C
hronic obstructive pulmonary disease (COPD) is a
very common condition, which causes shortness
of breath. COPD is an umbrella term for
conditions including emphysema, chronic bronchitis
and chronic asthma which is irreversible. The main
risk factor is smoking or a history of past smoking
cigarettes. At least one in 10 (10%) adults over the age
of 40 years have COPD.
Guidelines
Australian guidelines for the management of
COPD are called the COPD-X Guidelines. The key
recommendations are summarised in the COPDX Plan:
■
Case finding and confirm diagnosis
■
Optimise function
■
Prevent deterioration
■
Develop a plan of care
■
Manage eXacerbations
Research on COPD
medications usually measures
the change in FEV1 (forced expiratory volume in one
second), as well as patient-related clinical outcomes
such as:
■
St George’s Respiratory Questionnaire (SGRQ)
■
Transition Dyspnoea Index (TDI)
The St George’s Respiratory Questionnaire is a 50-
item questionnaire developed to measure health
status (quality of life) across symptoms (frequency
and severity), activity and impacts (psychosocial). TDI
focal score measures impact of dyspnoea on three
domains: functional impairment, magnitude of task
and magnitude of effort.
Treatment
Current therapies target airflow limitation and
pulmonary inflammation. The mainstay of treatment
involves:
■
Inhaled corticosteroids
■
Long-acting beta
2
-agonists (LABAs)
■
Long-acting muscarinic antagonists (LAMAs)
Other treatments include short-acting bronchodilators
(‘relievers’), oral bronchodilators (theophylline) and
phosphodiesterase type-4 inhibitors (cilomilast,
roflumilast).
Short-acting beta
2
-agonists (SABAs) (salbutamol,
terbutaline) improve lung function and daily
breathlessness scores. They are usually prescribed
for use as “rescue” medication, i.e. for relief of
breathlessness, rather than for regular use.
Short-acting muscarinic antagonists (SAMAs) such as
ipratropium bromide
(Atrovent)
have a longer duration
of action than short-acting beta
2
-agonists. They
improve lung function and quality of life. Ipratropium
bromide has a significantly greater effect on lung
function compared to beta
2
-agonists alone; in addition
to improving quality of life and decreasing need for
oral corticosteroid treatment. However, some studies
have found that ipratropium bromide is associated
with an increased risk of adverse cardiovascular
effects.
Inhaled bronchodilators (LAMAs and LABAs) provide
symptom relief, improve quality of life and may
increase exercise capacity. In some patients, a
response to bronchodilator therapy may require
treatment for up to two months.
Inhaled corticosteroids (ICS) should be considered
in people with moderate to severe COPD and
frequent exacerbations. ICS include fluticasone,
beclomethasone, budesonide and ciclesonide. They
all may increase the risk of local oropharyngeal
adverse effects and pneumonia; although risk of
any pneumonia event has been found to be higher
with fluticasone than budesonide. Long term use of
systemic corticosteroids (prednisone, prednisolone) is
not recommended.
LAMAs
Tiotropium improves quality of life, increases the
number of patients with a clinically significant
improvement, and reduces the number of patients
with a clinically significant deterioration in quality of
life. The newer LAMAs (umeclidinium, aclidinium and
glycopyrronium) have been shown to be non-inferior
to tiotropium, that is, they are just as effective as
tiotropium.
LAMA/LABAs
January 2016
LAMAs include:
■
Tiotropium
(Spiriva Handihaler
and
Respimat)
■
Umeclidinium
(Incruse Ellipta)
■
Aclidinium
(Bretaris Genuair)
■
Glycopyrronium
(Seebri Breezhaler)
Aclidinium is administered as one inhalation twice
daily. Twice daily dosing improves early-morning
symptoms (early morning cough, wheeze, shortness
of breath, phlegm) and night-time symptoms
(reduced frequency of breathlessness, cough, sputum
production, wheezing).
Other LAMAs are administered once daily. There is no
rationale to combine different LAMAs, either alone or
in combination with LABAs.
LABAs
Long-acting beta
2
-agonists cause prolonged
bronchodilatation and can be administered once
(indacaterol, Olodaterol, vilanterol) or twice daily
(salmeterol, eformoterol). LABAs used for at least four
weeks produce statistically significant benefits in lung
function, quality of life, use of ‘reliever’ short-acting
bronchodilators and acute exacerbations. LABAs do
not significantly reduce mortality or serious adverse
events.
LABAs include:
■
Salmeterol
(Serevent Inhaler
and
Accuhaler)
■
Indacaterol
(Onbrez Breezhaler)
■
Eformoterol
(Oxis Turbuhaler)
■
Olodaterol
(Striverdi Respimat)
■
Vilanterol
Vilanterol is currently only available in combination
products with a LAMA umeclidinium
(Anoro Ellipta)
and
ICS fluticasone furoate
(Breo Ellipta)
.
Combination therapy
When residents are not adequately controlled with a
single long-acting bronchodilator, combining a LAMA
and LABA may be beneficial.
A 2012 Cochrane systematic review of five studies
found that the combination of tiotropium and a long-
acting beta
2
-agonist provided small improvements
in health-related quality of life and bronchodilation,
compared to tiotropium alone. A recent systematic
review of currently available randomised trials
of LAMA/LABA combinations for stable COPD
demonstrated that LAMA/LABA combinations yield a
greater improvement in trough FEV1, and SGRQ and
TDI scores than monotherapies. The review concluded
that combination therapy is the most effective strategy
in improving lung function, quality of life, symptom
scores and moderate-to-severe exacerbation rates.
Safety outcomes and severe exacerbations are similar
with combination therapy when compared with
monotherapies.
Current COPD treatment guidelines recommend
a combination of a LAMA/LABA as an option for
patients with significant symptoms and a low risk of
exacerbations, patients with few symptoms and a
high risk of exacerbations, and patients with many
symptoms and high risk of exacerbations.
From 1 December 2015, four LAMA/LABA fixed-dose
combination bronchodilators are PBS listed for adults
with COPD:
■
Eformoterol /aclidinium
(Brimica Genuair)
■
Indacaterol/glycopyrronium
(Ultibro
Breezhaler)
■
Olodaterol/tiotropium
(Spiolto Respimat)
■
Vilanterol/umeclidium
(Anoro Ellipta)
Eformoterol /aclidinium
(Brimica Genuair)
must
be administered twice daily; whereas the other
combination products are once daily. Olodaterol/
tiotropium
(Spiolto Respimat)
requires two inhalations
once daily. The Respimat device should be loaded and
primed by the dispensing pharmacist. Indacaterol/
glycopyrronium
(Ultibro Breezhaler)
consists of
a capsule containing dry powder inhaled via a
Breezhaler once daily at same time each day, which
may require sufficient dexterity to load the capsule in
the device. Genuair and Ellipta devices are likely to be
easiest to use in older people with limited dexterity as
they are pre-loaded with the active ingredient.
Device technique
It is critical that the inhaler device is used correctly
during every administration. Metered dose inhalers or
puffers should always be used with a spacer in older
people.
A fixed-dose combination inhaler may be more
convenient for residents rather than separate single-
drug inhalers. Evidence suggests the drugs within each
class of LAMAs and LABAs are broadly similar, so the
choice of treatment may be tailored to ease of use of
the different devices.
References
Cochrane Database Syst Rev 2012;4:CD008989
Thorax 2016;71:15-25.
COPD-X Guidelines – Version 2.43 (September 2015)
LAMA/LABAs
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