Asthma therapies in African children: do current

ASTHMA THERAPIES IN AFRICAN CHILDREN: DO CURRENT INTERNATIONAL GUIDELINES APPLY?

Adaeze Ayuk University of Nigeria Teaching Hospital Enugu Nigeria

Disclosure • ATS – grant for spirometry in Nigerian children • AZ – key opinion leader/academic talks • GSK – key opinion leader/academic talks • This presentation is intended for educational purposes and does not replace independent professional judgment.

Objectives • To understand the origin of guidelines used in asthma management • To understand the asthma therapies as it relates to guideline recommendations - managing chronic stable state asthma - managing asthma during an exacerbation • To relate how guidelines apply in our African settings

Outline • • • •

• • • • •

Introduction General overview of asthma guidelines Management goals different guidelines Principles of drug treatment in chronic asthma (step ladder approach) Use of controllers- ICS/combination therapy Principles of acute asthma management Challenges that affect guideline adherence in Africa Way forward Conclusion

Introduction • Asthma is a chronic disease with increasing prevalence and no cure. • The goal of asthma treatment is therefore to control the disease. • Guidelines are documented principles that aim at achieving this goal • Asthma management guidelines play an important role in reducing asthma burden by standardising: - correct assessment of asthma symptoms/severity - effective asthma management

General overview of asthma guidelines history • The first clinical practice guidelines were published in New Zealand and Australia (mid-1980’s) ▫ Similarly guidelines were produced in other countries: Britain, Scotland and Canada. (late 1980’s)

• National Heart Lung and Blood Institute (NHLBI) ▫ produced three guidelines (EPR -1, 2, 3 in 1991, 1997, 2008)

• Global Initiative for Asthma (GINA), provided various guidelines since 1995. 1,2 • International Union Against Tuberculosis and Lung Disease IUTLD– Asthma guideline 3rd edition (2008) • WHO - Prevention and Control of Non-communicable

Diseases: Guidelines for primary health care in low-resource settings (2012)

Major guidelines that address the management of asthma in children3 • The EPR3 of the National Asthma Education Programme (NAEPP) • PRACTALL Consensus Report published by the European Academy of Asthma and Allergy • European Respiratory Society task force report • Global Initiative for Asthma management (GINA) (www.ginasthma.org).

Summary of management goals • • • •

To have a “normal life” free of symptoms To be able to have a restful sleep To grow and develop normally To attend school regularly and participate in all school activities including sports • To have minimal number of attacks of acute asthma/“flare-ups” • To avoid hospitalisation • To avoid medication related side effects.

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Before managing asthma • It is important to make the correct diagnosis and classify the asthma severity: - acute asthma/ ‘flare-up’ - chronic asthma (different severity/control levels)

• This involves clinical history and lung function measurement • This then guides the steps in asthma management

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A key component of asthma guidelines recommendations What asthma medicines to use When to use them  How to use them

Asthma medications recommended in guidelines Relievers for acute asthma: short acting beta agonist (albuterol, fenoterol) Controller medications for chronic asthma: • Leukotriene modifiers • Cromolyn sodium and nedocromil • Inhaled corticosteroids(ICS) • Long-acting inhaled beta2-agonists (LABA) • Methylxanthines • Oral corticosteroids • Immunomodulators

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Principles of drug treatment (chronic asthma) • Step-wise approach is recommended • Prescribe a SABA as reliever therapy for all with symptomatic asthma. • Start controller medication for persistent /uncontrolled asthma with low-dose ICS, monteleukast or inhaled cromone. • Gradually step up/step down • Once control is achieved, step down the dose of ICS to the lowest dose at which effective control of asthma is maintained. Global initiative on Asthma GINA www.ginasthma.org

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Inhaled Steroids • • • • • •

Budesonide Fluticasone Betamethasone Beclomethasone Ciclesonide Mometasone ▫ (patients ≥ 12 years old) • Triamcinolone acetonide

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ICS dose examples Dose level

CIC

BDP–HFA

FP

BUD

Ciclesonide

Beclomethasone dipropionate

Fluticasone Budesonide propionate

Low

80–160 mcg

100–200 mcg

100–200 mcg

200–400 mcg (100200)

Medium

160–320 mcg

200–400 mcg

200–400 mcg

400–800 mcg (200400)

High

320 mcg and above

Over 400 mcg

Over 400 mcg

Over 800 mcg (>400)

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Combination therapy use [ICS plus LABA] • In patients ≥ 12 years, numerous studies have found excellent control of moderate persistent asthma with combination therapy. - Improvements in lung function and symptoms - reduction in frequent need for SABAs.

• LABA combinations not as extensively studied particularly in children < 4 years old. • Thus recommendation of step 2/3 in 0-4 year olds - low dose ICS or LTRA then on to medium dose ICS National Heart, Lung, and Blood Institute; revised August 2007. NIH publication no. 07-4051

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Guideline recommendations • Maintain ICS treatment regimen for approximately 3 months (Improvement should be noted within a month). • Use MDI via a spacer device [4 years old and younger- spacer and face masks; 5 years or older use- spacer and mouthpiece/face masks

• Following exacerbation increase ICS dose for next 1-2 weeks Global initiative on Asthma GINA www.ginasthma.org

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What is the practice?

What do doctors prescribe? • Prescribing patterns asthma controller therapy for children in UK primary care: a crosssectional observational study ▫ ICS monotherapy- 90.6% ▫ ICS plus long-acting β2-agonist (LABA) -7.0% ▫ LTRA monotherapy - 0.9% ▫ ICS plus LTRA - 0.6% ▫ Other therapy - 1.0% (including 0.45% children who were prescribed LABA as monotherapy) Thomas et al. BMC Pulm Med. 2010; 10: 29.

Pattern of controller prescription

Use of medication according to physician classifications Thomas et al. BMC Pulm Med. 2010; 10: 29. of asthma severity did not always correspond to guideline recommendations

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Challenges in asthma treatment that affect guideline adherence for children in Africa Lack of locally adapted guidelines Significant lack of awareness of guidelines and its contents by managing physicians Lack of appropriate medication and delivery systems for children (ie supply by Pharmaceutical companies agents) Access to asthma medications – availability/cost Lack of Supportive equipment Safety and ethical issues.

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The big questions • How many practitioners in Africa especially at primary care level know about International guidelines? • How many African countries have locally adapted guidelines?

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Countries with locally adapted asthma guidelines – adult [GAN]

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Countries with locally adapted asthma guidelines – children

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Countries with locally adapted asthma guidelines – children [GAN website]

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Adequate delivery of inhaled drugs in children • In children, incorrect technique associated with use of Metered-dose inhalers (MDIs) is a problem • MDI used correctly, deposits 20 to 30 percent of the dose in the lungs. • The use of valved-holding chambers increases this percentage remarkably.5 • How many doctors in Africa use spacers to deliver MDI in children as recommended in guidelines ? Global initiative on Asthma GINA www.ginasthma.org

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….Dry powder inhalers (DPI) • Use of DPI in children with poor inspiratory effort poses a challenge with greater oral/pharyngeal deposition of the medication • The amount of force required for inspiration in DPI use, varies from device to device - diskhaler, cheisihaler, turbohaler etc. • How often do practitioners use inspiratory flow meter to asses appropriate delivery system?

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Effect of inspiratory rate on respirable particles generated from different DPI inhalation devices

———: budesonide Turbuhaler – –: beclomethasone dipropionate Chiesi Inhaler) -------: beclomethasone dipropionate Diskhaler) ; ·········: Fluticasone Diskhaler Barnes et al Eur Respir Rev December 1, 2005 vol. 14 no. 97 147-151

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Equipment challenges that affect asthma guideline adherence • Spacers – (recommended to be used with pMDI) - Bulky and still requires coordination of actuation/inhalation - Expensive: Commercially available ones vs. homemade spacers [Both are equally effective in acute exacerbation (Zar et al SA)]

- Unavailability: Desalu et al6 in Nigeria found that only 20.6% of the University hospitals had spacer devices available in the clinics • Nebulizers - cost/bulkiness • Lung function equipment – e.g. spirometers availability/skill

Access - medication availability (EML)

• The applicability of any guideline for asthma rests on access to medications in such guidelines. • In many developing countries the drugs for asthma treatment on EML are not available • Access to inhaled corticosteroids is they key to improving quality care for asthma in developing countries 8,9 • These are not included in the national essential drug lists in a number of African countries.10-12 • Differences in EML of different countries

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Asthma medicines on the WHO essential drug list

• A range of doses/types of inhaled corticosteroid is lacking • Includes only - Budesonide(100/200μg) - Epinephrine - Salbutamol

• LTRA/Ipratropium bromide not included • Difficult to apply current guidelines for the management of children especially for under 5 years WHO Essential Drug List, April 2015

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ICS in EML for various countries [GAN survey 2014]

• There were 99 responding countries, 79 (80%) had an EML [From LMICs 57 (97%) had an EML]. • Of the 79 countries Budesonide 100μg - 9 (23%) HICs and 15 (25%) LMICs Budesonide 200μg - 12 (30%) HICs and 21 (36%) LMICs  Beclometasone 50μg : 16 (40%) HICs and 33 (56%) LMICs  Beclometasone 100μg. - 16 (40%) HICs and 26 (44%) LMICs

……Access - medication availability • In Nigeria, the LABA combinations rather than “ICS only" are more readily available despite GINA recommendations for children and safety concerns for use of LABA in children.13 - ICS alone medications are available in South Africa - ?Kenya, Zambia, etc

• Supply from pharmaceutical companies are major determinants of medication availability thus a challenge to guideline adherence

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…. Access - medication cost • Asthma drugs are paid out-of-pocket in most African setting (most earn