COPD
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Chronic Obstructive Pulmonary Disease (COPD), also known as chronic obstructive airway diseases (COAD), is a group of diseases characterized by the pathological limitation of airflow in the airway that is not fully reversible. It refers to an obstruction of airflow, which results in air becoming trapped in the lungs. COPD is the umbrella term for chronic bronchitis, emphysema and a range of other lung disorders. It is most often due to tobacco smoking,^[1] but can be due to other airborne irritants such as solvents, as well as congenital conditions such as alpha-1-antitrypsin deficiency. It is the 4th leading cause of death in the U.S.^[2]

Signs and symptoms

The main symptoms of COPD are dyspnea (shortness of breath) lasting for months or perhaps years, possibly accompanied by wheezing, and a persistent cough with sputum production.^[3] It is possible the sputum may contain blood (hemoptysis) and become thicker, usually due to damage of the blood vessels of the airways. Severe COPD could lead to cyanosis (bluish decolorization usually in the lips and fingers) caused by a lack of oxygen in the blood. In extreme cases it could lead to cor pulmonale due to the extra work required by the heart to get blood to flow through the lungs.^[4]

COPD is particularly characterised by the spirometric measurement of a ratio of forced expiratory volume over 1 second (FEV₁) to forced vital capacity (FVC) being < 0.7 and the FEV₁ < 80% of the predicted value ^[5] as measured by a plethysmograph. Other signs include a rapid breathing rate (tachypnea) and a wheezing sound heard through a stethoscope. Pulmonary emphysema is not the same as subcutaneous emphysema, which is a collection of air under the skin that may be detected by the crepitus sounds produced on palpation.^[6]

• Shortness of breath (dyspnea) persisting for months to years
• Wheezing
• Decreased exercise tolerance
• Cough with or without phlegm^[7]

Etiology

Cigarette smoking

A primary risk factor of COPD is chronic tobacco smoking. In the United States, around 80 to 90% of cases of COPD are due to smoking.^[8] Not all smokers will develop COPD, but continuous smokers have at least a 25% risk, after 25 years.^[9]

Occupational pollutants

Some occupational pollutants, such as cadmium and silica, have shown to be a contributing risk factor for COPD. Coal workers who smoke have increased risk for concomitmant pneumoconiosis and emphysema. Asbestos workers who smoke are at increased risk for concomitant emphysema, asbestosis and mesothelioma.

Air pollution

Urban air pollution may be a contributing factor for COPD as it is thought to impair the development of the lung function. In developing countries indoor air pollution, usually due to biomass fuel, has been linked to COPD, especially in women.^[1]

Genetics

Very rarely, there may be a deficiency in a trypsin antagonist known as alpha 1-antitrypsin which causes a form of COPD.^[10]

Other risk factors

Increasing age, male gender, allergy, repeated airway infection and general impaired function are also related to the development of COPD.

COPD as an autoimmune disease

Main article: Autoimmunity

There is mounting evidence that there may be an autoimmune component in individuals with COPD. This is evidenced by the presence of autoreactive T-cells and autoantibodies found in patients. In addition, many individuals who have stopped smoking continue to have chronic inflammation and decline in lung function. ^[11][12][13]

Pathophysiology

Chronic bronchitis

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.^[14]

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 remodeling 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.^[15]

Emphysema

Main article: Emphysema

Emphysema is defined histologically as the enlargement of the air spaces distal to the terminal bronchioles, with destruction of their walls.^[14]

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.(D.A.ASIR JOHN SAMUEL M.D)

Diagnosis

The diagnosis of COPD is suggested by symptoms; it is a clinical diagnosis and no single test is definitive. A history is taken of smoking and occupation, and a physical examination is done. Measurement of lung function with a spirometer can reveal the loss of lung function.

The severity of COPD can be classified as follows using post-bronchodilator spirometry (see above)^[16]:

Exams and Tests

An examination often reveals increased work involved in breathing: nasal flaring may be evident during air intake, and the lips may be pursed (the shape lips make when you whistle) while exhaling.

During a flare of disease, chest inspection reveals contraction of the muscles between the ribs during inhalation (intercostal retraction) and the use of accessory breathing muscles. The respiratory rate (amount of breaths per minute) may be elevated, and wheezing may be heard through a stethoscope.

A chest X-ray can show an over-expanded lung (hyperinflation) and a flattened diaphragm while a chest CT scan may show emphysema.

A sample of blood taken from an artery (arterial blood gas) can show low levels of oxygen (hypoxemia) and high levels of carbon dioxide (respiratory acidosis). Pulmonary function tests show decreased airflow rates while exhaling and over-expanded lungs. ^[17]

Physical examination

A systematic review has concluded that no single medical sign or symptom can adequately exclude the diagnosis of COPD.^[18] One study found that the presence of either "a history of smoking more than 30 pack-years, diminished breath sounds, or peak flow less than 350 L/min" has a sensitivity of 98 percent.^[19]

Management

Although COPD is not curable, it can be controlled in a variety of ways. Clinical practice guidelines by Global Initiative for Chronic Obstructive Lung Disease (GOLD), a collaboration including the American National Heart, Lung, and Blood Institute and the World Health Organization, are available.^[16]

Smoking cessation

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.^[15]

Occupational change

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.

Pharmacotherapy

Bronchodilators

There are several types of bronchodilators used clinically with varying efficacy: β₂ agonists, M₃ antimuscarinics, leukotriene antagonists, cromones and xanthines.^[20] 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.

β₂ agonists

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. Long acting β₂ agonists (LABAs) such as Salmeterol act too slowly to be used as relief for dypsnea so these drugs should be used as maintenance therapy in the appropriate patient population. The TORCH study showed that LABA therapy reduced COPD exacerbation frequency over a 3 year period, compared to placebo.^[21] 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[2][3][4].

M₃ muscarinic antagonists (anticholinergics)

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. [5]. Ipratropium formerly was offered combined with salbutamol (Combivent) and with fenoterol (Duovent) but due to the CFC propellant, these products have been withdrawn.

Tiotropium provides improved specificity for M₃ muscarinic receptors. It is a long acting muscarinic antagonist that has shown good efficacy in the reduction of exacerbations of COPD, especially when combined with a LABA and inhaled steroid.^[22]

Cromones

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.^[23]

Leukotriene antagonists

More recently leukotriene antagonists block the signalling molecules used by the immune system. Montelukast, Pranlukast, Zafirlukast are some of the leukotrienes antagonists.^[24]These agents have not been tested in good, controlled trials, ^[25] and as such, there is no data to support the use of these agents in COPD.^[26]

Xanthines

Theophylline is the prototype of the xanthine class of drug. Teas are natural sources of methylxanthines, xanthines and caffeine while cocoa is a natural 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 IM dexamethasone.

Theophylline antagonizes phosphodiesterase, and small reductions in COPD exacerbation rates have been demonstrated.^[27] The investigative phosphodiesterase-4 antagonists, roflumilast and cilomilast have completed Phase-2 clinical trials.

Corticosteroids

Enteral and parenteral corticosteroid therapy has long been the mainstay of treatment of COPD, and is known to reduce length of stay in hospital. Similarly, inhaled corticosteroids (specifically glucocorticoids) act in the inflammatory cascade and improve airway function considerably,^[15] and have been shown in the ISOLDE trial to reduce the number of COPD exacerbations by 25%.^[28] Corticosteroids are often combined with bronchodilators in a single inhaler. Some of the more common inhaled steroids in use are beclomethasone, mometasone, and fluticasone.

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.^[29][30]

TNF antagonists

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 considered immunosopressive with attendant risks. These rather expensive drugs include infliximab, adalimumab and etanercept.^[31]Infliximab has been trialled in COPD with no evidence of benefit, with the possibility of harm. This was a relatively small study (77-79 patients in each arm).^[32]

Supplemental Oxygen

In general, long-term administration of oxygen is usually reserved for individuals with COPD who have arterial hypoxemia (PaO2 less than 55 mm Hg), or a PaO2 between 55 and 60 mm Hg with evidence of pulmonary hypertension, cor pulmonale, or secondary erythrocytosis (hematocrit >55%). In these patients, continuous home oxygen therapy (for >15 h/d) sufficient to correct hypoxemia has been shown to improve survival. ^[33] The use of low flow oxygen may be necessary in some patients because in the COPD patient, control of respiration is driven mainly by the blood oxygen level rather than the carbon dioxide level, increased oxygen delivery can diminish this response and cause respiratory failure. The American Thoracic Society Guidelines on COPD cover the use of oxygen therapy and its risks.^[34]

Vaccination

Patients with COPD should be routinely vaccinated against influenza, pneumococcus and other diseases to prevent illness and the possibility of death.^[20]

Pulmonary rehabilitation

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]

Diet

A recent French study conducted over 12 years with almost 43,000 men concluded that eating a Mediterranean diet "halves the risk of serious lung disease like emphysema and bronchitis". [6]

Treatment

Treatment for COPD includes inhalers that dilate the airways (bronchodilators) and sometimes theophylline. The COPD patient must stop smoking. In some cases inhaled steroids are used to suppress lung inflammation, and, in severe cases or flare-ups, intravenous or oral steroids are given.

Antibiotics are used during flare-ups of symptoms as infections can worsen COPD. Chronic, low-flow oxygen, non-invasive ventilation, or intubation may be needed in some cases. Surgery to remove parts of the disease lung has been shown to be helpful for some patients with COPD.^{citation needed}

Lung rehabilitation programs may help some patients.

Lung transplant is sometimes performed for severe cases.

Support Groups

The stress of illness can often be helped by joining a support group where members share common experiences and problems. ^[37]

Prognosis

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.

"End Stages" of COPD are diagnosed as the normal ratio of carbon dioxide being inordinately higher than the volume of oxygen in the bloodstream. Although end stage COPD may mean death is imminent in cases dealing with degenerative diseases, forced oxygen therapy and other treatments may successfully be used to prolong life but have not been proven to be successful for the long run. These types of therapy may be successfully used in COPD cases caused by curable diseases such as bronchitis.

Bronchitis

Acute bronchitis usually resolves in 2-10 years.

Emphysema

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.

Pneumoconiosis

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.

Pulmonary neoplasms

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]

Epidemiology

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 socioeconomic burden of COPD.^[20] In the UK, COPD accounts for about 7% of all days of sickness related absence from work.^[15]

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

References

External links

• National Heart, Lung and Blood Institute - COPD U.S. NHLBI Information for Patients and the Public page.
• Guidelines for Diagnosis And Treatment Of Stable COPD^{dead link}
• Chronic Respiratory Disease - leading research and articles on respiratory disease
• Global Initiative for Chronic Obstructive Lung Disease (GOLD)