Synopsis: Causes symptoms and treatment options for Chronic Obstructive Pulmonary Disease COPD.
Some persons with COPD experience airway obstruction that may be partially reversed through the use of medications that either dilate or enlarge their airways known as, 'Bronchodilators.' There are also persons with asthma who may develop more permanent airway obstruction should they experience chronic inflammation in their airways that lead to narrowing and scarring of their airways. The process of narrowing and scarring is referred to as, 'Lung Remodeling.'
COPD involves two diseases that are related; bronchitis and emphysema. Both bronchitis and emphysema involve a chronic obstruction of airflow out of a person's lungs which is commonly both permanent and progressive over time. Asthma; another pulmonary disease involving obstruction of airflow out of the lungs, is unlike chronic bronchitis or emphysema in that asthma is commonly reversible. Airflow between asthma attacks is usually good.
Persons with asthma who experience lung remodeling are considered to have COPD as well. People who have chronic bronchitis can exhibit characteristics of emphysema. Similarly; people who have emphysema may present characteristics of chronic bronchitis.
The main cause of COPD in America is smoking; approximately ninety-percent of persons with COPD have it because of smoking.
While not all people who smoke go on to develop COPD, it is estimated that approximately fifteen-percent of smokers will. People who smoke and have COPD experience higher death rates that nonsmokers who have COPD, as well as experiencing more frequent symptoms such as shortness of breath, coughing, and lung deterioration. The effects of second-hand exposure to tobacco smoke are not well-known, although there is evidence suggesting that asthma, and respiratory infections are more common among children and others who do not smoke in households where there is a smoker present.
Cigarette smoke damages a person's lungs in a number of ways.
The smoke from cigarettes; for example, attracts cells to a smoker's lungs that promote inflammation. The smoke from cigarettes stimulates these inflammatory cells to release something called, 'Elastase,' an enzyme which breaks down the elastic fibers in the person's lung tissues.
Air pollutants may cause problems for persons who have lung disease, although it is not clear whether or not outdoor air pollution is a contributing factor of COPD. In the non-industrialized world the most common cause of COPD is indoor air pollution. The use of indoor stoves for cooking is a cause of indoor pollution. There are also occupational pollutants such as silica and cadmium that increase the risk of COPD. Construction workers, coal miners, cotton workers, and metal workers are at risk for this type of occupational pollution. Persons who work in these occupational fields may find themselves associated with interstitial lung diseases such as, 'Pneumoconioses,' forms of disease. The negative effects of cigarette smoking on lung function are still greater than occupational exposure.
Normal functioning of the lungs depends on elastic fibers which surround the airways and alveolar walls.
These fibers are made of a protein referred to as, 'Elastin.' There is an enzyme referred to as, 'Elastase,' that is found in average lungs that is increased in persons who smoke cigarettes that can break down elastin, damaging their airways and alveoli. Another protein referred to as, 'Alpha-1 Antitrypsin (AAT),' which is produced by a person's liver and then released into their blood, is present in average lungs and may block damaging effects of elastase on elastin. An established cause of COPD is a deficiency of AAT. There is a rare, inherited genetic disorder that accounts for less than one-percent of persons with COPD in America that involves an AAT deficiency.
Production of AAT by a person's liver is controlled by genes that are contained in DNA-containing chromosomes which are inherited. People have two AAT genes - inheriting one from each of their parents. People who inherit two defective AAT genes experience low amounts of AAT in their blood, or AAT that does not work as it should. Because of this decreased AAT function, these people experience destruction of lung tissue by elastase that is unopposed, causing emphysema by age thirty to forty. People with this genetic disorder who smoke experience an earlier onset of COPD.
Persons who possess one regular and one defective AAT gene present AAT levels which are lower than average, yet higher than persons who have to defective genes. These people could have an increased risk for developing COPD if they do not smoke, although their risk is greater than average if they do smoke. While their AAT levels could be in the average range, the functioning of the enzyme may also be impaired in relation to normals.
Commonly, after smoking a pack of cigarettes per day for greater than twenty years, persons with COPD develop shortness of breath (referred to as, 'Dyspnea'), a chronic cough, and experience frequent respiratory infections. Persons affected by emphysema experience shortness of breath as a major symptom. Dyspnea is a symptom that is commonly noticeable during physical activity, although as emphysema progresses the person affected by emphysema may experience dyspnea even while at rest.
Persons with chronic bronchitis experience symptoms such as a chronic cough and sputum production. The sputum produced is commonly both thick and clear. They may also experience chest infections with associated dyspnea, fever, coughing, wheezing, and production of cloudy and discolored sputum. The infections they experience happen more frequently as bronchitis progresses.
In persons who have advanced COPD, development of cyanosis may occur because of a lack of oxygen in their blood. Cyanosis presents as a bluish discoloration of the lips and nail beds. The person may lose weight simply because of the energy required to breathe. Small blood vessels in the person's lungs are destroyed, blocking the flow of blood to their lungs, resulting in increased stress on their heart which must pump with increased force and pressure in order to get blood flow to through their lungs. The resulting elevation in blood pressure in the person's lungs is referred to as, 'Pulmonary Hypertension.'
There is the possibility that the person's heart may not be able to hand the additional work; if this is the case then right heart failure, also known as, 'Cor Pulmonale,' can result and lead to swelling of the person's feet and ankles. Persons with COPD can cough up blood, referred to as, 'Hemoptysis.' Hemoptysis is the result of damages to the inner lining of the person's airways and the airways' blood vessels. On occasion, hemoptysis can be a sign of the development of lung cancer.
COPD is diagnosed based upon a person's medical history that discloses symptoms of COPD along with a physical examination presenting signs of COPD. Testing for COPD may involve chest X-rays, CT or CAT scans, pulmonary function tests, and tests that measure the oxygen and carbon dioxide levels in the person's blood.
Chronic smokers who experience shortness of breath with or without exertion, frequent respiratory infections, and a chronic and persistent cough with sputum production, are suspected of having COPD. People are sometimes first diagnosed with COPD after being hospitalized with a respiratory illness. Physical findings associated with COPD include wheezing and an enlarged chest cavity. A health care professional will hear faint and distant breath sounds with a stethoscope when listening to the person's chest. Air is trapped in the person's lungs and is unable to empty with exhalation. The extra air dampens the sounds the health care professional hears, resulting in the over-inflation of the person's chest cavity. Those who are affected predominantly by emphysema have x-rays showing an enlarged chest cavity, as well as decreased lung markings that demonstrate destruction of their lung tissues and enlargement of their air-spaces. Persons who have predominantly chronic bronchitis present x-rays that show increased lung markings showing inflamed, thickened, and scarred airways.
Spirometry is the most common pulmonary test used to measure airway obstruction.
During this test, the person takes in a full breath of air and then exhales into a tube that is connected to a machine which measures the volume of air they exhale. The amount of air the person exhales in one second is referred to as the, 'FEV1,' amount and is both a useful and reliable measurement of airflow obstruction. The amount is compared to the total amount of air that is blown out of the person's lungs, or the forced vital capacity (FVC). The ratio between the person's FEV1 and the person's FVC is commonly seventy-percent. Should an obstruction be present the ratio is reduced. The lower the ratio, the greater the airway obstruction the person is experiencing. The person's FEV1 can help to determine treatment with bronchodilators.
If the person's FEV1 amount improves after they have received bronchodilator treatment, it means that the airway obstruction they are experiencing is reversible. Demonstrated improvement in the person's FEV1 also helps a doctor to select the appropriate bronchodilator for the person. Measurements of the person's FEV1 and FVC may be repeated over time in order to determine the progression of their airway obstruction.
Both oxygen and carbon dioxide levels may be measured through blood samples that have been obtained from a person's artery; this requires insertion of a needle into the person's artery, something that is invasive. A pulse oximetry is able to measure oxygen levels in a person's blood as well, and is less invasive. Pulse oximetry works through the principle that the, 'redness,' of hemoglobin, the protein in blood that carries oxygen, is proportional to the amount of oxygen in the blood. In other words, the more oxygen there is in a person's blood, the redder it will be. An, 'Oximeter;' a probe, is placed on the person's fingertip. The probe shines a light through the person's finger, measuring the amount of light that reaches the other side of the person's finger. By measuring the amount of light that passes through the person's finger, it is possible to determine the amount of oxygen in their blood.
There are some goals and strategies associated with the treatment of COPD. These goals include:
The treatment strategies include:
Quitting smoking is the most important treatment for COPD. People who continue to smoke experience a more rapid deterioration of lung functioning compared to those who have quit smoking.
The process of aging may contribute to a very slow decline in lung function. Smoking may result in a far more dramatic loss of lung function. When a person stops smoking, the decline in lung function they experienced eventually reverts to that experienced by a non-smoker. Unfortunately, approximately one-third of persons who smoke succeed in abstaining from smoking in the long-term. Reasons for difficulty in quitting smoking include stress, nicotine addiction, peer pressure, and depression.
Nicotine in cigarettes is clearly addictive; cessation of smoking can present symptoms of withdrawal that include irritability, anxiety, depression, anger, difficulty sleeping or concentrating, fatigue, and a craving for cigarettes. The people most likely to develop withdrawal symptoms are those who smoke more than a pack of cigarettes a day, and those who smoke shortly after waking up in the morning. Approximately twenty-five percent of people who smoke are able to quit without developing symptoms. For persons who do develop symptoms of withdrawal, the symptoms often decrease after several weeks of not smoking.
Products that can assist people with smoking cessation include nicotine chewing gum, and nicotine patches.
Both of these products may deliver enough nicotine into the person's blood stream to reduce, yet not totally eliminate, the withdrawal symptoms they experience. The use of nicotine replacement methods in conjunction with both education and behavioral modification programs have improved the rates at which people quit smoking. Nicotine patches are commonly used for a period of four to six weeks, they are easy to use, and often can be tapered off over a period of several additional weeks. The potential for addiction to the patches themselves is low.
There are some antidepressant medications that may assist people in quitting smoking as well.
These medications include Bupropion, also known by the brand names, 'Zyban,' or, 'Wellbutrin.' There is another medication; Varencline, also known as, 'Chantix,' that is available to help people quit smoking. Chantix works in a couple of ways; it cuts the pleasure people get from smoking, as well as reducing the withdrawal symptoms they experience. Chantix is taken over a twelve week course and may work in ways that Bupropion does not.
When a person quits smoking, the withdrawal symptoms associated with quitting are one thing they may experience; they may also experience a weight gain of between eight and ten pounds on average. Quitting smoking may lead to depression or symptoms of chronic ulcerative colitis. For these reasons, quitting smoking should be done under a doctor's supervision. Despite these things, the benefits of quitting smoking outweigh any potential negative effects.
The treatment of COPD with bronchodilators is similar, yet not identical, to treating bronchospasm in asthma.
Bronchodilators are medications which relax the preson's muscles that surround their airways, resulting in an opening of their airways. Bronchodilators may be administered orally, intravenously, or inhaled. Bronchodilators that are inhaled are popular because they go directly to the person's airways. Inhaled bronchodilators have fewer side-effects because the medication reaches fewer areas of the person's body.
Bronchodilators are delivered through, 'Metered-dose Inhalers (MDI's),' which are pressurized canisters that contain the medication that is released when the canister is compressed. A measured amount of medication is released when the MDI is compressed. The person using the MDI is taught how to coordinate their inhalation with the compression of the MDI. Improper use of the MDI can lead to administration of the medication on the person's tongue and the back of their throat instead of on their airways.
A, 'spacer,' is a device that can be used to increase the amount of medication that reaches a person's airways when they use an MDI. Spacers are tube-like chambers that are attached to the outlet of an MDI canister. A spacer can hold released medication long enough for the person to inhale slowly and deeply into their lungs, increasing the amount of medication that reaches their airways.
One of the first medications used in the past in association with asthma was Epinephrine (adrenaline).
While epinephrine had the benefit of rapidly opening a person's airways, it also had a number of side-effects. These side-effects include nausea, headache, rapid heart beat, vomiting, restlessness, and a sense of panic. For these reasons, epinephrine is not used for treatment of COPD.
Beta-2 agonists have the effects of bronchodilating that epinephrine has, yet do not have the unwanted side-effects. Beta-2 agonists can be delivered orally, or through an MDI inhaler.
The reason they are referred to as, 'agonists,' is because they activate the beta-2 receptor on the person's muscles surrounding their airways. Activating these beta-2 receptors relaxes the person's muscles that surround their airways, opening their airways and reducing symptoms of dyspnea. Beta-2 agonists relieve dyspnea in persons with COPD, even in persons who lack demonstrable reversibility in their airway obstruction. The medication starts within minutes after the person has inhaled it and lasts for around four hours. Beta-2 agonists have a short duration of action and should be used for symptoms instead of for maintenance. As a person uses these medications regularly, their effectiveness diminishes. Examples of beta-2 agonist include albuterol, metaproterenol, terbutaline, pirbuterol, and isotherine.
There are beta-2 agonists such as salmeterol xinafoate or formoterol fumarate that can be used as maintenance medications. These medications last up to twelve hours and may be taken twice daily. These forms of inhalers are referred to as, 'Maintenance Inhalers.' The side-effects of beta-2 agonists can include tremor, anxiety, increased heart rate or palpitations, and low blood potassium.
People's nerves release a chemical called, 'Acetylcholine,' that attaches to receptors on their muscles surrounding their airways, causing their muscles to contract and their airways to narrow. Anti-cholinergic medications like Ipratropium Bromide dilate a person's airways through blocking their receptors for acetylcholine, preventing them from narrowing. Ipratropium bromide is often administered through an MDI. In persons who have COPD, ipratropium alleviates dyspnea, improves their ability to exercise, as well as improving their FEV1.
Ipratropium takes longer to start working, but last longer than beta-2 agonists. Ipratropium has fewer side-effects, even at high doses, is long lasting and is more effective. Ipratropium is well-suited for persons who are older, or who have difficulty with a fast heart rate or tremor from beta-2 agonists. People who have responded poorly to beta-2 agonists or ipratroprium alone can benefit from using both medications.
Examples of methyxanthines include Theophylline and Aminophylline, which can be administered either orally or intravenously.
Long-acting theophylline can be administered orally once or twice a day. Theophylline relaxes a person's muscles that surround their airways, but also prevents their mast cells around their airways from releasing bronchconstricting chemicals.
Theophylline can increase urination, and may increase the force of contraction of the person's heart, lowering the pressure in their pulmonary arteries. Theophylline can help persons with COPD who have heart failure or pulmonary hypertension because of this. People who have difficulty using inhalers but do not have difficulty taking oral medications can find theophylline useful.
Methylxanthines have to be closely monitored through blood testing. High blood levels of these medications can lead to vomiting, nausea, heart rhythm problems, or even seizures. In persons with cirrhosis or heart failure, the amount of methylxanthines they take are lowered to avoid high levels in their blood. There is also the potential for interactions with other medications the person is taking, such as cimetidine, calcium channel blockers, and allpurinol, that may alter the blood level of methylxanthines the person is taking.
Corticosteroids such as Prednisone or Prednisolone can help to reduce swelling that contributes to airflow obstruction.
These medications are anti-inflammatory medications, and twenty to thirty-percent of persons with COPD show improvement in their lung function when taking oral corticosteroids. Taking high doses of corticosteroids over long periods of time can have serious side-effects such as bone fractures, osteoporosis, diabetes, high blood pressure, insomnia, bruising easily, thinning skin, weight gain, and emotional changes. Many doctors use corticosteroids as a last resort, prescribing them at the lowest dose possible.
Corticosteroids are also available through MDI's.
Inhaled corticosteroids have fewer side-effects than corticosteroids taken orally. Examples of inhaled corticosteroids include beclomathsone dipropionate, triamcinoloe acetonide, budesonide, fluticasone, mometasone furoate, and flunisolide. Persons with asthma have been successfully treated with corticosteroids, yet persons with COPD have left doctors with an unclear picture of whether treatment with these medications is beneficial.
Doctors are concerned about the use of corticosteroids because of their safety.
The side-effects of inhaled corticosteroids include loss of voice, hoarseness, and oral yeast infections. Use of a spacer between the MDI and the person's mouth can help to improve delivery of the medication while reducing side-effects on the person's mouth and throat. Rinsing out your mouth after using a steroid inhaler can also decrease the risk of side-effects.
Bronchial asthma has been researched for twenty years; COPD has not been fully studied.
There is evidence that COPD is an inflammatory process, much like bronchial asthma. COPD presents different patterns of lung inflammation among people who are affected by it. There is minimal or no information related to the molecular mechanisms of inflammation in persons with COPD who are stable, something that is important in relation to areas of treatment. There are a number of clinical trials seeking means of intervention concerning the various inflammatory pathways.
There is a new class of medications that work to reduce inflammation under development, referred to as, 'PDE4 Inhibitors.' These medications include Rolipram, Piclamilast, Cilomilast, and Roflumilast. These medications reduce the number and activity of various types of inflammatory cells and substances associated with COPD.
There is an area of study that is pursuing the genetic mechanisms behind why only a fraction of smokers develop emphysema. Another area of research involves the role nerve receptors in the lungs, which are currently the focus of final clinical trials.
Benralizumab - A randomized, double-blind, placebo-controlled, phase 2a study:
Chronic obstructive pulmonary disease (COPD) is associated with eosinophilic airway inflammation in 10 to 20% of patients. Benralizumab, a monoclonal antibody, has been shown to decrease the number of blood and sputum eosinophils. In a trial of 101 patients with COPD whether benralizumab reduces the number of acute exacerbations was investigated. Benralizumab was found to be no more effective at preventing acute COPD exacerbations than placebo overall. However, the authors conclude that subgroup analysis suggest more research into the use of benralizumab in patients with COPD and eosinophilia is required. Source: The Lancet