COPD stands for Chronic Obstructive Pulmonary Disease, a condition characterized by persistent, irreversible limitation of airflow through the lungs. In normal circumstances, air is brought into the lungs by passing through the conducting zone of the airways, which extends from the nose to the bronchioles, before getting to the respiratory zone where gases are exchanged at the alveoli. In inspiration, the diaphragm and intercostal muscles contract, causing a flattening of the diaphragm and elevation of the chest wall respectively. This increases the volume of the lungs causing pressure within them to fall and so air is drawn in. Exhalation features the opposite. The diaphragm relaxes and elevates, the intercostal muscles relax and the lung volume reduces, causing pressure to rise and forcing air out. In COPD there is limitation to this airflow, which happens mostly as a result of two main mechanisms. The first is loss of elastic recoil and the second is narrowing of the airways. A big driver for both of these is inflammation, which is generated within the lungs as a result of exposure to inhaled toxins, most commonly cigarette smoking. When a patient is in a coma, the first thing they do is to take a pill. and secrete proteases like neutrophil elastase and matrix metalloproteinases, which are enzymes involved in breaking down proteins as part of normal repair. These are usually counterbalanced by anti-proteases like alpha-1 antitrypsin. But as a result of the chronic inflammation, there is excess protease activity causing destruction of the lung tissue. This leads to less support for the alveoli. and so a reduced elastic recoil causing them to enlarge giving emphysema. It also gives a tendency for the small airways to collapse during expiration due to the reduced structural support. When this happens air is effectively trapped eventually causing hyperinflation. The inflammation and recruitment of neutrophils increases oxygen free radicals, and ultimately also causes mucosal edema, mucus hypersecretion and bronchoconstriction, causing the airways to be narrower, and so have increased resistance to airflow. These changes are also accompanied by fibrosis and tend not to be reversible. Patients with COPD have impaired mucociliary clearance and so are more prone to having infections and repeating infections increases the inflammation and so contributes to the disease progression. Together, these two mechanisms mean an increase in the work of breathing, which gives reduced ventilation of the alveoli. This leads to hypoxia and hypercapnia, meaning low levels of oxygen and high levels of carbon dioxide respectively. The principal cause of COPD is exposure to inhaled chemicals, primarily smoking, where it is thought that up to 70% of cases are due to cigarette smoking. Other exposures such as pollution, mineral dust or chemicals also increase the risk but is not as commonly the cause as smoking. Genetics are also a cause, with many genetic variants showing increased likelihood of developing COPD, but in particular to remember is Alpha-1 antitrypsin deficiency, again leading to a relative excess of protease activity. The symptoms of COPD are usually gradual in onset and typically appear in those with over a 20-pack year history of smoking. Dyspnea, meaning shortness of breath, is the most common finding, that is typically persistent and worsening. Initially getting worse with exercise, but as the disease progresses, it may even be present at rest. A cough is also common, which may be productive or non-productive, although 30% of patients do present with a chronic productive cough. In this instance, sputum characteristics like colour and volume can be useful markers for exacerbations. Traditionally for a diagnosis of chronic bronchitis to be made, the cough must be present for more than 3 months in 2 consecutive years with no other explanation. Recurrent wheezing and respiratory tract infections, fatigue, weight loss and chest tightness are other common findings. A classic description of the two main phenotypes in COPD is the blue bloaters and pink puffers, to describe chronic bronchitis and emphysema. This refers to blue bloaters being those with predominantly features of productive cough, dyspnea, obesity and cyanosis as a result of reduced oxygen levels in the blood, and pink puffers characterised by a normal or thin body habitus and pursed lip breathing that helps prevent the bronchioles from collapsing and so improving ventilation. But in reality, remember that most patients have an overlap of both. Physical exam findings are not diagnostic or specific, but they can include tachypnea, meaning a raised respiratory rate, and use of accessory muscles. Barrel chest is also common due to the hyperinflation and on auscultation there may be coarse crackles, coming from reopening of collapsed airways and the presence of mucus. In cases where hypercapnia is present, there can also be asterixis, where there is a flapping tremor of the arms. Complications include acute deteriorations called exacerbations, defined as a worsening of the person's symptoms from their usual stable state, with a timeframe of within 14 days being used to define this. They can often happen in the context of recurrent infections, but other causes include pulmonary embolisms, heart failure, arrhythmias and myocardial infarctions. Pulmonary hypertension may develop due to chronic hypoxemia, where the lung vasculature responds and remodels, which itself can lead to right-sided heart failure. Pneumothorax can also be a result of rupture of the bullae. Diagnosis is suspected from the clinical history but is made by demonstrating the presence of an obstructive pattern on spirometry that is irreversible. The Global Initiative for COPD criteria include a post-bronchodilator forced expiratory volume in 1 second to forced vital capacity ratio of less than 0.7. The FEV1 can also be used to indicate the severity of obstruction. With more than 80% of predicted value being the mildest form, while less than 30% indicates very severe COPD. The COPD assessment test, known as the CAT score, can be used to assess symptom severity. The number of exacerbations in the past can help produce future exacerbation risk. Based on these two features, patients are divided into GOLD group A, B or E. Group A reflects low symptom burden, so a CAT score less than 10, and one or less moderate exacerbations per year. Group B is for increased symptom burden, with CAT scores 10 or above, but still less than one exacerbation per year. And Group E, if there are two or more exacerbations per year. We'll see how this impacts treatment shortly. Additional testing can include pulse oximetry, an ABG may be done to rule out respiratory failure and to help assess for long term oxygen therapy. Other blood tests can include a full blood count to look for anemia or polycythemia as a result of chronic hypoxemia. Chest x-ray is not diagnostic but features an increased anterior-posterior ratio, large intercostal spaces and a flattened diaphragm which are suggestive of COPD. Genetic testing is not routinely done in practice, but patients under the age of 45 years or in rapidly progressing cases should particularly be screened for alpha-1 antitrypsin deficiency. In acute exacerbations, treatment generally involves the use of short-acting beta agonists like salbutamol, either inhaled or through a nebuliser, and a short-acting muscarinic antagonist like ipatropium bromide, again inhaled or nebulised. In general, most patients with COPD will have target oxygen saturations of 88-92. This is because excess oxygen may suppress the drive for ventilation and precipitate hypercapnia and type 2 respiratory failure. Alongside these, a systemic steroid is given, like prednisolone or hydrocortisone, and antibiotics may be used if an infection is suspected. Ventilation may be required in some cases, especially type 2 respiratory failure where non-invasive ventilation may be used. The overall aims of treatment in stable COPD are to reduce the symptom burden, as well as number and severity of exacerbations, as well as reducing mortality. First-line measures include smoking cessation or removal of the exposure to the damaging substance, shown to be the factor with the greatest capacity to influence the course of the disease. Pulmonary rehabilitation includes aerobic exercise, strength training and education. And vaccines, for example flu, pneumococcal and more recently COVID vaccines, are also first-line measures. The pharmacological management involves beta agonists that increase intracellular cyclic AMP and lead to smooth muscle relaxation, while muscarinic antagonists block cholinergic receptors on the respiratory smooth muscle and so also promote smooth muscle relaxation. These are usually inhalers and so bear in mind that technique of using them is incredibly important. Looking at the initial treatment based on the gold groups, we have bronchodilators in group A which can include short or long term options, more specifically short or long acting beta 2 agonists like salbutamol and formotero or short or long acting anti muscarinic antagonists like ipratropium or tyrotropium. Long acting agents are more commonly used but short acting therapy should be available to all patients for immediate relief. Group B instead typically have a combination of long acting muscarinic antagonists and long acting beta agonists but may have monotherapy, while group E usually have a combination of vlamma and labba. Inhaled corticosteroids are not generally encouraged, but may be added if the eosinophil count is above 300 cells per microlitre initially or above 100 on follow up. A history of asthma or multiple severe exacerbations are also indications. Remember that these are gold recommendations and practice in different countries may vary from this. Depending on the response to therapy, patients can be stepped up through this regime, and if there are ongoing exacerbations on triple therapy, macrolide antibiotics prophylactically or roflumilast, a phosphodiesterase IV inhibitor, can be added. It prevents the breakdown of cyclic AMP and can be added if the FEV1 is less than 50%. In cases of predominant bronchitis with troublesome mucus production, Agents like Erdosthene and Cabocysthene can be used to help break it down. Long term oxygen therapy is recommended in stable patients with an arterial partial pressure of oxygen below 7.3 kPa and up to 8 kPa if there is evidence of cardiac failure or polycythemia. Additional options include bulectomy, volume reduction surgery and transplant.