Asthma is an autoimmune disease that reduces an individual’s ability to breathe. It is common for young individuals to be diagnosed with asthma however the majority loses the symptoms, as they grow older. It’s recognized as an allergic disease and is characterized by reversible flow of air causing obstruction that can cause episodes of heavy breathing or lack of air. There is an additional disease that shows similar symptoms to asthma, however has been proven to be associated with smoking. Chronic Obstructive Pulmonary Disease (COPD) is commonly diagnosed to patients that are heavy smokers. This disease is not genetic, but instead formed after roughly the fourth decade of smoking. This disease is like asthma because of its ability to obstruct airflow, and it also causes a decline in lung function, contributing to potential premature death.
Narrowing of Airways Mechanism in Asthma
The narrowing of airways can cause severe shortness of breath, failure of the respiratory system and in very severe cases death. This is due to the smooth muscle bands contracting in the airways of the lungs. The contractions of airway smooth muscle (ASM) can be triggered by the release of histamine and cysteinyl leukotrienes from mast cells.
Figure 1- The core signalling pathways responsible for airway smooth muscle contraction (The Cell Biology of Asthma- David J. Erle, Dean Sheppard. June 9, 2004)
The force exceeded by the ASM is created by the cyclic cross-bridging of actin and smooth muscle myosin. This is dependent upon myosin phosphorylation. Calcium is the regulator for myosin phosphorylation that activates calmodulin to phosphorylate MLCK (Myosin Light Chain Kinase). At the same time, the GTPase, RhoA, through calcium-independent and –dependent pathways, is triggered. Rho then activates Rho-associated coiled-coil protein kinase (ROCK), which phosphorylates and deactivates the MLCP. [6]
The American Thoracic Society (ATS) devised 11 distinct syndromes for Asthma and COPD. 6 of the 11 syndromes overlapped between the two diseases. A total of 25 million Americans (18 million adults to 7 million children split) have asthma, and 9 cases of deaths per year on average. COPD affects around 14.2 million adults in the United States, which about an estimated 9.8 million who may have COPD but go undiagnosed. COPD has a significantly higher death rate than asthma; on average 377 patients die a year from COPD. According to statistics, more patients are admitted into hospital with COPD (26%) than acute myocardial infarctions (7.8%). Exacerbations increase morbidly, mortality and the economic burden of disease, 50-75% of COPD healthcare cost in the USA is due to the treatment of acute exacerbations. Severe to very severe COPD patients experience two or more exacerbations annually, as much as asthmatics experience, while overlap patients suffer from significantly more exacerbations, up to 2 to 2.5 times as many as those with lone COPD.
Bronchial Hyper-responsiveness
Bronchial hyperresponsiveness (BHR) is a response that can be caused from a person reacting to different types of stimuli. Some of the stimuli that can cause BHR are: pollen, pets, fungus, smoke, strong odors, all stuff in which someone could potentially be allergic too which would cause shortness of breath as well as exacerbations . With proper treatments which usually are done by oral steroids, someone with BHR will develop Bronchodilator response meaning the bronchi will widen allow for easier flow of air. BHR is common amongst most Asthma and COPD patients, the bronchi tends to close allowing for lack of air to flow out, making it hard to breathe and causing the episodes we usually see in asthma and COPD patients. BHR is directionally proportional with age and smoking. One can hear symptoms on a patient when hearing wheezing, and/or chronic coughing. Smoking is the leading risk factor of BHR. Knowing symptoms of BHR will allow for patients to have a better understanding and be able to see pre signs in order to get proper treatment to not develop BHR.
Overlap Between Asthma and COPD
Having already analyzed all the potentially important common risk factors for overlapping asthma and COPD, such as increasing age, smoking, BHR, inflammation, remodeling and exacerbations. The big question is why does overlap happen? The ‘Dutch Hypothesis’ states that asthma and BHR predispose to COPD later in life and that asthma, COPD, chronic bronchitis, and emphysema are different expressions of a single airway disease. Epidemiological studies, on the other hand, proved a correlation between respiratory illnesses during childhood and impaired adult lung function. In summary, it has been already understood that specificity of a separate clinical entity called ACOS. Even though ACOS develops indistinct clinical and pathophysiological features that often are complicated with those of asthma or COPD, we must emphasize the importance of the syndrome. Studying the syndrome further we may discover mechanic pathways leading to the development of COPD. This is important because it is widely known that patients with COPD often are undiagnosed, potentially for decades. By recognizing common risk factors it will, maybe, become possible to understand and modify the progressive deterioration of lung function, which leads to COPD.
Differentiating between COPD and Asthma
Asthma is typically reversible depending on the severity, whereas COPD is typically not completely reversible. They both limit airflow and the inflammatory response of the lungs can be triggered by noxious gases such as cigarette smoke, in turn causing airflow limitation. Patients that developed fixed airflow limitation because difficult to diagnose, because it is hard to distinguish between COPD and asthma when subjects develop chronic respiratory symptoms.
Classification of Asthma and Common Medications
The table below includes the four different categories clinically diagnosed to patients based on the degree of their asthmatic symptoms, the four categories being Intermittent, Mild Persistent, Moderate Persistent, and Severe Persistent.
Intermittent
• Symptoms occur less than once a week
• Brief Exacerbations
• Nocturnal Symptoms not more than twice a month.
Mild Persistent
• Symptoms occur less than once a week but more than once a day
• Exacerbations may affect activity and sleep
• Nocturnal symptoms more than twice a month
Moderate Persistent
• Symptoms are daily
• Exacerbations may affect activity and sleep
• Nocturnal symptoms more than once a week
• Daily used of inhaled short-acting agonist
Severe Persistent
• Symptoms daily
• Frequent exacerbations
• Frequent nocturnal asthma symptoms
• Limitation of physical activities
Table 1- Information gathered from table 2 from “Global Strategy for Asthma Management and Prevention: GINA Executive Summary (2007)
There was typically three different ways adults can administer medication for asthma; inhalation, orally or parenterally. Inhaled administration of the drug is usually favored because it is delivered straight to the airways, whilst reducing side effects due to the high localized concentration at the site of the symptoms in the body. One common drug inhaled is Glucocorticosteroids that are one of the leading anti-inflammatory medications used to treat persistent asthma. Studies have proven the drugs ability to reduce asthmatic symptoms, as well as improve lung function, control airway inflammation and decreasing airway hyper-responsiveness.
“Omalizumal Treatment for Adults and Children with Allergic Asthma: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines”
With asthma comes a major toll on one’s body, the effects of asthma make it harder for them to breathe, and episodes can occur randomly. In the article “Omalizumal Treatment for Adults and Children with Allergic Asthma: A Review of the Clinical Effectiveness, Cost-Effectiveness, and Guidelines” they focused on allergy asthma. This type of asthma is triggered by allergens, such as dust mites and pollen, this is attributable to immuglobin I (IgE)- mediated mechanism. The article focused on the different types of treatments such as the use of low dose inhaled corticosteroids (inhalers). For individuals whose asthma remains uncontrolled, they were supposed to increase the dosage of the inhaler. If that treatment was unsuccessful the alternative was omalizumab, a treatment that dampens the effects. “Omalizumab is a humanized, recombinant, IgG, anti- IgE monoclonal antibody that binds to IgE and prevents it from binding to its high affinity receptor on mast cells and basophils… thereby reducing the release of histamine.” The main research question was, “ what is the cinical effectiveness of omalizumab for the treatment of allergic asthma in adults and children who are not responsive to other therapies?”. The clinical results that were conducted through a study which involved 25 double blind- RCT’s (random controlled trial) state that omalizumab resulted in a statistically significant reduction in the odds of having more than one exacerbation, compared to placebo in the steroid use than in the placebo. Most patients in which were involved fully got off their inhalers after taking omalizumab. The method was an RCT, which is common throughout the medical field when conducting such studies. This was beneficial because not evertone will come in with the same diagnosis of the severity of the asthma, so with the RCT it allows for a broader spectrum of patients or candidates in which can participate in the study, therefore heightening the accuracy of the data. This data comes from a wide variety of patients allowing the data to be more accurate and representative of the population of individuals with asthma.
“Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma”
As asthma is an extremely common disease among humans, scientist wanted to find a precursor or different levels that may be elevated in order to maybe minimize the symptoms in which the asthma is giving the patient. In this article they hypothesized that different miRNA (micro RNA) strands that go with different pathways are driving the symptoms in which we see present in asthma. Scientist used female 6-8 week Balb/c mice were intraperitoneally (i.p.) sensitized with 1μg ovalbumin (OVA)… followed by two aerosol challenges with 1% OVA for 20min. Mice were sacrificed on day 29 or 72 this allowed for the generation of similar to human allergic airway inflammation. The total RNA was isolated from lung tissue of the mice, using the miRNeasy MiniKit. After taking the top 100 miRNA from the initial LNA ( locked nucleic acid) microarray they choose to further investigate Creb1. Creb1 is important when it comes to immune response and directly relates to asthma and COPD so they wanted to investigate further. After trying IL-13 treatment, interleukin-13 is responsible for the elevation of bronchial hyperresponsiveness, which caused exacerbations as well as inflammation of the bronchi, the saw an improvement. The experiment in which was conducted was beneficial in order to allow for all different miRNA to be tested to see which one to further investigate. Using the mice and doing the LNA microarray, allowed for researchers to narrow down which gene was causing this, and find out why. After further research they concluded that there was a dysregulation in Creb1 and its transcriptional target Sec14l3, within the early stages of asthma. MiRNA can detect early triggering signs in which patients can get treatment in order to reduce the amount of pain or symptoms they are showing.
The MicroRNA article best addresses the research question in which is stated. They stated that different miRNA strands were triggering the symptoms in which were present in asthma, and they were correct they just did not know which one it was. With further experiments they were able to narrow down there results and look into certain genes to potentially see as to why it was happening. With certain medications, they were able to see an improvement of symptoms that were elevated before. The study was well laid out and they took a lot of time to do it, so the data they collected was valuable, and allows for more studies to be conducted to go further in depth with it.
Asthma: The effect of sports and exercise
A lot of people question if asthma can be affected by sports or doing other physical activities, the answer is yes. Researchers from the Conchrane Collaboration wanted to find out what effect sports and exercise have on people with asthma. To further their research they analyzed studies within these fields. The mains goal of the experiment was to see whether or not sports and exercise affected the symptoms. The article gathered 19 different studies and approximately 700 participants. The participants exercised between 6 and 16 weeks in order to gather good data. The activity was about 20 minutes, three times a week.
After further reviewing the data and analyzing it, they deciphered that sports and exercise have a positive effect on asthma patients. It was stated that people who did some exercise showed fewer symptoms after. Physical activity can result in asthma attacks however is poorly monitored and managed, or if the exercise is extremely difficult for the individual, the study was an acute study, so the data wasn’t broad, so some answers couldn’t be answers due to missing information. Cold weather can cause risks when dealing with asthma, so individuals do have to be made aware of that also. The methods in which were used were gathered from 19 other different studies where individuals undergone physical activity at least 20 minutes 3 times a week. This is significant when very active individuals question their ability to continue their active lifestyle due to asthma, or whether proceeding with regular exercise actually reduces their symptoms.
High Prevalence of asthma in Cross Country skiers
Cross-country skiing is quite unique in comparison to other sports in that the athletic effort is conducted at low temperature. Training a competition is usually in conditions around -15 degrees Celsius. This implies that large amounts of ventilation with cold air for several hours a week, for several moths a year. There is a relationship between inhaling cold air and triggering bronchoconstriction in asthmatic subjects. However there is not evidence that suggests healthy patients will get asthmatic symptoms as a result of inhaling cold air regularly. This study invited 47 elite skiers from 6 Swedish cross-country ski clubs. 42 skiers participated (36 men, 6 women, mean age 24 (range 16-50))[5]. They have been active competitors for an average of 13 years, training for an average time of 406 hours a year. They also included 29 non-skiing referents. The experiment was designed as a cross sectional study during the winter and in the summer. [5]
The main outcome measures were bronchial responsiveness, asthma symptoms, and lung function. The results showed bronchial responsiveness was significantly greater and asthma symptoms more prevalent in the skiers than in the referents. There was no difference in bronchial responsiveness between winter and summer. 15 of the 42 skiers used antiasthmatic drugs regularly and 23 had a combination of hyper-responsive airways or physician diagnosed asthma, or both. This totaled 33 skiers out of the 42 that showed symptoms of asthma or bronchial hyperresponsiveness. The study was concluded with stating asthma, or asthma-like symptoms, or bronchial hyperresponsiveness was far more prevalent in cross-country skiers than the general population and non-skiers. “Strenuous exercise at low temperatures entailing breathing large volumes of cold air is the most probably explanation of persistent asthma in skiers.”[5]
Environmental influence on the prevalence and pattern of airway dysfunction in elite athletes.
This study looks at elite swimming and boxing, and how these sports require athletes to achieve relatively high minute ventilation. The training and competitive environment may influence the athletes susceptibility to Exercise-Induced Bronchoconstriction (EIB). The purpose of the study was to evaluate the prevalence of EIB in elite Great British Boxers and Swimmers. The athletes completed an exercise-induced respiratory symptom questionnaire, baseline assessment of fraction of exhaled nitric oxide (FeNO), maximal spiometry maneuvers and a eucapnic voluntary hyperpnoea (EVH). The results showed the prevalence of EIB was greater in elite swimmers (30 of 44) than in boxers (3 of 38)[6]. 22 of the 33 EVH-positive athletes had no prior diagnosis of asthma/EIB. In conclusion “the prevalence of EIB was nine fold greater in swimmers when compared with boxers. Athletes who train and compete in provocative environments at sustained high ventilation may have an increased susceptibility to EIB”[6]. The study did not find out whether there was any affect on long-term airway health or elite sporting performance.
The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics
This study is determining the relation between the zyxin actin regulator and the ASM (airway smooth muscle) and its impact on asthmatics. The study found an increased zyxin gene expression in the airways of dead asthmatic subjects. The ASM begins to stretch due to a disturbance of actin-myosin interactions. This causes a decrease in rigidity, leading to contraction. In the study they cultured both Wild type ASM cells and ASM cells lacking zyxin. The wild type has the ability to repair fragmented stress fibers, meaning the wild type ASM cells were able to return to a stable contractile force[9]. The ASM cells that lacked zyxin were not able to make these repairs, resulting in the fragmented stress fibers persisting. The study then looked at this at a subcellular level and noticed that an accumulation of zyxin would occur to repair the ‘cyto-architecture’[9]. Once the actin had been reinforced the zyxin would rapidly dissipate. The actually investigation used mice as the subject and they found that the loss of zyxin in the mouse airways decreased the contracting ability after a deep inhalation. They found there was an increased number of zyxin in fatal asthmatics and not in non-fatal asthmatics, meaning the zyxin number in the airways of asthmatics has a significant influence of the severity of the individual’s asthma.
After analyzing all three articles, the article on Cross-Country Skiers best addressed its hypothesis and carried out a method that allowed them to support or deny their hypothesis. The purpose was to study the prevalence of asthma in Swedish Cross-Country skiers compared with non-skiers. Throughout the experiment (over the course of the year) the changes in symptoms were monitored. The experiment included elite skiers and non-skiing referents. This meant both skiers and a representative group of the rest of the population could be compared. The results they gathered proved that the high prevalence of asthma in skiers is due to regular ventilation of cold air. Moreover the skiers showed more asthmatic or asthma-like symptoms compared to the non-skier referents.
Asthma and COPD are both diseases that show similar effects but have some different traits and treatments. Procedures such as bronchial thermoplasty can be used to treat severe cases of asthma. Bronchial thermoplasty heats the airways using radiofrequency energy through a catheter. The purpose is to reduce the amount of smooth muscle present in the airway, therefore allowing for me airflow, and reduceing the likelihood of asthma attacks in the future. There are also medications, commonly inhaled corticosteroids, which have a more daily purpose and relieve inflammation. But the typically asthma occurs during childhood and it is common for children to ‘grow out’ of the symptoms as they get older. The symptoms will reduce over time with persistent monitoring of exercise and diet, plus using the required medications, especially if they are highly active. COPD however is common in adults, especially adults that have been smokers for a significant period of time during their lives. It is usually a combination of two diseases, Emphysema and Chronic Bronchitis. Emphysema damages the air sacs in the lungs causes them to lose their ability to stretch. This means that less air can be breathed in, making the individual becoming short of breath. Chronic Bronchitis is the build of mucus leading to a persistent cough that lasts for a prolonged time, plus wheezing. The effects of COPD grow over time, and cannot be reversed. However steps and treatments can be administered to prevent further damage and to relieve patients from the symptoms.
Asthma and COPD are tied to a number of other conditions such as BHR, Bronchospasms, Emphysema, and Chronic Bronchitis. Both Asthma and COPD cause an increase in the number of B and T lymphocytes in the airway walls of the lungs. However Histamine causes bronchoconstriction and inflammation in asthma, whereas proinflammatory cytokines amplify the inflammatory process in COPD. In addition the function of long-acting agonists and inhalatory corticosteroids in prophylaxis of exacerbations are different.
With research and medication technology advancing around the world, the ability to diagnose and treat both COPD and Asthma will become more effective and faster. With early detection of asthma and COPD will reduce the severity of symptoms and most likely reduce the fatalities from these diseases. Hopefully with time, procedures and medications will be able to relieve asthmatics of symptoms and limitations when it comes to their lifestyle. In regards to COPD, more awareness of the effects of smoking need to be highlighted in order to reduce the amount COPD patients around the world.