Chronic Obstructive Pulmonary

Disease

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-----------------Chronic obstructive pulmonary disease (COPD), also known as

chronic obstructive airway disease (COAD), is a group of

diseases characterized by the pathological 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 lung

disorders. It is most often due to tobacco smoking, but can be

due to other airborne irritants such as coal dust, asbestos or

solvents, as well as congenital conditions such as alpha-1-antitrypsin deficiency.

Signs and symptomsThe main symptoms of COPD include dyspnea (shortness of breath) lasting for

months or perhaps years, possibly accompanied by wheezing, and a persistent

cough with sputum production.It

is possible the sputum may

contain blood and become thicker

(hemoptysis), 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.

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 < 70% of the predicted value 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.

Causes

Cigarette smoking :

A primary risk factor of COPD is chronic tobacco

smoking. In the United States, around 90% of cases

of COPD are due to smoking .Not all smokers will

develop COPD, but continuous smokers have at

least a 25% risk.

Occupational pollutants :

Some occupational pollutants, such as cadmium and silica, have shown to be

a contributing risk factor for COPD. The people at highest risk for these

pollutants include coal workers.

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.

Genetics :

Very rarely, there may be a deficiency in an enzyme known as alpha 1-

antitrypsin which causes a form of COPD.

Other risk factors :

Increasing age, male gender, allergy, repeated airway infection and general

impaired lung function are also related to the development of COPD.

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.

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.

Emphysema :

Emphysema is defined histologically as the enlargement of the air spaces

distal to the terminal bronchioles, with destruction of their walls.

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.

DiagnosisThe 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 spirograph

can reveal the loss of lung function.

The severity of COPD can be classified as follows using post-bronchodilator

spirometry :

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 or 30-50 with Chronic

Respiratory Failure symptoms

Physical examination :

A systematic review by the Rational Clinical Examination concluded that no

single medical sign or symptom can adequately exclude the diagnosis of

COPD.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.

ManagementAlthough 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.

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.

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 :

1. Bronchodilators :

There are several types of bronchodilators used clinically with varying

efficacy: β2 agonists, M3 antimuscarinics, leukotriene antagonists,

cromones and xanthines.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.

2. 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 .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. M3 muscarinic antagonists (anticholinergics) :

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. . Ipratropium is offered

combined with salbutamol (Combivent) and with fenoterol (Duovent).

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.

4. 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.

5. Leukotriene antagonists :

More recently leukotriene antagonists block the signalling molecules

used by the immune system. Montelukast, Pranlukast, Zafirlukast are

some of the leukotrienes antagonists.

6. Xanthines :

Theophylline is the prototype of the xanthine class of drug. Teas are

natural sources of methylxanthines, xanthines and caffeine while

chocolate 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.

Theophylline works by inhibiting phosphodiesterase, and small

reductions in COPD exacerbation rates have been shown with this

medication. There are two new PD-4 inhibitors, roflumilast and cilomilast

which have been shown in separate trials to reduce COPD exacerbations,

though more studies are needed.

7. Corticosteroids :

Enteral and parenteral corticosteroid therapy has long been the

mainstay of treament of COPD, and is known to reduce hospital length of

stay. Similarly, inhaled corticosteriods (specifically glucocorticoids) act in

the inflammatory cascade and improve airway function considerably,

and have been shown in the ISOLDE trial to reduce the number of COPD

exacerbations by 25%. 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.

8. 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 considerered immunosopressive with attendant

risks. These rather expensive drugs include infliximab, adalimumab and

etanercept.

9. 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.

10. Vaccination :

Patients with COPD should be routinely vaccinated against influenza,

pneumococcus and other diseases to prevent illness and the possibility

of death.

11. Pulmonary rehabilitation :

Pulmonary rehabilitation is a program of disease management,

counseling and exercise coordinated to benefit the individual. 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.

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".

PrognosisA 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.

Bronchitis :

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.

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.

Asbestosis :

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.

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.

The 5-year overall survival rate for pulmonary neoplasms is 14%.

References

http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_SignsAndSymptoms.html

http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page4.htm

http://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_disease

http://www.medicinenet.com/chronic_obstructive_pulmonary_disease_copd/page3.htm7whatcauses

http://www.patient.co.uk/showdoc/40002357/

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=4166895&dopt=Abstract

http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_Treatments.html

http://www.who.int/respiratory/copd/en/

Created By:

Ahmed Hasan El-banna Sa’d

Ahmed Hamed Abd El-Fattah

Ahmed Gameel El-Beshbeeshy

Ahmed Gamal Abd El-Mon’em