Kirk Jurgens – Respiratory ScientistCRFS (ANZSRS), GradCertRespSci (CSU), BSc (Otago)

β-2 AGONISTS

GP cost

0.23

22.41

32.39

0

5

10

15

20

25

30

35

<6 6-17 18+

Age (years)

Co

st

per

vis

it (

$)

GP cost

Ministry of Health NZ statistics Feb 2015

Dependentchildren

Lung function & asthma severityC Tharmrin et al. Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity. Thorax (2011) 66; 1036-1042

Indicators for exacerbation (using PEF)

• Mild - moderate asthma – change from previous function• Severe asthma – movement from %pred

• Mild – moderate asthma = greater fluctuation than severe asthma

β-2 use as predictor for asthma

• Higher average β-2 use is a strong predictor for severe exacerbation

Future severe exacerbation- higher daily β2 use- higher days of β2 use- higher max 24hr β2 use

Increase risk of future β-2 overuse- higher daily β2 use- number of days of use- max daily use

M Patel et al. Metrics of salbutamol use as predictors of future adverse outcomes in asthma. Clinical & Experimental Allergy (2013) 43; 1144-1151

β-2 use prior to hospital attendanceM Patel et al. The use of β-2 agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis. Npj Primary Care Respiratory Medicine (2015) 25. 2015

Severe exacerbations leading to hospital admission lead up:• Delaying review by medical professionals• High β-2 agonist use

SMART reduced non-adherence to ICS therapy

What is going on?S Oehme et al. Agonist induced β2-adrenoceptor desensitization and downregulation enhance pro-inflammatory cytokine release in human bronchial epithelial cells. Pulmonary Pharmacology & Therapeutics (2015) 30; 110-120

β-2 agonists are pro-inflammatory in the long term- Inflammatory cytokines IL6, IL8 (Interleukin)- cAMP production increase – desensitization of B-2

receptors

O.T.C β-2 and ICS

Medication

step

Participants

(n)^

Mean

asthma

control

score

Mean

adherence

score

No prior

medication11 1.58

GINA 1 129* 1.20 0.28

GINA 2 24 1.41 0.28

GINA 3 45 1.40 0.45

GINA 4 88 1.73 0.40

GINA 5 15 3.00 0.11

Jo A. Douglass et al. Over the counter β-2 agonist purchase verses script: A cross sectional study. Respiratory Medicine (2012) 106, 223-229

191 (60%) SABA by Dr. prescription

^: 4 participants with insufficient data

*: 16 were from other GINA but claimed ICS were PRN

125 (40%) SABA O.T.C.

Mean Age: 53.6 Mean Age: 38.7

126 (65%) on controller med

62 (50%) on controller med

Adherence: 0.25 Adherence: 0.34

O.T.C. PROJ K. Gerald et al. Asthma medications should be available for over-the-counter use: pro. Ann Annals American Thoracic Society (2014) 11:6 969-974

• Asthma Treatment Gap

• Prescription Status

• Non-recommended therapy (old wives tales)

O.T.C. CONL J H. Milgram. Asthma medications should be available for over-the-counter use: con. Annals American Thoracic Society (2014) 11:6 975-979

• Chronic disease - risks with independent self management

• Lack of patient education

• Australian (and many other) studies – SABA and ICS

High β-2 agonist risk of fatal asthmaS Suissa et al. Patterns of increasing β-agonist use and the risk of fatal or near fatal asthma.European Respiratory Journal (1994) 7; 1602-1609

• Pattern of increasing β-agonist use is a more accurate predictor of fatal asthma than overall quantity

Total canisters during year (n)

Average canisters per month (n)

Canisters in first month (n)

Canisters in last month (n)

Relative Risk (RR)

21 1.75 1 3 24.4

36 3 3 3 2.6

24 2 2 2 1.6

21 1.75 1.75 1.75 1.4

12 1 1 1 1.0 (Reference pattern)

Relative risk estimates for various asthmatics with different patterns of inhaled β-agonist use over 12 months

ICS recommended for mild asthma in children

More effective control and prevention of exacerbation in children using ICS with β-2 compared to using β-2 alone.

F D. Martinez et al. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial.Lancet (2011); 377; 650-657

GroupParticipants

(n)

Preventer

(BID)

Reliever

(PRN)

Exacerbations

vs. placebo

treatment

failure

1 71 beclomethasone bec + sal -31% 5.6%

2 72 beclomethasone placebo + sal -28% 2.8%

3 71 placebo bec + sal -35% 8.5%

4 74 placebo placebo + sal 23%

O.T.C. Medication safety

• Ibuprofen

• Paracetamol

• Codeine

• Aspirin

•Salbutamol???

Are any of these safe?

Conclusions – Mind The Gap

• Need and greed

• the devil you know, the devil you don’t

• Are we doing enough of the right stuff?

• How can you make a difference?to reduce incidence to reduce impactto remove barriers to treatment of asthma and respiratory disease