Pharmacological Management of Obstructive Airways in Humans. Introduction to Scientific Research. Submitted: 12/4/08

Transcription

1 Pharmacological Management of Obstructive Airways in Humans Introduction to Scientific Research Submitted: 12/4/08

2 Introduction: Obstructive airways can be characterized as inflammation or structural changes of the lungs with an FEV 1 (forced expiratory volume in 1 second) <80% of normal lung capacity (Wijnhoven et al. 2001), resulting in symptoms of wheezing, coughing, expectoration, and dyspnea on exertion (Mannino 2002). Medical advancements allow for the treatment of such afflictions as asthma and COPD (chronic obstructive pulmonary disease), which account for more than 50% of deaths from respiratory diseases in America. With increasing populations diagnosed each year, the importance of maintaining lung health becomes imperative. Medical treatment helps patients cope with or try to eliminate symptoms from a disease. Increasing the quality of life for patients drives members of the medical field and pharmaceutical companies to prescribe and make better medicines. Since the respiratory system is a critical part of healthy humans, science strives to extend life expectancy by sustaining its physical condition. Reasons to study medications are to notify the public and prescribers of possible illnesses or to explain newly founded treatment options. The objective of my study is to compare 3 different medicines over a one year period by their effectiveness in treating obstructive airways. I will use technology that will score the FEV 1 performance in each patient compared to expected values. I will control the study by have exclusion criteria, attempting to get the best data possible to help out present and future sufferers.

3 Review of Literature: First when reviewing literature I had to gain a firm grasp on the subject matter. In obstructive airway diseases symptoms often overlap, causing confusion. Recognizing minute differences in the separate diseases leads to effective diagnosis. Two major obstructive diseases are asthma and COPD. Each are characterized by an FEV 1 <80% of a normal lung (Mannino 2002). Differences stem from age, symptoms, risk factors, and spirometry (Decramer and Selroos 2005). The average age of an asthma diagnosis is younger than the mean age of COPD sufferer who tend to be older. Most symptoms overlap, but in asthma wheezes are unique in sound while a persistent cough with sputum production is observed in COPD. Asthma can be a genetically passed trait through family lineage, whereas COPD is often caused from exposure to smoke. Also, Asthma reactions result from allergens where as COPD is from the failure to rid the lungs of old air. The two conditions are related because asthmatics who smoke run a higher risk for developing COPD later in life (Decramer and Selroos 2005). Asthmatics have reversibility in their airway constrictions by using ICS (inhaled corticosteroids) and bronchodilators while COPD sufferers do not share the same luxury. The disease is a constant crippling burden deterring affected individuals from physical activity with little to no reversibility. COPD can progress into emphysema, destruction of lung tissues resulting in air pockets, if treatments do not start and smoking does not cease (Mannino 2002). Obstructive airway diseases can be controlled or limited by short or long term β 2 -agonist, anticholinergics, and corticosteroids (Richter et al. 2006). Short or long acting β 2 -agonist affect the β 2 receptors of the smooth muscles of the lungs. The mechanism of action is much the opposite of atropine, a β 2 -antagonist (Decramer and

4 Selroos 2005). The receptors open the air ways because of a reaction from the sympathetic nervous system. A fight or flight sequence is enacted and β 2 -agonist open the airways for increased respiration. Anticholinergics block the neurotransmitter acetylcholine from entering the M2 receptors in smooth muscle tissues in the lungs. These two are the most important bronchodilators used in therapy for obstructive airway disorders (Richter et al. 2006). Also, when paired with an ICS, which has mechanisms of action producing stress-like response conditions, much like in a fight or flight response where airways open to allow more air in (Lalloo et al. 2003). One study compared the effectiveness of budesonide and formoterol combined to single budesonide and also a placebo in mild-moderate asthma (Lalloo et all 2003). It was a randomized, double blind study stretched over 2 continents with a major focus on the budesonide/formoterol versus the budesonide alone. Peak Expiratory Flow (PEF) was measured along with the FEV 1 and FVC (Forced Vital Capacity). Results show the PEF improved over the 12 week period as well as the baseline % increased for the FEV 1. Baseline PEF improved 9.4% more in the combination medication versus the single budesonide. The occurrence of a mild asthma attack reduced by 26% by using the budesonide/formoterol compared to the single budesonide (Lalloo et al 2003). Another study observed the advancement of condition in COPD patients by comparing the combination therapy of budesonide/formoterol, salmeterol/fluticasone propionate, budesonide alone, and formoterol alone (Miller-Larsson and Selroos 2006). Using 2 groups to measure the amount of exacerbations per year, budesonide 200mcg had roughly 1 and the budesonide/formoterol 200/12mcg had closer to 0.7. When upping the dose to 800mcg budesonide the event dropped to 0.5 while the 800/12mcg budesonide/formoterol combination

5 was 0.3. The second group used the budesonide and combination with the same mcg strength as the 200 group but altered the budesonide to 400 mcg and budesonide/formoterol 400/12mcg. Results for the 200mcg and 200/12mcg were relatively similar to the first group, but the 400mcg budesonide was at the same level (0.9) as the 200 mcg. The combination of 400/12mcg was seen to be just as effective as the 800/12 of the first group (Miller-Larsson and Selroos 2006). Research on comparing the onset and duration of formoterol and tiotropium with patients diagnosed with moderate to severe COPD was taken by Richter et al. (2006). Subjects had FEV 1 rates of 30%<x<80% and must have had at least 10 pack years of smoking. Subjects would receive either 12mcg formoterol bid (twice daily) or 18mcg tiotropium od (once daily). This study was mainly to measure the onset and lasting effect over a 12 h period. Figure 1 represents the 12 h time plot comparing FEV 1 of formoterol and tiotropium (Richter et al. 2006). Their study showed that the formoterol was more effective within the first 2 h after administering while the tiotropium maintained a better FEV 1 volume throughout the 12 h period. Scientist studied variables such as education, region of habitat, and wealth when looking a severity of COPD and asthma. Subject were treated with a bronchodilator and asked to keep a diary for 2 weeks noting morning and evening PEF, respiratory medications taken, and if any respiratory complications arose. A quality of life survey related to the clinical condition was also polled. In COPD, patients were older, less educated, used more medication, had less PEF changes through the day, and scored lower on the quality of life survey (Wijnhoven et al 2001). Asthma subjects were affected by region of living which suggests site-specific allergens, duration of disease, and current smoking habits. PEF was variable from morning to night as well.

6 After research the 3 types of drugs I believe that the combination therapy of Long Acting β 2 -Agonist (LABA) and Inhaled Corticosteroids will be more effective than the anticholinergics bronchodilators (tiotropium). Of the two LABAs being measured I hypothesize that the budesonide/formoterol blend will raise or decrease slower FEV 1 rates more than the salmeterol/fluticasone propionate grouping after a one year period. Design and Methods: Many studies have similar designs to mine, but many use only one type of treatment and compare it to placebos rather than to competing therapies on the market. Most of the analyses I have found looked at the effectiveness of therapy after a short period of time. I would like to see how a patient reacts to therapy over a longer period of time. Many drugs work faster (Figure 2) but begin to level out (Figure 1) and management is seen as a treatment for daily symptoms (Richter et al. 2006, Goldsmith and Keating 2004). I would like to see how ones life changes as a result of taking the medication, since obstructive airway disorders are so devastating to the patient, the search for a medicine that can be of assistance is important. I planned to do the study at a pulmonary clinic named Central Pennsylvania Pulmonary Associates LLC. Here are charts from thousands of patients, and it is known that all three medications under study are administered. I am very lucky because, I have had an internship here for the last three years and access to chart data is allowed. No patients names will be assessed during any part of my exam so there is no need for a privacy waver from each patient under study. The study will look at results over a 1 year time period with updates taken every three months if possible.

7 All patients who are diagnosed with either asthma or COPD with an FEV 1 <80%, and were prescribed one of the three medicine choices, Advair, Symbicort, or Spiriva will be analyzed. Advair contains the combination therapy of salmeterol and fluticasone propionate which was seen to be effective as a LABA and ICS. Symbicort is budesonide and formoterol grouping which is also a LABA and ICS. Spiriva is tiotropium whose mechanism of action is an anticholinergic bronchodilator. The strengths used in Advair will be its 250/50mcg and 500/50mcg bid combination. Symbicort will use its 80/4.5mcg and 160/4.5mcg bid combination and Spiriva will have its only strength of 18mcg once daily. Measurements will be taken for each strength of drug. While these patients have met criteria there will be criteria for exemption from the study. If a patient is a current smoker they will not be able to take part in the study. For the treatment to be effective one must try to maintain lung function and smoking will not aid in that attempt. Obesity of a patient with a BMI (Body mass index) over 30 will not be taking part in the study due to excessive stress on the body. Pulmonary hypertension, where the heart can not keep up demand for physical activity is a more serious lung condition may vary the results. Also if a patient has diabetes or a history of non-compliance they will not be in my data. The data for my experiment will be on lung function. The FEV 1 will be the consistent data point for all in the study. The ability to predict expected values from a person s age, gender, and BMI make it a good choice. Using the spirometry machine and/or a PFT (Pulmonary Function Test), we will be able to get an FEV 1. The machines do a series of lung exercises that measure volumes and force of inhalations and expirations.

8 I will be the sole researcher of all the data and even though it may not be adventurous and daring, it could impact the lives of many patients for the better. Scientists strive to find understanding in the world around us or to help others live to their fullest. One less exacerbation could mean my research was worthwhile. Literature Cited Decramer, M. and Selroos, O Asthma and COPD: Differences and Similarities with special reference to the usefulness of budenoside/formoterol in a single inhaler for both diseases. International Journal of Clinical Practice [serial online] 59: Available from: Academic Search Premier. Goldsmith, D.M. and Keating G. M Budesonide/Foroterol: A review in its use in Asthma. Drugs [serial online] 64: Available from: Academic Search Premier Lalloo, U., Malolepszy, J., Kozma, D., Krofta, K., Ankerst, J., Johansen, B., and Thomson, N Budesonide and Formoterol in a Single Inhaler Improves Asthma Control Compared with Increasing the Dose of Corticosteroid in Adults with Mild-to-Moderate Asthma. Chest [serial online] 123: Available from: Academic Search Premier. Mannino, David M COPD: Epidemiology, Prevalence, Morbidity and Mortality, and Disease Heterogeneity. Chest [serial online] 121: Available from: Academic Search Premier. Miller-Larson, A. and Selroos, O Advances in Asthma and COPD Treatment: Combination Therapy with Inhaled Corticosteroids and Long-Acting Beta 2 -Agonist. Current Pharmaceutical Design [serial online] 12: Available from: Academic Search Premier. Richter, A., Stenglein, S., Mucke, M., Sieder, C., Schmidtmann, S., Harnest, U., Weidinger, G., and Magnussen, H Onset and Duration of Action of Formoterol and Tiotropium in Patients with Moderate to Severe COPD. Respiriation [serial online] 73: Available from: Academic Search Premier. Wijnhoven, H., Kriegsman D., Hesselink A., Penninx B., and de Haan, M Determinants of Different Dimensions of Disease Severity in Asthma and COPD. Chest [serial online] 119: Available from: Academic Search Premier.

9 1 Richter et al. 2006

10 2 Goldsmith and Keating 2004