1. Importance of guidelines in the management of Asthma
William Worodria
Consultant Physician
Mulago Hospital & Complex

2. Outline Introduction The basis of asthma treatment guidelines
Guidelines for the management of asthma
Guidelines in practice
Future priorities

3. Introduction

4. Epidemiology of Asthma
An estimated 235 million people have asthma
The global prevalence is increasing.
High prevalence of diagnosed asthma in low-income countries (8.2%)
Few patients consistently use asthma medicines.
Patients that do not have access to ongoing care end up in emergency rooms and hospitals.
The implication: added costs (greater than the preventive strategy)

5. U.N. Summit on Non-Communicable Diseases (19th -20th September 2011)
The 4 major groups of non-communicable diseases (NCDs) – cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases- have been identified by the WHO as the main threat to human health…..
Responsible for 60% of total deaths and
44% of premature deaths world-wide (35 million deaths each year, 80% of which occur in low and middle-income countries).…………..
The prevention and treatment of NCDs receive only 0.5% of the funds allocated to global assistance for development initiatives.

7. Press Release
“……..when asthma is not diagnosed, not treated or poorly managed, and when people can not access or afford treatment, they regularly end up having to miss school or work, they are unable to contribute fully to their families, communities and societies, they may require expensive emergency care, and everyone loses. The obstacles to well-managed asthma can be overcome. Asthma is a public health problem that can – and should be addressed now.”……… Dr Nils E Billo, Executive Director of The Union

8. Uganda Limited prospective data.
Bitimwine et al indicate 13.8% in peri-urban Kampala of school going age children (8- 14yrs) have asthma.
Kirenga et al, from a hospital based study found asthma accounted for 17% of the attendances in chest clinic.

9. Prevalence of asthma in Africa
Addis Ababa, Ethiopia
10.7*
Ibadan, Nigeria
10.7*
Jima, Ethiopia
1.9*
Eldoret, Kenya
10.4*
Nairobi, Kenya
17.1*
Cape Town, South Africa
16.1*
ISAAC. Eur Respir J 1998;12:315–335
*% of study population

10. The basis of asthma treatment guidelines

11. Guidelines for asthma First guidelines:
1989: Thoracic society of Australia and New Zealand
1990: Canadian Thoracic Society
Other guidelines:
British Thoracic Society (BTS) and Scottish Intercollegiate Guideline Network (SIGN)
National Heart Lung Blood Institute (NHLBI)
The Global INitiative for Asthma – GINA, a joint effort between NHBLI and the World Health Organization

13. Global Initiative for Asthma (GINA)
Initiated in 1993 to produce recommendations for the management of asthma based on the best scientific information available by:
Increasing awareness of asthma among
Health professionals
Public health authorities
General public
Improving prevention and management of asthma through a world-wide effort.
Yearly updates are made to these guidelines

14. Guidelines in management of Asthma
Objectives:
To find the most effective approach to management of Asthma considering the
Diagnosis
Treatment
Monitoring of asthma
To find the least costly product that is suitable for an individual within its marketing authorization
(NICE technology appraisal guidance)

15. Guideline Development - weighing the evidence
Evidence Categories A: Data from high quality Randomized Clinical Trials showing consistent effects B: Limited body of data from Randomized Clinical Trials, or from a population that is different from the population where the recommendation will be applied or the results of these trials are somewhat inconsistent C: Results from non randomized trials or observational studies D: Expert opinion/Panel Consensus judgment

16. The process of asthma treatment guidelines
Based on evidence for clinically relevant questions from systematic reviews or metanalysis data, e.g.
“What is the minimum effective dose of steroids in asthma?”
“What is the more clinically effective approach to the introduction of a Long acting β agonist?”
single or
combination inhalers

17. Guidelines for the management of Asthma

18. Guideline diagnosis of asthma
Clinical diagnosis is prompted by breathlessness, cough, wheezing and chest tightness
History of episodic symptoms following antigen exposure, seasonal variability, family history of allergy – are useful
Physical examination: normal, wheezing, “silent chest”; cyanosis, drowsiness, difficulty in speaking, hyper inflated chest
Measurement of airway reversibility by lung function is key to the diagnosis of asthma
(GINA , 2010)

19. Diagnosis of asthma
Based on the basis of symptoms & objective tests of lung function:
Peak expiratory flow rate (≥20% from pre-bronchodilator function)
FEV1 (12% variability)
% of predicted FEV1 (< = airflow limitation)
Severity is based on symptoms and medication required to control symptoms
Objective measurements are useful, especially for patients with poor perception of symptoms

20. Perception was diminished with longer duration of disease.
Normalizing pulmonary function and airway responsiveness improves perceptual response to bronchoconstriction
(AJRCCM, 2000)

21. Treatment of Asthma Aims of asthma treatment: To control symptoms
To prevent exacerbations
To achieve the best possible lung function
To minimize side effects of treatment
A step-wise approach is recommended as patients are targeted to prevent asthma exacerbation

22. (any measure present in last one week) Uncontrolled
Classification according to the level of Asthma control – GINA 2010
Level of Asthma Control
Characteristic
Controlled
Partly Controlled
(any measure present in last one week)
Uncontrolled
Day time Symptoms
None
> twice/week
Three or more features of partly controlled asthma present in any week
Limitation of Activities
Any
Nocturnal symptoms/
Awakening
Need for reliever/
rescue medication
>twice/week
Lung Function
(PEF or FEV1)
Normal
<80% of personal best
Exacerbations
One or more/year
One in any week

23. Tools for the assessment of Asthma control
Spirometry
Other tools based on expert opinion:
Asthma Control Test (ACT)
Asthma Control Questionnaire (ACQ)
Asthma Therapy Assessment Questionnaire (ATAQ)
These have been validated

26. Step-wise management of Asthma

27. KAPTLD Asthma Symposia

28. Rationale for step-wise approach
Step 1: as needed rapid acting inhaled β-agonist.
Step 2-5: include a controller option
Inhaled corticosteroids (ICS) are the most effective controller therapy for asthma for both children and adults
ICS also reduces the risk of severe asthma
There is no convincing evidence of the use of ICS and long acting β-agonist (LABA) in mild disease

29. Asthma control
Asthma management guidelines agree on the importance of establishing a correct diagnosis
Objective measures of airway hyper responsiveness
Consistency in the definition of ideal asthma control
Asthma severity = intensity of the underlying disease process before treatment
Asthma control = adequacy of response to treatment

30. Is asthma control possible?

31. 134 (16.9%) of chest clinic attendances were due to asthma
47.4% received recommended asthma therapy
Africa Health Sciences Vol 12 No

32. 2,803 patients (current asthma patients) interviewed (telephone survey)
Only 5.6% of the population met all goals of GINA guidelines
Despite availability of therapies asthma control was suboptimal
Asthma may be dangerously undertreated

33. 3273 households, 2509 persons (including 721 children interviewed)
72.5% used ICS
11.4% leukotrienes
18.6% cromolyn nedocromil
1275 (50.8%) had persistent asthma
Of these 26.2% reported current use of anti- inflammatory medication

34. Gaining Optimal Asthma ControL Study
Objectives:
To compare the efficacy of two recommended control therapies to achieve control
Increasing dose of fluticasone propionate alone or
In combination with the long acting β2-agonist salmeterol
Design:
A stratified, randomized double blind, parallel group study to determine safety and efficacy
Bateman et al. Am J Respir Crit Care Med 2004

35. GOAL – study design
During the 4 week run-in period patients continued with their usual dose of ICS
Those who did not achieve at least two well-controlled weeks in the 4-week period were randomized to one of three strata (based on ICS dose before screening)
Stratum 1: no ICS
Stratum 2: 500µg or less of beclomethasone or equivalent
Stratum 3: >500 to <1000µg of beclomethasone or equivalent Bateman et al. Am J Respir Crit Care Med 2004

36. GOAL – study design
Phase 1: Dose escalation. Treatment stepped up every 12 weeks until control was achieved or the highest dose of the study drug was reached (salmeterol/ fluticasone 50/500µg or fluticasone 50/500µg )
Phase 2: After totally controlled asthma or the maximum does of study medication until the one year of double blind treatment
Patients who still did not achieve control by the end of phase 2 had 4-weeks of open label
Bateman et al. Am J Respir Crit Care Med 2004

37. GOAL: study design Phase I Phase II 8-week control assessment
Oral prednisolone +
ICS/LABA 50/500 bd
ICS/LABA 50/500 bd
or ICS 500 bd
ICS/LABA 50/250 bd
or ICS 250 bd
ICS/LABA 50/100 bd
or ICS 100 bd
- 4 4 12 24 36 52 56
Week
Bateman et al. Am J Respir Crit Care Med 2004
GSKI/AST-PPT/03/10/11

38. Patient baseline demographics
Stratum 1
Stratum 2
Stratum 3
ICS/LABA
ICS N
548
550
585
578
576
579
FEV1
(% Pred)
77%
79%
78%
75%
76%
Reversibility
(Median %)
23%
22%
Rescue use
(mean occasions/ day)
1.9
1.7
Exacerbation rate
0.4
0.3
0.6
0.5
0.7
Bateman et al. Am J Respir Crit Care Med 2004
GSKI/AST-PPT/03/10/11

39. Achieving GINA guideline-defined well-controlled asthma
ICS/LABA Phase II
ICS/LABA Phase I
ICS Phase II
ICS Phase I 80
78*
75** 70 60
62** 60 47
% Patients 40 20
Steroid naïve
(Stratum 1)
Low-dose ICS
(Stratum 2)
Moderate-dose ICS
(Stratum 3)
*P=0.003; **P<0.001
Bateman et al. Am J Respir Crit Care Med 2004
GSKI/AST-PPT/03/10/11

40. GINA guideline-defined control is achieved with ICS/LABA at reduced corticosteroid dose80
500 60
250
500
guideline-defined control in Phase I
% of patients who achieved 40
250 20
100
100
Stratum 2, phase I
ICS
ICS/LABA
Bateman et al. Am J Respir Crit Care Med 2004
GOAL Study
GSKI/AST-PPT/03/10/11

41. Goal study - conclusions
In majority of patients with uncontrolled asthma comprehensive guideline-defined control can be achieved and maintained
The approach of aiming for total control and maintaining treatment resulted in elimination of exacerbations and near-normal quality of life
Bateman et al. Am J Respir Crit Care Med 2004

42. Treatment beyond total control
Between each phase is 6-12 weeks
(National Asthma Council Australia)

43. Conclusion Many patients have poorly controlled asthma
GINA guideline-defined control of asthma is achievable
ICS/ LABA combination is the mainstay of treatment of persistent asthma

44. Towards Total Control of Asthma