Long-acting inhaled bronchodilators for COPD—lack of
Long acting inhaled bronchodilators—beta agonists
and anti-cholinergic—can improve symptoms, enhance quality of life,
increase exercise ability, and reduce exacerbation rates in patients with COPD.
PHARMAC needs to change policy so that these patients have easy access to this
effective group of drugs.
Long acting beta agonists (LABAs)—formoterol and
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
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.
Executive Summary updated 2004 [as at reference 5], page 22)
from the literature
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
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
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
Conflict of interest
statement: I do not receive funding from any pharmaceutical or health
product company. Over my career I have assisted various companies by
contributing to educational activities, and have received support to enable
attendance at meetings.
I have previously held positions on the medical
advisory panel and the Council of the Asthma Foundation. In 1997, I chaired the
organising committee of the annual scientific meeting of the Thoracic Society of
Australia & NZ, which received considerable support from the pharmaceutical
and equipment industry.
I am a member of the organising committee of the annual
Respiratory Workshop, which is supported by Boehringer Ingelheim. The workshop
subject themes in the last three years have been airway immunology, mucociliary
clearance, and pleural disease.
David Jones, Respiratory Physician, Capital & Coast DHB, Wellington
David Jones, Respiratory Medicine Dept, Wellington Hospital, Riddiford St,
Wellington South. Fax (04) 385 5550. email: firstname.lastname@example.org
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