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Patient Oriented Evidence that Matters

Introduction COPD POEM PDF
The COPDX Plan
Confirm diagnosis & assess severity
Optimise function
Prevent deterioration
Develop support network & self-management plan
eXacerbations manage appropriately
Review of drug use in COPD
Appendix One - Resources and contacts

Review of drug use in COPD

Antibiotics | Inhaled bronchodilators | Inhaled corticosteroids | Oral corticosteroids | Theophylline | Mucolytics

Drugs currently available for treatment of COPD can reduce or eliminate symptoms, increase exercise capacity and lung function, reduce the number and severity of exacerbations and improve quality of life. However, there are no drug treatments currently available that modify the rate of decline in lung function. The improvement in lung function often seen with brief drug treatment does not necessarily predict other clinically related outcomes (ATC, 2004). The combination of different drug treatments can produce a greater change in spirometry and symptoms than single agents given alone.


The benefits of long term antibiotic use do not outweigh the harms of treatment and the risk of promoting antibiotic resistance (Clinical Evidence, 2004).

Antibiotics should be used in exacerbations when patients have an increase in cough, dyspnoea, sputum production or purulence (NZGG, 2002).

Inhaled bronchodilators

Short acting beta-2agonists (salbutamol, terbutaline)

These act directly on smooth muscle to cause bronchodilation. They also appear to reduce hyperinflation by reducing air-trapping in the lungs. This may explain why some patients benefit from them without an improvement in spirometry or PEFR. Effects last for about four hours and time to peak response is slower than in asthma. There is evidence that they increase FEV1 and reduce breathlessness, dyspnoea and fatigue. They can be used intermittently or regularly. There is no evidence that regular use of short acting beta-2 agonists adversely affects survival in patients with COPD (Prodigy, 2004).

Short acting anticholinergics (ipratropium)

Ipratropium blocks cholinergic nerves therefore blocking bronchoconstrictor effects. Mucus secretion is reduced by blockade of muscarinic receptors. They may also reduce hyperinflation providing similar benefits to beta-2agonists. Ipratropium increases FEV1 but like short acting beta-2 agonists it has no effect on the rate of progression of COPD. They can be used intermittently or regularly.

Short acting beta-2 agonists or ipratropium

In practice there is little to choose between ipratropium and a short acting beta-2 agonist and either can be used as initial therapy. Ipratropium has a slower onset of action than beta-2 agonists and is less suitable for as required use (Prodigy, 2004).

There have been no long term comparisons of short acting inhaled anticholinergics and short acting inhaled beta-2 agonists. One non-systematic review found that short term (3 months) regular treatment with ipratropium is more effective at improving FEV1 than regular treatment with short acting beta-2 agonist bronchodilators (Rennard, 1996).

The response to treatment should be assessed over at least four weeks. Therapy should be continued if there is documented improvement in lung function, symptoms of breathlessness, objective measures of breathlessness (MRC scale) or exercise capacity. If the response to a short acting beta-2 agonist is unsatisfactory a short acting anticholinergic should be trialed and vice-versa (NZGG, 2002).

Long acting inhaled anticholinergics (tiotropium)

Tiotropium has a similar mode of action to ipratropium but has a duration of action >24 hours and is administered once daily. It increases FEV1 compared with placebo and it improves dyspnoea, and reduces exacerbation rates compared with placebo and regular ipratropium (NZGG, 2002; Prodigy, 2004).

Tiotropium has been compared with long acting beta-2 agonists in three randomised controlled trials. Two trials found that tiotropium improved FEV1 , and health related quality of life compared with salmeterol over six months. However, another trial found no significant difference between the same treatments in health related quality of life or exacerbation rates at six months (Clinical Evidence, 2004).

Tiotropium is funded in New Zealand for the treatment of severe COPD on completion of a Special Authority Subsidy form.

Long acting beta-2 agonists (salmeterol, eformoterol)

The bronchodilator effects are similar to the short acting drugs but the duration of action is around 12 hours. These drugs have been found to reduce dyspnoea and symptom scores for COPD when compared with placebo (Prodigy, 2004).

Long acting bronchodilators provide sustained relief of symptoms in moderate to severe COPD (NZGG, 2002). The evidence for effects on lung function and exacerbation rates is conflicting. Some trials have shown significant benefit whereas others have found no effect (Clinical Evidence, 2004; Prodigy, 2004).

Long acting beta-2 agonists are not currently funded in New Zealand for use in COPD.

Inhaled corticosteroids

Inhaled corticosteroids are not first line treatments for COPD. The inflammation that occurs in COPD is different to that seen in asthma and does not generally respond to inhaled corticosteroids. They have no effect on symptom scores or rate of decline in FEV1. They reduce exacerbation rates in severe COPD (FEV1 < 50%) but have no effect on exacerbation rates in mild COPD (Prodigy, 2004). Short term (10 days to 10 weeks) randomised controlled trials of inhaled corticosteroids in patients with COPD have found no evidence of superiority over placebo at improving FEV1. A systematic review of long term trials (3 trials, 197 patients, treated for 2-2.5 years) also found no improvement in FEV1 compared with placebo.

A trial of inhaled corticosteroids is recommended in patients with an FEV1 less than or equal to 50% of predicted, who have had two or more exacerbations requiring treatment with oral corticosteroids or antibiotics in a 12 month period (NICE, 2005). They could also be trialed in patients with moderate or severe COPD with monitoring of objective measures of response. If there is no response they should be discontinued (NZGG). There is a possibility of exacerbation following withdrawal and re-instituting therapy may be necessary (Jarad, 1999).

Inhaled corticosteroid and long acting beta-2 agonist combination

Recent trials (Clinical Evidence, 2004) have demonstrated some benefits from the combined administration of inhaled corticosteroids and long acting beta-2 agonists. When the combination was compared with placebo there was a reduced number of exacerbations, improved lung function and improved health related quality of life scores. Furthermore the combination was more effective than for either drug used alone.

However these trials have been performed in patients with moderate to severe disease (FEV1 < 50%) and therefore the results cannot be generalised to patients with less severe COPD.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD, 2003) advocates that the combination should only be used in patients with an FEV1 of less than 50% predicted and frequent exacerbations (at least 3 in the last 3 years) (GOLD, 2003).

The combinations are not funded for COPD in New Zealand

Oral corticosteroids

Maintenance use of oral corticosteroids is not usually recommended but they may be required in patients with advanced COPD, especially if withdrawal is difficult following an exacerbation. The dose of corticosteroid should be kept as low as possible and patients should be monitored for the development of osteoporosis and diabetes. Long term use of oral corticosteroids is not recommended.

Oral corticosteroid reversibility tests do not predict if the patient will respond to inhaled corticosteroids (NICE, 2004).


Some patients with severe COPD and disabling breathlessness may benefit from slow release theophylline added to existing therapy.

Theophylline is a bronchodilator and may have an anti-inflammatory effect and reduce muscle fatigue but the exact mechanism of action is unknown. Its use is limited by the potential for drug toxicity as the drug has a narrow therapeutic index requiring plasma concentration monitoring. Levels should be at the lower end of the therapeutic range, that is 40-60 micromol per litre.

Significant adverse drug reactions and drug interactions are associated with theophylline use. Hypokalaemia may be potentiated by combined use with beta-2 agonists and is potentially hazardous. The elderly are at greater risk of adverse effects.

Theophylline increases FEV1 and FVC compared with placebo but there is no significant improvement in wheeze, dyspnoea, walking distance, use of rescue medication or exacerbations (Prodigy, 2004).


A trial of a mucolytic agent can be considered in patients who have difficulty in expectorating sputum.

Mucolytics (e.g. Bromhexine) have been available for many years and most of the evidence supporting their use comes from trials conducted in patients with chronic bronchitis. A systematic review of 22 trials (20 chronic bronchitis and not further defined, 2 COPD) found that 3-6 months treatment with mucolytics was more effective than placebo in reducing the number of exacerbations. It is not clear if these results can be extrapolated to patients with a confirmed diagnosis of COPD, but a trial of a mucolytic agent can be considered in patients who have difficulty in expectorating sputum. If symptoms improve the mucolytic should be continued (NICE, 2004).

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