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Relationship Of The Level Of Vitamin D In Serum To Partial Th1/Th2 Cytokine And Pulmonary Function In Adults With Asthma

Posted on:2016-07-08Degree:MasterType:Thesis
Country:ChinaCandidate:F R ZengFull Text:PDF
GTID:2284330482451515Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Background Bronchial asthma (asthma) is a serious global health problem. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation, the pathogenesis of asthma is a chronic disorder characterized by airway inflammation, reversible airway obstruction, and airway hyperresponsiveness. In the process of airway inflammation of asthma, a variety of cells, such as eosinophils, T lymphocytes, mast cells, air epithelial cell, and dendritic cells (DCs), are involved.People of all ages throughout the world are affected by this chronic airway disorder. It is said that the prevalence of asthma has increased in many countries including countries with high rates of asthma, intermediate rates of asthma or low rates of asthma, especially among children. It remains the most common chronic disease of childhood in the world and incurs significant healthcare costs.The Global Initiative for asthma reported that the prevalence of asthma in both children and adult is significant and increasing rapidly with more than 300 million people affected worldwide at present. Asthma is a common disease affecting 1-18% of the population in different countries.The burden of asthma is experienced not only in terms of healthcare costs but also as lost productivity and reduced participation in family life.The World Health Organization estimated that 235-330 million people worldwide were affected by asthma in 2011. It is said that 15 million disability-adjusted life-yrs are lost annually due to asthma, representing 1% of the total global disease burden.Annual worldwide deaths from asthma have been estimated at 250,000 and mortality does not appear to correlate well with prevalence. As of 2025,400 million people worldwide were affected by asthma. Akinbami,et al. conducted that Asthma prevalence increased from 2001 to 2010:An estimated 25.7 million persons had asthma in 2010. Asthma prevalence increased from 7.3% in 2001 to 8.4%in 2010. For the period 2008-2010, asthma prevalence was higher among children than adults.The international epidemiological large cross-sectional studies shown that the prevalence of asthma in either different countries or different regions of the same country in children was 3.3 to 29% and adult asthma from 1.2 to 5.5. Asthma is also considerately prevalent in our country. The prevalence of asthma is 0.5 to 2.0 approximately at percent. There is still low compared to Europe and other developed countries. The third national epidemiological survey of children asthma demonstrated that, the prevalence of asthma in children from in 2000 to in 2010was1.54 to 3.02%. During the 10 years, it was increased 96.1%. Asthma increasingly serious threat to human health and affect the quality of people’s lives, and therefore, as a clinician, we should correctly understand the treatment of asthma management and health education worldwide.Asthma has been recognized as a typical complex disease with a high number of factors modulating the expression of asthma-related phenotypes and/or outcomes. Its exact cause remains unknown and likely has its origin in complex interactions among multiple genetic, environmental factors,immune systems and infection.Domestic and foreign many scholars believe that the pathogenesis of asthma and innate immunity and acquired immune exist close relationship,thought the Thl/Th2 cell imbalance is the important foundation of asthma.In recent years, with the heat rising research on asthma and asthma prevention study progress ceaselessly, more and more scholars focus on asthma immune-inflammation theory.The CD4+T cells play an important role in the pathogenesis of asthma.Vitamin D is a nutrient and a hormone that can be obtained from a few natural foods and fortified foods and it can be generated endogenously from sunlight exposure via a photosynthetic mechanism in the skin. It is widely recognized as a modulator of calcium absorption and bone health and further regulates neuromuscular function, cellular differentiation, insulin secretion and immunoregulation. Vitamin D deficiency has been reported in many populations, even in those living in areas with abundant sun exposure.25-Hydroxyvitamin D(25(OH)D) is the major circulating form of vitamin D, and its concentration in serum has been thought to reflect the status of vitamin D. Although there is no consensus regarding optimal 25(OH) Dserum levels, based on epidemiologic studies, a desirable level of serum vitamin D, i.e.,25(OH)D, for general health is at least 30-40 ng/mL (75-100 nmol/L).Vitamin D metabolites are important immune-modulatory hormones. In vitro, vitamin D has been shown to increase the proliferation and maturation of monocytes to macrophages.The presence of the vitamin D receptor (VDR) in peripheral blood monocytes and activated T cells suggests a relationship between the vitamin and the immune system. Vitamin D has been shown to have a role in both innate and adaptive immunity by promoting phagocytosis and modulating the effects of Th1, Th2 and regulatory T cells.Studies have shown that vitamin D deficiency is associated with defective macrophage function, such as impaired chemotaxis, phagocytosis and increased production of proinflammaitory cytokines. By other allergens or antigens after stimulation of naive CD4+T cells differentiate into activated CD4+Th2 cells, produce a series of cytokines, such as IL-4, IL-5 and IL-13, induce specific IgE promote mucus secretion, airway smooth muscle contraction, causing airway hyperresponsiveness, airway inflammation leads to induce asthma.Vitamin D can suppress Th2-mediated allergic airway disease and may modulate the suppressive activity of local regulatory cells.Further evidence suggests that vitamin D alters human airway smooth muscle expression of chemokines and inhibits the expression of a steroid resistant gene. It has been demonstrated that insufficient vitamin D levels (defined by serumconcentrations<30 ng/mL) were associated with an increased risk of severe asthma during childhood by Brehm et al. Sandhu et al. said that Vitamin D deficiency has been associated with increased airway hyperresponsiveness, lower pulmonary function, worse asthma control and steroid resistance.The existence of associations of vitamin D with asthma and allergy remains uncertain. While some suggest that higher maternal intake of vitamin D during pregnancy was associated with a decreased risk of recurrence of wheezing in young children,others suggest that vitamin D supplementation may increase the risk of allergy.therefore, the aim of this study was to evaluate the state of vitamin D in asthmatic patients and its potential relationship with Cell inflammatory markers and pulmonary function. In order to understand the impact of vitamin D to adult asthma and to provide new ideas and clinical evidence for treatment of asthma.Part one Clinical Study on the correlation between serum vitamin D level and pulmonary function in adult with asthmaObjective The aim of this study is to assess the level of serum vitamin D in patients with bronchial asthma. To study whether vitamin D status is associated with lung function in adults with diagnosed asthma.Methods Our study included 90 subjects chosen randomly from patients who attended the chest out clinic and admitted at The our hospital during acute exacerbation between July 2012 and July 2014, their ages ranged from 19 to 70 y. They were divided into two groups:Control group:28 matched healthy individuals(12 males and 16 females) with a mean age of 45.04±10.58 y and Asthmatic patient group:62 patients (28 males and 34 females)with bronchial asthma with a mean age of 45.04±10.58 y. It was divided into third groups:Mild Group:6 patients with mild exacerbation (FEV1≥80%predicted) of bronchial asthma. Moderate Group:13patients with moderate exacerbation of bronchial asthma (FEV1 60-80% predicted). Severe Group:43 patients with severe exacerbation of bronchial asthma (FEV1<60%predicted). Serum total (25-OHD-the main circulating form of vitamin-D) was measured using the enzyme immunoassay method according to the manufacturer’s instructions.Pulmonary function parameters, including FVC(forced vital capacity), FEV1 (forced expiratory volume in 1 s), FEV1% predicted, and FEV1/FVC%, were determined by a pulmonary function testing device. Data collected were tabulated and analyzed by SPSS statistical package version 13.0 on an IBM compatible computer, and drawed by Excle software. The results of this study were analyzed and presented as numbers, percentage or mean±standard deviation (SD). Student t test, SNK-q test,analysis of variance (ANOVA) and Chi-square were used for comparison between groups. The correlations were analyzed by Pearson correlation coefficients. A P value less than 0.05 was considered to be significant for statistical hypothesis testing.Results1. The mean serum 25OHD level of all asthmatic patients was (29.69±20.45)and the control group was (75.16±4.06)nmol/L.There was significant differences in two group(t=-16.793, P=0.000).2. The mean serum 25OHD level of man was (33.86±20.79) and woman was (26.26±19.80)nmol/L in asthma group. There was no significant difference was detected in the 25OHD levels of male and female participants.3.71% asthmatic participants having serum 25OHD level<50nmol/L,22.5% had a level of 50 to 75nmol/L,6.5% had a level>75nmol/L.4. The mean FEV1%pred of all asthmatic patients was(50.26±18.13)%, mild Group was (78.45±13.82)%, moderate group was (68.31±5.29)%, severe group was (40.87±11.92)%。5. The mean serum 25OHD level of mild Group was (63.74±21.88)nmol/L, moderate group was (48.38±15.0)nmol/L, severe group was (19.28±10.06)nmol/L。 There was significant differences in third group(F=51.94, P=0.000),The serum 25OHD level of severe group was significantly lower than that of the mild and moderate group.6. A significant positive correlation between serum 25OHD and FEV1%pred was observed in the studied asthmatic patients (r=0.839,P=0.000).7. A significant positive correlation between serum 25OHD and FEV1%pred among mild (r=0.955,P=0.03), moderate (r=0.780,P=0.02), severe (r=0.483,P=0.000) asthma groups.Conclusion1. The mean serum 25QHD level of all asthmatic patients was significantly lower than normal level (75 nmol/L).It is shown that Vitamin D deficiency was highly prevalent in asthmatic patients.2. It is demonstratd that significant damage to lung function as of low FEV1%pred.3. There was a strong correlation between asthma severity and 25(OH) vitamin D concentrations.4. There was a directand a positive significant correlation between vitamin D levels and pulmonary function tests in asthmatic patients, so the measurement of serum vitamin D levels in patients with bronchial asthma is very useful.Part two Relationship of the level of vitamin D in serum to partial Thl/Th2 cytokine in adults with asthmaObjective The aim of this study is to assess the level of serum vitamin D in patients with bronchial asthma. To study whether vitamin D status is associated with partial Thl/Th2 cytokine in adults with diagnosed asthma.Methods Our study included 90 subjects chosen randomly from patients who attended the chest out clinic and admitted at our hospital during acute exacerbation between September 2012 and October 2014, their ages ranged from 19 to 70 y.They were divided into two groups:Control group:30 matched healthy individuals(16 males and 14 females), their ages ranged from 18 to 60 y with a mean age of 42.33±11.16 y and Asthmatic patient group:60 patients (33 males and 27 females)with bronchial asthma, their ages ranged from 19 to 65 y with a mean age of 39.52±12.24y. It was divided into two groups:30 patients with bronchial asthma in between attack, the other 30 with bronchial asthma in between remission.Serum total (25-OHD-the main circulating form of vitamin-D)、Tumor necrosis factor -α、 Interferon-y、Total IgE、Interleukin-2、Interleukin-6 and Interleukin-8 was measured using the enzyme immunoassay method according to the manufacturer’s instructions.Data collected were tabulated and analyzed by SPSS statistical package version 13.0 on an IBM compatible computer. Data collected were tabulated and drawed by Excle software.The results of this study were analyzed and presented as numbers, percentage or mean±standard deviation (SD). Student t test, SNK-q test,analysis of variance (ANOVA) and Chi-square were used for comparison between groups. The correlations were analyzed by Pearson correlation coefficients. A P value less than 0.05 was considered to be significant for statistical hypothesis testing.Results1. The mean serum 25OHD level of all asthmatic patients was (34.27±15.75)nmol/L and the control group was (73.47±9.19)nmol/L. Asthmatic subgroup was (26.61±13.84) and (43.19±13.84)nmol/L.There was significant differences in third group and comparison between any two groups.2. The mean serum Tumor necrosis factor -α、Interferon-γ、Total IgE、 Interleukin-2、Interleukin-6 and Interleukin-8 level of patients with bronchial asthma in between attack was (234.37 ± 71.61)pg/ml, (25.39±10.78)pg/ml, (140.84± 23.34)Iu/ml, (25.21±7.26)pg/ml, (66.03±16.38)pg/ml, (614.66±158.61)pg/ml;and patients bronchial asthma in between remission was (157.19±26.02)pg/ml, (31.76+ 10.12)pg/ml, (101.79±25.48)Iu/ml, (31.76±10.13)pg/ml, (18.91±8.65)pg/ml, (179.70±62.16)pg/ml;and the control group was (116.54±14.50)pg/ml, (62.47± 8.99)pg/ml, (57.66±13.30)Iu/ml, (66.91±13.83)pg/ml, (13.68±4.47)pg/ml, (51.48 ±13.75)pg/ml;There was significant differences in third group and comparison between any two groups.3. A significant positive correlation between serum 25OHD and Interferon-γ、 Interleukin-2 between patients with bronchial asthma in between attack was (r=0.623,P=0.000;r=0.833,P=0.000) and patients bronchial asthma in between remission was (r=0.869,P=0.000;r=0.904,P=0.000). A significant negative correlation between serum 25OHD and Tumor necrosis factor-α、Total IgE、Interleukin-6、 Interleukin-8 between patients with bronchial asthma in between attack was (r=-0.904,P=0.000;r=-0.689,P=0.000;r=-0.781,P=0.000;r=-0.897,P=0.000); and patients bronchial asthma in between remission was (r=-0.849,P=0.000;r=-0.698,P=0.000;r=-0.639,P=0.000;r=-0.778,P=0.000).4. A significant positive correlation between serum Tumor necrosis factor -α and Interleukin-6-Interleukin-8 between patients with bronchial asthma in between attack was (r=0.597, P=0.000; r=0.741, P=0.000; r=0.892, P=0.000); and patients bronchial asthma in between remission was (r=0.706, P=0.000; r=0.605, P=0.000; r=0.749, P=0.000).5. A significant positive correlation between serum Total IgE and Interferon-γ、Interleukin-2 was observed in the studied asthmatic patients (r=-0.716, P=0.000; r=-0.710, P=0.000). A significant negative correlation between serum Total IgE and Tumor necrosis factor-α、Interleukin-6 and Interleukin-8 was observed in the studied asthmatic patients (r=0.720, P=0.000; r=0.720, P=0.000; r=0.738, P=0.000).6. It is reported that a significant positive correlation between serum 25OHD and Interferon-γ、Interleukin-2 was observed in the studied asthmatic patients and negative correlation Tumor necrosis factor -α by Multiple linear regression analysis.Conclusion1. It is shown that Vitamin D deficiency was highly prevalent in asthmatic patients.especially in acute exacerbation.2. Vitamin D deficiency can be clinically significant predictors of asthma,and Tumor necrosis factor -α;Interleukin-6 and Interleukin-8 an be used as important predictors of acute asthma attacks.3. The state of vitamin D in asthmatic patients has been associated with Cell inflammatory markers.Improve the level of vitamin D helps reduce asthma inflammation Symptom.4. Supplement Vitamin D may become a new choice in clinical asthma treatment.
Keywords/Search Tags:Bronchial asthma, 25 hudroxy vitamin D, Adult, Pulmonary function, Interleukin, Tumor necrosis factor-α, Interferon-γ, Cellular immunity
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