Chronic Obstructive Pulmonary Disease (COPD)

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

Humans have been domesticating and improving plants and animals since 30,000 BCE (25). Initially, ancestors 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. Modern genetic modifications did not begin until 1973 when two scientists, Herbert Boyer and Stanley Cohen, designed a method to splice a 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.

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 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).

Economic Burden of COPD

Mechanism of Disease

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Environmental Factors - Air Pollution

Efficiency is determined by the optimal yield of a product, considering the costs associated with producing this yield. Genetic modification of organisms increases the efficiency of products, rendering beneficial factors for both producer and consumer. The use of bovine somatotropin (bST)/ recombinant bovine growth hormone (rbGH) in lactating dairy cows demonstrates such efficiency.

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 signals. Indirect effects are suspected to be mediated by the insulin-like growth factor (IGF) and have been found to impact mammary glands. The environment and management factors, such as nutritional status, play regulatory roles in such effects and responses (3).

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).

The Relationship Between COPD Deaths and Air Pollution

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 farming. Transgenic plants or animals are utilized for producing pharmaceuticals synthesized for human or animal consumption (7). Animal pharming is promoted as a cost-effective method of biopharmaceutical production (14) and has the potential to become a highly lucrative industry (7).

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 abundance, deriving and producing pharmaceuticals in this manner is determined to be cost efficient (14).

Environmental Factors- Smoking

Noxious agents produced from cigarette smoke have a detrimental effect on the airways. The toxins damage airway epithelium and drive the processes that lead to certain airway inflammation and structural changes (Bourdin et al., 2009). Accordingly, cigarette smoking is the leading cause of COPD in North America (Bourdin et al., 2009). All smokers exhibit inflammation within their lungs, but those who have developed COPD demonstrate amplified or abnormal responses to inhaling noxious agents (MacNee, 2006). Airway remodelling may be a protective mechanism of airway epithelium to injury caused by cigarette smoke. Furthermore, the subsequent structural changes may be a reparative mechanism in response to damage caused by the toxic substance (Chung, 2005).

Bronchiolar epithelium is altered in smokers, notably in COPD patients (Chung, 2005). Bronchiolar epithelial cells are triggered by interleukin (IL)-1, interleukin (IL)-8, and granulocyte colony-stimulating factor causing them to release increased levels of neutrophil and monocytic chemotactic activities (Chung, 2005). Structural changes to the airway take place as a result of abnormal repair processes promoted by activated fibroblasts. Fibroblast activation is induced by the increased production of neutrophil, macrophages, and lymphocytes (MacNee, 2006). Moreover, an influx of neutrophils and macrophages result in an imbalance between proteases and anti-proteases. The imbalance of proteases and imbalances ultimately leads to destruction of the alveolar wall, while an overabundance of proteases alone results in the increased production and release of mucous (MacNee, 2006). Alveolar wall destruction and the presence of excessive mucous are both distinct characteristics of COPD (Bourdin et al., 2009).

Biological Perspectives- Structural Changes

Chronic airflow obstruction is associated with airway remodelling and inflammation of peripheral airways. Airway remodelling, consistent with structural changes found in the airways of COPD patients, are more prominent in the small airways than in the large airways (Chung, 2005). Small airways are defined as peripheral airways that are less than 2mm in internal diameter (Berge et al., 2011). A strong association exists between disease progression and an increase in epithelium, lamina propria, adventitial compartments of the airway walls, and smooth muscle. The amount of smooth muscle is increased by nearly 50% in patients diagnosed with more severe COPD, stages 3 or 4, as categorized by the Global Initiative on Obstructive Lung Disease (GOLD) (Chung, 2005). Lung functionality is inversely correlated with the amount of smooth muscle found in the small airway (Chung, 2005). Structural changes, such as muscle thickening, may lead to muscle shortening against elastic loads. Muscle thickening also increases ability to generate force, which may play a part in bronchial hyper-responsiveness, loss of lung recoil, and fibrosis of the small airways (Chung, 2005).

Smooth muscles of the small airways not only demonstrate contractile properties, but may also contribute to the inflammatory and airway wall remodelling processes. This takes place as a result of the expression or release of cytokines, chemokines, proteases, and growth factors (Chung, 2005). Increased production of cytokines and chemokines increases the number and activation of neutrophil, a granulocyte associated with COPD (Bourdin et al., 2009). Notable cytokines and chemokines include interleukin (IL)-8 and CXC chemokine ligand 10 (CXCL10), respectively. IL-8 is a powerful chemoattractant and activator of neutrophil, and the receptor is present on blood and sputum neutrophils and epithelial cells (Bourdin et al., 2009). CXCL10 is also a chemoattractant for neutrophil as well as for human monocytes, natural killer cells, and T cells (Chung, 2005).

Neutrophil levels are elevated in COPD patients, resulting in the increased release of proteases and oxidants (Bourdin et al., 2009). The imbalance of proteases and anti-proteases, as well as the imbalance of oxidants and antioxidants (MacNee, 2006) perpetuate the progression of processes in favour of lung destruction (Bourdin et al., 2009).

Biological Perspectives- Genetics

Spirometry

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.

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 metabolites, levels 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).

Results showed that GLYP was not detected in maternal and fetal blood, but 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.

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.

Chest X-Rays

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.

“Gluten sensitivity can range in severity from mild discomfort, such as gas and bloating, to celiac disease, a serious autoimmune condition that can, if undiagnosed, result in a 4-fold increase in death,” said Jeffrey M. Smith, executive director of IRT.

The Institute for Responsible technology is a world leader in educating policy makers and the public about GMO foods and crops. The institute reports and investigates the impact GM foods can have on health, environment, agriculture and more (26). 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 glyphosate, a pesticide was found to have a negative effect on intestinal bacteria. Unfortunately, GMO crops contain high concentrations of this toxin during harvest and consumption by humans (26).

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).

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).

Outcomes of Pulmonary Rehabilitation

Genetically modified crops have the potential to improve crop yield in developing countries, such as Southeast Asia and Africa, which 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 corn, which 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 climates, these 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 future, thus promoting land and habitat conservation (37).

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 soil, sediments and surface waters (37). These plants overexpress metabolism enzymes and are able to remove organic pollutants, included 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 soil. This 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).

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).

Diet and Nutrition

Being underweight and/or unintentional weight loss is associated with increased mortality and morbidity in COPD patients. So it is very important to help patients avoid losing weight or help them regain the weight that they lost. Many patients will experience a decline in respiratory muscles, physical performance and health status resulting from a loss of lean muscle mass. Detecting and reversing weight loss should be done as soon as possible to limit this functional decline. Increasing dietary intake or including energy dense foods may help to combat the onset of COPD. Some epidemiological studies have shown that diet and nutrition may contribute to COPD risk and could play a role in prevention (Burg, 2004).

There is not enough evidence to give dietary advice to reduce the risk of COPD, however studies show the benefits of fatty fish, fruits, antioxidants and high protein intake. Polyunsaturated fatty acids found in fish have been found to indirectly inhibit the production of inflammatory factors. Multiple cohort studies have indicated a protective effect from fruit intake and COPD incidence and mortality. Antioxidant nutrients, like vitamin C found in fruits and vegetables, may be responsible for preventing oxidative stress in the lungs from air pollution (Burg, 2004). 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.

Smoking Cessation

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).

Types of Bronchodilators

Which is Better?

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 value. In a lab study, Monarch larvae on milkweed leaves were dusted with Bt maize pollen and left to grow. It was found that the larvae with BT pollen ate less, grew slower and experienced higher mortality compared to the larvae cultivated with non-GM pollen. It is still difficult to measure the effect of Bt pollen on monarchs in the wild due to many natural factors, including; the required dosage of pollen, the likelihood of exposure to pollen, and the effect of degradation of Bt from rain (37).

Controversies

Controversy is mainly surrounding health and environmental risk factors of GMOs. This 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 hand, labelling 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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