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

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

Introduction

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)

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.

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

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.

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

The basis of asthma treatment guidelines

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

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

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)

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

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

Guidelines for the management of Asthma

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)

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 (<0.75-0.80 = 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

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

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

(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

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

Step-wise management of Asthma

KAPTLD Asthma Symposia

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

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

Is asthma control possible?

134 (16.9%) of chest clinic attendances were due to asthma 47.4% received recommended asthma therapy Africa Health Sciences Vol 12 No 1 2012

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

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

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

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

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

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

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

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

GINA guideline-defined control is achieved with ICS/LABA at reduced corticosteroid dose 80 500 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

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

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

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

Towards Total Control of Asthma