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group_4_presentation_2_-_chronic_obstructive_pulmonary_disease_copd [2016/11/01 22:35]
hongjj
group_4_presentation_2_-_chronic_obstructive_pulmonary_disease_copd [2018/01/25 15:18] (current)
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 ====== Chronic Obstructive Pulmonary Disease (COPD) ====== ====== Chronic Obstructive Pulmonary Disease (COPD) ======
  
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 +{{:​4._copd-_presentation.pdf|}}
  
 ===== Introduction ===== ===== Introduction =====
-A Genetically Modified Organism is any organism created by gene splicing techniques and often involves merging DNA from different species (31). Scientists directly manipulate an organism’s genome to isolate traits or characteristics deemed of value. Currently, the safety of GMOs is under research as they are relatively recent developments (22). 
  
 **What is COPD** **What is COPD**
  
-Humans have been domesticating and improving plants and animals since 30,000 BCE (25)Initiallyancestors began genetically modifying dogs through selective breeding of traits (25). This is achieved ​by only allowing dogs with desirable characteristics to reproduce until such trait is amplified. +Chronic obstructive pulmonary diseasedenoted as COPD is a type of obstructive lung disease ​(n.d., 2013). It is characterized ​by long-term poor airflow and displays symptoms including cough with sputum production and shortness of breathFigure 1 displays ​visual representation of lung tissue of a healthy individual ​and of an individual with COPDFrom the beginning of its diagnosis, these symptoms from individuals with COPD tend to worsen over timeIt is the fourth leading cause of death in the world as of 2013.
-Modern genetic modifications did not begin until 1973 when two scientists, Herbert Boyer and Stanley Cohen, designed ​method to splice ​gene from one organism ​and insert it into the genome ​of another (25)Bacteria were the initial organisms manipulated ​to have antibiotic resistance, followed by inserting foreign DNA into mice a year later (11)The field continued to grow exponentially with many foreseeable possibilities.+
  
-As GMOs began to be used in industry by farmers and countries they were thought of as the answer to world hunger. GMOs were used to achieve many different results; a more visually attractive organism, one that is easier to cultivate and breed, pest resistance, drought resistance and an increase in nutritional value were all goals of the developing GMO market. Agencies such as the government, natural resources, environmental groups, and the media worried about the effect of GMOs on the environment and the food chain (25). There have also been changes in public opinion as many of the long-term side effects have yet to be determined both from an environmental and biological health perspective. 
  
-<box width classes round white centre|>​{{:​timeline_of_the_development_of_gmo_s.png|}}</box| Figure 1: A timeline ​of the development ​of GMOs. +<box width classes round white centre|>​{{:​normal_and_copd_lung.png}}</​box| Figure 1: Lung tissues ​of a normal individual and of an individual with COPDRetrieved ​fromhttp://www.nhlbi.nih.gov/health/health-topics/topics/copd>
-Modifed ​from  http://sitn.hms.harvard.edu/flash/2015/from-corgis-to-corn-a-brief-look-at-the-long-history-of-gmo-technology/> +
- +
- +
- +
-**Prevalence and Epidemiology of the Disease** +
- +
-  +
-Step 1: Identifying the trait of interest. +
-Scientists identify the trait they wish to include. For example, increased resistance in an environment and look for an organism that is naturally resistant/ has that trait (22). Then they must identify that gene sequence responsible.+
  
-Step 2: Isolate the genetic trait of interest 
-Comparative analysis is used to decode what part of the genetic makeup contains the gene (22). Then genomes of the same species with and without the trait are compared to identify varying regions containing the gene of interest (5). If no database exists scientists will knock out parts of the genome until the gene of interest is lost. Seed chipping is a method where a piece of the seed is shaved off before it is planted so that its DNA can be studied. Then plants are allowed to grow and the one with the desired traits are traced back to initial DNA harvested (5). 
  
-Step 3: Insert the desired genetic trait into a new genome ​ 
-Gene guns are the most common mechanisms of gene transfer (22). A metal particle coated with DNA is inserted into a plant (22). Enzymes insert DNA of interest into a plasmid, then shuck the plasmid to guarantee replication and incorporation of the gene into the organism'​s genome. 
  
-Step 4: Growing ​the GMO +**Epidemiology and Economic Burden of the Disease**
-Must monitor the organism to ensure proper growing conditions with the correctly modified genome. A huge effort is made to keep desired plants alive and reproducing once working to monitor optimal growing conditions for seeds (22).+
  
 +As of 2010, 329 million people, approximately 4.8% of the population are affected by COPD (n.d. 2010). The primary cause of COPD is due to the rise in tobacco use among both men and women. The increase in the developing world since 1970 is believed to influence the increase in smoking within the region. The global numbers are expected to progressively increase as risk factors remain prevalent and the aging population continues to increase. As expected, COPD is more common in older people; on average, it affects 34-200 out of 1000 people older than 65 years. ​
  
-<box width classes round white centre|>​{{:​procedure_to_make_a_gm_plant.jpeg|}}</​box| Figure 2: The procedure ​to make a GM plant. +COPD is also considered one of the most expensive conditions to treat in U.S. hospitals in 2011, averaging ​to approximately $5.7 billionThe global estimated cost of treating COPD is $2.1 trillion; $1.9 trillion goes to direct medical care costs such as patient care and $0.2 trillion goes to indirect medical care costs such as sick pay for medical professionals. Costs are projected to more than double by 2030.
-Modified from: http://sitn.hms.harvard.edu/​flash/​2015/​how-to-make-a-gmo/>​+
  
  
-**Economic Burden of COPD** 
  
 **Mechanism of Disease** **Mechanism of Disease**
  
-- IMAGE - +COPD is an airway inflammation syndrome which consists of structural changes and mucociliary dysfunction.
  
 +**Structural Changes**
  
-===== Causes ​and Pathophysiology =====+The pulmonary system undergoes structural changes as a direct result of the inflammatory response that is associated with COPD. Eventually, this leads to the narrowing of the airways, making it harder for the individual to breathe. Parenchymal destruction is associated with loss of lung tissue elasticity (Takeda, 2012), implicating that the small airways collapse during exhalation ​and impedes airflow.
  
-**Environmental Factors - Air Pollution** 
  
 +**Mucociliary Dysfunction** ​
  
-Efficiency is determined by the optimal yield of a productconsidering the costs associated with producing this yieldGenetic modification of organisms increases the efficiency of productsrendering beneficial factors ​for both producer and consumerThe use of bovine somatotropin (bST)/ recombinant bovine growth hormone (rbGH) ​in lactating dairy cows demonstrates such efficiency.+Chronic smoking and COPD inflammation forces mucous glands that line the airway lung walls to enlarge. This in turncauses healthy cells to be replaced by excessive mucus-secreting cellsOver timeCOPD also causes damage to the mucociliary transport system which is primarily responsible ​for clearing the mucus from airwaysFigure 2 shows a visual representation ​of the mechanism ​in how the presence of mucus worsens airflow.
  
-The anterior pituitary gland naturally secretes somatotropin,​ a peptide hormone which stimulates growth, cell regeneration,​ and reproduction in human and animals (3). Bovine somatotropin (bST), otherwise referred to as recombinant bovine growth hormone (rbGH), is produced through recombinant DNA techniques (3). The direct effects of bSt/ rbGH result in alterations to numerous tissues, metabolic processes involving all nutrient ​classes, and cellular mechanisms such as intracellular signal transduction systems and response to homeostatic signalsIndirect ​effects ​are suspected to be mediated by the insulin-like growth factor (IGF) and have been found to impact mammary glandsThe environment and management factors, such as nutritional status, play regulatory roles in such effects and responses (3).+<box width classes ​round white centre|>​{{:​untitled6.png}}</​box| Figure 2: Mechanism of Mucociliary ​effects ​from COPDRetrieved from: https://en.wikipedia.org/​wiki/​Chronic_obstructive_pulmonary_disease>​
  
-Bovine somatotropin (bST)/ recombinant bovine growth hormone (rbGH) is utilized within cows to increase milk production (WHO). Milk response in these cows is greatest during the declining phase of lactation and milk quality is reportedly unaltered (3). 
  
 +===== Causes and Pathophysiology =====
  
 +**Environmental Factors - Air Pollution**
  
-**The Relationship Between ​COPD Deaths ​and Air Pollution**+Biological dust exposure in the workplace is a risk factor for chronic obstructive pulmonary disease. Matheson, M.C., et al., performed a cross sectional study of the risk factors of COPD relating to job history of 1200 participants. Those exposed to biological dust had increased risk of chronic bronchitis, emphysema and COPD with incidence being higher in women compared to men even though they reported less exposure to biological dust than men. Biological dust includes microbes such as plant and animal, bacteria, fungi, allergens, endotoxins, peptidoglycans,​ glucans and pollens. Occupations affected by biological dust are those in the cotton industry, farmers, grain handlers, bakers, saw mill workers, nurses, artists, and cleaners. 
 +The duration and type of exposure plays a role in increasing risk of COPD. Gas, fumes, ​and mineral dust do not pose a risk. The only way to reduce risk is to reduce exposure to these in the workplace (Matheson, M., 2005).
  
  
-Advances in molecular and reproductive technology ​have driven ​the practice ​of commercial animal pharming over the past twenty years (14). Pharming ​is a branch of biotechnology which bridges together the contrasting fields of pharmaceuticals ​and farmingTransgenic plants or animals are utilized for producing pharmaceuticals synthesized for human or animal consumption (7). Animal pharming ​is promoted as cost-effective method of biopharmaceutical production (14) and has the potential to become a highly lucrative industry (7)+**Outdoor Air Pollution** 
 +Urban areas have the worst air pollution with some countries having more air 
 +pollution than others. Air pollutants have harmful effects on the airways, they increase oxidative stress, pulmonary and systemic inflammation,​ amplification ​of viral infections and reduction in air ciliary activity ​(Ko, F. & Hui, D., 2012). Higher traffic density ​is proven to be associated with higher pollution ​and lower forced expiratory volume (Ko, F& Hui, D., 2012). Therefore it is biologically possible that air pollutants damage lungs, but it is not determined to be causative factor due to lack of long-term studies.
  
-The need for pharmaceutical intervention is evident amongst patients possessing hereditary antithrombin deficiencies. In 2006, an anticoagulant called Antithrombin became the first recombinant protein to be approved for commercialization by the United States’ Food and Drug Administration (FDA) (18). Antithrombin is extracted and purified from the milk of transgenic dairy goats (16). Transgenic animals, such as these goats, are produced via one of two contemporary methods: intra-pronuclear zygotic DNA microinjection (MI) or somatic cell nuclear transfer (NT). As linear DNA enters the nucleus, it is capable of integrating into the genome of cell lines or living organisms (18).  
  
-The most promising site for production of recombinant proteins is the mammary gland due to the large quantities of protein ​that can be produced ​(16). Since milk is often produced in abundancederiving ​and producing pharmaceuticals ​in this manner is determined to be cost efficient ​(14).+**Indoor Air Pollution** 
 +Indoor air pollutants include tobacco smoke and biological allergens/ exposure are the 
 +major indoor pollutants. A cross sectional study in China and the USA proved ​that tobacco smoke from others is associated with development of COPD (Ko, F. & Hui, D., 2012). Biomass as a fuel source includes burning wood, crop residues, and animals during cooking or heating the home which releases toxins. Toxins are released because these fuels have low combustion efficiency. In rural and developing countries biomass fuel burning happens inside resulting ​in increased amounts of indoor air pollution ​(Ko, F. & Hui, D., 2012). Women are also more affected by indoor and outdoor air pollution (Ko, F. & Hui, D., 2012). 
 +COPD results from the combination of genetic and environmental factors; having more than one risk factor increases odds of getting the disease.
  
-<box width classes round white centre|>​{{:​producing_transgenic_animals.jpg|}}</​box| Figure 3. Producing Transgenic Animals. (Maksimenko,​ Deykin, Khodarovich & Georgiev, 2013)> 
  
 +<box width classes round white centre|>​{{:​summary_of_pathways_and_candidate_genes_involved_in_copd.png|}}</​box| Figure 3: Summary of Pathways and Candidate Genes Involved in COPD. Retrieved from:
 +http://​citeseerx.ist.psu.edu/​viewdoc/​download?​doi=10.1.1.629.4676&​rep=rep1&​type=pdf>​
  
  
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-<box width classes round white centre|>​{{:​Screenshot 2016-10-26 02.45.04 copy 2.png|}}</​box| Figure 4. Age Effects on Cholinergic Innervation ​in Rhesus Monkeys. (Tuszynski, 2012)>+<box width classes round white centre|>​{{:​inflammatory_mechanisms_in_copd._macnee_2006_.png|}}</​box| Figure 4. Inflammatory mechanisms ​in COPDModified from: MacNee ​(2006)>
  
  
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-**Biological Perspectives- Genetics**+<box width classes round white centre|>​{{:​a._normal_small_airway_b._abnormal_small_airway_exhibiting_airway_remodeling_in_copd._berge_et_al._2011_.png|}}</​box| Figure 5: A. Normal Small Airway, B. Abnormal Small Airway Exhibiting Airway Remodeling in COPD. Modified from: Berge et al. (2011)>
  
  
 +**Biological Perspectives- Genetics**
  
-===== Diagnosis =====+Genes might play a significant role in COPD, and might even explain why some people who smoke develop the disease and others do not. There is a genetic component accounting for a small number of COPD cases associated with alpha1-antitrypsin protein deficiency (AATD). Treatment for this involves increasing amounts of AAT protein in the body through intravenous injection of the protein derived from human plasma, therefore halting further damage to lung (Castalsi., P.J., et al., 2010). ​ AATD inhibits proteases and protects tissues from enzymes of inflammatory cells, when it is absent neutrophils can break eastin down resulting in pulmonary complications including COPD (Castalsi., P.J., et al., 2010). Many researchers have performed genome-wide association studies (GWAS) which provides an unbiased and complete search of the genome for susceptibility to COPD. Pillai and colleagues studies the association between COPD and the CHRNA3/​CHRNA5/​IREB2 region on chromosome 15 (Pillai, S., et al., 2009). MeMeo and colleagues performed gene expression studies comparing normal to COPD lung tissue resulting in the discovery of IREB2 region on chromosome 15 as a contributing genetic factor (DeMeo, D., et al., 2009). Large population genome studies have also found that SNPs near HHIP can also be associated with COPD (Hancock, D., et al., 2010). Overall, although many things were found the overall conclusions amongst the COPD community and researchers is that there is strong evidence concluding that IREB2, HHIP, and FAM13A loci are association with COPD susceptibility (Hancock, D., et al., 2010).
  
-**Spirometry**+Comparison of monozygotic and dizygotic twins used to assess environmental versus genetic effects (MZ share 100% genes, DZ share 50%) showing heritability ranges from 0.5-0.8 (Hancock, D., et al., 2010). The study discovered genes coding for various proteins can exacerbate COPD. Proteases and antiproteases,​ such as MMP-12, play a role in tissue repair associated with inflammation on chromosomes 11,​14,​16,​20,​22 (Pendas, A., et al, 1996). Presence of MMP-12 polymorphisms increase the risk of developing COPD when smoking; in MMP-12 knockout mice they did not develop emphysema when exposed to cigarette smoke (Hautamaki, R., et al., 1997). It is the Asn357Ser polymorphism associated with decline in lung function (Hautamaki, R., et al., 1997). Xenobiotic Metabolizing Enzymes, such as EPHX, are involved in metabolizing high reactive epoxide intermediates formed from cigarette smoke that cause injury (Joos, L., Pare, P., Sandford, A., 2002). Two polymorphisms in EPHX gene with 2 substitutions at exon 3 and 4 result in slower metabolizing enzymes more commonly found in COPD patients and emphysema patients, (Smith, C & Harrison, D., 1997). Additionally,​ genes coding for inflammatory mediators, antioxidants,​ and mucociliary clearance factors can all have mutations causing these proteins not to work perfectly resulting in increased COPD symptoms (Joos, L., Pare, P., Sandford, A., 2002).
  
-A first of its kind, research from Canada was successfully able to identify the presence of pesticides that were associated with genetically modified foods in maternal, fetal and non-pregnant women’s blood (2). Moreover, the presence of Monsanto’s Bt toxin was detected as well. The study was published in the Journal Reproductive Toxicology in 2011. 
  
-<box width classes round white centre|>​{{:​aris_leblanc_2011_.jpg|}}</​box| Figure 5: Characteristics of Subjects in the study (Aris, Leblanc 2011)>+===== Diagnosis =====
  
-Subjects consisted of pregnant and non-pregnant women living in Sherbrooke, an urban area of Eastern Townships of Quebec, Canada (2). None of the subjects had worked or lived with a spouse that were working in contact with pesticides. In order to determine the presence of herbicide and metaboliteslevels of glyphosate (GLYP) ​and its metabolite aminomethyl phosphoric acid (AMPA), gluphosinate ammonium (GLUF) and its metabolite 3-methylphosphinicopropionic acid (3-MMPA) were measured using gas chromatography-mass spectrometry (2)+There are several ways to diagnose COPD including spirometrychest x-rays ​and blood tests
  
 +Spirometry is a way to test if the lungs are functioning properly. The patient will breath into the spirometer, and after inhalation, a bronchodilator will be released to widen the airways. The spirometer measures the volume of air the patient can exhale in one second and the total amount of air they inhale. The measurements can then be compared to standardized results for the patient’s age group, to find out if their airways are obstructed. ​
  
-<box width classes round white centre|>​{{:​aris_leblanc_2011_-.png|}}</​box| Figure 6a, 6b: Relative Concentrations of Serum Cry1Ab, GLYP, 3-MPPA, and GLUF (mg/ml) in Pregnant and Non-Pregnant Women (Aris, Leblanc 2011)>+Chest x-rays are used to look at the lungs for problems that may cause symptoms of COPD
  
-Results showed ​that GLYP was not detected in maternal and fetal bloodbut present in the blood of some non-pregnant women, whereas its metabolite AMPA was not detected in any of the samples (2). However, GLUF was also only detected in non-pregnant women, its metabolite 3-MPPA was detected in 100% of maternal ​and umbilical cord blood samples, and in 67% of the non-pregnant women'​s blood samples. This implies that the metabolite is more detectable than its precursor GLUF and therefore seems to easily cross the placenta to reach the fetus (2). GLUF in general has demonstrated in mouse embryos to cause growth retardation,​ increased death or hypoplasia.+Blood tests can detect other conditions ​that cause symptoms similar to COPDincluding anemia ​and polycythaemia ​(NHS).
  
-Furthermore,​ Cry1Ab toxin was detected in 93% and 80% of maternal and fetal blood samples, respectively and in 69% of tested blood samples from non-pregnant women (2).  
  
-Given the potential toxicity of these environmental pollutants and the fragility of the fetus, more studies are needed, particularly those using the placental transfer approach. Researchers state that these results will provide a baseline data for future studies in the area related to nutrition, toxicology and reproduction in women. 
  
 +<box width classes round white centre|>​{{:​spirometry_traces_representing_healthy_patients_and_copd_patients.png|}}</​box| Figure 6: Spirometry Traces Representing Healthy Patients and COPD Patients. Retrieved from: http://​www.thinkcopdifferently.com/​en/​About-COPD/​Diagnosing-COPD/​Spirometric-assessment>​
  
  
-** Chest X-Rays**+===== Management and Treatment=====
  
-This study was recently released by the Institute for Responsible Technology (IRT), and uses data from the US department of Agriculture,​ US Environmental Protection Agency, medical journal reviews as well as other independent research. ​+**Pulmonary Rehabilitation**
  
-"​Gluten sensitivity can range in severity from mild discomfort, such as gas and bloating, to celiac disease, a serious autoimmune condition that canif undiagnosedresult in a 4-fold increase in death," said Jeffrey MSmithexecutive director ​of IRT.+Across North America, pulmonary rehabilitation has become an extremely popular method for long-term management of COPD (Goldstein et al., 1994). It aims to manage and improve some of the disabilities that are associated with COPD, such as decreased motor function ​and weight loss (Goldstein et al.1994). There are three facets of pulmonary rehabilitation are: the multidisciplinary nature of, individualized programs and attention ​to physical and social function (Ries & Squier1996). The collaboration between various kinds health care professionals makes pulmonary rehabilitation very successful because it encompasses ​variety of health care fields. Individuals involved include: physiciansnursesoccupational therapistspsychologists,​ nutritionists and exercise specialists(Ries & Squier1996). Additionally,​ the emphasis on an individualized rehabilitation plans leads to successful outcomes because patients are able to focus on the areas that they need to develop the most (Ries & Squier, 1996). Finally, by focusing on both the physical and social function ​of these individuals,​ pulmonary rehabilitation allows patients to work on emotional issues. This aspect has been correlated with better outcomes in physical symptoms, such as lung function and exercise tolerance (Ries & Squier, 1996)
  
-The Institute for Responsible technology is a world leader in educating policy makers and the public about GMO foods and cropsThe institute reports and investigates the impact GM foods can have on health, environment,​ agriculture and more (26). +<box width classes round white centre|>​{{:​nutrition.png|}}</​box| Figure 7: Foods Full of NutritionRetrieved from: http://​blog.copdstore.com/​the-official-guide-to-copd-nutrition>​
-In soy, corn, canola oil, zucchini, yellow squash, Hawaiian papaya, and alfalfa, "Bt-toxin, glyphosate, and other components of GMOs, are linked to five conditions that may either initiate or exacerbate gluten-related disorders,"​ according ​to Smith.+
  
-The genetically modified (GM)-related damage was linked to five different areas of symptoms: 
-  * Intestinal Permeability 
-  * Imbalanced Gut Bacteria 
-  * Immune Activation and Allergic Response 
-  * Impaired Digestion 
-  * Damage to the Intestinal Wall  
  
-IRT has also released a statement that glyphosatea pesticide was found to have a negative effect ​on intestinal bacteriaUnfortunatelyGMO crops contain high concentrations ​of this toxin during harvest ​and consumption ​by humans ​(26). +The main elements of pulmonary rehabilitation include: exercise trainingeducation ​on the disease, nutritional intervention and psychosocial support (Ries et al., 2007). Due to the decreased appetite ​of COPD patients, individuals often experience weight loss (Schols et al., 1998). This weight loss is mainly stemming from a loss of muscle, specifically respiratory muscles and consequently, ​this makes breathing even more difficult for these individuals (Schols et al., 1998). By focusing on both nutritional support ​and strength training exercise, pulmonary rehabilitation helps rebuild the muscle loss as well as prevent future loss in COPD patients. Often times, this kind of rehabilitation can be offered as an outpatient treatment, thus making it accessible to patients who are not hospitalized (Ries et al., 2007). Overall, ​by making the disabilities of COPD individuals more manageable, pulmonary rehabilitation improves the overall quality of life of individuals by making them more independent and improving health status ​(Goldstein et al., 1995; Ries et al., 2007). 
  
-With these symptoms, Dr. Tom O'​Bryan,​ with his expertise on gluten sensitivity and Celiac Disease stated that "the introduction of GMOs is highly suspect as a candidate to explain the rapid rise in gluten-related disorders over the last 17 years" (26). 
  
- +<box width classes round white centre|>​{{:​pulmonary_rehabilitation_in_action.png|}}</​box| Figure ​8Pulmonary Rehabilitation ​in Action. Retrieved from: http://​drvijaynair.8m.com/ ​>
- +
-===== Management and Treatment- Pulmonary Rehabilitation ===== +
- +
-**What is Pulmonary Rehabilitation?​** +
- +
- +
-In a study published and peer reviewed Public Library of Science (PLOS) in 2013, researchers emphasize that there is sufficient evidence that meal-derived DNA fragments carry complete genes that can enter into the human circulation system through an unknown mechanism (30). +
- +
-In one of the blood samples taken from the subjects, relative concentrations of plant DNA was significantly higher than human DNA. Sample size was based on the analysis of over 1000 human samples from four different independent studies (30).  +
- +
-“Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system"​ (30). +
- +
-As the process of digestion occurs, proteins and DNA are recognized to be degraded into smaller counterparts,​ which are amino acids and nucleic acids respectively. This is then absorbed through an active process and subsequently distributed to various regions of the body using the circulatory system. Results from the study have shown that the plant DNA concentration displayed a precise log-normal distribution in the plasma samples while non-plasma control sample was found to be free of it. According to the demonstration of the study'​s results, this implies that these meal-derived DNA fragments are large enough to carry complete genes that can avoid degradation through an unknown mechanism to enter the human circulatory system.  +
- +
-Although this study was not conclusive as pure evidence that GMOs are able to enter into our cells, it is an assumption that can be made into a possibility. Results from this study demonstrate another cause for concern and reason to research further into the safety of GMO consumption. +
- +
-**Primary Reason for Attending Pulmonary Rehabilitation- Weight Loss** +
- +
-Genetically modified insect-resistant plants have the potential for reducing usage of pesticides (37). After the adoption of genetically modified crops in the 1990s, there was a reduction in approximate 8.22 million pounds of pesticides used within the first year of usage (33). Reducing amounts of pesticides in the environment can benefit the environment in multiple ways. There has been increasing amounts of evidence regarding the hazards that pesticides pose to the environment. Specifically,​ pesticides have the ability to contaminate soil, ground water and other vegetation present (1). A study done by the U.S Geological Survey across multiple river basins in the United States found that greater than 90% of water and fish samples tested from these bodies of water contained one or more pesticides (15). Furthermore,​ this study revealed that levels of pesticides present in most urban streams exceeded the recommended guidelines that were created to protect aquatic wildlife from harm (35). The trend noticed within the first few years after the adoption of genetically modified crops has been encouraging as it has shown an overall reduction of pesticides used (37). +
- +
-<box width classes round white centre|>​{{:​impacts_of_gm_corn_and_cotton_on_insecticide_use.png|}} </box| Figure ​7After the adoption of genetically modification corn and cotton ​in the last 1990’s the USDA recorded a rapid decline in the usage of insecticides (United States Department of Agriculture,​ 2014)>+
  
  
 **Outcomes of Pulmonary Rehabilitation** **Outcomes of Pulmonary Rehabilitation**
  
-Genetically modified crops have the potential ​to improve crop yield in developing countries, such as Southeast Asia and Africawhich stand to most to gain since agricultural output is limited (37). The current majority ​of genetically modified crops have traits that infer resistance ​of insects ​and herbicides ​(12)Bt cornwhich is a genetically modified crop, which produces the toxin bacillus thuringiensis,​ has been widely used since its approval in 2002 (24). Data obtained from 2001 trials of 157 farms using Bt and non-Bt corn in India showed average yields of Bt- hybrids was 80-87% higher. These genetically modified crops in developing areas have a great potential. Farmers in these areas have limited accessibility to insecticides ​and other chemical alternatives. Additionally, ​due to tropical ​and subtropical weather climatesthese areas experience ​the most pest pressure ​(20). The hypothesis that these crops can improve crop yield was tested ​by field-trial results from India, which experience conditions similar to Sub-Saharan Africa and Southeast Asia (10). Overall, an increase ​in crop yield has the potential ​for preservation ​of natural habitats since less land will need to be converted into agricultural use in the futurethus promoting land and habitat conservation (37).  +Although pulmonary rehabilitation does not reverse ​the pathophysiology of the disease it is able to reduce the symptoms ​and disabilities associated with COPD (Ries et al.2007). This kind of therapy is able to help individuals become more physically active and teaches them how to cope with the disease, both with better understanding ​of the condition ​and emotional support ​(Lacasse et al., 2006). Physical improvements are often seen in COPD patients ​and are due to the exercise ​and nutritional supports that pulmonary rehabilitation provideswhich can last up to 9 months after discontinuation of the program ​(Cambach et al., 1999). In a clinical study done by Berry et al. (1999), when compared to a control group that did not participate in pulmonary rehabilitation, an active group showed significant improvements ​in exercise tolerance. After participating in a 6-week pulmonary rehabilitation program, these COPD patients saw significant improvements in regards to the amount walked in six minutes. Improvements were maintained ​for at least 3 months after the conclusion ​of the experiment (Berry et al.1999). These findings are illustrated ​in the diagram below.
- +
-<box width classes round white centre|>​{{:​projected_yields_of_insect-resistant_gm_crops.png|}}</​box| Figure 8: Projected Yields of insect-resistant genetically modified crops based on field-trials ​in IndiaAssessments of pest pressures, use of chemical alternatives and expected yields were evaluated (Qiam and Zilberman, 2003)> +
- +
- +
-**Clinical Evidence of Pulmonary Rehabilitation**+
  
-Two main ways genetically modified crops can improve soil integrity and conservation is through phytoremediation and promoting no-till weed management.  ​ 
  
-Some genetically modified plants have the ability to provide ​in situ remediation of polluted soilsediments and surface waters (37). These plants overexpress metabolism enzymes and are able to remove organic pollutantsincluded herbicides and insecticides commonly found in soils. An enzyme that is regularly selected for is Chytochrome P450, which is typically involved ​in the metabolism ​of herbicides in mammalian livers (9)Through phytoremediation,​ absorbed pollutants are able to be converted into non-toxic metabolites and accumulate in the plants or be released back into the soilThis has been proven to both a sustainable and effective technology ​(27). Plants that have this ability must themselves be resistant to the pollutants being removed as well as have a large biomass so they can remediate large amounts of chemicals. Positive implications for the environment include decreased levels of pollutants in soil and less need for harmful and costly physical or chemical remediation processes (37).  ​+<box width classes round white centre|>​{{:​significant_improvement_in_exercise_improvement.png|}}</​box| Figure 9: Significant improvement ​in exercise endurancefor up to 3 months, in individuals who participated ​in 6 weeks of pulmonary rehabilitationModified from: Berry et al. (1999)>
  
-<box width classes round white centre|>​{{:​phytoremediation.png|}}</​box| Figure 9. Retrieved from: http://​systemsbiology.usm.edu/​BrachyWRKY/​WRKY/​Phytoremediation.html>​ 
  
 +Furthermore,​ a study done by Lacasse et al. (2006), showed significant improvements with the participation in pulmonary rehabilitation in other symptoms common to COPD patients as well. It was proven that pulmonary rehabilitation relieved symptoms of dyspnea (labored breathing) and fatigue, which is common found in COPD patients due to the muscle loss and increased energy expenditure of movement (Lacasse et al. 2006). Additionally,​ improvements to the emotional state of COPD patients were shown to enhance an individual’s sense of mastery and control over their condition (Lacasee et al., 2006). Results of this study are shown below. After much research, the significant yield of results illustrate why pulmonary rehabilitation is a crucial component in the long-term management of COPD. 
  
-Increased usage of genetically modified herbicide-tolerant and resistant crops can lead to environmental benefits by facilitating a shift towards conservation tillage practices. These crops allow farmers to apply herbicides to crops after they emerge, since now these genetically modified crops can tolerate them (37). Post-emergent weed control encourages ​the use of soil-friendly weed control mechanisms that promote conservation of the land. Now farmers will not need to rely on tilling, which is a mechanism of mechanical weed control. Due to the rough nature of this process, tilling causes degradation of topsoil and overall soil moisture as well as leads to soil erosion (28)By using herbicide-resistant plants, farmers will now benefit ​from improved soil quality due to the change from tilling to light-chemical and no-till weed control mechanisms ​(6)+<box width classes round white centre|>​{{:​improvement_of_symptoms.png|}}</​box| Figure 10: Illustration ​of the improvement ​of symptoms, which are common in COPD patients, with the participation in pulmonary rehabilitationModified ​from: Lacasse et al. (2006)>
  
-<box width classes round white centre|>​{{:​tilling.png|}}</​box| Figure 10: Tilling eroding the top layer of soil.  
-Retrieved from: https://​iowaagliteracy.wordpress.com/​2015/​04/​27/​why-do-they-do-that-plowing-or-tilling-fields/>​ 
  
 ===== Popular Aspects of Pulmonary Rehabilitation ===== ===== Popular Aspects of Pulmonary Rehabilitation =====
Line 188: Line 144:
 COPD patients need higher supplies of energy and protein to fuel greater energy expenditure from the increased effort of breathing and the inflammatory processes of the disease. Based on a study done by Bauer (2013) it is recommended to COPD patients to take high protein oral nutritional supplementation with 20% kcal from protein. COPD patients need higher supplies of energy and protein to fuel greater energy expenditure from the increased effort of breathing and the inflammatory processes of the disease. Based on a study done by Bauer (2013) it is recommended to COPD patients to take high protein oral nutritional supplementation with 20% kcal from protein.
  
- +<box width classes round white centre|>​{{:​cycle_of_weight_loss.jpg|}}</​box| Figure 11: Cycle of Weight Loss. Retrieved from: http://weight.sdghealth.com/copd_and_weight_loss.html#​8>
-<box width classes round white centre|>​{{:​amanda.jpg|}}</​box| Figure 11: GM salmon compared to Farm salmon. +
-Retrieved from: https://www.sott.net/article/​231692-First-Study-into-GM-Atlantic-Salmon-Mating-Reveals-Danger-of-Escape-to-Wild-Gene-Pool> +
- +
  
 **Smoking Cessation** **Smoking Cessation**
Line 198: Line 150:
 Stopping smoking is one of the main treatments for patients with COPD to effectively slow down disease progression (Willemse, 2005). The most evident clinical characteristics in COPD is respiratory symptoms and the accelerated decline in forced expiratory volume in one second (FEV1). By not smoking there will be an improvement to respiratory symptoms, which may be because of the decrease of goblet cells. It will also stabilize the accelerated decline in FEV1, strongly indicating that stopping smoking will positively influence inflammatory and remodelling processes in the lungs. ​ It was seen that during the first year after stopping smoking, FEV1 improved by 57 mL in quitters, but fell by 32 mL in patients that continued to smoke. An improvement of inflammation is also seen, resulting from a combination of increased anti-inflammatory receptor levels and reduced neutrophil chemoattractants (Willemse, 2004). Stopping smoking is one of the main treatments for patients with COPD to effectively slow down disease progression (Willemse, 2005). The most evident clinical characteristics in COPD is respiratory symptoms and the accelerated decline in forced expiratory volume in one second (FEV1). By not smoking there will be an improvement to respiratory symptoms, which may be because of the decrease of goblet cells. It will also stabilize the accelerated decline in FEV1, strongly indicating that stopping smoking will positively influence inflammatory and remodelling processes in the lungs. ​ It was seen that during the first year after stopping smoking, FEV1 improved by 57 mL in quitters, but fell by 32 mL in patients that continued to smoke. An improvement of inflammation is also seen, resulting from a combination of increased anti-inflammatory receptor levels and reduced neutrophil chemoattractants (Willemse, 2004).
  
 +<box width classes round white centre|>​{{:​effect_of_smoking_cessation_on_postbronchodilator_forced_expiratory_volume_in_one_second_fev1_decline._willemse_2004_.jpeg|}}</​box| Figure 12: Effect of Smoking Cessation on Postbronchodilator Forced Expiratory Volume in One Second (FEV1) Decline. Modified from: Willemse (2004)>
  
 +===== Medical Treatment =====
  
-==== Medications- ​Bronchodilators ​====+**Bronchodilators**
  
-**Types of Bronchodilators**+Bronchodilators ​are a class of medications that are widely used to treat COPD and aid in preventing airflow obstruction in COPD patients (Shim, 1989). These drugs provide relief of some symptoms commonly associated with COPD, such as dyspnea or decreased exercise tolerance, through the relaxation of smooth muscle that line airways (Barnes, 1995). Due to the increase build-up of smooth muscle in COPD patients and subsequent impairment of lung function, these bronchodilators are extremely important in the prevention/​reduction of airway obstruction (Berge et al., 2011). The two main bronchodilators used in the treatment of COPD are beta-agonist’s and anti-cholinergic’s (Barnes, 1995). Beta-agonist’s are the most widely used bronchodilator typically used to treat COPD patients (Barnes, 1995). Beta-agonist’s act by binding to the adrenergic receptors on smooth muscle cells and cause an increase of cyclic-AMP (cAMP), a secondary messenger, within the smooth muscle cell. The increase in cAMP causes an intra-cellular cascade that ultimately leads to a relaxation of the smooth muscle surrounding the airway and thus causing bronchodilation (Tashkin & Fabbri, 2010). Long-acting beta-agonist’s in specific, such as formoterol or salmeterol, have been proven to more effectively than regular beta-agonist medications,​ primarily due to their rapid onset and long duration of action (Barnes, 1995). ​
  
 +<box width classes round white centre|>​{{:​action_of_beta-agonists.png|}}</​box| Figure 13: Mechanism of Action of Beta-Agonists>​
  
-<box width classes round white centre|>​{{:​gene_transfer_from_gm_crops_to_their_wild_relative.jpg|}}</​box|Figure 12: Gene transfer ​from GM crops to their Wild Relative. +The other kind of bronchodilator used are anti-cholinergic’s,​ also known as muscarinic antagonistsThese not used as often as beta-agonist’s but have been shown to aid in improvement of airway flow in COPD patients as well (Barnes, 1995). Anti-cholinergic’s act by blocking the binding of acetylcholine,​ which is released ​from the pre-synaptic cleft of a neuron, ​to the smooth muscle acetylcholine receptorBy blocking the binding, anti-cholinergic’s are able to prevent bronchoconstriction (Tashkin & Fabbri, 2010) 
-Retrieved From: http://​bch.cbd.int/​cpb_art15/​training/​module3.shtml>+
  
  
 +<box width classes round white centre|>​{{:​action_of_anti-cholinergics.png|}}</​box| Figure 14: Action of Anti-Cholinergics>​
  
-**Which is Better?** 
  
 +**Efficacy of Bronchodilators**
  
-There are several different ways in which GM crops can impact non-target insects. A prevalent example in the public has been the monarch butterfly and is considered a species ​of conservational valueIn a lab studyMonarch larvae on milkweed leaves were dusted ​with Bt maize pollen ​and left to growIt was found that the larvae with BT pollen ate lessgrew slower ​and experienced higher mortality compared to the larvae cultivated ​with non-GM pollenIt is still difficult to measure ​the effect ​of Bt pollen on monarchs ​in the wild due to many natural factorsincluding; the required dosage ​of pollen, the likelihood of exposure to pollenand the effect ​of degradation of Bt from rain (37)+Studies have shown the long-acting beta-agonist’s (LABAs), such as formoterol, are the best course ​of medical treatments for individuals with COPD (Rossi, Khirani & Cazzola, 2008)These LABAs are more effective due to their rapid onset and prolonged duration (Barnes1995). When used, COPD patients saw improvement ​with common symptoms, such as dyspnea ​and decreased exercise tolerance, within minutes-hours after ingestionAdditionallythese drugs also helped improved lung function, reduce exacerbations ​and overall improve ​the health status of symptomatic patients ​with moderate-severe COPD (Rossi, Khirani & Cazzola, 2008)In a clinical study done by Van Noord et al. (2005), results showed that the efficacy ​of LABAs improved with the combined use of anti-cholinergic drugs. These results were only found in patients with severe COPD and only for the first 12-24 hours after ingestion (Van Noord et al.2005).  
 + 
 +<box width classes round white centre|>​{{:​improvement_of_lung_capacity.png|}}</​box| Figure 15: Improvement ​of lung capacitywithin ​the first 12-24 hoursin individuals with severe COPD after the ingestion ​of both long-acting beta-agonist’s and anticholingeric medications. Modified ​from: Van Noord et al. (2005)>
  
-<box width classes round white centre|>​{{:​monarch_butterfly_on_milkweed.jpg|}}</​box| Figure 13: Monarch Butterfly on Milkweed. 
-Retrieved from: http://​www.bigblogofgardening.com/​home-gardeners-can-save-the-monarch-butterfly-with-milkweed/>​ 
  
 ===== Conclusion ===== ===== Conclusion =====
  
- +Overall, COPD is becoming an increasingly prevalent cause of death worldwide. The disease is thought ​to be caused by a variety of genetic factors, which can be triggered ​or exacerbated by environmental factorssuch as smoking or air pollutionUnless caused by an alpha-1-antitrypsin deficiency, there is no cure for COPD but only management options for helping individuals struggling with this diseasePulmonary rehabilitation,​ which includes exercisenutritional ​and psychosocial support, combined with bronchodilator medication ​have been proven ​to improve common symptoms of COPD and improve long-term outcomes of COPD patients 
- +
-  +
- ​**Controversies** +
- +
-Controversy ​is mainly surrounding health and environmental risk factors ​of GMOsThis includes factors that are known and unknown due to lack of research. Rumours and stigmas about GMOs that are portrayed by the media are often results from scientific papers that have been exaggerated. +
-The USA does not currently have labelling laws for GM food (25). It remains ​to be decided if labelling GM products is good or bad. On one handlabelling something ​as GMO makes the consumer more aware but means that less will buy the product (as mentioned in Public Opinions)This results in increased food market prices and resource strain as companies attempt to satisfy the demand ​for non-GMOs. +
-By 2050 the UN predicts that humans will need to produce 70% more food than we currently do now in 2016 (19). This increase in food production alone will strain resources, and GMOs have the potential ​to help by providing food with more nutrients, the ability to grow in harsh climates ​and many other altercations that could be a solution to our growing population’s food demands. +
-The question remains, is a world without GMOs sustainable?​+
    
  
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