Choosing an inhaler for COPD

made simple

Dr Simon Hart
Castle Hill Hospital

1
 Declaration of interests

I have received speaker fees, sponsorship to

attend conferences, and funding for research
from companies that make COPD treatments
 £29.32
£27.50 £32.50
£29.32 £32.19
£59.48
£33.50
£32.50

£32.50 £29.97
£32.50
£26.35 £5.56 £1.50 £40.92

£45.56
£38.00 £33.50
£28.60 £27.50 £27.80
 What is COPD?
• characterized by persistent airfow limitation (reduced FEV1 and
FEV1/FVC ratio) that is usually progressive
• a leading cause of morbidity and mortality worldwide and
results in an economic and social burden that is both
substantial and increasing.
Chronic bronchitis Emphysema
Hyperinflation in COPD
Treating airflow obstruction

bronchodilators
 Bronchodilators:
relax airway smooth muscle
 The impact of effective bronchodilation

• Bronchodilators increase the radius of the small airways and so reduce the
resistance of the airflow during breathing

Air flow resistance ∝ 1/r4

• Airflow is inversely proportional to the radius of the small airway to the

power of four 1

r A small change makes a big difference r

Bronchoconstriction Bronchodilation

1) Chang DW. Clinical Application of Mechanical Ventilation 2nd Edition. 2005

β2 agonist
Muscarinic
antagonist
LAMA/LABA combination inhalers
Long acting Long acting beta Daily dosing
muscarinic agonist (LABA)
antagonist
(LAMA)

Umeclidinium Vilanterol One dose

Anoro
55 mcg 22 mcg Once daily

Glycopyrronium Indacaterol One dose

Ultibro
50 mcg 110 mcg Once daily

Aclidinium Formoterol One dose

Duaklir
340 mcg 12 mcg Twice daily

Tiotropium Olodaterol Two doses

Spiolto
2.5 mcg 2.5 mcg Once daily
 Summary effects of LABA/LAMA combination versus comparators on
changes in trough FEV1 at 3 months, 6 months and 12 months.

Yuji Oba et al. Thorax 2016;71:15-25

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
 Summary effects of LABA/LAMA combination versus comparators on
changes in (A) St. George’s Respiratory Questionnaire and
(B) Transition Dyspnoea Index at 3 months and 6 months.

Yuji Oba et al. Thorax 2016;71:15-25

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
 Summary effects of LABA/LAMA combination versus comparators on
proportion of SGRQ and TDI responders at 6 months.

Yuji Oba et al. Thorax 2016;71:15-25

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
 Summary effects of LABA/LAMA combination versus comparators on
COPD exacerbations.

Yuji Oba et al. Thorax 2016;71:15-25

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
 LAMA/LABA combination
How much do they cost?

LAMA alone £32.50

£33.50

£32.50

£33.50
£32.50

£32.50
 Treating airflow obstruction

bronchodilators

Use a LAMA/LABA combination

inhaler
Treating airways inflammation

Inhaled steroids
 Exacerbation rate
1.32/yr on placebo
vs
0.99/yr on fluticasone
ISOLDE 2000

TORCH 2007: exacerbations

Placebo Salmeterol Fluticasone Salm/Flut

mod/severe 1.13 0.97* 0.93* 0.85*

requiring 0.8 0.64* 0.52* 0.46*

steroids
hospitalised 0.19 0.16* 0.17 0.16*
pneumonia 12.3% 13.3% 18.3%* 19.6%*
3 year rate
 ICS in COPD:
benefit vs risk

more pneumonia
local side effects
fewer exacerbations systemic side effects
cost
 Dose–response curves for the rate ratio (solid lines) and 95% CIs (dashed lines) of
pneumonia as a function of inhaled fluticasone (blue lines) and budesonide (red lines) dose in
μg (measured in fluticasone equivalents) estimated by cubic splines model fit by conditional
logistic regression.

fluticasone

budesonide

Suissa S et al. Thorax 2013;68:1029-1036

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
Steroid molecule Options?
beginning with F

Seretide Fostair
fluticasone propionate fine particle beclometasone
+ salmeterol + formoterol

Relvar
fluticasone furoate
+ vilanterol
Duoresp Spiromax Symbicort
budesonide
+ formoterol
Targeted steroid therapy
J. bras. pneumol. vol.32 no.3 São Paulo May/June 2006
Percentage reduction in moderate/severe exacerbation rates with fluticasone
propionate (FP)/salmeterol (SAL) and monocomponents for treatment
comparisons of interest in ≥1-year studies by percentage baseline blood
eosinophil level in (A) INSPIRE, (B) TRISTAN and (C) SCO30002.

Ian D Pavord et al. Thorax 2016;71:118-125

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
 Patient 1, aged 72 yrs, COPD
eosinophil count
0.16
0.14
0.12
0.1
0.08
eosinophil count
0.06
0.04
0.02
0
04/09/2015 04/10/2015 04/11/2015 04/12/2015

eosinophil reference range 0.04-0.4 x 109/L

 Patient 2, aged 71 yrs, COPD
eosinophil count
1.2

0.8

0.6

0.4 eosinophil count

0.2

eosinophil reference range 0.04-0.4 x 109/L

 Conclusions

Treatable traits
Airflow obstruction 
LAMA/LABA combination inhaler

Eosinophilic airway inflammation 

inhaled corticosteroid
 ICS/LABA LAMA

+ £57.92
1.
LAMA/LABA cheap ICS

2. + £37.66

Cost saving 35%

 Targeted oral steroid therapy
for acute exacerbations of COPD
Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic
obstructive pulmonary disease: a randomized placebo-controlled trial
Bafadhel, M, et al Am J Respir Crit Care Med 2012, 186, 48-55.
Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic
obstructive pulmonary disease: a randomized placebo-controlled trial
Bafadhel, M, et al Am J Respir Crit Care Med 2012, 186, 48-55.
 Consort figure for all analysed data taken from the three randomised control trials

Blood
eosinophils <2% ≥2%
Intervention placebo prednisolone placebo prednisolone

Treatment
failure 16/80 22/84 18/27 12/109
(retreatment,
hospitalisation 20% 26% 66% 11%
or death
within 90 days
of
randomisation)

Mona Bafadhel et al. Eur Respir J 2014;44:789-791

©2014 by European Respiratory Society
 Learning point

Blood eosinophils ≥2% (≈0.15 x 109/L)

identify risk and likely steroid responsiveness
40