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BIOCHEMICAL EVALUATION OF MICRO NUTRIENTS FOUND IN SELENIUM, VITAMIN D, ZINC) IN CHRONIC OBSTRUCTIVE THE PULMONARY DISEASE

ABSTRACT
Malnutrition is a common problem in moderate or severe Chronic Obstructive Pulmonary Disease (COPD) patients which affects body composition and food intake of these patients. In this study, the relationship of the stage of COPD with nutritional intake and body mass index in COPD patients were investigated and compared with healthy people and Dietary Reference Intake tables. A total of 93 COPD patients were referred by pulmonary physicians in Motahari and Faghihi medical centers. Pulmonary Function Test (PFT) was used in order to confirm the diagnosis of COPD and also categorize the patients into three categories (mild, moderate and sever). The control group consisted of 108 adults matched to the cases by age and gender. Anthropometric indices and physical activity and a 24 h dietary recall were recorded. All analyses were performed using the SPSS 14. All data presented as means (±SD). The mean intake of energy (p = 0.002), protein (p<0.001), fat (p = 0.007), vitamin C (p = 0.003), vitamin E (p<0.001), magnesium (p<0.001) and omega-3 (p<0.001) was significantly lower in COPD patients compared with controls. The mean BMI of the severe group was significantly lower than the controls (p = 0.016). The mean intake of energy, carbohydrate, fat, vitamin E, magnesium and omega-3 was significantly lower in both case and control groups compared to the RDA (p<0.001) for all of the mentioned nutrients). Vitamin C intake was lower than RDA in the case (p<0.001) and also in the control males (p<0.001). In COPD patients, there is a significant relationship between the stage of COPD and nutrients intake and their BMI.

CHAPTER ONE

1.0 INTRODUCTION

1.1 BACKGROUND OF THE STUDY

       COPD is a major and increasing global health problem and is currently the third leading cause of death in the world(Lozano, etal., 2012). COPD is defined as a preventable and treatable disease characterized by persistent airflow limitation that is not fully reversible (Decramer, Janssens, Miravitlles, 2012). The airflow limitation is usually progressive and associated with an enhanced chronic inflammatory response of the airways and the lungs to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients (Decramer, Janssens, Miravitlles, 2012; Gold PM (2007). COPD results from the interplay between genetic susceptibility and exposure to environmental stimuli (Barnes, 2000). A well established genetic cause of COPD is α1 antitrypsin deficiency whereas, among environmental stimuli, cigarette smoking is the main cause (Gooptu, Ekeowa, Lomas, 2009). Other exposures, such as outdoor air pollution, occupational exposure to dusts and fumes, exposure to second-hand smoke, and biomass smoke inhalation might increase the risk of and lead to disease in nonsmokers (Mannino, Buist, 2007). Cigarette smoke in particular contains 1017 oxidant molecules per puff (Eisner, etal., 2010). Such exposure causes direct injury of airway epithelial cells leading to airway inflammation in which a variety of cells such as neutrophils, macrophages and lymphocytes, are involved. Proteolytic enzymes and reactive oxygen species (ROS) are released and, if not sufficiently counterbalanced by antiproteases and antioxidant factors, will produce further damage (Eisner, etal., 2010). The term ROS indicates a large variety of free oxygen radicals such as superoxide anion (O2 ) and hydroxyl radical (OH), but also derivatives of oxygen that do not contain unpaired electrons, such as hydrogen peroxide (H2O2). Formation of ROS takes place constantly in every cell during normal metabolic processes. Moreover, activated phagocytic cells such as neutrophils and macrophages produce large amounts of ROS when are stimulated by encounter inhaled particles or other mediators of inflammation (Am J Respir Crit Care Med. 2010). When ROS are produced in excess of the antioxidant defense mechanisms, oxidative stress occurs resulting in harmful effects, including damage to lipids, proteins and DNA. Although the pathogenesis of COPD remains incompletely understood, the central role of oxidative stress in this regard is well established.

       Chronic Obstructive Pulmonary Disease (COPD) is characterized by obstruction of the airways which is progressive and is associated with an anomalous inflammatory response of the lungs to harmful gases or particles, primarily tobacco smoke (Agusti et al., 2003). COPD is a leading cause of morbidity and mortality worldwide (Asia Pacific COPD Roundtable Group, 2005) and the fourth leading cause of mortality in the United States and in Europe (Murray and Lopez, 1997). COPD will be the third leading cause of death worldwide by 2020 (Murray and Lopez, 1997). Exacerbations in COPD patients lead to an increase in the need for medical care and hospitalization, thereby causing increases in health-care costs (Siafakas et al., 1995). Attention to nutritional status in patients with respiratory diseases is important because of malnutrition has direct effect on the lung’s function, respiratory muscles and the lung parenchyma, consequently contributing to worsening of the disease (Batres et al., 2007). There is Malnutrition in at least one third of moderate or severe cases of COPD. Malnutrition affect functional performance and quality of life of these patients and independent of other aspects of the disease it is indicator of both morbidity and mortality (Foley and ZuWallack, 2001). Imbalance in dietary intake and energy expenditure contributed to weight loss. In contrast to an adaptive decreased energy metabolism during starvation, total daily energy expenditure has been increased in COPD patients (Slinde et al., 2003). The low intake in these patients can be explained by a cytokine leptin link leading to increased levels of leptin. These increased leptin levels lead to reduced food intake and higher energy demand and therefore, poor response to nutritional support (Saudny-Unterberger et al., 1997). It seems that patients with COPD are at high risk for malnutrition, making it essential that these patients undergo careful assessment and screening to identify those who require dietary treatment. So in this study, we evaluated the nutritional status in COPD patients and compared it with healthy control groups. Inflammatory bowel disease (IBD) is a chronic relapsing disease that causes significant morbidity (Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK, 1979). Malnutrition is one of its major comorbidities and is present in up to 85% of patients with IBD (Weisshof R, Chermesh I, 2015; Dawson AM, 1972).  Malnutrition can be classified as macronutrient deficiency and micronutrient deficiency. Macronutrient deficiency, which means protein energy malnutrition, usually occurs in patients with active and severe disease. Many novel treatment modalities such as immunomodulators and biologics have been introduced, and a great proportion of IBD cases are now in clinical remission. Patients with IBD in remission usually have a macronutrient intake similar to that of healthy controls. As a consequence, the prevalence of macronutrient deficiency has decreased (Filippi J, Al-Jaouni R, Wiroth JB, Hébuterne X, Schneider SM, 2006). Micronutrients play an important part in metabolism and maintenance of tissue function the maintenance of the integrity and vitality of the periodontal tissues depends on the availability of adequate nutrients, and it is possible that deficiencies can produce pathological alterations in the periodontal tissues. However, the association between nutritional factors and periodontal health is not fully understood. The essential micronutrients for maintaining health include zinc, copper, selenium, and iron. These micronutrients are required for a variety of biomolecules to maintain the normal structure, function, and proliferation of cells and also immune functions. Periodontal disease and diabetes mellitus (DM) are considered to have a bidirectional relationship, and periodontitis is recognized as the 6th major complication of DM. The number of studies on the role of micronutrients with regard to periodontal disease is limited.

        However, micronutrient deficiency can occur in the mild form of IBD or in the remission state of IBD; numerous forms of micronutrient deficiencies have been reported (Weisshof R, Chermesh I., 2015; Hwang C, Ross V, Mahadevan U, 1981; Massironi, etal., 2013). Evaluation of micronutrient status at least once per year has been recommended;8 however, most clinicians focus little attention on nutritional support in patients with IBD. Vitamin D is a fat-soluble vitamin important for normal bone metabolism because it facilitates intestinal calcium absorption and increases osteoblastic differentiation. Vitamin D deficiency in adults can result in osteopenia and osteoporosis, induce osteomalacia and muscle weakness, and increase the risk of fracture.9 Patients with IBD are at increased risk for vitamin D deficiency (Siffledeen JS, Siminoski K, Steinhart H, Greenberg G, Fedorak , 2003; J, Shanahan F, Cashman KD., 2006). Long-term use of corticosteroids in patients with IBD increases the risk of osteoporosis; therefore, maintenance of appropriate vitamin D levels might be more critical for these patients. In addition, some studies suggest that vitamin D deficiency is not the result of disease and instead has a substantial role in the pathogenesis of IBD (Li YC, Chen Y, Du J, 2015; Ooi JH, Li Y, Rogers CJ, Cantorna MT, 2013).  Therefore, monitoring and appropriate supplementation of vitamin D are important.

       Another essential micronutrient, zinc, has several physiologic roles in growth and immune system modulation (Livingstone C, 2015).  Vagianos K, Bector S, McConnell J, Bernstein CN , (2007), Zinc deficiency can cause susceptibility to infection, poor growth, and impaired wound healing. Approximately 15% of patients with IBD reportedly have zinc deficiency. In previous studies, zinc deficiency was shown to affect inflammation in IBD by aggravating mucosa leakage, by increasing the number of pro-inflammatory cells, and by modulating inflammatory cytokine response (Wong CP, Rinaldi NA, Ho E., 2015). Selenium is a nonmetal trace element that acts as a catalyst and antioxidant (Stoffaneller R, Morse NL, 2015). Selenium levels are reportedly decreased in patients with Crohn’s disease (CD), and a low selenium concentration may facilitate inflammatory and immune responses (Reimund JM, Hirth C, Koehl C, Baumann R, Duclos B, 2000).

       In another experiment, selenium deficiency worsened colitis and promoted tumorigenesis (Barrett CW, Singh K, Motley AK, et al , 2013). Selenium supposedly modulates the expression of the nuclear factor κB pathway and influences development of inflammation and carcinogenesis (Barnett M, Bermingham E, McNabb W, et al, 2010). The role of micronutrients has been investigated actively in IBD, leading to the discovery of problems in the evaluation of micronutrient status and in the correction of micronutrient deficiency. The majority of recent studies of micronutrient deficiency were performed in America and Europe. These studies reported that 30.8% to 49.8% of IBD patients had vitamin D deficiency  and prevalence of zinc deficiency in IBD patients were reported as 15% (Ulitsky A, Ananthakrishnan AN, Naik A, et al., 2011; Fu YT, Chatur N, Cheong-Lee C, Salh B. Hypovitaminosis D, 2012; Vagianos K, Bector S, McConnell J, Bernstein CN, 2007). In another study performed in France, selenium concentration was significantly decreased in CD patients (Reimund JM, Hirth C, Koehl C, Baumann R, Duclos B. , 2000). Little information is available regarding the micronutrient status of Asian patients with IBD. The aim of this study was to evaluate the prevalence of micronutrient (vitamin D, zinc, and selenium) deficiency in Korean patients with IBD and to verify the factors that affect micronutrient deficiency in patients with IBD by using multivariate analysis.

1.2  OBJECTIVE OF THE STUDY

1. To examine the causes of chronic obstructive pulmonary disease.

2. To carry out the biochemical evaluation of micro nutrients found in chronic obstructive d pulmonary disease.

3. To evaluate the role of micronutrients-zinc, copper, selenium, and iron, in the serum of chronic periodontitis patients and chronic periodontitis with DM Type II patients, to see whether they can serve as potential markers for chronic periodontitis and also to assess whether periodontitis can have systemic effects.

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