucial. Stress consitutes a negative aspect of current lifestyles that increase asthma morbidity and mortality. Adequate stress management could be an important and positive intervention.
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Affiliation(s)
- María Laura Palumbo
- Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires (UNNOBA-UNSADA-CONICET), Junín, Argentina
| | - Andrés Prochnik
- Instituto de Investigaciones Biomédicas (UCA-CONICET), Buenos Aires, Argentina
| | - Miriam Ruth Wald
- Instituto de Investigaciones Biomédicas (UCA-CONICET), Buenos Aires, Argentina
| | - Ana María Genaro
- Instituto de Investigaciones Biomédicas (UCA-CONICET), Buenos Aires, Argentina; Departamento de Farmacología, Facultad de Medicina, UBA Paraguay, Buenos Aires, Argentina.
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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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Noland D, Drisko JA, Wagner L. Respiratory. INTEGRATIVE AND FUNCTIONAL MEDICAL NUTRITION THERAPY 2020. [PMCID: PMC7120155 DOI: 10.1007/978-3-030-30730-1_51] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Lung disease rivals the position for the top cause of death worldwide. Causes and pathology of the myriad lung diseases are varied, yet nutrition can either affect the outcome or support treatment in the majority of cases. This chapter explores the modifiable risk factors, from lifestyle changes to dietary intake to specific nutrients, anti-nutrients, and toxins helpful for the nutritionist or dietitian working with lung disease patients. General lung health is discussed, and three major disease states are explored in detail, including alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Although all lung diseases have diverse causes, many integrative and functional medical nutrition therapies are available and are not being utilized in practice today. This chapter begins the path toward better nutrition education for the integrative and functional medicine professional.
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Affiliation(s)
| | - Jeanne A. Drisko
- Professor Emeritus, School of Medicine, University of Kansas Health System, Kansas City, KS USA
| | - Leigh Wagner
- Department of Dietetics & Nutrition, University of Kansas Medical Center, Kansas City, KS USA
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Szymczak-Pajor I, Kleniewska P, Wieczfinska J, Pawliczak R. Wide-Range Effects of 1,25(OH)2D3 on Group 4A Phospholipases Is Related to Nuclear Factor κ-B and Phospholipase-A2 Activating Protein Activity in Mast Cells. Int Arch Allergy Immunol 2019; 181:56-70. [PMID: 31707382 DOI: 10.1159/000503628] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 09/24/2019] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Phospholipases are enzymes that occur in many types of human cells, including mast cells, and play an important role in the molecular background of asthma pathogenesis, and the development of inflammation NF-κB activities that affect numerous biological processes has been reported in many inflammatory diseases including asthma. Vitamin D is a widely studied factor that affects many diseases, including asthma. The aim of this study is to assess the influence of 1,25-(OH)2D3 on regulation of chosen phospholipase-A2 (PLA2) expression-selected inflammation mediators. METHODS LUVA mast cells were stimulated with 1,25(OH)2D3, and inhibitors of NF-κB p65 and ubiquitination. Expression analysis of phospholipases (PLA2G5, PLA2G10, PLA2G12, PLA2G15, PLA2G4A, PLA2G4B, PLA2G4C, PLAA, NF-κB p65, and UBC) was done utilizing real-time PCR and Western blot. Eicosanoid (LTC4, LXA4, 15[S]-HETE, and PGE2) levels and sPLA2 were also measured. RESULTS We found that 1,25(OH)2D3 decreased the expression of PLA2G5, PLA2G15, PLA2G5,UBC, and NF-κB p65 but increased expression of PLAA and PLA2G4C (p < 0.05). Moreover, the expression of PLA2G5 and PLA2G15 decreased after inhibition of NF-κB p65 and UBC. Increased levels of released LXA4 and 15(S)-HETE, decreased levels of LTC4, and sPLA2s enzymatic activity in response to 1,25(OH)2D3 were also observed. Additionally, NF-κB p65 inhibition led to an increase in the LXA4 concentration. CONCLUSION Future investigations will be needed to further clarify the role of 1,25(OH)2D3 in the context of asthma and the inflammatory process; however, these results confirm a variety of effects which can be caused by this vitamin. 1,25(OH)2D3-mediated action may result in the development of new therapeutic strategies for asthma treatment.
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Affiliation(s)
- Izabela Szymczak-Pajor
- Department of Immunopathology, Faculty of Biomedical Science and Postgraduate Training, Medical University of Lodz, Lodz, Poland
| | - Paulina Kleniewska
- Department of Immunopathology, Faculty of Biomedical Science and Postgraduate Training, Medical University of Lodz, Lodz, Poland
| | - Joanna Wieczfinska
- Department of Immunopathology, Faculty of Biomedical Science and Postgraduate Training, Medical University of Lodz, Lodz, Poland
| | - Rafal Pawliczak
- Department of Immunopathology, Faculty of Biomedical Science and Postgraduate Training, Medical University of Lodz, Lodz, Poland,
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Liu J, Dong YQ, Yin J, Yao J, Shen J, Sheng GJ, Li K, Lv HF, Fang X, Wu WF. Meta-analysis of vitamin D and lung function in patients with asthma. Respir Res 2019; 20:161. [PMID: 31590675 PMCID: PMC6781357 DOI: 10.1186/s12931-019-1072-4] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 05/13/2019] [Indexed: 12/27/2022] Open
Abstract
Background There is growing literature suggesting a link between vitamin D and asthma lung function, but the results from systematic reviews are conflicting. We conducted this meta-analysis to investigate the relation between serum vitamin D and lung function in asthma patients. Methods Major databases, including OVID, MEDLINE, Web of Science and PUBMED, were searched until 10th October 2018. All published observational studies related to vitamin D and asthma were extracted. All meta-analyses were performed using Review Manager 5.3.5. Results This quantitative synthesis found that asthma patients with low vitamin D levels had lower forced expiratory volume In 1 s (FEV1) (mean difference (MD) = − 0.1, 95% CI = − 0.11 to − 0.08,p < 0.01;I2 = 49%, p = 0.12) and FEV1% (MD = − 10.02, 95% CI = − 11 to − 9.04, p < 0.01; I2 = 0%, p = 0.82) than those with sufficient vitamin D levels. A positive relation was found between vitamin D and FEV1 (r = 0.12, 95% CI = 0.04 to 0.2, p = 0.003; I2 = 59%,p = 0.01), FEV1% (r = 0.19, 95% CI = 0.13 to 0.26, p < 0.001; I2 = 42%, p = 0.11), forced vital capacity (FVC) (r = 0.17, 95% CI = 0.00 to 0.34, p = 0.05; I2 = 60%, p = 0.04), FEV1/FVC (r = 0.4, 95% CI = 0.3 to 0.51, p < 0.001; I2 = 48%, p = 0.07), and the asthma control test (ACT) (r = 0.33, 95% CI = 0.2 to 0.47, p < 0.001; I2 = 0%, p = 0.7). Subgroup analysis indicated that the positive correlation between vitamin D and lung function remained significant in both children and adults. Conclusions Our meta-analysis suggested that serum vitamin D levels may be positively correlated with lung function in asthma patients. Future comprehensive studies are required to confirm these relations and to elucidate potential mechanisms.
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Affiliation(s)
- Jian Liu
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Yong-Quan Dong
- Department of Respiratory Disease, Yinzhou No. 2 Hospital, Ningbo, Zhejiang Province, China
| | - Jie Yin
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jian Yao
- Department of Emergency, People's Hospital of Jinyun County, LiuShui, Zhejiang Province, China
| | - Jie Shen
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Guo-Jie Sheng
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Kun Li
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Hai-Feng Lv
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Xing Fang
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Wei-Fang Wu
- Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
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46
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Tzilas V, Bouros E, Barbayianni I, Karampitsakos T, Kourtidou S, Ntassiou M, Ninou I, Aidinis V, Bouros D, Tzouvelekis A. Vitamin D prevents experimental lung fibrosis and predicts survival in patients with idiopathic pulmonary fibrosis. Pulm Pharmacol Ther 2019; 55:17-24. [DOI: 10.1016/j.pupt.2019.01.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 01/13/2019] [Accepted: 01/14/2019] [Indexed: 12/22/2022]
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47
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Cingi C, Bayar Muluk N, Scadding GK. Will every child have allergic rhinitis soon? Int J Pediatr Otorhinolaryngol 2019; 118:53-58. [PMID: 30580075 DOI: 10.1016/j.ijporl.2018.12.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 12/13/2018] [Accepted: 12/13/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Given the increasing prevalence of AR amongst children, we aimed to review the literature regarding the future of AR in this population. METHODS We searched the PubMed, Google and Proquest Central databases at Kırıkkale University Library. Search terms used were: "allergic rhinitis", "children", "paediatric", "allergy", "future", "risk factors", "treatment", "pharmacotherapy" and/or "allergen - specific immunotherapy". With regard to risk factors for allergic rhinitis, the terms "Environmental factors", "Improved hygiene", "Increased indoor allergen exposure", "Farms, villages, worms, and other parasites", "Environmental toxicants", "Diet", "Lifestyle changes", "Air pollution" and "Climate factors" were searched for. "Prevention of allergic diseases" and "Allergen-specific immunotherapy in the future" were also included in the search. RESULTS AR has a high prevalence and causes considerable morbidity, has associated comorbidity and features specific complications. The principal treatments rely on avoiding the allergens responsible, and administering drug treatment or immunotherapy, which targets specific antigens. Genetic drift does not explain the rising prevalence of allergic disorders, but multifactorial environmental factors are likely culprits. Amongst such environmental factors to consider are the rise in caesarean births, decreases in breast feeding, dietary changes resulting in less fresh produce being consumed, the eradication of intestinal worm infestations, alterations in the way homes are aired and heated, children taking less exercise and being outdoors for shorter periods, whilst also having more contact with pollution. CONCLUSION Barring substantial lifestyle alterations, more and more children are likely to develop AR. It may prove feasible to stop allergy developing in the first place through manipulation of the microbiome, but the exact format such a modification should involve remains to be discovered. Molecular allergological techniques do offer the prospect of more precisely targeted immunotherapy, the sole disease modifier at present. However, at present the complexity and cost of such interventions prevents their widespread use and research in this area is still needed. The majority of children with AR are going to be managed using nasal saline sprays, since they are the most straightforward and least risky alternative for first line treatment.
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Affiliation(s)
- Cemal Cingi
- Eskisehir Osmangazi University, Medical Faculty, Department of Otorhinolaryngology, Eskisehir, Turkey.
| | - Nuray Bayar Muluk
- Kirikkale University, Medical Faculty, Department of Otorhinolaryngology, Kirikkale, Turkey.
| | - Glenis K Scadding
- Honorary Consultant Allergist & Rhinologist, RNTNE Hospital, University College Hospitals, London, United Kingdom.
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48
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Huang Y, Wang L, Jia XX, Lin XX, Zhang WX. Vitamin D alleviates airway remodeling in asthma by down-regulating the activity of Wnt/β-catenin signaling pathway. Int Immunopharmacol 2019; 68:88-94. [PMID: 30616171 DOI: 10.1016/j.intimp.2018.12.061] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 01/04/2023]
Abstract
Vitamin D exerts a protective role in asthma; however, the molecular mechanisms underlying the vitamin D-attenuated asthma airway remodeling are yet to be elucidated. In this study, Sprague-Dawley (SD) rats were randomly divided into four groups: control, asthma, vitamin D 50 ng/mL, and vitamin D 100 ng/mL. The treatment with 100 ng/mL vitamin D remarkably reduced the thickness of the airway smooth muscle, collagen deposition, and the alpha-smooth muscle actin (α-SMA) mass and airway inflammation. Conversely, the treatment by vitamin D significantly up-regulated the serum levels of 25(OH)2D3 that were decreased in asthma. The putative signaling pathway of vitamin D was based on Wnt5a and β-catenin expression assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and Western blot, which revealed that the administration of vitamin D significantly decreased the activity of Wnt/β-catenin signaling pathway. These results suggested that administration of vitamin D alleviated the airway remodeling in asthma by down-regulating the activity of Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Yue Huang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Lei Wang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Xiao-Xiao Jia
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China
| | - Xi-Xi Lin
- Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
| | - Wei-Xi Zhang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
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49
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Mishra NK, Mishra JK, Srivastava GN, Shah D, Rehman M, Latheef NA, Maurya A, Rajak BK. Should vitamin D be routinely checked for all chronic obstructive pulmonary disease patients? Lung India 2019; 36:492-498. [PMID: 31670296 PMCID: PMC6852226 DOI: 10.4103/lungindia.lungindia_141_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Aims and Objectives: This study aimed to compare the vitamin D levels between chronic obstructive pulmonary disease (COPD) patients and healthy controls and to describe the correlation between vitamin D levels and lung functions. Methods: Fifty COPD patients (cases) and 30 healthy volunteers (controls) were recruited and their serum vitamin D level was measured together with lung function (forced vital capacity and forced expiratory volume in 1 s [FEV1]) by spirometry. vitamin D was categorized as ≤20 nmol/l: deficient, 21–50 nmol/l: inadequate, and ≥51 nmol/l as sufficient. Results: In this case–control cross-sectional study, lower vitamin D levels were associated with lower lung function in both cases as well as controls, the effect being more pronounced in cases. Mean FEV1 at vitamin D ≤20 nmol/l (0.98 ± 0.40 vs. controls 1.93 ± 0.24 with P = 0.006), mean FEV1 at vitamin D 21–50 nmol/l (1.55 ± 0.54 vs. 2.20 ± 0.31 with P = 0.000), and mean FEV1 at vitamin D ≥51 nmol/l (2.06 ± 0.54 vs. 2.20 ± 0.31 with P = 0.002). Moreover, the severity of predicted postbronchodilator FEV1% was also much lower among COPD cohort versus healthy volunteers (mean FEV1%: cases 47.88 ± 14.22 vs. controls 58.76 ± 15.05 with P = 0.002). Conclusions: Importantly, lung function in both the groups was affected by decreased vitamin D level; decrease in FEV1 was more pronounced among COPD patients compared to controls showing more expiratory airflow limitation. Vitamin D levels are associated with changes in lung function in cases of COPD as well as healthy controls. Larger studies to confirm the association in Indian context are required and routine assessment of vitamin D may be undertaken to obviate the effects of low vitmain D level on lung function.
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Affiliation(s)
- Navin Kumar Mishra
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Jai Kishan Mishra
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - G N Srivastava
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - D Shah
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - M Rehman
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - N A Latheef
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - A Maurya
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Bhupendar K Rajak
- Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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50
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Rajaram M, Selvarajan S, Neelamegan R, Kamalanathan S, Gunaseelan V, Xavier AS, Das S, Karthikeyan V, Saka V, Chandrasekaran A. Effects of genetic polymorphisms in Vitamin D metabolic pathway on Vitamin D level and asthma control in South Indian patients with bronchial asthma. Lung India 2019; 36:483-491. [PMID: 31670295 PMCID: PMC6852217 DOI: 10.4103/lungindia.lungindia_23_19] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objectives: The study was designed to evaluate the single-nucleotide polymorphisms (SNPs) of genes involved in Vitamin D actions (rs2228570) and metabolic pathways (rs2248137 and rs10766197) and their associations with serum 25-hydroxy Vitamin D (25(OH)D) level and asthma control in South Indian patients with bronchial asthma. Materials and Methods: One hundred and two patients of South Indian origin with bronchial asthma either naive to inhaled corticosteroids (ICSs) or not receiving ICS for ≥1 month were included and were treated with ICS (beclomethasone 200 μg twice daily) for 8 weeks. One hundred and one unrelated healthy South Indians were used as controls. Pulmonary function test and fractional exhaled nitric oxide were used to assess asthma control. Serum 25(OH)D levels (chemiluminescence immunoassay) and SNPs in Vitamin D pathway (real-time polymerase chain reaction) were assessed. The associations of SNPs and serum 25(OH)D with asthma control was determined using linear regression. All analyses were performed using SPSS (version 19) and “SNPStats.” P < 0.05 was considered as statistically significant. Results: Vitamin D receptor (VDR) polymorphism (rs2228570) was found to be protective against asthma (P = 0.022), while there were no significant associations between the other two SNPs and asthma. Similarly, poor correlation and insignificant associations between the SNPs and serum 25(OH)D levels were observed in both cases and controls. There were also insignificant associations between the SNPs and asthma control. Conclusion: VDR polymorphism (rs2228570) was found to be protective against asthma in South Indians, while other genes involved in the metabolic pathway of Vitamin D did not show associations with asthma.
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Affiliation(s)
- Manju Rajaram
- Department of Pulmonary Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sandhiya Selvarajan
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Revathy Neelamegan
- Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | | | - Alphienes Stanley Xavier
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Saibal Das
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Vignesh Karthikeyan
- Centre for Biotechnology, Cell Signaling Laboratory, Anna University, Chennai, Tamil Nadu, India
| | - Vinodkumar Saka
- Department of Pulmonary Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Adithan Chandrasekaran
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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