asthma masterclass
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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).
GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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?
GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GSKI/AST-PPT/03/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GINA Guideline 2010GSKI/AST-PPT/01/10/11
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
GSKI/AST-PPT/01/10/11
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
GSKI/AST-PPT/01/10/11
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
GSKI/AST-PPT/01/10/11
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
GSKI/AST-PPT/03/10/11
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
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