Chronic obstructive pulmonary disease overview

# Overview
Chronic obstructive pulmonary disease is characterized by the pathological limitation of airflow in the airway that is not fully reversible . COPD is the umbrella term for chronic bronchitis, emphysema which could be differentiated according to pathologic findings. Airflow limitation may lead to shortness of breath (dyspnea), cough, wheezing, and finally respiratory failure. In clinical practice, COPD is defined by its characteristically low airflow on lung function tests. In contrast to asthma, this limitation is poorly reversible and usually gets progressively worse over time. Hallmark pathologic features of chronic bronchitis include: hyperplasia (increased number) and hypertrophy (increased size) of the goblet cells (mucous gland) of the airway, resulting in an increase in secretion of mucus, which contributes to the airway obstruction. Emphysema is determined by destruction of pulmonary acinus. Acinus is the structures distal to the terminal bronchiole, consisting of the respiratory bronchiole, alveolar ducts, alveolar sacs, and alveoli. COPD is mostly due to tobacco smoking; but can be due to other airborne irritants such as coal dust, asbestos or solvents, congenital conditions such as alpha-1-antitrypsin deficiency and as well as preserved meats containing nitrites. Diagnosis of COPD is based on spirometry findings in appropriate clinical setting. Smoking cessation is the main stay in the treatment. Bronchodilators and anticholinergic inhalers are the main pharmacologic therapy in COPD patients. Pulmonary rehabilitation and sometimes lung volume reduction surgery are required in specific circumstances.

# Historical Perspective
For the first time, in 1679, Bonet described a condition of  voluminous lungs. Matthew Baillie illustrated an emphysematous lung in 1789 and described the destructive character of the condition. In 1808, bronchitis was first described by Charles Badham in England. The terms chronic bronchitis and emphysema were formally defined at the CIBA guest symposium of physicians in 1959. COPD has probably always existed but has been called by different names in the past. The term COPD was first used by William Briscoe in 1965 and has gradually overtaken other terms to become established today as the preferred name for this disease.

# Classification
COPD may be classified based on pathology, into two types: chronic bronchitis, emphysema. Emphysema may be classified further in to four sub-types such as panacinary, centroacinary, congenital lobar emphysema and paraseptal.

# Pathophysiology
Pathologic changes in chronic obstructive pulmonary disease (COPD) occur in the large (central) airways, the bronchioles, and the lung parenchyma. Increased numbers of activated polymorphonuclear leukocytes and macrophages release elastases, proteinase-3 and macrophage-derived matrix metalloproteinases (MMPs), cysteine proteinases, and a plasminogen activator resulting in lung destruction. The antiprotease in the body cannot counteract effectively these elastases. Additionally, increased oxidative stress caused by free radicals in cigarette smoke, phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis. In addition to macrophages, T lymphocytes, particularly CD8+, play an important role in the pathogenesis of smoking-induced airflow limitation.

# Causes
Chronic obstructive pulmonary disease (COPD), is most often due to tobacco smoking; but can be due to other airborne irritants such as coal dust, asbestos or solvents, congenital conditions such as alpha-1-antitrypsin deficiency and as well as preserved meats containing nitrites. In the United States, tobacco use is a key factor in the development and progression of COPD, exposure to air pollutants in the home and workplace, genetic factors, and respiratory infections also play a role. In developing countries, indoor air quality is thought to play a larger role in the development and progression of COPD than it does in the United States.

# Differentiating Chronic Obstructive Pulmonary Disease from other Diseases
COPD should be differentiated from other diseases presenting with chronic cough, shortness of breath and tachypnea, such as congestive heart failure, chronic asthma, bronchiectasis, and bronchiolitis obliterans.

# Epidemiology and Demographics
The Global Burden of Disease Study  reports a prevalence of 251 million cases of COPD globally in 2016. According to WHO estimates, 65 million people have moderate to severe chronic obstructive pulmonary disease (COPD) worldwide. COPD occurs in 34 out of 1000 greater than 65 years old. In England, an estimated 842,100 of 50 million people have a diagnosis of COPD; translating into approximately one person in 59 receiving a diagnosis of COPD at some point in their lives. In the most socioeconomically deprived parts of the country, one in 32 people were diagnosed with COPD, compared with one in 98 in the most affluent areas. In the United States, the age adjusted prevalence of COPD is approximately 6.4%, totalling approximately 15.7 million people in USA, or possibly approximately 25 million people if undiagnosed cases are included. COPD is the third cause of death among adult population in the United States.

# Risk Factors
Common risk factors in the development of COPD, are cigarette smoking, occupational pollutants, air pollution and genetics. Other risk factors are increasing age, male gender, allergy and repeated airway infection.

# Natural History, Complications and Prognosis
COPD is a slowly progressive disease that may 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 corpulmonale, 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. There is no cure for COPD. However, COPD can be managed and disease progression can be mitigated. Prognosis depends largely on the timing of diagnosis. Its complications include, recurrent pneumonia, cor pulmonale, anemia, depression, and even respiratory failure.

# Diagnosis
The diagnosis of COPD requires lung function tests.

## History and Symptoms
Chronic obstructive pulmonary disease is a group of diseases that can present with symptoms such as shortness of breath, wheezing, persistent cough and sputum production. Some clinical differences can help distinguish between the types of COPD. While chronic bronchitis patient present with productive cough with gradual progression to intermittent shortness of breath; recurrent pulmonary infections; and in later stage progressive cardiac/respiratory failure presenting with edema and weight gain. Classic findings for patients with emphysema include a long history of progressive shortness of breath with late onset of nonproductive cough; usually mucopurulent; and eventual decrease in appetite and respiratory failure.

## Physical Examination
Chronic obstructive pulmonary disease can be diagnostically evaluated by physical examination through auscultation. Physical examination are quite specific and sensitive for severe disease. The signs are usually difficult to detect in cases of mild to moderate diseases. Findings on general physical examination can be cyanosis, tachypnea, use of accessory respiratory muscles, paradoxical indrawing of lower intercostal spaces is evident (known as the Hoover sign), elevated jugular venous pulse and peripheral edema. Pulmonary examination in can be barrel chest (emphysema), wheezing, hyperresonance, crackles and rhonchi

## Laboratory Findings
Chronic obstructive pulmonary disease has irreversible airflow limitation specially during forced expiration. This is due to the destruction of lung tissue and increase in resistance to flow in the conducting airways. Thus, it doesn't show an improvement in FEV1 post bronchodilator administration (unlike asthma). This characteristic feature is used as an diagnostic criteria for COPD, i.e. a COPD is diagnosed by spirometry if FEV1/FVC < 70% for a matched control. Arterial blood gas may show hypoxemia with or without hypercapnia depending on the disease severity. pH may be normal due to renal compensation. A pH less than 7.3 usually indicate severe respiratory compromise. 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.

## Electrocardiogram
Electrocardiogram can be used in establishing that hypoxia is due to underlying respiratory cause and not cardiac.

## Chest X Ray
On chest x-ray, the classic signs of COPD are overexpanded lung (hyperinflation), a flattened diaphragm, increased retrosternal airspace, and bullae. It can be useful to help exclude other lung diseases, such as pneumonia, pulmonary edema or a pneumothorax.

## CT
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.

## Echocardiography
Echocardiography helps in a diagnosis of pulmoanry hypertension in the patients with COPD.

## Other Diagnostic Studies
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. Six minute walk tests act as an predictor of mortality in patients with moderate COPD (patients who desaturate have worse mortality compared with those who don't desaturate.)

# Treatment
Important management strategies are smoking cessation, vaccinations, rehabilitation, and drug therapy (often using inhalers). Some patients go on to require long-term oxygen therapy or lung transplantation.

## Medical Therapy
Treatment of COPD requires a careful and thorough evaluation by a physician. The most important aspect of treatment is avoiding tobacco smoke and removing other air pollutants from the patients home or workplace. Symptoms such as coughing or wheezing can be treated with bronchodilator medications like Beta 2 receptor agonist, anticholinergic drugs. The drugs used cause benefit via relaxation of smooth muscle or decreasing inflammatory factors.
. Respiratory infections should be treated with antibiotics, if appropriate. Patients who have low blood oxygen levels in their blood are often given supplemental oxygen. Currently, no treatment has been found to be totally curative against COPD except lung transplant. The treatments aim to improve lung function and quality of life. The initial treatment can be done either with Beta 2 agonist or anticholinergic. Both anticholinergics or Beta adrenergic receptor agonists have proved to be equally beneficial  but the combination of the two has shown synergistic effects. Long acting bronchodilators are more beneficial than short-acting ones , .

## Surgery
Patients with emphysema may have big bullae ranging from 1-4 cm and may occupy third of lung space. These bullae can cause compromise to ventilation and perfusion. Bullectomy is the surgical removal of these bullae. It is commonly done in patients with FEV1 < 50% of predicted and who are symptomatic. Bullectomy helps in re-expansion of the lung tissue. Lung reduction surgery may be an option for patients with severe symptoms that are not responding to maximal medical therapy.

## Primary Prevention
Smoking cessation, control of air pollutants and decrease job exposure to dusts or fumes are the main preventive measures for chronic obstructive pulmonary disease.

## Secondary Prevention
To decrease the number and rate of COPD deaths, public health programs should continue efforts to reduce all personal exposure to 1) tobacco smoke, including passive smoke exposure; 2) occupational dusts and chemicals; and 3) other indoor and outdoor air pollutants linked to COPD. Once COPD is diagnosed, chronic disease management programs should work to prevent further deterioration in lung function and reduce COPD mortality.