There was a time when chronic obstructive pulmonary disease (COPD) was a relatively unknown term. Today, its prevalence is on the rise and deaths due to COPD are increasing in alarming numbers worldwide. It is expected to be the third leading cause of death by the year 2020.One Indian study has reported that nearly 12 million Indians are affected by COPD, above the age of 30, with a prevalence rate of five percent among males and three percent in women. 1 All available data indicate that COPD is often under-diagnosed, detected very late and/or misdiagnosed as asthma.

 

 

COPD is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. It is important to note two key aspects:

• COPD is not fully reversible. This suggests the presence of reversible components.

• COPD is progressive. Therefore, early diagnosis and treatment are important.

 

 

A diagnosis of COPD is usually made on ‘exclusion of asthma'
(Table 1: Difference between COPD and asthma). It is necessary to differentiate between COPD and asthma because the two diseases differ:

1. In their aetiology

2. With respect to inflammatory cells, mediators and inflammatory consequences

3. In affected sites in the lungs

4. In their response to different treatments

5. In their prognosis

COPD should be considered in any individual who presents with characteristic symptoms and history of exposure to a risk factor of the disease (especially smoking). (Table 2)

The diagnosis of COPD can be confirmed with the help of spirometry (if available).

The differences between COPD and asthma have an important bearing on treatment.

Asthma: Backbone of treatment inhaled corticosteroid.

COPD: Backbone of treatment inhaled bronchodilators.

 

 

Management of COPD is largely symptom-driven and aims to improve the patient's quality of life. An effective COPD management plan includes four components:

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

4. Manage exacerbations

 

While disease prevention is the ultimate goal, once COPD has been diagnosed, effective management should aim at:

• Best control of symptoms

• Improve patient ability to undertake activities of daily living.

• Decrease in exacerbations and hospitalisations

• Improvement in quality of life

• Decrease in accelerated decline in lung function

It is also important to ensure that the patients have optimal support and education to help them cope with their disease.

 

The GOLD guidelines offer a valuable framework for COPD management. Figure 1 depicts a step-wise approach to COPD treatment. Bronchodilators are required in all stages of treatment, as and when needed (in very early stages) or regularly (as the disease progresses).

Fig. 1:
COPD treatment according to GOLD Guidelines

 

Since the treatment of COPD is mainly symptomatic, bronchodilators form the cornerstone of management.

 

 

Bronchodilators reverse the increased bronchomotor tone associated with COPD patients. These drugs relax the smooth muscles and reduce airway resistance (Figure 2).

As hyperinflation goes down, it becomes easier for the patient to breathe. Breathlessness and the effort required to breathe go down so that the patient can walk longer.

 

 

As in asthma, the preferred way to use a bronchodilator is by inhalation. Although oral bronchodilators may be just as effective in providing symptom relief, they have the disadvantages of more side effects, potential interactions with other drugs and a slower onset of action.

Metered dose inhalers (MDI5) are inexpensive yet effective, and work rapidly to provide symptom relief. However, the need for correct timing and coordination makes them difficult to use and less than 50 percent of patients can use them effectively. With the addition of a spacer, a large number of patients can use MDls effectively.

Dry powder devices are simpler to use and equally effective.

 

 

The potential of bronchodilation offered by antictiolinergic agents is based on the premise that the parasympathetic branch of the autonomic nervous system maintains a. basal tone in the bronchial smooth muscle.

Normal airways have a small degree of vagal cholinergic tone, but because the airways are patent this has no perceptible effect and does not reduce airflow.

When the airways are irreversibly narrowed in COPD, vagal cholinergic tone has a much greater effect on airway resistance for geometric reasons. So, when the increased constriction is relieved by an anticholinergic drug there is a perceptible improvement in airflow. (The flow through a tube is roughly proportional to the fourth power of the radius of the tube (Rµ1/r4) Thus, if the bronchial radius is halved because of a mixture of inflammation, smooth muscle contraction and swelling of the bronchial mucosa the flow through the bronchus may be only one-sixteenth of its previous value. Thus small changes in the diameter of the airways have drastic implications on the flow through those airways.)

In addition anticholinergics may reduce the mucus hypersecretion. Anticholinergics have no apparent effect on pulmonary vessels and therefore do not cause a fall in PaO2 , as may sometimes be seen with b2 -agonists and theophylline.

Among the anticholinergic drugs, ipratropium bromide is the most widely administered therapy for COPD. However, as ipratropium has a short duration of action, it has to be given four times a day.

In the interest of better compliance, there is a need for anticholinergic agents with a longer duration of action. This need led to the development of tiotropium bromide that has a longer duration of action than that of ipratropium bromide.

 

 

1. Tiotropium is a quaternary ammonium compound. Therefore, inhalation is associated with lower systemic absorption and no penetration of the blood-brain barrier (fewer systemic side effects).

2. Tiotropium has a unique kinetic selectivity. It binds with all three muscarinic receptors but gets dissociated very quickly from the M 2 receptor. This facilitates sustained bronchodilation and once-a-day dosing.

3. Tiotropium has impressive and sustained effects on symptoms and health-related quality of life.

4. Tiotropium can be administered at any time of the day, as timing does not affect the outcome.

5. Tiotropium offers a simple treatment regime 18 mcg once a day.

6. Tiotropium reduces the number of exacerbation days and hospitalisation due to exacerbations.

 

 

The effects of oral and inhaled glucocorticosteroids in COPD are much less dramatic than in asthma, and their role in the management of stable COPD is limited to very specific indications. Patients with severe COPD or frequent exacerbations or a significant asthmatic component may benefit from inhaled glucocorticosteroids. Oral/systemic corticosteroids are beneficial in the management of exacerbations of COPD. They shorten recovery time and help restore lung function more quickly.

 

 

1. Prim Care Resp J 2003;12(1):16-20

2. Prim Care Resp J 2002;1 1: Suppl 1

3. The Practitioner 2003;21 7:289-304

4. Postgraduate Medicine 2002;1 11 (6):27-75

5. Halpin D in ‘COPD : Rapid Reference';2001 ;Mosby Publication

6. Drugs of Today 2002;38(9):585-600

 

The first once daily anticholinergic bronchodiator1

24-hour relif of COPD symptoms1

Controls breathlessness and improves lung function2

Significantly improves exercise tolerance2

Significantly improves quality of life2