asthma masterclass

Asthma Masterclass

Chinhoyi CPCPZ CME DAYDr. C. Pasi

Consultant Physician

ASTHMA EPIDEMIOLOGY

• IntroductionWHO-Scale of the problem• 100-150 million cases of asthma worldwide • More in developed countries-1 in 6 <16yr have

asthma[ Australia ]• Kenya – 20 % incidence• India- prevalence rates 10-15% in 5 to 11yrs age group• Recorded deaths annually of 180 000 globally• In one ER in Zimbabwe 40-60 cases per month of acute

asthma.

GINA Burden Report 2004

In this report an arbitrary figure of 50% of the prevalence of ‘current wheezing’ in children (self-reported wheezing in the previous 12-month period in 13- to 14-year old children) has been used as the prevalence of ‘clinical asthma’. The prevalence rates for ‘clinical asthma’ reported in this report represent a conservative estimate. Data from: International Study of Asthma and Allergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS).

GSKI/AST-PPT/01/10/11

Prevalence of asthma

%

GINA Burden Report 2004

In this report an arbitrary figure of 50% of the prevalence of ‘current wheezing’ in children (self-reported wheezing in the previous 12-month period in 13- to 14-year old children) has been used as the prevalence of ‘clinical asthma’. The prevalence rates for ‘clinical asthma’ reported in this report represent a conservative estimate. Data from: International Study of Asthma and Allergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS).


Operational definition

• “Asthma is a chronic inflammatory condition of the airways in which many cells play a role, in particular mast cells, eosinophils and T-lymphocytes. In susceptible individuals this inflammation causes recurrent wheezing, breathlessness, chest tightness and cough, particularly at night and/or in the early morning. These symptoms are usually associated with widespread but variable airflow limitation that is at least reversible either spontaneously or with treatment. There is also associated increased responsiveness of the airways to a variety of stimuli”

What is asthma?

• Asthma is a chronic disorder of the airways with two main characteristics:

– Inflammation (swelling and excess mucus build-up in airways)

– Airway constriction (tightening of muscles surrounding the airways)

• Asthma is characterised by episodic shortness of breath, particularly overnight often accompanied by a cough

• Greek: “Panting”

GINA Guideline 2010GSKI/AST-PPT/01/10/11

Asthma pathophysiology• Asthma is a chronic inflammatory disease associated with airway

hyperresponsiveness (AHR)

Airway obstruction andsymptoms by: Bronchoconstriction Mucus plugs Mucosal oedema

Inflammatory cell infiltration/activation

Remodelling:Increased vascularity

Epithelial cell disruption

Increased airway smooth muscle mass (hyperplasia)

Reticular basement membrane thickening


Pathology

• Vasodilatation• Oedema• Plasma exudate• Smooth muscle hypertrophy/ hyperplasia• Mucus plugging• Epithelial changesAbove mediated through pro-inflammatory cells, inflammatory

mediators and bronchial afferent nerves

RISK FACTORS

• Host factors Vs Environment• Inate immunity in the host-Th1 vs Th2 response-Th1 cellular based immunity-Th2 allergy based immunity-hygiene theory• Genetics – complex but discernible

Risk factors for asthma

GINA Guideline 2010

Factors influencing the development and expression of asthma

Host factors•Genetic

• Genes pre-disposing to atopy• Genes pre-disposing to airway hyper-responsiveness

•Obesity•Sex

Environmental factors•Allergens

• Indoor: Domestic mites, furred animals (dogs, cats, mice), cockroach allergens, fungi, moulds, yeasts

• Outdoor: Pollens, fungi, moulds, yeasts•Infections (predominantly viral) RSV-bronchiolitis in childhood •Occupational sensitizers•Tobacco smoke

• Passive smoking• Active smoking

•Outdoor/Indoor Air Pollution•DietGSKI/AST-PPT/01/10/11

Diagnosis

• Clinical diagnosis of asthma should be based on:– Medical history– Physical examination– Lung function measurement


Diagnosis

• SYMPTOMS-cough, worse`at night-recurrent wheezing-Recurrent difficulty in breathing-Recurrent chest tightness

• Symptoms may occur or worse with:-exercise-URTI- viral-Inhaled allergens/irritants-Changes in weather-Emotional excesses or stress

Medical history• Symptoms

– Coughing

– Wheezing

– Shortness of breath

– Chest tightness

• Symptom patterns and severity

– Related to physical activity?

– Related to potential allergens/triggers?

– Seasonal?

• Family history of asthma

GINA Guideline 2010

Questions to consider in the diagnosis of asthma

• Has the patient had an attack or recurrent attacks of wheezing?

• Does the patient have a troublesome cough at night?

• Does the patient wheeze or cough after exercise?

• Does the patient experience wheezing, chest tightness, or cough after exposure to airborne allergens or pollutants?

• Do the patient’s colds “go to the chest” or take more than 10 days to clear up?

• Are symptoms improved by appropriate asthma treatment?


EXAMINATION

• UPPER AIRWAYS

• CHEST

• SKIN

• CARDIOVASCULAR SYSTEM

Lung function measurement• Spirometry

– Measures lung capacity (airflow limitation) and reversibility (rapid improvement in airflow limitation in response to treatment: ≥12% improvement indicates diagnosis of asthma)

– Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are measured

– Recommended method for establishing diagnosis of asthma

• Peak expiratory flow

– Measures the speed of lung emptying

– Can be used to confirm diagnosis of asthma

– Patients can be asked to keep a peak flow diary at home, which enables healthcare professionals to assess the variability of symptoms


Lung function Lab.

STEP WISE APPROACH TO ASTHMA• STEP 1Mild intermittent asthma – Intermittent symptoms less than once a week

- Brief exacerbations- no daily medication required-FEV1 >80%, less than 20% variability

• STEP 2Mild persistent – symptoms more than once a week but not daily

- nocturnal symptoms more than twice per month- FEV1 >80%, with 20% variability

• STEP 3Moderate persistent – daily symptoms

- exacerbations affect sleep-FEV1 60-80%

• STEP 4Severe persistent –continuous symptoms

- Frequent nocturnal symptoms- FEV1 <60%

Asthma Control

Goals of asthma management

• Achieve and maintain control of symptoms

Maintain normal activity levels, including exercise

Maintain pulmonary function as close to normal as possible

Prevent asthma exacerbations

Avoid adverse effects from asthma medications

Prevent asthma mortality


Assessing control in practice• Reliable, validated questionnaires

are available to distinguish between different levels of asthma control– Asthma Control Test (ACT)1,2

– Asthma Control Questionnaire (ACQ)3

– Asthma Control Scoring System (ACSS)4

1. Nathan et al. J Allergy Clin Immunol 20042. Liu A et al. J Allergy Clin Immunol 2007

3. Juniper et al. J Allergy Clin Immunol 19994. Boulet et al. Chest 2002GSKI/AST-PPT/01/10/11

Asthma control test

http://www.asthmacontroltest.comGSKI/AST-PPT/01/10/11

ACT score and risk of subsequent exacerbation over 12 months

ACT score Odds Ratio

(Relative to ACT score of 20)

95% CI

19 1.09 1.07-1.11

18 1.21 1.19-1.23

17 1.33 1.31-1.35

16 1.46 1.44-1.48

15 1.60 1.58-1.62

Schatz M, et al. J Allergy Clin Immunol 2009

ACT of 15 means 60% greater risk of exacerbation than if ACT is 20


What does control really mean?• 2010 GINA guideline definition of control – a gold standard

Characteristic Controlled (all of the following)

Daytime symptoms Twice or less per week

Limitations on activities None

Nocturnal symptoms or awakenings None

Need for reliever/‘rescue’ treatment Twice or less per week

Lung function Normal


Why is stability of control important?

• Stability of control leads to decreased future risk of exacerbations

Variability in control increases likelihood of exacerbations, hospitalisations and emergency

treatments


Key aspects of asthma management

1. Patient/doctor partnership

– Patient educated and empowered to manage their asthma

2. Identify risk factors and reduce exposure to them

– Avoidance of triggers

– Lifestyle modification, e.g. smoking cessation

3. Assess, treat and monitor asthma

– Pharmacological treatments

– Regular monitoring

4. Manage exacerbations

– Pharmacological treatments


Asthma medicines

GINA Guideline 2010

Reliever medicines Preventer medicines Protector medicines

• Are quick acting• Give instant relief• Relax the muscles of the

airways• Are usually inhaled

• Are steroids• Act over a longer period• Reduce swelling and

inflammation in the airways• Are usually inhaled but can

be taken as tablets or injected

• Help keep the airways open• Act in a similar way to

relievers, but have a slower onset of action

• Act over a longer period than relievers, so need to be taken regularly

• Are given in addition to a preventer for extra protection

• Are not used for short-term relief


Relievers-Asthma medicinesDrug

Short acting Beta Agonist-Salbutamol-Albuterol-Terbutaline

MDI or nebulisedDrug of choice for acute bronchospasmPre-exercise

Anticholinergics-Ipratropium bromide

MDI or nebulisedMay be given in addition to SABAAs alternative to SABA

Short Acting Theophylline-Aminophylline

IV in Acute emergencyMonitor toxicity

Adrenaline In desperate situations in absence of SABA0.2-0.5mg SC q10-20mins (1:1000)

Preventers-Asthma MedicinesDrug

Inhaled Corticosteriods-Fluticasone propionate-Beclamethasoe-Budesonide

Use the lowest dose that will control symptomsHigh doses have been associated with systemic side effectsMouth rinsing after use may reduce oropharyngeal candiasis

Long Acting Beta Agonist (LABA)-Formoterol-Salmeterol

Salmeterol is not for acute exacerbationsNot for use as mono-therapy/to used in conjuction with ICS

Anti-leukotrienes-Montelukast-Zafirlukast

For mild persistent asthma

Sodium Cromoglycate May take up to a month to achieve maximum effect

Oral slow release medication-Slow release Theophylline

Advantages of pulmonary route for locally acting drugs

• Drug delivered direct to its target site in the lungs

– Systemic absorption and distribution throughout the body not required

– Lung dose does not undergo hepatic first-pass metabolism

• Achieve similar or superior therapeutic effect at low dose

• Minimise risk of systemic side-effects

– Particularly useful for inhaled corticosteroids

• Rapid clinical response

Labiris & Dolovich. Br J Clin Pharmacol 2003GSKI/AST-PPT/01/10/11

Inhalers

GINA Guideline 2010

Inhaler type Notes

1. Metered dose inhalers (MDI)

Pressurised (pMDI) • Requires to coordinate activation of inhaler and inhalation

• Can be used during exacerbations

Breath-actuated MDI • Useful for patients having difficulty with pMDIs

2. Dry powder inhalers (DPI) • Easy to use but require minimal inspiratory flow rate

3. Nebulised aerosols • Rarely used in chronic adult asthma


Formulation: usually ordered mixture of drug and carrier

Patient inhales through device

Drug Carrier

Inhale with maximal inspiratory effort to disperse powder as efficiently as possible

Passive DPI: Schematic

Most adult patients and older children can generate sufficient inhaled air flow to benefit from DPI therapy1

But many patients do not use sufficient inspiratory effort when using DPIs in clinical practice2

1. Borgstrom et al. J Aerosol Med 20012. Melani et al. Clin Drug Invest 2005GSKI/AST-PPT/01/10/11

DPIs: easier to use correctly than pressurised MDI?

Inhaler technique assessed in >3800 patients in 575 general practices:

•pMDI: 1/3 patients made crucial errors– Mainly poor coordination

•Turbuhaler DPI: 1/3 patients made crucial errors– Incorrect loading of the dose– Blowing out into the device

Accuhaler DPI: 1/10 patients made crucial errors

Crucial errors in DPIs are device-specific

Molimard et al. J Aerosol Med 2003GSKI/AST-PPT/01/10/11

Step 1 Step 2 Step 3 Step 4 Step 5

Low-dose ICS plus sustained-release

theophyline

Sustained release theophyline

Low-dose ICS plus leukotriene modifier

Anti-IgE treatmentLeukotriene

modifierMedium- or

high-dose ICSLeukotriene modifier

Oral glucocorticosteroid

(lowest dose)

Medium- or high-dose ICS

plus long-acting ß2-agonist

Low-dose ICS plus long-acting ß2-agonist

Low-dose inhaled ICS

Add one or moreAdd one or moreSelect oneSelect one

Controlleroptions

As needed rapid-acting ß2-agonistAs needed rapid-acting ß2-agonist

Asthma education

Environmental control

Management approach based on control

In most cases, preferred controller option is an ICS/LABA combinationGINA Guideline 2010


Equipotent daily doses of inhaled doses of corticosteroids

Drug Low Dose (mcg)

Medium dose (mcg)

High dose (mcg)

Beclamethasone Dipropionate -CFC

200-500mcg >500-1000mcg >1000-2000mcg

Budesonide 200-400mcg >400-800mcg >800-1600mcg

Fluticasone propionate

100-250mcg >250-500mcg >500-1000mcg

Gaining optimal asthma control (GOAL) Study (Bateman ED et al 2004)

• 1 year • Randomised, stratified, double blind, parallel • 3,421 patients• 3 strata of patients previously on:

– Corticosteroid free– Low dose corticosteroid– Moderate dose corticosteroid

• Patients demonstrated median reversibility of 20% to inhaled SABA

GOAL Study

• Patients where put on FP/Salmeterol VS FP alone

• Treatment was stepped up until control was achieved (or maximum dose of 500mcg FP reached)

• Definition of control was based on the GINA guidelines

Patient demographics

Bateman et al. Am J Respir Crit Care Med 2004

Stratum 1 Stratum 2 Stratum 3

ICS/LABA ICS ICS/LABA ICS ICS/LABA ICS

N 548 550 585 578 576 579

FEV1

(% Pred) 77% 79% 78% 77% 75% 76%

Reversibility(Median %)

23% 22% 22% 22% 23% 22%

Rescue use(mean occasions/ day)

1.9 1.7 1.7 1.7 1.9 1.9

Exacerbation rate 0.4 0.3 0.6 0.5 0.7 0.7


WELL-CONTROLLED asthmaContinued improvements with sustained treatment

20

80

100

0

60

40

Patie

nts

cont

rolle

d ea

ch w

eek

(%)

Week

ICS/LABA (n=1709)

ICS (n=1707)

–4 0 4 40 44 4812 16 24 28 32 36 528 20

All patients

Bateman et al. Am J Respir Crit Care Med 2004Proportion of patients achieving a well-controlled week (noncumulative)over Weeks 4 to 52 for all strata combined on treatmentwith salmeterol/fluticasone or fluticasone propionate GSKI/AST-PPT/03/10/11

asthma masterclass

Documents

prevalence of clinical

cases of asthma

international study

prevalence of current

prevalence rates

gina burden report

recurrent wheezing

proinflammatory cells