Respiratory Arrest From Wikipedia, the free encyclopedia Respiratory arrest, is the cessation of normal respiration due to failure

of the lungs to contract effectively. A respiratory arrest is different from (but may be caused by) a cardiac arrest, where the heart muscles fail to contract properly Respiratory arrest prevents delivery of oxygen to the body. Lack of oxygen to the brain causes loss of consciousness. Brain injury is likely if respiratory arrest goes untreated for more than three minutes, and death is almost certain if left untreated for more than five minutes. For the best chance of survival and recovery, immediate and decisive treatment is imperative. Respiratory arrest is a medical emergency that, in certain situations, is potentially reversible if treated early. The treatment for respiratory is artificial ventilation.

Chest trauma From Wikipedia, the free encyclopedia Chest trauma (or thoracic trauma) is a serious injury of the chest. Thoracic trauma is a common cause of significant disability and mortality, the leading cause of death from physical trauma after [1] head and spinal cord injury. Blunt thoracic injuries are the primary or a contributing cause of [1] [2] about a quarter of all trauma-related deaths. The mortality rate is about 10%. Chest injuries [3] were first described in detail in around 1600 BC in the ancient Egyptian Edwin Smith Papyrus. Classification

A chest X-ray of a right sided pulmonary contusion associated with flail chest and subcutaneous emphysema Chest trauma can be classified as blunt or penetrating. Blunt and penetrating injuries have different pathophysiologies and clinical courses. Specific types of chest trauma include: Injuries to the chest wall Chest wall contusions or hematomas. Rib fractures Flail chest

 Sternal fractures Fractures of the shoulder girdle Pulmonary injury (injury to the lung) and injuries involving the pleural space Pulmonary contusion Pulmonary laceration Pneumothorax Hemothorax Hemopneumothorax Injury to the airways Tracheobronchial tear Cardiac injury Pericardial tamponade Myocardial contusion Blood vessel injuries Traumatic aortic rupture, thoracic aorta injury, aortic dissection And injuries to other structures within the torso Esophageal injury (Boerhaave syndrome) Diaphragm injury Diagnosis Most blunt injuries are managed with relatively simple interventions like tracheal intubation and mechanical ventilation and chest tube insertion. Diagnosis of blunt injuries may be more difficult and require additional investigations such as CT scanning. Penetrating injuries often require surgery, and complex investigations are usually not needed to come to a diagnosis. Patients with penetrating trauma may deteriorate rapidly, but may also recover much faster than patients with blunt injury.

Pulmonary embolism From Wikipedia, the free encyclopedia Pulmonary embolism (PE) is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream (embolism). Usually this is due to embolism of a thrombus (blood clot) from the deep veins in the legs, a process termed venous thromboembolism. A small proportion is due to the embolization of air, fat, talc in drugs of intravenous drug abusers or amniotic fluid. The obstruction of the blood flow through the lungs and the resultant pressure on the right ventricle of the heart leads to the symptoms and signs of PE. The risk of PE is increased in various situations, such as cancer or [1] prolonged bed rest. Symptoms of pulmonary embolism include difficulty breathing, chest pain on inspiration, and palpitations. Clinical signs include low bloodoxygen saturation and cyanosis, rapid breathing, and a rapid heart rate. Severe cases of PE can lead to collapse, abnormally low blood pressure, [1] and sudden death. Diagnosis is based on these clinical findings in combination with laboratory tests (such as the Ddimer test) and imaging studies, usuallyCT pulmonary angiography. Treatment is typically with anticoagulant medication, including heparin and warfarin. Severe cases may requirethrombolysis with drugs such as tissue plasminogen activator (tPA) or may require surgical [1] intervention via pulmonary thrombectomy. Signs and symptoms Symptoms of PE are sudden-onset dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of a "pleuritic" nature (worsened by breathing), cough and hemoptysis(coughing up blood). More severe cases can include signs

such as cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability due to decreased blood flow through the lungs and into the left side of the heart. About [1] 15% of all cases of sudden death are attributable to PE. On physical examination, the lungs are usually normal. Occasionally, a pleural friction rub may be audible over the affected area of the lung (mostly in PE with infarct) . A pleural effusion is sometimes present that is transudative, detectable by decreased percussion note, audible breath sounds and vocal resonance. Strain on the right ventricle may be detected as a left parasternal heave, a loud pulmonary component of the second heart sound, and raised jugular venous [1] pressure. A low-grade fever may be present, particularly if there is associated pulmonary [2] hemorrhage or infarction. More rarely, inability of the right ventricle to remove fluid from the tissues leads to fluid accumulation in the legs (peripheral edema), congestion of the liver with mild jaundice and tenderness, and ascites (fluid in the abdominal cavity).

Risk factors The most common sources of embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation, which happens in up to 15% of all DVTs. The conditions are generally regarded as a continuum termed venous thromboembolism(VTE). The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present. Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) Factors in the vessel wall: of limited direct relevance in VTE Factors affecting the properties of the blood (procoagulant state): Estrogen-containing hormonal contraception Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia andplasminogen/fibrinolysis disorders) Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria) Cancer (due to secretion of pro-coagulants) Diagnosis The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation (shortness of breath, chest pain) cannot be definitively differentiated from other causes of chest pain and shortness of breath. The decision to do medical imaging is usually based on clinical grounds, i.e. the medical history, symptoms and [1] findings on physical examination, followed by an assessment of clinical probability. The most commonly used method to predict clinical probability, the Wells score, is a clinical prediction rule, whose use is complicated by multiple versions being available. In 1995, Wells et al. initially developed a prediction rule (based on a literature search) to predict the likelihood of [3] [4] PE, based on clinical criteria. The prediction rule was revised in 1998 This prediction rule was [5] further revised when simplified during a validation by Wells et al. in 2000. In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same [5] prediction rule. In 2001, Wells published results using the more conservative cutoff of 2 to

create three categories. An additional version, the "modified extended version", using the more [3][4] [7] recent cutoff of 2 but including findings from Wells's initial studies were proposed. Most [5] recently, a further study reverted to Wells's earlier use of a cutoff of 4 points to create only two [8] categories. There are additional prediction rules for PE, such as the Geneva rule. More importantly, the use [9] of any rule is associated with reduction in recurrent thromboembolism. The Wells score:
[10]

[6]

clinically suspected DVT - 3.0 points alternative diagnosis is less likely than PE - 3.0 points tachycardia (heart rate > 100) - 1.5 points immobilization (>= 3d)/surgery in previous four weeks - 1.5 points history of DVT or PE - 1.5 points hemoptysis - 1.0 points malignancy (with treatment within 6 months) or palliative - 1.0 points
[5][6][11]

Traditional interpretation

Score >6.0 - High (probability 59% based on pooled data ) [12] Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data ) [12] Score <2.0 - Low (probability 15% based on pooled data )
[5][8]

[12]

Alternative interpretation

Score > 4 - PE likely. Consider diagnostic imaging. Score 4 or less - PE unlikely. Consider D-dimer to rule out PE.

Blood tests Early primary research has shown that in low/moderate suspicion of PE, a normal D-dimer level [13] (shown in a blood test) is enough to exclude the possibility of thrombotic PE. This has been corroborated by a recent systematic review of studies of patients with low pre-test probability (PTP) of PE and negative D-dimer results that found the three month risk of thromboembolic events in patients excluded in this manner was 0.14%, with 95% confidence intervals from 0.05 to 0.41%, though this review was limited by its use of only onerandomized[14] controlled clinical trial, the remainder of studies being prospective cohorts. D-dimer is highly sensitive but not very specific (specificity around 50%). In other words, a positive D-dimer is not synonymous with PE, but a negative D-dimer is, with a good degree of certainty, an indication of [15] absence of a PE. When a PE is being suspected, a number of blood tests are done, in order to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, aPTT,TT), and some screening tests (erythrocyte sedimentation rate, renal function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted. Imaging Selective pulmonary angiogram CT pulmonary angiography Ventilation-perfusion scintigraphy Non-invasive imaging CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages are

clinical equivalence, its non-invasive nature, its greater availability to people, and the possibility of identifying other lung disorders from the differential diagnosis in case there is no pulmonary embolism. Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) [16] machines. According to a cohort study, single-slice spiral CT may help diagnose detection [17] among people with suspected pulmonary embolism. In this study, the sensitivity was 69% and specificity was 84%. In this study which had a prevalence of detection was 32%, thepositive predictive value of 67.0% and negative predictive value of 85.2% (click here to adjust these results for people at higher or lower risk of detection). However, this study's results may be biased due to possible incorporation bias, since the CT scan was the final diagnostic tool in people with pulmonary embolism. The authors noted that a negative single slice CT scan is insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of 4 slice and 16 slice scanners reported a sensitivity of 83% and a specificity of 96%. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging [18] results. CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily [19] improving the outcome) compared to VQ scanning. Ventilation/perfusion scan (or V/Q scan or lung scintigraphy), which shows that some areas of the lung are being ventilated but not perfusedwith blood (due to obstruction by a clot). This type of examination is used less often because of the more widespread availability of CT technology, however, it may be useful in people who have an allergy to iodinated contrast or [20][21] in pregnancy due to lower radiation exposure than CT. Low probability diagnostic tests/non-diagnostic tests Tests that are frequently done that are not sensitive for PE, but can be diagnostic. Chest X-rays are often done on patients with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely [22] normal, but usually lack signs that suggest the diagnosis of PE (e.g. Westermark sign,Hampton's hump). Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown onultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism.

Electrocardiogram

Electrocardiogram of a patient with pulmonary embolism showing sinus tachycardia of approximately 150 beats per minute and right bundle branch block. An electrocardiogram (ECG) is routinely done on patients with chest pain to quickly diagnose myocardial infarctions (heart attacks). An ECG may show signs of right heart strain or acute cor pulmonale in cases of large PEs - the classic signs are a large S wave in lead I, a large [23] Q wave in lead III and an inverted T wave in lead III ("S1Q3T3"). This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value. The most commonly seen signs in the ECG is sinus tachycardia, right axis [24] deviation and right bundle branch block. Sinus tachycardia was however still only found in 8 [25] 69% of people with PE. Echocardiography In massive and submassive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every patient with a (suspected) pulmonary embolism requires an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart [26] strain and warrant an echocardiogram. The specific appearance of the right ventricle on echocardiography is referred to as the McConnell's sign. This is the finding of akinesia of the mid-free wall but normal motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the diagnosis of acute [27] pulmonary embolism in the setting of right ventricular dysfunction. Algorithms Recent recommendations for a diagnostic algorithm have been published by the PIOPED investigators; however, these recommendations do not reflect research using 64 slice [12] MDCT. These investigators recommended: Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and based treatment on results. Moderate clinical probability. If negative D-dimer, PE is excluded. However, the authors were not concerned that a negative MDCT with negative D-dimer in this setting has an 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based treatment on results. High clinical probability. Proceed to MDCT. If positive, treat, if negative, additional tests are needed to exclude PE. Pulmonary Embolism Rule-out Criteria The Pulmonary Embolism Rule-out Criteria, or PERC rule, helps assess people in whom pulmonary embolism is suspected, but unlikely. Unlike the Wells Score and Geneva score, which

are clinical prediction rules intended to risk stratify patients with suspected PE, the PERC rule is designed to rule out risk of PE in patients when the physician has already stratified them into a low-risk category. Patients in this low risk category without any of these criteria may undergo no further diagnostic testing for PE: Hypoxia - Sa02 <95%, unilateral leg swelling, hemoptysis, prior DVT or PE, recent surgery or trauma, age >50, hormone use, tachycardia. The rationale behind this decision is that further testing (specifically CT angiogram of the chest) may cause more harm (from radiation [28] exposure and contrast dye) than the risk of PE. The PERC rule has a sensitivity of 97.4% and [29] specificity of 21.9% with a false negative rate of 1.0% (16/1666). Treatment In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, are often required. Anticoagulation Main article: anticoagulant In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins (such as enoxaparin and dalteparin), or fondaparinux is administered initially, while warfarin, acenocoumarol, or phenprocoumon therapy is commenced (this may take several days, usually while the patient is in the hospital). Low molecular weight heparin may reduce bleeding among patients with pulmonary embolism as compared to heparin according to [30] a systematic review of randomized controlled trials by the Cochrane Collaboration. The relative risk reduction was 40.0%. For patients at similar risk to those in this study (2.0% had bleeding when not treated with low molecular weight heparin), this leads to anabsolute risk reduction of 0.8%. 125.0 patients must be treated for one to benefit. It is possible to treat low risk patients (risk class I or class II) as outpatients. A randomised trial of 344 patients (171 outpatients and 168 inpatients) found that outcomes were equivalent whether patients were treated in hospital or at home (there was one death at 90 days [31][32] in each group). This confirms the findings of an earlier systematic review ofobservational [33] studies. Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin. In patients with an underlying malignancy, therapy with a course of low [34] molecular weight heparin may be favored over warfarin based on the results of the CLOT trial. Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the [citation needed] known teratogenic effects of warfarin, especially in the early stages of pregnancy. People are usually admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until INR has reached therapeutic levels. Increasingly, low-risk cases are managed [35] on an outpatient basis in a fashion already common in the treatment of DVT. Warfarin therapy is usually continued for 36 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. An abnormal D-dimer level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked [36] pulmonary embolus. Thrombolysis Main article: Thrombolysis Massive PE causing hemodynamic instability (shock and/or hypotension, defined as a systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for>15 min if not caused by new-onset arrhythmia, hypovolemia or sepsis) is an indication for thrombolysis, the enzymatic destruction of
[31]

the clot with medication. It is the best available medical treatment in this situation and is [37][38][39] supported by clinical guidelines. The use of thrombolysis in non-massive PEs is still debated. The aim of the therapy is to dissolve [40] the clot, but there is an attendant risk of bleeding or stroke. The main indication for thrombolysis is in submassive PE where right ventricular dysfunction can be demonstrated [41] on echocardiography, and the presence of visible thrombus in the atrium. Surgery

Used inferior vena cava filter. Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit [42] selected patients. Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy. Inferior vena cava filter Main article: inferior vena cava filter If anticoagulant therapy is contraindicated and/or ineffective, or to prevent new emboli from entering the pulmonary artery and combining with an existing blockage, an inferior vena cava [43] filter may be implanted.

Chronic obstructive pulmonary disease From Wikipedia, the free encyclopedia Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive lung disease (COLD), chronic obstructive airway disease (COAD), chronic airflow limitation (CAL) and chronic obstructive respiratory disease (CORD), is the occurrence ofchronic bronchitis or emphysema, a pair of commonly co-existing diseases of the lungs in which [1] the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs, causing shortness of breath (dyspnea). In clinical practice, COPD is defined by its [2] characteristically low airflow on lung function tests. In contrast to asthma, this limitation is poorly reversible and usually gets progressively worse over time. In England, an estimated 842,100 of [3] 50 million people have a diagnosis of COPD. COPD is caused by noxious particles or gas, most commonly from tobacco smoking, which [4] triggers an abnormal inflammatory response in the lung.

The diagnosis of COPD requires lung function tests. Important management strategies are smoking cessation, vaccinations, rehabilitation, and drug therapy (often using inhalers). Some [4] patients go on to require long-term oxygen therapy or lung transplantation. Worldwide, COPD ranked as the sixth leading cause of death in 1990. It is projected to be the fourth leading cause of death worldwide by 2030 due to an increase in smoking rates and [5] demographic changes in many countries. COPD is the third leading cause of death in the U.S. and the economic burden of COPD in the U.S. in 2007 was $42.6 billion in health care costs and [6][7] lost productivity. Classification The twofold nature of the pathology has been studied in the past. Furthermore, also in recent studies, many authors found that each patient could be classified as presenting a predominantly bronchial or emphysematous phenotype by simply analyzing clinical, functional, and radiological [9][10][11] findings or studying interesting biomarkers. A statistical model reflecting the specific predominant mechanism of airflow limitation for a specific patient has been developed and trained over a database of hundreds of patients. The model is availablehere as a free online application. Chronic bronchitis Main article: chronic bronchitis Lung damage and inflammation in the large airways results in chronic bronchitis. Chronic bronchitis is defined in clinical terms as a cough with sputum production on most days for [12] 3 months of a year, for 2 consecutive years. In the airways of the lung, the hallmark of chronic bronchitis is an increased number (hyperplasia) and increased size (hypertrophy) of the goblet cells and mucous glands of the airway. As a result, there is more mucus than usual in the airways, contributing to narrowing of the airways and causing a cough with sputum.Microscopically there is infiltration of the airway walls with inflammatory cells. Inflammation is followed by scarring and remodeling that thickens the walls and also results in narrowing of the airways. As chronic bronchitis progresses, there is squamous metaplasia (an abnormal change in the tissue lining the inside of the airway) and fibrosis (further thickening and [13] scarring of the airway wall). The consequence of these changes is a limitation of airflow. Patients with advanced COPD that have primarily chronic bronchitis rather than emphysema were commonly referred to as "Blue Bloaters" because of the bluish color of the skin and lips [14] (cyanosis) along with hypoxia and fluid retention seen in them.
[8]

Emphysema Main article: emphysema Lung damage and inflammation of the air sacs (alveoli) will result in emphysema. Emphysema is defined as enlargement of the air spaces distal to the terminal bronchioles, with destruction of [12] their walls. The destruction of air space walls reduces the surface area available for the exchange of oxygen and carbon dioxide during breathing. It also reduces the elasticity of the lung itself, which results in a loss of support for the airways that are embedded in the lung. These airways are more likely to collapse causing further limitation to airflow. There are 4 types of emphysema: 1. Centriacinar / centrilobular: proximal to central parts of acini (air spaces closer to bronchioles) are affected 2. Panacinar / panlobular: enlargement of all air spaces (from bronchioles to terminal blind alveoli). This type is associated with alpha-1-antitrypsin deficiency 3. Distal acinar / paraseptal: proximal acinus normal, distal acinus affected [15] 4. Irregular: various parts of acinus involved. Associated with fibrosis. Signs and symptoms

Essentials of diagnosis include: History of cigarette smoking. Chronic cough and sputum production (in chronic bronchitis) Dyspnea Rhonchi, decreased intensity of breath sounds, and prolonged expiration on physical examination Airflow limitation on pulmonary function testing that is not fully reversible and most often progressive.

One of the most common symptoms of COPD is shortness of breath (dyspnea). People with COPD commonly describe this as: "My breathing requires effort," "I feel out of breath," or "I can't [16] get enough air in". People with COPD typically first notice dyspnea during vigorous exercise when the demands on the lungs are greatest. Over the years, dyspnea tends to get gradually worse so that it can occur during milder, everyday activities such as housework. In the advanced stages of COPD, dyspnea can become so bad that it occurs during rest and is constantly present. Other symptoms of COPD are a persistent cough, sputum or mucus production, wheezing, chest [17][18] tightness, and tiredness. People with advanced (very severe) COPD sometimes develop respiratory failure. When this happens, cyanosis, a bluish discoloration of the lips caused by a lack of oxygen in the blood, can occur. An excess of carbon dioxide in the blood can cause headaches, drowsiness or twitching (asterixis). A complication of advanced COPD is cor pulmonale, a strain on the heart due to the [19] extra work required by the heart to pump blood through the affected lungs. Symptoms of cor pulmonale are peripheral edema, seen as swelling of the ankles, and dyspnea. There are a few signs of COPD that a healthcare worker may detect although they can be seen in other diseases. Some people have COPD and have none of these signs. Common signs are: tachypnea, a rapid breathing rate wheezing sounds or crackles in the lungs heard through a stethoscope breathing out taking a longer time than breathing in enlargement of the chest, particularly the front-to-back distance (hyperaeration) active use of muscles in the neck to help with breathing breathing through pursed lips increased anteroposterior to lateral ratio of the chest (i.e. barrel chest). Cause Smoking The primary risk factor for COPD is chronic tobacco smoking. In the United States, 80 to 90% of [20][21] cases of COPD are due to smoking. Exposure to cigarette smoke is measured in pack[22] years, the average number of packages of cigarettes smoked daily multiplied by the number of years of smoking. The likelihood of developing COPD increases with age and cumulative smoke exposure, and almost all life-long smokers will develop COPD, provided that smoking-related, extrapulmonary diseases (cardiovascular, diabetes, cancer) do not claim their lives [23] beforehand. Occupational exposures Intense and prolonged exposure to workplace dusts found in coal mining, gold mining, and the cotton textile industry and chemicals such as cadmium, isocyanates, and fumes fromwelding have been implicated in the development of airflow obstruction, even in [24] nonsmokers. Workers who smoke and are exposed to these particles and gases are even more likely to develop COPD. Intense silica dust exposure causes silicosis, a restrictive lung disease distinct from COPD; however, less intense silica dust exposures have been linked to a

COPD-like condition. The effect of occupational pollutants on the lungs appears to be [26] substantially less important than the effect of cigarette smoking. Air pollution Studies in many countries have found people who live in large cities have a higher rate of COPD [27] compared to people who live in rural areas. Urban air pollution may be a contributing factor for COPD, as it is thought to slow the normal growth of the lungs, although the long-term research needed to confirm the link has not been done. Studies of the industrial waste gas and COPD/asthma-aggravating compound, sulfur dioxide, and the inverse relation to the presence of the blue lichen Xanthoria (usually found abundantly in the countryside, but never in towns or cities) have been seen to suggest combustive industrial processes do not aid COPD sufferers. In many developing countries, indoor air pollution from cooking fire smoke (often using biomass [28] fuels such as wood and animal dung) is a common cause of COPD, especially in women. Genetics Some factor in addition to heavy smoke exposure is required for a person to develop COPD. This factor is probably a genetic susceptibility. COPD is more common among relatives of COPD [29] patients who smoke than unrelated smokers. The genetic differences that make some peoples' lungs susceptible to the effects of tobacco smoke are mostly unknown. Alpha 1-antitrypsin deficiency is a genetic condition that is responsible for about 2% of cases of COPD. In this condition, the body does not make enough of a protein, alpha 1-antitrypsin. Alpha 1-antitrypsin protects the lungs from damage caused by protease enzymes, such as elastase and trypsin, that [30] can be released as a result of an inflammatory response to tobacco smoke. Autoimmune disease Main article: Autoimmunity There is mounting evidence that there may be an autoimmune component to COPD, triggered by [31] lifelong smoking. Many individuals with COPD who have stopped smoking have active [32] inflammation in the lungs. The disease may continue to get worse for many years after [32] stopping smoking due to this ongoing inflammation. This sustained inflammation is thought to [32][33][34] be mediated by autoantibodies and autoreactive T cells. Acute exacerbations of COPD Main article: Acute exacerbation of chronic obstructive pulmonary disease An acute exacerbation of COPD is a sudden worsening of COPD symptoms (shortness of breath, quantity and color of phlegm) that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can be found in roughly 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Pulmonary emboli can also cause exacerbations of COPD. Airway inflammation is increased during the exacerbation, resulting in increased hyperinflation, reduced expiratory air flow and worsening of gas transfer. This can also lead to hypoventilation and eventually hypoxia, insufficient tissue perfusion, and then cell [4] necrosis. Other risk factors A tendency to sudden airway constriction in response to inhaled irritants, bronchial hyperresponsiveness, is a characteristic of asthma. Many people with COPD also have this tendency. In COPD, the presence of bronchial hyperresponsiveness predicts a worse course of [26] the disease. It is not known if bronchial hyperresponsiveness is a cause or a consequence of COPD. Other risk factors such as repeated lung infection and possibly a diet high in cured meats (possibly due to the preservative sodium nitrite) may be related to the development of COPD.

[25]

Pathophysiology

Enlarged view of lung tissue showing the difference between healthy lung and COPD It is not fully understood how tobacco smoke and other inhaled particles damage the lungs to cause COPD. The most important processes causing lung damage are: Oxidative stress produced by the high concentrations of free radicals in tobacco smoke Cytokine release due to inflammation as the body responds to irritant particles such as tobacco smoke in the airway Tobacco smoke and free radicals impair the activity of antiprotease enzymes such as alpha 1-antitrypsin, allowing protease enzymes to damage the lung

Potential role of coagulation and thecomplement system in COPD; a complex cascade of blood plasma proteins and platelet activation as molecular perturbations associated with patients suffering from COPD Narrowing of the airways reduces the rate at which air can flow to and from the air sacs (alveoli) and limits the effectiveness of the lungs. In COPD, the greatest reduction in air flow occurs when breathing out (during expiration) because the pressure in the chest tends to compress rather than expand the airways. In theory, air flow could be increased by breathing more forcefully, increasing the pressure in the chest during expiration. In COPD, there is often a limit to how much this can [35] actually increase air flow, a situation known as expiratory flow limitation. If the rate of airflow is too low, a person with COPD may not be able to completely finish breathing out (expiration) before he or she needs to take another breath. This is particularly common during exercise, when breathing has to be faster. A little of the air of the previous breath remains within the lungs when the next breath is started, resulting in an increase in the volume of [35] air in the lungs, a process called dynamichyperinflation. Dynamic hyperinflation is closely linked to dyspnea in COPD. It is less comfortable to breathe with hyperinflation because it takes more effort to move the lungs and chest wall when they are already stretched by hyperinflation.
[36]

Another factor contributing to shortness of breath in COPD is the loss of the surface area available for the exchange of oxygen and carbon dioxide with emphysema. This reduces the rate of transfer of these gases between the body and the atmosphere and can lead to low oxygen and high carbon dioxide levels in the body. A person with emphysema may have to breathe faster or more deeply to compensate, which can be difficult to do if there is also flow limitation or hyperinflation. Some people with advanced COPD do manage to breathe fast to compensate, but usually have dyspnea as a result. Others, who may be less short of breath, tolerate low oxygen and high carbon dioxide levels in their bodies, but this can eventually lead to headaches, drowsiness and heart failure. Advanced COPD can lead to complications beyond the lungs, such as weight loss (cachexia), pulmonary hypertension and right-sided heart failure (cor pulmonale). Osteoporosis, heart disease, muscle wasting and depression are all more common in [4] people with COPD. Several molecular signatures associated to lung function decline and corollaries of disease severity have been proposed, a majority of which are characterized in easily accessible surrogate tissue, including blood derivatives such as serum and plasma. A recent 2010 clinical study proposes alpha 1B-glycoprotein precursor/A1BG, alpha 2-antiplasmin, apolipoprotein A-IV precursor/APOA4, and complement component 3 precursor, among other coagulation andcomplement system proteins as corollaries of lung function decline, [37] although ambiguity between cause and effect is unresolved. Diagnosis

A chest X-ray demonstrating severe COPD. Note the small size of the heart in comparison to the lungs. The diagnosis of COPD should be considered in anyone who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease such as regular

tobacco smoking. No single symptom or sign can adequately confirm or exclude the [39] diagnosis of COPD, although COPD is uncommon under the age of 40 years. Spirometry The diagnosis of COPD is confirmed by spirometry, a test that measures the forced expiratory volume in one second (FEV1), which is the greatest volume of air that can be breathed out in the first second of a large breath. Spirometry also measures the forced vital capacity (FVC), which is the greatest volume of air that can be breathed out in a whole large breath. Normally, at least 70% of the FVC comes out in the first second (i.e. the FEV1/FVC ratio is >70%). A ratio less than normal defines the patient as having COPD. More specifically, the diagnosis of COPD is made [2] when the FEV1/FVC ratio is <70%. The GOLD criteria also require that values are after bronchodilatormedication has been given to make the diagnosis, and the NICE criteria also [2] require FEV1%. According to the ERS criteria, it is FEV1% predicted that defines when a [2] patient has COPD, that is, when FEV1% predicted is < 88% for men, or < 89% for women. Spirometry can help to determine the severity of COPD. The FEV1 (measured after bronchodilator medication) is expressed as a percentage of a predicted "normal" value based on a person's age, gender, height and weight: The severity of COPD also depends on the severity of dyspnea and exercise limitation. These and other factors can be combined with spirometry results to obtain a COPD severity score that [40] takes multiple dimensions of the disease into account. Other tests On chest x-ray, the classic signs of COPD are overexpanded lung (hyperinflation), a flattened [41] diaphragm, increased retrosternal airspace, and bullae. It can be useful to help exclude other [41] lung diseases, such as pneumonia, pulmonary edema or a pneumothorax. Complete pulmonary function tests with measurements of lung volumes and gas transfer may also show hyperinflation and can discriminate between COPD with emphysema and COPD without emphysema. A high-resolution computed tomography scan of the chest may show the distribution of emphysema throughout the lungs and can also be useful to exclude other lung diseases. A blood sample taken from an artery, i.e. Arterial Blood Gas (ABG), can be tested for blood gas levels which may show low oxygen (hypoxaemia) and/or high carbon dioxide (respiratory acidosis if pH is also decreased). A blood sample taken from a vein may show a high blood count (reactive polycythemia), a reaction to long-term hypoxemia. Management There is currently no cure for COPD; however, COPD is both a preventable and treatable disease. Clinical practice guidelines for the management of COPD are available from theGlobal [42] Initiative for Chronic Obstructive Lung Disease (GOLD), a collaboration that includes the World Health Organization and the U.S. National Heart, Lung, and Blood Institute. The major current directions of COPD management are to assess and monitor the disease, reduce the risk factors, [4] manage stable COPD, prevent and treat acute exacerbations and manage comorbidity. The only measures that have been shown to reduce mortality is smoking cessation and [43] supplemental oxygen. Risk factor reduction Smoking cessation Main article: Smoking cessation Smoking cessation is one of the most important factors in slowing down the progression of COPD. Once COPD has been diagnosed, stopping smoking slows down the rate of progression of the disease. Even at a late stage of the disease, it can significantly reduce the rate of [13] deterioration in lung function and delay the onset of disability and death. It is the only standard [43] intervention that can improve the rate of progression of COPD.
[4] [4]

[4][38]

Smoking cessation starts with an individual decision to stop smoking that leads to an attempt at quitting. Often several attempts are required before long-term smoking cessation is [44] achieved. Some smokers can achieve long-term smoking cessation through "willpower" alone. [45] However, smoking is highly addictive, and many smokers need further support to quit. The chance of successfully stopping smoking can be greatly improved through social support, engagement in a smoking cessation programme and the use of drugs such asnicotine [44] replacement therapy, bupropion and varenicline. The policies of governments, public health agencies and antismoking organizations can reduce smoking rates by encouraging smoking cessation and discouraging people from starting [44] [citation needed] smoking. These policies are important strategies in the prevention of COPD. Occupational health Measures can be taken to reduce the likelihood that workers in at-risk industries such as coal mining, construction and stonemasonry will develop COPD. Some examples of these measures are: education of workers and management about the risks, promoting smoking cessation, surveillance of workers for early signs of COPD, the use of personal dust monitors, the [46] use of respirators and dust control. Dust control can be achieved by improving ventilation, [47] using water sprays and by using mining techniques that minimize dust generation. If a worker develops COPD, further lung damage can be reduced by avoiding ongoing dust exposure, for example by changing the work role. Air pollution Air quality can be improved by pollution reduction efforts which should lead to health gains for people with COPD. A person who has COPD may experience fewer symptoms if they stay [4] indoors on days when air quality is poor. Bronchodilators Bronchodilators are medicines that relax smooth muscle around the airways, increasing the calibre of the airways and improving air flow. They can reduce the symptoms of shortness of breath, wheeze and exercise limitation, resulting in an improved quality of life for people with [48] COPD. They do not slow down the rate of progression of the underlying [4] disease. Bronchodilators are usually administered with an inhaler or via a nebulizer. There are two major types of bronchodilator, 2 agonists and anticholinergics. Anticholinergics appear to be superior to 2 agonists in COPD. Anticholinergics reduce respiratory deaths while [49] 2 agonists have no effect on respiratory deaths. Each type may be either long-acting (with an effect lasting 12 hours or more) or short-acting (with a rapid onset of effect that does not last as long). 2 agonists 2 agonists stimulate 2 receptors on airway smooth muscles, causing them to relax. There are several 2 agonists available. Salbutamol (common brand name: Ventolin) andterbutaline are widely used short acting 2 agonists and provide rapid relief of COPD symptoms. Long acting 2 agonists (LABAs) such as salmeterol and formoterol are used as maintenance therapy and [50] lead to improved airflow, exercise capacity, and quality of life.

Anticholinergics Anticholinergic drugs cause airway smooth muscles to relax by blocking stimulation from cholinergic nerves. Ipratropium provides short-acting rapid relief of COPD symptoms.Tiotropium is a long-acting anticholinergic whose regular use is associated with improvements in airflow, exercise capacity, and quality of life. Ipratropium is associated with [51] increased cardiovascular morbidity. While tiotropium in pill form reduces the risk of all cause

mortality, cardiovascular mortality and cardiovascular events [53] mortality. Corticosteroids

[52]

that in mist form increases

Corticosteroids are used in tablet or inhaled form to treat and prevent acute exacerbations of COPD. Well-inhaled corticosteroids (ICS) have not been shown to be of benefit for people with mild COPD, however, they have been shown to decrease acute exacerbations in those with [54] either moderate or severe COPD. They however have no effect on overall one-year mortality [43] and are associated with increased rates of pneumonia. Other medication Theophylline is a bronchodilator and phosphodiesterase inhibitor that in high doses can reduce symptoms for some people who have COPD. More often, side effects such as nausea and [4] stimulation of the heart limit its use. The investigative phosphodiesterase-4 antagonists, roflumilast and cilomilast have completed Phase-2 clinical trials. Tumor necrosis factor antagonists such as infliximab suppress the immune system and reduce inflammation. Infliximab has been trialled in COPD but there was no evidence of benefit with the possibility of [55] harm. Supplemental oxygen Oxygen can be delivered in different forms: in large containers, in smaller containers with liquid oxygen, or with the use of a oxygen concentrator (shown here) which derives oxygen from room air. The latter two options improve mobility of people requiring long-term oxygen therapy. Supplemental oxygen can be given to people with COPD who have low oxygen levels in the body. Oxygen is provided from an oxygen cylinder or an oxygen concentrator and delivered to a person through tubing via a nasal cannula or oxygen mask. Supplemental oxygen does not greatly improve shortness of breath but can allow people with COPD and low oxygen levels to do more exercise and household activity.Long-term oxygen therapy for at least 16 hours a day can improve the quality of life and survival for people with COPD and arterial hypoxemiaor with complications of hypoxemia such as pulmonary hypertension, cor pulmonale, or [56] secondary erythrocytosis. High concentrations of supplemental oxygen can lead to the accumulation of carbon dioxide and respiratory acidosis for some people with severe COPD; lower oxygen flow rates are generally safer for these individuals. Another safety issue concerning the use of oxygen for patients with COPD is smoking, because the combination of smoking and oxygen can result in fire accidents. Nowadays oxygen is generally only given to patients who have stopped smoking. Other measures Pulmonary rehabilitation is a program of exercise, disease management and counselling [57] coordinated to benefit the individual. Pulmonary rehabilitation has been shown to improve shortness of breath and exercise capacity. It has also been shown to improve the sense of control [58] a patient has over their disease as well as their emotions. Being either underweight or overweight can affect the symptoms, degree of disability and prognosis of COPD. People with COPD who are underweight can improve their breathing muscle [4] strength by increasing their calorie intake. When combined with regular exercise or a pulmonary rehabilitation programme, this can lead to improvements in COPD symptoms. Surgery is sometimes helpful for COPD in selected cases. A bullectomy is the surgical removal of a bulla, a large air-filled space that can squash the surrounding, more normal lung. Lung volume reduction surgery is similar; parts of the lung that are particularly damaged by emphysema are removed allowing the remaining, relatively good lung to expand and work better. Lung transplantation is sometimes performed for severe COPD, particularly in younger individuals. Patients should be given annual influenza vaccinations and pneumococcal vaccinations if appropriate. Obesity, poor nutrition, depression and social isolation are looked at. Palliative care

for end of life needs is important. Morphine and benzodiazepines are used in low doses to reduce anxiety. In advanced critical illness, decisions about resuscitation are addressed. Prognosis COPD usually gradually gets worse over time and can lead to death. The rate at which it gets worse varies between individuals. The factors that predict a poorer prognosis are: Severe airflow obstruction (low FEV1) Poor exercise capacity Shortness of breath Significantly underweight or overweight Complications like respiratory failure or cor pulmonale Continued smoking Frequent acute exacerbations

Prognosis in COPD can be estimated using the Bode Index. This scoring system uses FEV1, body-mass index, 6-minute walk distance, and the modified MRC dyspnea scale to estimate outcomes in COPD.