Long acting beta agonists (LABAs)—formoterol and salmeterol.

Long acting anticholinergic—tiotropium.

Bronchodilatation, for control of symptoms in chronic obstructive pulmonary disease (COPD).

Formoterol (Oxis® and Foradil®) inhaled from dry powder device 12-24 mcg bd.

Salmeterol (Serevent®) inhaled from MDI or dry powder device, 25–50 mcg twice a day.

Tiotropium (Spiriva®) inhaled from dry powder handihaler device, 18 mcg once a day

Both LABAs are only allowed for asthma, not for COPD. For Oxis 6 mcg, the prescriber has to vouch that the drug is for a “certified condition”; and for the other LABAs, a special authority is required.

Tiotropium requires a special authority application giving a diagnosis of COPD, a 100-metre walking limit, and an FEV1 below 40% predicted (i.e. severe disease).

These two classes of inhaled drug are very effective bronchodilators in COPD, being superior to short-acting agents in improving lung function, breathlessness, exercise tolerance, and quality of life.

Their use also leads to a reduction in severe exacerbations, resulting in a favourable pharmacoeconomic profile.

COPD is a major cause of death and disability in New Zealand. Our country’s burden is probably similar to the United Kingdom where 7.5% of adults have chronic cough and phlegm1 and 1% carry a doctor’s diagnosis of COPD.2 Indeed, in the United Kingdom there are 2–4 times as many GP consultations for COPD as for angina; and in 65–74 year old men, 7.3% of hospital admissions are due to COPD.3 Although the burden of COPD disease is increasing (it is projected to be the fourth leading cause of disability worldwide by 2020), it comes bottom of a list of 21 common diseases in attracting monetary resources.4

COPD causes breathlessness, exercise limitation, social isolation, and dependence. Exacerbations disrupt normal life, and result in major community cost when hospital admissions result. Because the COPD population tends to be elderly and stoically uncomplaining, we do not hear a loud clamour demanding their share of the health dollar. Many of them feel self-blame about this largely tobacco-related problem, and perhaps some in the corridors of power take this view too.

The modern management of COPD puts aside nihilism. It involves a multidiscipline approach of layered interventions depending on severity, with the aims being to relieve symptoms, improve quality of life, reduce exacerbations, and (if possible) extend useful life. The approach is codified in several guideline documents, with GOLD5 (Global Initiative in Obstructive Lung Disease) being the most generally accepted.

Common to all guidelines is the central role of inhaled bronchodilators, because—contrary to the old idea of COPD being “irreversible”—these agents do have a useful effect in reducing airflow limitation in the vast majority of such patients. It is worth stating here that although a bronchodilator delivered to the airways of a COPD patient may produce just a small increase in FEV1, dilatation of smaller airways produces beneficial effects not reflected in this standard measure. The residual volume falls, improving diaphragm function, and freer airflow through small airways delays the dynamic hyperinflation that occurs with exercise and is probably the main cause of exercise limitation.6,7

A summary of the management recommended by GOLD is reproduced below (see Table 1). Attention is drawn to the recommendation that patients classed as moderate or severe (FEV1 less than 80% predicted) should use “regular treatment with one or more long-acting bronchodilators”.8

LABAs were introduced to the UK market in 1990, and have been used commonly for COPD as well as asthma since 1997. Tiotropium has been available in the UK since 2003, with no restriction in its prescription by any medical practitioner for treatment in COPD.

(From: GOLD Executive Summary updated 2004 [as at reference 5], page 22)

Bronchodilator studies have usually used lung function measurements as the outcome demonstrating effectiveness—and there are several confirming that LABAs9,10 and tiotropium14,18 compare favourably against placebo and the short-acting agents in COPD. A recent example showed that once-daily tiotropium and twice-daily formoterol alone (and in combination) improved morning and evening spirometry.11

Of more relevance to the sufferers of COPD are those studies showing improvement in symptoms and in quality of life. In a randomised parallel group study of 674 COPD patients,9 salmeterol improved day and night symptoms and the need for salbutamol as well as the FEV1.

Salmeterol improved symptoms and quality of life more effectively than qid ipratropium in 408 COPD patients12 and, in another study, was better than the fenoterol/ipratropium combined inhaler.13

Tiotropium once daily was shown to improve day to day breathlessness and increase respiratory health status in 921 COPD patients in a 12 month study.14

Impaired exercise capability is the universal limiting symptom in severe COPD. In a recent study of COPD patients undergoing a rehabilitation programme, tiotropium convincingly improved exercise capacity and reduced dyspnoea.15 The effectiveness of salmeterol was shown last year.16

If a pharmaceutical agent is able to reduce exacerbations of COPD, especially those resulting in hospital admission, it will be welcomed by the COPD sufferer and by health service funders. Tiotropium has been demonstrated to do this in placebo-comparison studies.17,18 Both salmeterol and tiotropium reduced exacerbations in a 6-month study comparing each drug and placebo.19 Both drugs—tiotropium moreso—had a beneficial effect on clinical outcomes and reduced health service use, with consequent economic advantage.

Economic savings were estimated in a Dutch/Canadian pharmacoeconomic study and found especially favourable for tiotropium.20,21 A similar finding was described in the US context in two 12-month studies.22

Long-acting bronchodilators are a logical treatment in COPD, because studies have shown them to be better than short-acting agents in relieving symptoms, improving exercise capacity and quality of life, and reducing rate of exacerbations. The newest agent —tiotropium—is probably better than long-acting beta-agonists in COPD patients, and a combination of the two drugs may be additionally effective.

At this point, Pharmac still does not allow prescription of LABAs for COPD, despite ample evidence that they provide substantial benefit and GOLD guidelines recommending their use. Also, for tiotropium, the Special Authority Pharmac has set the qualifying severity level well below what is supported by evidence and what is recommended by GOLD.

The time has now come for Pharmac to recognise the body of literature and expert opinion, and to extend the availability of long-acting bronchodilators for this vulnerable group of people.

For COPD patients with an FEV1 below 80% predicted, a long-acting beta-agonist or long-acting anticholinergic should be prescribable without bureaucratic hurdles. Tiotropium is probably the better first-line choice. A combination of both groups may help the more severe patients with FEV1 below 50%, but more secure evidence for this recommendation is still needed.