MANAGEMENT OF ASTHMA
Dr M. Dikgang
Definitions
Chronic inflammatory disease of airways Increased responsiveness of
tracheobronchial tree Multiplicity of stimuli Episodic disease Narrowing of airways (acutely and
gradually), relieved spontaneously or after therapy.
Risk Factors(for development of asthma)
Risk Factors(for development of asthma)
INFLAMMATIONINFLAMMATION
Airway
Hyperresponsiveness
Airway
Hyperresponsiveness Airflow ObstructionAirflow Obstruction
Risk Factors(for exacerbations) Risk Factors(for exacerbations)
SymptomsSymptoms
Epidemiology Asthma is one of the most common chronic
diseases worldwide —160 million patients suffer from asthma
Prevalence increasing in many countries, especially in children — 1~4% in adult, 3~5% in children in China
A major cause of school/work absence An overall increase in severity of asthma
increases the pool of patients at risk for death
Worldwide Variation in Prevalence of Asthma Symptoms
International Study of Asthma and Allergies in Children (ISAAC)
Lancet 1998;351:1225
Aetiology
Genetic factorsEnvironmental factors
Mixed factorsAtopic
asthmaNon-atopic/idiosyncratic asthma
Late onsetEarly onset
Pathogenesis
Stimuli: Allergens (mites, fur, feathers,molds etc) Pharmacological (NSAIDS, B-blockers etc) Environmental (NO2, sulphur dioxide) Occupational (wood/vegetable
dust,pharmaceuticals etc) Infections (viruses-RSV, para-influenza) Exercise Emotional stress (vagal efferent activity,
endorphins)
Antigen PresentingCell
TH2
MastCell
Mediators
SurvivalActivation
AttractionAdhesion
Priming
Eosinophil
Endothelium
Ag:
Production
M I nman
BronchoconstrictionHyperresponsiveness
Pathology
Gross overdistention of lungs, non-collapsible
Gelatinous plugs of exudate in bronchial branches, down to terminal bronchioles
Hypertrophy of bronchial smooth muscle Hyperplasia of mucosal & submucosal
blood vessels Mucosal oedema Thickening of basement membrane Eosinophilic infiltrates in the bronchial
walls
Asthma Diagnosis
History and patterns of symptoms
Physical examination
Measurements of lung function
Measurements of allergic status to identify risk factors
Clinical Manifestation of Asthma
Recurrent episodes of wheezing Troublesome cough at night Cough or wheeze after exercise Cough, wheeze or chest tightness after
exposure to airborne allergens or pollutants Colds “go to the chest” or take more than 10
days to clear
Investigations
Lung function tests- FEV1/FVC ratio (<70%or normal), PEFR
Bronchodilator test- reversibility (>15% improvement in FEV1)
CXR Sputum (thick, with eosinophils +
Charcots-Leyden crystals), blood (IgE levels, eosinophilia)
Allergy tests- skin, inhalants, catecholamines etc.
COPD and Asthma are different diseases!
Asthma
cannot be fully prevented can be fully controlled
does not progress
COPD
can be preventedcannot be fully reversed
is progressive
COPD
Small airway narrowing
&Bronchospas
m&
Airway collapse
Maintain bronchodilatat
ion with regular
bronchodilator
COPD and Asthma are different diseases!
COPD&
Asthma(15%)
Control inflammation with ICS
Minimal bronchodilator
Allergic inflammation
of airways
Hyper-responsivenes
s
Bronchospasm
Asthma
History COPD AsthmaSmoker or ex-smoker
Nearly always Variable
Onset Usually > 40 years
Most < 30 years
Breathlessness Gradual and progressive
Paroxysmal
Chronic cough with sputum
Common Infrequent
Investigations
COPD Asthma
FEV1 Always reduced Variable
Daily variation in PEF
Minimal “Morning dip” + day-to-day
Reversibility <15% >15%
Treatment
GINA 2006: The goal of management
To effectively controll asthma by…
A. Suppressing and reversing inflammation
B. Treating bronchoconstriction and related symptoms
Managing Severe Asthma Exacerbations
Life-threatening medical emergencies
Treatment is often most safely undertaken in a hospital or hospital-based emergency department
Acute Asthma
Good Response
Observe for at least 1
hour
If Stable, Discharge to Home
Initial AssessmentHistory, Physical Examination, PEF or FEV1
Initial TherapyBronchodilators; O2 if needed
Incomplete/Poor Response
Add Systemic Glucocorticosteroids
Good Response
Discharge
Poor Response
Admit to Hospital
Respiratory Failure
Admit to ICU
Goals of Long-term Management
Achieve and maintain control of symptoms Prevent asthma episodes or attacks Maintain pulmonary function as close to normal
levels as possible Maintain normal activity levels, including
exercise Avoid adverse effects from asthma medications Prevent development of irreversible airflow
limitation Prevent asthma mortality
Components of Asthma Control
CharacteristicControlled (mild
intermittent)(All of the following)
Partly controlled (mild persistent)
(Any present in any week)
Uncontrolled (moderate-severe persistent)
Daytime symptomsNone (2 or less / week)
More than twice / week
3 or more features of partly controlled asthma present in any week
Limitations of activities
None Any
Nocturnal symptoms / awakening
None Any
Need for rescue / “reliever” treatment
None (2 or less / week)
More than twice / week
Lung function (PEF or FEV1)
Normal< 80% predicted or
personal best (if known) on any day
Exacerbation None One or more / year 1 in any week
Asthma Guidelines:Classes of Drugs
Preventers - anti-inflammatory
Relievers - short acting bronchodilators that provide rapid relief of
symptoms Controllers - sustained bronchodilator
action with unproven or mild anti-inflammatory
action
Classification of drugs used in the maintenance treatment of asthma
** Provisional categorisation pending further data
Inhaled corticosteroids
BeclomethasoneBudesonideFluticasoneFlunisolideTriamcinolone
Oral corticosteroidsPrednisonePrednisoloneMethylprednisolone
Anti-inflammatory
action to prevent asthma attacks
PREVENTERS
Long-acting ß2 agonists
SalmeterolFormoterol
Methylxanthines
Sustained-releasetheophyllines
Leukotriene receptor antagonists**
MontelukastZafirlukast
Sustained broncho-dilator action but weak or unproven anti-inflammatory effect
CONTROLLERS
Short-acting ß2 agonists
SalbutamolFenoterolTerbutalineHexoprenaline
OrciprenalineAnti-cholinergics
IpratropiumShort-acting
theophyllines
For quick relief of symptoms and use in acute
attacks as p.r.n. dose only
RELIEVERS
MILD INTERMITTENT SEVERE
Inhaledcorticostero
ids> 1000 µg/day(BDP
equivalent)+/-
Oral corticosteroid
s+/-
Long-acting ß2
agonist +/-SR
theophyllinesRefer pulmonologist
Inhaledcorticoster
oids500 - 1000
µg/day(BDP
equivalent)+
Long-acting ß2
agonist (preferred)
and/or SR
theophyllines
Inhaled corticosteroids
200 - 500 µg/day(BDP
equivalent)+
Long-acting ß2 agonist
(preferred) or SR theophyllines
orInhaled
corticosteroids 500 - 1000
µg/day (BDP equivalent)
Inhaled corticosteroi
ds200 - 500
µg/day(BDP
equivalent)ß2 agonists
prnß2 agonists
prnß2 agonists
prnß2 agonists
prnß2 agonists prn may
be required 4-6 x/day
Increasing Severity
LTRA? LTRA? LTRA
Pressurised Metered Dose Inhaler (pMDI)
A convenient and reliable multi-dose device
New propellant is HFA (ozone-friendly)
Rapidly moving, short-duration plume
Impaction of spray in oropharynx likely
Evaporating spray feels cold 70% of dose lodges in
pharynx and much may be swallowed, 15 -20% in lung
pMDIs: CORRECT USE
Remove mouthpiece cap
Shake inhaler (suspensions only)
Breathe out Place actuator
mouthpiece between lips Fire while breathing in
slowly and deeply Continue to inhale Hold breath (for 10 sec)
Errors with MDIs CRUCIAL ERRORS
Firing device at or after end of inhalation Stopping inhalation / inhaling through nose (“cold
Freon” effect) Bizarre errors (e.g. not removing mouthpiece cap)
NON-CRUCIAL ERRORS Firing device before start of inhalation Fast inhalation No breath-hold / short breath-hold Failure to shake inhaler (suspensions only)
SPACERS (HOLDING CHAMBERS): CORRECT USE
Useful for small children (used with snug-fitting face mask)
Useful in improving inhaled steroid deposition in those with difficulty co-ordinating firing of pMDI during or before inhalation
Shake inhaler (suspensions only) Insert pMDI into spacer Breathe out Fire while (or before) breathing in slowly
and deeply Continue to inhale Hold breath (for 10 sec) Repeat with second puff
DRY POWDER INHALERS
DRY POWDER INHALERS: CORRECT USE
Remove cover (device-specific) Prepare device / load dose (device-specific) Pierce capsule (single-dose devices only) Breathe out gently Place mouthpiece between lips Inhale deeply and quickly* Breath-hold (device-specific) Replace cover and store in dry cool environment
LEUKOTRIENE RECEPTOR ANTAGONISTS
Montelukast - SingulairZafirlukast - AccolateAdvantages:• Unique mode of action• Anti-inflammatory – no bronchodilator effect• Very simple dosing: taken by mouth; single dose strength for children, another for adults• Safe• Use:
– Add to inhaled corticosteroids– Monotherapy in mild allergic asthma (children)
Disadvantages:• Poor efficacy (not better than theophylline for most endpoints especially in adults( More useful in children)• Expensive !
NEBULIZERS – NOT recommended for regular use by asthmatics
ADVANTAGES Easy to use correctly
once prepared: relaxed tidal breathing
Convenient way of delivering high doses
Patients find them reassuring
Dose control possible in sophisticated devices
No propellants needed
DISADVANTAGES Bulky, inconvenient Electricity supply usually needed Preparation and assembly a problem, especially
for the elderly? Long treatment times Cleaning / contamination issues Expensive Patients rely on them instead of using controller
medications Their use can delay patients presenting to
emergency departments and lead to asthma deaths (false sense of security)
They are air and not oxygen-driven, so do not correct hypoxia
Misunderstanding about need for both long-term preventive and quick-relief medications
Difficulty with inhaler devices Fear of side effects or addiction Cost of medication Dislike of medication
Reasons for poor patient adherence to treatment
At regular visits (every one to six months): Monitor asthma control – Review symptoms
– Measure lung function – Assess compliance
Modify the treatment plan – Reinforce compliance
– Adjust medications
Follow-up
References
Kasper et-al. Harrison’s Principles of Internal Medicine, 16th edition: 2005; McGraw-Hill, New York, USA: pp1508-1516
Zhiwen Zhu. Pulmonary & Critical Care Medicine, 1st Affiliated Hospital of Sun Yat-Sen University, China
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