Treatment of asthma; basics can save lives!

1. Dr M. Dikgang

2.  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.

3. Risk Factors
(for development of asthma)
INFLAMMATION
Airway
Hyperresponsiveness Airflow Obstruction
Risk Factors Symptoms
(for exacerbations)

4.  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

5. Worldwide Variation in Prevalence of
Asthma Symptoms
International Study of
Asthma and Allergies in
Children (ISAAC)
Lancet 1998;351:1225

6. Environmental
Genetic factors factors
Mixed
Atopic factors Non-
asthma atopic/idiosyncratic
asthma
Early onset
Late onset

7. 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)

9.  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

10.  History and patterns of symptoms
 Physical examination
 Measurements of lung function
 Measurements of allergic status to identify risk
factors

11.  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

12.  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.

13. Asthma COPD
cannot be fully prevented can be prevented
can be fully controlled
cannot be fully reversed
does not progress is progressive

14. COPD and Asthma are different
diseases!
Asthma COPD
Allergic
Small airway
inflammation of
COPD narrowing
airways
& &
Asthma Bronchospasm
Hyper- (15%) &
responsiveness
Airway collapse
Bronchospasm
Maintain
Control inflammation
bronchodilatation
with ICS
with regular
Minimal bronchodilator
bronchodilator

15. History COPD Asthma
Smoker or ex- Nearly always Variable
smoker
Onset Usually > 40 Most < 30 years
years
Breathlessness Gradual and Paroxysmal
progressive
Chronic cough Common Infrequent
with sputum

16. Investigation COPD Asthma
s
FEV1 Always reduced Variable
Daily variation in Minimal ―Morning dip‖
PEF + day-to-day
Reversibility <15% >15%

18. To effectively controll asthma by…
A. Suppressing and reversing
inflammation
B. Treating bronchoconstriction
and related symptoms

19.  Life-threatening medical emergencies
 Treatment is often most safely undertaken in a
hospital or hospital-based emergency
department

20. Initial Assessment
History, Physical Examination, PEF or FEV1
Initial Therapy
Bronchodilators; O2 if needed
Good Response
Incomplete/Poor Response Respiratory Failure
Observe for at Add Systemic Glucocorticosteroids
least 1 hour
Good Response Poor Response
If Stable,
Discharge to Discharge Admit to Hospital Admit to ICU
Home

21. 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

22. Uncontrolled
Controlled (mild Partly controlled (moderate-
Characteristic intermittent) (mild persistent) severe
(All of the following) (Any present in any week)
persistent)
None (2 or less / More than
Daytime symptoms
week) twice / week
Limitations of 3 or more
None Any features of
activities
partly
Nocturnal controlled
symptoms / None Any asthma
awakening present in
Need for rescue / None (2 or less / More than any week
“reliever” treatment week) twice / week
< 80% predicted or
Lung function
Normal personal best (if
(PEF or FEV1)
known) on any day
Exacerbation None One or more / year 1 in any week

23.  Preventers - anti-inflammatory
 Relievers - short acting bronchodilators
that provide rapid relief of
symptoms
 Controllers - sustained bronchodilator
action with unproven or mild
anti-inflammatory action

24. Classification of drugs used in the
maintenance treatment of asthma
PREVENTERS CONTROLLERS RELIEVERS
Anti-inflammatory Sustained broncho- For quick relief of
action to prevent dilator action but weak symptoms and use in
asthma attacks or unproven anti- acute attacks as p.r.n.
inflammatory effect dose only
Inhaled Long-acting ß2 Short-acting ß2
corticosteroids agonists agonists
Beclomethasone Salmeterol Salbutamol
Budesonide Formoterol Fenoterol
Fluticasone Methylxanthines Terbutaline
Flunisolide Hexoprenaline
Triamcinolone
Sustained-release Orciprenaline
theophyllines
Oral Anti-cholinergics
corticosteroids Leukotriene Ipratropium
Prednisone receptor Short-acting
Prednisolone antagonists** theophyllines
Methylprednisolone Montelukast
Zafirlukast
** Provisional categorisation pending further data

25. MILD
Increasing Severity SEVERE
INTERMITTENT
Inhaled
corticosteroids
> 1000 µg/day
Inhaled (BDP
corticosteroids equivalent)
500 - 1000 +/-
Inhaled µg/day
corticosteroids Oral
(BDP corticosteroids
200 - 500 µg/day equivalent)
(BDP equivalent) +/-
+ Long-acting ß2
+
Long-acting ß2 Long-acting ß2 agonist
agonist (preferred) agonist +/-
or SR theophyllines (preferred) SR
Inhaled and/or
or theophyllines
corticosteroids SR
Inhaled
200 - 500 µg/day theophyllines
corticosteroids 500
(BDP
- 1000 µg/day (BDP
equivalent)
equivalent)
Refer pulmonologist
ß2 agonists prn ß2 agonists prn ß2 agonists prn ß2 agonists prn ß2 agonists prn may be
required 4-6 x/day
LTRA? LTRA

26.  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

27.  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)

28.  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)

29.  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

31.  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

32. Montelukast - Singulair
Zafirlukast - Accolate
Advantages:
• 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 !

33. DISADVANTAGES
ADVANTAGES  Bulky, inconvenient
 Easy to use correctly once Electricity supply usually needed
prepared: relaxed tidal  Preparation and assembly a problem,
breathing especially for the elderly?
 Convenient way of  Long treatment times
delivering high doses
 Patients find them  Cleaning / contamination issues
reassuring  Expensive
 Dose control possible in  Patients rely on them instead of using
sophisticated devices controller medications
 No propellants needed  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

34. Reasons for poor
patient adherence to treatment
 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

35. Follow-up
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

36.  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