ASTHMA

Background
Asthma is a heterogeneous
disease, usually characterized by
chronic airway inflammation.
It is defined by the history of
respiratory symptoms such as
wheeze, shortness of breath, chest
tightness and cough that vary over
time and in intensity, together with
variable expiratory airflow
limitation.
Prevalence
 Atopic Asthma
Most patients with asthma in affluent
countries are atopic
genetically determined production of
specific IgE, +ve skin test with
allergen, commonly with family hx
Patient mostly suffer from other atopic
diseases, particularly allergic rhinitis
and atopic dermatitis (eczema).
 Non-atopic Asthma
approximately 10% have negative skin
tests to common inhalant allergens
normal serum concentrations of IgE.
usually show later onset of disease
(adult-onset asthma)
Commonly have concomitant nasal
polyps, and may be aspirin-sensitive
usually have more severe, persistent
asthma.
Postulated Hygiene Hypothesis
hygiene hypothesis proposes that lack of
infections in early childhood preserves the
Th2 cell bias at birth, whereas exposure to
infections and endotoxin results in a shift
toward a predominant protective Th1
immune response.
Pathogenesis
Pathology
Pathology
 Pathophysiology
AHR is the characteristic physiologic
abnormality of asthma and describes
the excessive bronchoconstrictor
response to triggers that would have
no effect on normal airways.
leading to excessive narrowing with
consequent reduced airflow and
symptomatic wheezing and dyspnea.
 Pathophysiology
Early closure of peripheral airway results
in lung hyperinflation, (air trapping) and
increased residual volume, particularly
during acute exacerbations and in severe
persistent asthma.
In more severe asthma, reduced
ventilation and increased pulmonary blood
flow result in mismatching of ventilation
and perfusion and in bronchial hyperemia.
 Pathophysiology
Reduction in FEV 1 , FEV 1 /forced vital
capacity (FVC) ratio, and peak expiratory
flow (PEF), as well as an increase in airway
resistance.
Clinical features of
Asthma
 Symptoms
recurrent episodes of wheezing
chest tightness
breathlessness
Cough
 History
Classical precipitants include exercise, cold weather,
exposure to airborne allergens or pollutants, laughter,
strong smells and viral upper respiratory tract infections.
mild intermittent asthma are usually asymptomatic
between exacerbations.
persistent asthma ongoing breathlessness and wheeze
diurnal pattern: cough and wheeze disturb sleep/ worse
in the early morning.
Cough + the lack of wheeze or breathlessness may lead
to a delay in reaching the diagnosis of cough-variant
asthma.
Symptoms vary over time and in intensity
 Signs
Wheeze
inspection for eczema
Rarely, a vasculitic rash may
suggest Churg Strauss syndrome
 DIAGNOSTIC FEATURE

1. History of variable respiratory

symptoms
2. Confirmed variable expiratory
airflow limitation
 1. History of variable
respiratory symptoms
Wheeze, shortness of breath, chest tightness and
cough
Generally more than one type of respiratory symptom
(in adults, isolated cough is seldom due to asthma)
Symptoms occur variably over time and vary in
intensity
Symptoms are often worse at night or on waking
Symptoms are often triggered by exercise, laughter,
allergens, cold air
Symptoms often appear or worsen with viral infections
2. Confirmed variable expiratory
airflow limitation
Documented excessive variability in
lung function
AND documented airflow limitation
 2. Confirmed variable
expiratory airflow limitation
spirometry
to measure FEV1 and VC.
identifies the obstructive defect and defines its
severity
provides a baseline for bronchodilator reversibility
At least once during diagnostic process when FEV1 is
low, confirm that FEV1/FVC is reduced (normally
>0.750.80 in adults, >0.90 in children)
Positive bronchodilator (BD) reversibility test
Adults: increase in FEV1 of >12% and >200 mL from
baseline, 1015 minutes after 200400 mcg albuterol or
equivalent (greater confidence if increase is >15% and
>400 mL).
Children: increase in FEV1 of >12% predicted
2. peak flow meter
record peak flow readings after rising in
the morning and before retiring in the
evening.
Dx by :Excessive variability in twice-daily
PEF over 2 weeks
Adults: average daily diurnal PEF variability
>10%
Children: average daily diurnal PEF variability
>13%
3. Significant increase in
lung function after 4
weeks of anti-
inflammatory
treatment(trial of
corticosteroids )

Adults: increase in FEV1

by >12% and >200 mL
(or PEF by >20%) from
baseline after 4 weeks
of treatment, outside
respiratory infections
4. Positive
exercise
challenge test
Adults: fall in
FEV1 of >10%
and >200 mL
from baseline
Children: fall in
FEV1 of >12%
predicted, or
PEF >15%
5. Positive bronchial
challenge test
(usually only
performed in adults)

Fall in FEV1 from

baseline of 20%
with standard doses
of methacholine or
histamine, or 15%
with standardized
hyperventilation,
hypertonic saline or
mannitol challenge
6. Excessive variation in lung function
between visits (less reliable)
Adults: variation in FEV1 of >12%
and >200 mL between visits, outside
of respiratory infections
Children: variation in FEV1 of >12%
in FEV1 or >15% in PEF between
visits (may include respiratory
infections)
 7. Other tests
Measurement of allergic status:
skin prick tests atopy
Measurement of total and allergen-specific IgE.

Exhaled nitric oxide

fractional concentration of exhaled nitric oxide
(FENO)
FENO is increased in eosinophilic asthma but also
in non-asthma conditions (e.g. eosinophilic
bronchitis, atopy and allergic rhinitis)
FENO is decreased in smokers and during
bronchoconstriction
increased or decreased during viral respiratory
infections
not been established as being useful
 MANAGEMENT OF
ACUTE SEVERE ASTHMA
acerbations of asthma
nagement of mild to moderate exacerbatio
Doubling the dose of ICS does not prevent an impending exacerbation. Short courses of
rescue oral corticosteroids (prednisolone 3060 mg daily) therefore are often required to
regain control. Tapering of the dose to withdraw treatment is not necessary, unless given
for more than 3 weeks.
Indications for rescue courses include:
symptoms and PEF progressively worsening day by
day, with a fall of PEF below 60% of the patients
personal best recording
onset or worsening of sleep disturbance by asthma
persistence of morning symptoms until midday
progressively diminishing response to an inhaled
bronchodilator
symptoms sufficiently severe to require treatment
with nebulised or injected bronchodilators.
nagement of acute severe asthm
 Reference:
1. Global Initiative for Asthma. Global
Strategy for Asthma Management and
Prevention, 2016. Available from:
www.ginasthma.org
2. Davidsons Principles & Practice of
Medicine , 22nd edition (2014);
Churchill Livingstone, Chapter 18.
Management of asthma
 Since patients are encouraged to take
responsibility for managing their symptoms,
detailed explanations on :
- The relationship between symptom and
inflammation
- The different types of medication and
- The use of PEF to guide management
decisions .

Next, patients should be encouraged to

avoid the aggravating factor
( housemites, dust, pets , smoking and certain
medication )
 Stepwise approach to the
management of asthma
Step 1 : occasional use of a short acting B 2 agonist
Salbutamol or terbutaline
When are they used ?
- If the patient has symptoms less than 1 a week for 3
months or fewer than 2 nocturnal symptoms per month
Mode of action:
- 2 agonists stimulate adenylyl cyclase and cAMP in
smooth muscle cells, results in a powerful bronchodilator
response.
- Their effects last for 4 h or less.
- Not effective for prophylaxis.
- Different devices can be used to deliver the drug
 Step 2: Introduction of regular preventer therapy
Inhaled Corticosteroids like; fluticasone,
budesonide beclometasone
When are they used ?
If the patient has:
- Experienced an acute exacerbation in the last 2 years
- Requires the B2agonist inhaler more than 3 times a
week
- symptoms more than 3 times a week
- Has nocturnal symptoms once a week
Mode of action:
- Corticosteroids reduce the synthesis of arachidonic acid
by phospholipase A2. hence reduced synthesis of
leukotriene an inflammatory mediator that place a role
in the pathophysiology of asthma
Dosage should be increased in smokers
 Other agents that could be used at step 2
include ;
1. Leukotriene receptor antagonist
LTD4 leukotriene receptor.
LTE4 receptor is also blocked.

2. Theophylline-
Inhibit phosphodiesterase (PDE) enzyme that
degrades cAMP to AMP, & thus cAMP. This
effect requires high concentrations of the drug.
 Step 3: Add on therapy
Further increase the ICS dosage
LABA ( Salmetrol and formoterol )
LABA + An increase in ICS
Oral leukotriene receptor antagonist

When are they used ?

If the patient remains poorly controlled
despite the use of ICS
Patient should be reviewed for adherence,
inhaler technique and the ongoing
exposure to modifiable aggravating factors
 Step 4: poor control on moderate
dose ICS and add on therapy:
addition of a fourth drug

- Increase dose of ICS to 2000

- Or add a fourth drug : oral
leukotriene receptor antagonist or
Theophylline may be considered
 Step 5: continuous or frequent use of
oral steroids
- At this stage use of oral prednisolone
tablets keeping it at the minimal dose
- There is a risk of systemic side effects
- patients with atopy can be given
omalizumab, a monoclonal antibody
against IgE which could be used instead of
prednisolone
- Other steroid sparing therapies may be
considered such as methotrexate,
ciclosporin or oral gold, may be considered
Osteoporosis
can be
controlled by
giving pt. on
oral
corticosteroids

bisphosphonat
es
Asthma in pregnancy