Previous posts on COPD:
A bit more on classification of COPD...
First, just a couple of notes on COPD classification that I haven't spoken about before. Two different sets of criteria that can be used for classifying the severity of someone's COPD are the GOLD criteria and the COPD Assessment Test (CAT). The GOLD criteria is based off someone's FEV1/FVC ratio, with 1 (mild) being >80%, 2 (moderate) being 50-80%, 3 (severe) being 30-50% and 4 (very severe) being <30%. The CAT is basically a questionnaire that asks questions about quality of life related stuff, like "When I walk uphill I am not breathless" vs. "When I walk uphill I am breathless." A CAT score of more than 10 indicates that COPD may be interfering with quality of life.
Treatment varies depending on COPD severity. Someone with low GOLD and CAT scores may only require short-acting as-needed bronchodilators. As the severity increases, long-acting beta-agonists and muscarinic antagonists may be required.
Treatments for COPD
Beta-agonists
Beta-agonists activate Gs, which activates adenylate cyclase, which converts ATP to cAMP. Aside from the relaxation effects of cAMP discussed here, cAMP can also inhibit MLCK, which is important in contraction of smooth muscle (like the muscle of the airways). Beta-agonists come in two main varieties: short-acting beta-agonists which are given as needed, and long-acting beta-agonists which are taken once daily (such as indacaterol) or twice daily (such as salmeterol or eformeterol).
Why aren't short-acting beta-agonists able to be taken more often? Unfortunately, short-acting beta-agonists may increase the risk of cardiovascular adverse effects, including myocardial infarction and stroke. Hence, they are only taken as needed.
Muscarinic antagonists (anticholinergics)
Muscarinic antagonists, as their name suggests, act on muscarinic receptors. There are three main kinds of muscarinic receptors in the lung: M1, M2 and M3. M1 receptors facilitate transmission of acetylcholine from one nerve to another. M2 receptors are located near the end of the neuron and limit further ACh release if there's already a lot floating around in the neuromuscular junction. There are also M2 receptors on the airway muscle cells, which help to counteract muscle relaxation. Finally, M3 receptors on the airway muscle are responsible for contraction of the smooth muscle cells.
Many muscarinic antagonists, such as tiotropium and aclidinium bromide, are long-acting and are taken once daily. They preferentially act on M1 and M3 receptors. Adverse effects of these drugs include an increased risk of dry mouth and urinary retention.
Theophylline
Theophylline has a modest effect on FEV1 and FVC, but it's not used very much because it has a very small therapeutic window (i.e. it's hard to get the dose just right so that it has an effect without being toxic).
Roflumilast
Roflumilast is a relatively new drug used to treat COPD. It is a PDE4 (phosphodiesterase 4) inhibitor that is taken once daily. Unfortunately, it has some unpleasant side effects, such as nausea and vomiting.
Anti-oxidants
Antioxidants, such as N-acetylcysteine and carbocysteine, are also being investigated as potential therapies.
Nutrition
Excess and low weight are both associated with increased morbidity. In the case of excess weight, obesity can increase the work of breathing and predispose to sleep apnoea.
Statins
Statins, which are drugs primarily used to treat high cholesterol, have also been investigated as potential COPD therapies. Why statins? Well, they lower lipid levels and have anti-inflammatory and anti-oxidant effects, so there's a chance that they might help COPD patients.
Lung volume reduction surgery (LVRS)
Obviously, this is a more "extreme" way of treating COPD. It literally just involves removing the more severely affected areas of the lung, improving lung elastic recoil and diaphragmatic function. So far surgery does not appear to improve chances of survival, but it does improve exercise capacity.
Antibiotics
At one stage antibiotics were looked at to prevent exacerbations, but current evidence does not support this practice due to problems like antibiotic resistance, etc. Antibiotics are still used in certain kinds of exacerbations, though.
Oxygen therapy
This basically involves giving the patient a tank full of oxygen that they need to cart around with them all day. 'Nuff said.
Cellular therapies
There has been some research into stem cell therapies to treat COPD, but by the sounds of things it is very much in its infancy.
Co-morbidities of COPD
Some conditions that are comorbid with COPD include cachexia (muscle wasting), pulmonary hypertension, ischaemic heart disease, osteoporosis, anxiety and depression.
Pulmonary hypertension is seen in around 50% of patients with severe emphysema. Unfortunately, there are no pharmacological therapies to treat it. It can be diagnosed by using echocardiography, but sometimes this diagnostic tool is not as effective if there is hyperinflation.
Osteoporosis is an issue not only due to the disease itself, but due to other factors such as inhaled corticosteroids, reduced muscle mass due to immobilisation (hard to exercise when you can't breathe) and so on.
Exacerbations
Exacerbations are basically a change in baseline dyspnea, cough and/or sputum. These often happen due to factors such as bacterial and viral infections. There are some biomarkers which can hint at whether the cause is bacterial or viral: sputum IL-1b is the best predictor of bacterial exacerbation, whereas serum CXCL10 is the best predictor of viral exacerbations. Treatment includes antibiotics (for bacterial infections), glucocorticoids, and ventilatory assistance.
Treatment varies depending on COPD severity. Someone with low GOLD and CAT scores may only require short-acting as-needed bronchodilators. As the severity increases, long-acting beta-agonists and muscarinic antagonists may be required.
Treatments for COPD
Beta-agonists
Beta-agonists activate Gs, which activates adenylate cyclase, which converts ATP to cAMP. Aside from the relaxation effects of cAMP discussed here, cAMP can also inhibit MLCK, which is important in contraction of smooth muscle (like the muscle of the airways). Beta-agonists come in two main varieties: short-acting beta-agonists which are given as needed, and long-acting beta-agonists which are taken once daily (such as indacaterol) or twice daily (such as salmeterol or eformeterol).
Why aren't short-acting beta-agonists able to be taken more often? Unfortunately, short-acting beta-agonists may increase the risk of cardiovascular adverse effects, including myocardial infarction and stroke. Hence, they are only taken as needed.
Muscarinic antagonists (anticholinergics)
Muscarinic antagonists, as their name suggests, act on muscarinic receptors. There are three main kinds of muscarinic receptors in the lung: M1, M2 and M3. M1 receptors facilitate transmission of acetylcholine from one nerve to another. M2 receptors are located near the end of the neuron and limit further ACh release if there's already a lot floating around in the neuromuscular junction. There are also M2 receptors on the airway muscle cells, which help to counteract muscle relaxation. Finally, M3 receptors on the airway muscle are responsible for contraction of the smooth muscle cells.
Many muscarinic antagonists, such as tiotropium and aclidinium bromide, are long-acting and are taken once daily. They preferentially act on M1 and M3 receptors. Adverse effects of these drugs include an increased risk of dry mouth and urinary retention.
Theophylline
Theophylline has a modest effect on FEV1 and FVC, but it's not used very much because it has a very small therapeutic window (i.e. it's hard to get the dose just right so that it has an effect without being toxic).
Roflumilast
Roflumilast is a relatively new drug used to treat COPD. It is a PDE4 (phosphodiesterase 4) inhibitor that is taken once daily. Unfortunately, it has some unpleasant side effects, such as nausea and vomiting.
Anti-oxidants
Antioxidants, such as N-acetylcysteine and carbocysteine, are also being investigated as potential therapies.
Nutrition
Excess and low weight are both associated with increased morbidity. In the case of excess weight, obesity can increase the work of breathing and predispose to sleep apnoea.
Statins
Statins, which are drugs primarily used to treat high cholesterol, have also been investigated as potential COPD therapies. Why statins? Well, they lower lipid levels and have anti-inflammatory and anti-oxidant effects, so there's a chance that they might help COPD patients.
Lung volume reduction surgery (LVRS)
Obviously, this is a more "extreme" way of treating COPD. It literally just involves removing the more severely affected areas of the lung, improving lung elastic recoil and diaphragmatic function. So far surgery does not appear to improve chances of survival, but it does improve exercise capacity.
Antibiotics
At one stage antibiotics were looked at to prevent exacerbations, but current evidence does not support this practice due to problems like antibiotic resistance, etc. Antibiotics are still used in certain kinds of exacerbations, though.
Oxygen therapy
This basically involves giving the patient a tank full of oxygen that they need to cart around with them all day. 'Nuff said.
Cellular therapies
There has been some research into stem cell therapies to treat COPD, but by the sounds of things it is very much in its infancy.
Co-morbidities of COPD
Some conditions that are comorbid with COPD include cachexia (muscle wasting), pulmonary hypertension, ischaemic heart disease, osteoporosis, anxiety and depression.
Pulmonary hypertension is seen in around 50% of patients with severe emphysema. Unfortunately, there are no pharmacological therapies to treat it. It can be diagnosed by using echocardiography, but sometimes this diagnostic tool is not as effective if there is hyperinflation.
Osteoporosis is an issue not only due to the disease itself, but due to other factors such as inhaled corticosteroids, reduced muscle mass due to immobilisation (hard to exercise when you can't breathe) and so on.
Exacerbations
Exacerbations are basically a change in baseline dyspnea, cough and/or sputum. These often happen due to factors such as bacterial and viral infections. There are some biomarkers which can hint at whether the cause is bacterial or viral: sputum IL-1b is the best predictor of bacterial exacerbation, whereas serum CXCL10 is the best predictor of viral exacerbations. Treatment includes antibiotics (for bacterial infections), glucocorticoids, and ventilatory assistance.
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