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Chronic obstructive pulmonary disease
Classification & external resources

ICD-10	J40. - J44., J47.
ICD-9	490 - 496
OMIM	606963
DiseasesDB	2672
MedlinePlus	000091
eMedicine	med/373  emerg/99
MeSH	C08.381.495.389

Chronic obstructive pulmonary disease (COPD), also known as chronic obstructive airway disease (COAD), is a group of diseases characterized by limitation of airflow in the airway that is not fully reversible. COPD is the umbrella term for chronic bronchitis, emphysema and a range of other disorders. It is most often due to tobacco smoking^[1] but can be due to other airborne irritants such as coal dust, asbestos or solvents.

Contents 1 Signs and symptoms 2 Causes 2.1 Tobacco Addiction 2.2 Apnea 2.3 Pulmonary Hypertension 2.4 Sarcoidosis 2.5 Occupational Diseases 2.5.1 Coal 2.5.2 Asbestos 2.5.3 Solvents 2.5.4 Beryllium 2.5.5 Iron 2.5.6 Arsenic, Zinc & Cadmium 2.5.7 Cotton, Flax & Hemp Fibers 2.5.8 Silica 2.5.9 Fungi, Guano & other Organic Dusts 2.5.10 Radon 2.6 Genetics 3 Pathophysiology 3.1 Chronic Bronchitis 3.2 Emphysema 3.3 Asbestosis 3.4 Pneumoconiosis 3.5 Pulmonary Neoplasms 4 Diagnosis 5 Management 5.1 Smoking cessation 5.2 Occupational Change 5.3 Pharmacotherapy 5.3.1 Bronchodilators 5.3.1.1 β2 Agonists 5.3.1.2 M3 Muscarinic Antagonists 5.3.1.3 Cromones 5.3.1.4 Leukotriene antagonists 5.3.1.5 Xanthines 5.3.2 Corticosteriods 5.3.3 TNF Antagonists 5.3.4 Vaccination 5.3.5 Pulmonary rehabilitation 6 Prognosis 6.1 Bronchitis 6.2 Emphysema 6.3 Asbestosis 6.4 Pneumoconiosis 6.5 Pulmonary Neoplasms 7 Epidemiology 8 References

The main symptoms of COPD include dyspnea (shortness of breath) lasting for months or perhaps years, possibly accompanied by wheezing, persistent cough with sputum and rarely atelectasis .^[2] It is possible the sputum may contain blood (hemoptysis), usually due to damage of the blood vessels of the airways but this may be a sign of a pulmonary neoplasm.^[3]

COPD is particularly characterised by a ratio of forced expiratory volume over 1 second (FEV₁) to forced vital capacity (FVC) being < 0.7 and the FEV₁ < 70% of the predicted value.^[4] Other signs include a rapid breathing rate (tachypnea) and a wheezing sound heard through a stethoscope. Emphysema may be detected by the sounds produced on palpation.^[5]

Neoplasms and occupational diseases are readily detected by radiography.

The leading cause of COPD is chronic tobacco smoking. Continuous smokers have at least a 25% risk of developing COPD.^[6]

Sleep apnea is usually observed in people with central nervous system dysfunction, such as following a stroke or in those with neuromuscular diseases like amyotrophic lateral sclerosis (ALS). It is also common in people with heart failure and other forms of heart and lung disease. The risk of apnea increases with obesity.

The popular diet combination of dexfenfluramine (Redux), phentermine and fenfluramine (Pondimin) called fen-phen were found to cause pulmonary hypertension in approximately 33% of users and is extremely difficult to distinguish from primary pulmonary hypertension (PPH).^[7]

No direct cause of sarcoidosis has been identified, although there have been reports of cell wall deficient bacteria that may be possible pathogens. These bacteria are not identified in standard laboratory analysis. It has been thought that there may be a hereditary factor because some families have multiple members with sarcoidosis.^[8]

Occupationally exposed workers to hazardous materials frequently develop lung disease(s).

Ocupationally exposed coal workers often develop Pneumoconiosis, commonly referred to as black lung.^[9].^[10]

Occupational exposure to asbestos can lead to asbestosis. Grunerite and Crocidolite asbestos varieties are particularly carcinogenic. Low levels of asbestos is in the air we breathe and some of the water we drink, including water from natural sources.^[11] Studies have shown that members of the general (nonoccupationally exposed) population have tens of thousands to hundreds of thousands of asbestos fibers in each gram of dry lung tissue, which translates into millions of fibers and tens of thousands of asbestos bodies in every person's lungs.^[12]. Asbestosis can lead to mesothelioma^[13] in which neoplasms in the mesothelium or peritoneum. There is no link between mesothelioma and smoking.^[14]. In the early 1950s the Kent brand of cigarettes used asbestos in the filter resulting in a few cases of mesothelioma.

Workers in the chemical industry often develop COPD-like symptoms. Often certain chemicals were also found to be mutagenic and teratogenic making them especially hazardous. Inhaled solvent addicts are at risk for developing dypsnea and possible neoplasms. Many aromatic hydrocarbons are mutagenic.^[15]

Aerospace workers are often exposed to various metals such as beryllium which can cause COPD-like symptoms. Berylliosis is a pulmonary and systemic granulomatous disease caused by exposure to beryllium.^[16]

Siderosis is the deposition of iron oxides in lung tissue. Effects are similar to asbestosis.

Environmental or occupational exposure to arsenic, zinc or cadmium dust or vapors can cause pulmanary disease.^[17]

Occupational exposure to dusts from hemp, flax, and cotton processing can cause Byssinosis.^[18]

Occupational exposure to free crystalline silica in mines, foundries, blasting operations, stone, clay and glass manufacturing can cause silicosis.^[19]

Repeated exposure to fungus spores from moldy hay, guano or other organic dusts that causes the aveoli inflammation leading to fibrosis.^[20]

Radon gas exposure is second after cigarettes as the leading cause of lung cancer([1]). In the US, the EPA estimates that one in 15 homes has radon levels above the recommended guideline of 4 pCi/L (150 Bq/^m3)([2]).

Rarely, there may be a deficiency in an enzyme known as alpha 1-antitrypsin deficiency.^[21] Also there may be a heterozygous deficency in causing mild Cystic Fibrosis that may present as COPD.

Chronic bronchitis is defined in clinical terms as a cough with sputum production on most days for 3 months of a year, for 2 consecutive years.^[22]

Chronic bronchitis is hallmarked by 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. Microscopically there is infiltration of the airway walls with inflammatory cells, particularly neutrophils. Inflammation is followed by scarring and remodelling that thickens the walls resulting in narrowing of the small airway. Further progression leads to metaplasia (abnormal change in the tissue) and fibrosis (further thickening and scarring) of the lower airway. The consequence of these changes is a limitation of airflow.^[23].

Main article: Emphysema

Emphysema is defined histologically as the enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls.^[22]

The enlarged air sacs (alveoli) of the lungs reduces the surface area available for the movement of gases during respiration. This ultimately leads to dyspnea in severe cases. The exact mechanism for the development of emphysema is not understood, although it is known to be linked with smoking and age. Loss of elasticity and recoil capacity of the alveoli (compliance)

Asbestosis is defined histologically by the presence of asbestos fibers contaminating the aveoli. Asbestos fibers have been found to penetrate to the cell nucleus of macrophages leading to a strong mutagenic potential. Fibers have been found to bind to DNA.

Pneumoconiosis is histologically defined as pneumological parenchyma characterized by macules, micronodules, macronodules, or progressive massive fibrosis.

Pulmonary neoplasms occur in approximately 10% of smokers (see cigarette smoking). Malignant mesothelioma is usually specialized from other pulmonary neoplasms (see Lung Cancer)

The diagnosis of COPD is usually suggested by symptoms; it is a clinical diagnosis and no single test is definitive. A comprehensive history from the patient is very important with regard to smoking and occupation. Physical examination with a plethysmograph can reveal the true extent of COPD. Radiography and biopsies are vital to an accurate diagnosis.

The severity of COPD can be classified as follows:

Severity	Post-bronchodilator FEV1/FVC	FEV1 % predicted
At risk	>0.7	≥80
Mild COPD	≤0.7	≥80
Moderate COPD	≤0.7	50-80
Severe COPD	≤0.7	30-50
Very Severe COPD	≤0.7	<30

X-ray results may prompt an oncological referral for smokers and occupationally exposed asbestos and coal workers.

Patients exposed to Radon usually present with dypsnea, hemoptysis or chest pain. Metastasis is common by the time symptoms are clinically apparent.^[24].

Pneumoconiosis may be in the form of an industrial bronchitis, a condition which abates 3 to 6 months following the ceasation of exposure, or permanent changes in the lung parenchyma. Radiological assesment can confirm diagnosis.^[25].

When the exact etiology is unknown, bronchitis becomes a catch-all diagnosis. Wheezing is a symptom common to both asthma and bronchitis. A chronic cough is a symptom shared by bronchitis, asthma, rhinitus and gastroesophageal reflux disease (GERD). Hemoptysis can be due to bronchitis or pneumonia most commonly, but also to pulmanary neoplasm (in smokers, when hemoptysis is persistent), aspergilloma, tuberculosis, bronchiectasis, coccidioidomycosis, pulmonary embolism, or pneumonic plague.^[26][27]

Although COPD is not curable, it can be controlled in a variety of ways.

Main article: Smoking cessation

Smoking cessation is one of the most important factors in slowing down the progression of COPD. Even at a late stage of the disease it can reduce the rate of deterioration and prolong the time taken for disability and death.^[23]

Workers may be able to transfer to a significantly less contaminated area of the company depending on circumstances. Often however, workers may need complete occupational change.

There are several types of bronchodilators used clinically with varying efficacy: β₂ agonists, M₃ antimuscarinics, leukotriene antagonists, cromones and xanthines.^[28] These drugs relax the smooth muscles of the airway allowing for improved airflow. The change in FEV₁ may not be substantial, but changes in the vital capacity are significant. Many patients feel less breathless after taking bronchodilators.

There are several highly specific β₂ agonists available. Salbutamol (Ventolin) is the most widely used short acting β₂ agonist to provide rapid relief and should be prescribed as a front line therapy for all classes of patients. Other β₂ agonists are Bambuterol, Clenbuterol, Fenoterol, and Formoterol. Longer acting β₂ agonists such as Salmeterol act too slowly to be used as relief for dypsnea so these drugs should be used as a secondary therapy. An increased risk is associated with long acting β₂ agonists due to decreased sensitivity to inflammation so generally the use of a concomitant corticosteroid is indicated[3][4][5].

Derived from the deadly agaric Amanita muscaria, specific antimuscarinics were found to provide effective relief to COPD. Inhaled antimuscarinics have the advantage of avoiding endocrine and exocrine M₃ receptors. The quaternary M₃ muscarinic antagonist Ipratropium is widely prescribed with the β₂ agonist salbutamol. [6]. Ipratropium is offered combined with salbutamol (Combivent) and with fenoterol (Duovent). Tiotropium provides improved specificity for M₃ muscarinic receptors.

Cromones are mast cell stabilizers that are thought to act on a chloride channel found on mast cells that help reduce the production of histamine and other inflammatory factors. Chromones are also thought to act on IgE-regulated calcium channels on mast cells. Cromoglicate and Nedocromil, which has a longer half-life, are two chromones available.^[29]

More recently leukotriene antagonists block the signalling molecules used by the immune system. Montelukast, Pranlukast, Zafirlukast are some of the leukotrienes antagonists.^[30]

Theophylline is the prototype of the xanthine^[31] class of drug. Teas are natural sources of methylxanthines, xanthines and caffeine while chocholate is a source of theobromine. Caffeine is approximately 16% metabolized into theophylline. Nebulized theophylline is used in the EMR for treatment of dyspnea (Difficulty in breathing). Patients need continual monitoring as theophylline has a narrow therapeutic range. More aggressive EMR interventions include IV H₁ antihistamines and IV dexamethasone.

Inhaled corticosteriods (specifically glucocorticoids) act in the inflammatory cascade and may improve airway function considerably,^[23] however the long term value has not been proven. Corticosteroids are often combined with bronchodilators in a single inhaler. Beclomethasone, mometasone and fluticasone are some of the more common inhaled steroids in use.

Salmeterol and fluticasone are combined (Advair) however the reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance.^[32][33]

Tumor necrosis factor antagonists (TNF) are the most recent class of medications designed to deal with refractory cases. Tumor necrosis factor-alpha is a cachexin or cachectin and is considered a so-called biological drug. They are considerered immunosopressive with attendant risks. These rather expensive drugs include infliximab, adalimumab and etanercept.^[34]

Patients with COPD should be routinely vaccinated against influenza, pneumococcus and other diseases to prevent illness and the possibility of death.^[28]

Pulmonary rehabilitation is a program of disease management, counseling and exercise coordinated to benefit the individual.^[35] Pulmonary rehabilitation has been shown to relieve difficulties breathing and fatigue. It has also been shown to improve the sense of control a patient has over their disease as well as their emotions.^[36]

A good prognosis of COPD relies on an early diagnosis and prompt treatment. Most patients will have improvement in lung function once treatment is started, however eventually signs and symptoms will worsen as COPD progresses. The median survival is about 10 years if two-thirds of expected lung function was lost by diagnosis.^[37]

Acute bronchitis usually resolves in 7-10 days with no underlying lung disease. Chronic bronchitis however is dependent on early recognition and smoking cessation which improves the outcome significantly.

The outcome is better for patients with less damage to the lung who stop smoking immediately. Still, patients with extensive lung damage may live for many years so predicting prognosis is difficult. Death may occur from respiratory failure, pneumonia, or other complications.

The outcome is clouded by the many complications associated with asbestosis. Malignant mesothelioma is refractory to management affording patients with 6-12 months of life expectancy upon clinical presentation.

The outcome is good for patients with minimal damage to the lung. However, patients with extensive lung damage may live for many years so predicting prognosis is difficult. Death may occur from respiratory failure, pneumonia, cor pulmonale or other complications.

The stage of the tumor(s) has a major impact on neoplasm prognosis. Staging is the process of determining tumor size, growth rate, potential metastasis, lymph node involvement, treatment options and prognosis. Two-year prognosis for limited small cell pulmonary neoplasms is twenty percent and for extensive disease five percent. The average life expectancy for someone with recurrent small cell pulmonary neoplasms is two to three months.[7]

The 5-year overall survival rate for pulmonary neoplasms is 14%.^[38]

According to the World Health Organization (WHO), 80 million people suffer from moderate to severe COPD and 3 million died due to it in 2005. The WHO predicts that by 2030, it will be the 4th largest cause of mortality worldwide.^[39]

Since COPD is not diagnosed until it becomes clinically apparent, prevalence and mortality data greatly underestimate the socio-economic burden of COPD.^[28] In the UK, COPD accounts for about 7% of all days of sickness related absence from work.^[23]

Smoking rates in the industrialized world have continued to fall causing rates of emphysema and pulmonary neoplasms to slowly decline.

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