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Definition
Asthma is a clinical syndrome of unknown etiology
characterized by three distinct components:
(1) recurrent episodes of airway obstruction that
resolve spontaneously or as a result of treatment
(2) exaggerated bronchoconstrictor response to
stimuli that have little or no effect in nonasthmatic
subjects (airway hyperresponsiveness)
(3) inflammation of the airways
Epidemiology
 Asthma is an extremely common disorder
affecting boys more commonly than girls in
childhood and, after puberty, women more
commonly than men
 Although most cases begin before the age of
25 years, asthma may develop at any time
throughout life
 The worldwide prevalence of asthma has
increased more than 45% since the late
1970s. The greatest increases in asthma
prevalence have occurred in countries that
have recently adopted an “industrialize”
lifestyle
 Asthma is among the most common reasons
to seek medical treatment
Pathobiology
 Asthma has about 60% heritability,
indicating that both genetic and
environmental factors are important in its
etiology
Pathophysiology
 Airway hyper-reactivity (AHR)—the
tendency for airways to contract too easily
and too much in response to triggers that
have little or no effect in normal
individuals—is integral to the diagnosis of
asthma
 The degree of airway narrowing
 With increasing severity and chronicity of
the disease, remodelling of the airway
occurs, leading to fibrosis of the airway wall,
fixed narrowing of the airway and a reduced
response to bronchodilator medication
 Relationship between atopy (tendecy to
produce IgE) and asthma is well established
 Proved in many individuals by clear
relationship between sensitisation
(demonstration of skin prick reactivity or
elevated serum specific IgE) and allergen
exposure
 Common allergens include house dust
mites, pets such as cats and dogs, pests such
as cockroaches, and fungi (Aspergillus:
allergic bronchopulmonary aspergillosis)
 In aspirin-sensitive asthma, symptoms
follow the ingestion of salicylates
Intrinsic Asthma
 A minority of patients (approximately 10%)
have negative skin tests to common inhalant
allergens and normal serum concentrations
of IgE.\
 These patients, usually show later onset of
disease (adult-onset asthma), commonly
have concomitant nasal polyps, and may be
aspirin-sensitive
 In exercise-induced asthma,
hyperventilation results in water loss from
the pericellular lining fluid of the
respiratory mucosa, which
in turn triggers mediator release
 Heat loss from the respiratory mucosa may
also be important
Hygiene Hypothesis
 Lower levels of infection may be a factor in
affluent societies that increase the risks of
asthma
 Children who are exposed to a high level of
infection & endotoxin are less likely to
develop allergic sensitization than children
raised in hygienic environment
 Intestinal parasite infection may also be
associated with a reduced risk of asthma
Diet
 Diets low in antioxidants such as vitamin C
and vitamin A, magnesium, selenium, and
omega-3 polyunsaturated fats (fish oil) or
high in sodium are associated with an
increased risk of asthma
 Vitamin D deficiency may also predispose
to the development of asthma
 However, interventional studies with
supplementary diets have not supported an
important role for these dietary factors
 Obesity is also an independent risk factor
for asthma, particularly in women, but the
mechanisms are unknown
 In persistent asthma, a chronic and complex
inflammatory response ensues
 Smooth muscle hypertrophy and
hyperplasia, thickening of the basement
membrane, mucous plugging and epithelial
damage results
Clinical features
 Typical symptoms include recurrent
episodes of wheeze, chest tightness,
breathlessness and cough
 Not uncommonly, asthma is mistaken for a
cold or chest infection that is failing to
resolve (e.g. after more than 10 days)
 Symptoms may be worse at night and
patients typically awake in the early
morning hours
 Prodromal symptoms may precede an
attack, with itching under the chin,
discomfort between the scapulae, or
inexplicable fear (impending doom)
 Some patients, particularly children, may
present with a predominant nonproductive
cough (cough-variant asthma)
 Typical physical signs are inspiratory, and
expiratory, rhonchi throughout the chest
 There may be no abnormal physical findings
when asthma is under control
Classical precipitants
Allergens
 Inhaled allergens activate mast cells with
bound IgE directly leading to the immediate
release of bronchoconstrictor mediators
 The most common allergens to trigger
asthma are Dermatophagoides species
(house dust mite) and environmental
exposure leads to low-grade chronic
symptoms that are perennial
 Other perennial allergens are derived from
cats and other domestic pets, as well as
cockroaches
 Other allergens, including grass pollen, tree
pollen, and fungal spores, are seasonal
 Pollens usually cause allergic rhinitis rather
than asthma, but in thunderstorms the
pollen grains are disrupted and the particles
that may be released can trigger severe
asthma exacerbations (thunderstorm
asthma)
Virus Infections
 Upper respiratory tract virus infections such
as rhinovirus, respiratory syncytial virus,
and coronavirus are the most common
triggers of acute severe exacerbations and
may invade epithelial cells of the lower as
well as the upper airways
 Why these viruses cause exacerbations is
poorly understood, but there is an increase
in airway inflammation with increased
numbers of eosinophils and neutrophils
 In asthmatic patientsfor production of type I
interferons by epithelial cells is reduced,
resulting in increased susceptibility to these
viral infections and a greater inflammatory
response
Pharmacologic Agents
 Beta-adrenergic blockers commonly acutely
worsen asthma, and their use may be fatal
 All beta blockers need to be avoided and
even selective beta blocker or topical
application (e.g., timolol eye drops) may be
dangerous
 Aspirin may worsen asthma in some
patients (aspirin-sensitive asthma)
Exercise
 Exercise is a common trigger of asthma,
particularly in children. The mechanism is
linked to hyperventilation, which results in
increased osmolality in airway lining fluid
and triggers mast cell mediator release,
resulting in bronchoconstriction
 Exercise-induced asthma (EIA) typically
begins after exercise has ended, and recovers
spontaneously within about 30 minutes
 EIA is worse in cold, dry climates than in
hot, humid conditions
 It may be prevented by prior administration
ofbeta 2-agonists and antileukotrienes, but
is best prevented by regular treatment with
ICS, which reduce the population of surface
mast cells required for this response
Physical Factors
 Cold air and hyperventilation may trigger
asthma through the same mechanisms as
exercise
 Laughter may also be a trigger
 Many patients report worsening of asthma
in hot weather and when the weather
changes

Some asthmatics become worse when
exposed to strong smells or perfumes, but
the mechanism of this response is uncertain
Food
 There is little evidence that allergic
reactions to food lead to increased asthma
symptoms, despite the belief of many
patients that their symptoms are triggered
by particular food constituents
 Exclusion diets are usually unsuccessful at
reducing the frequency of episodes
Air Pollution
 Increased ambient levels of sulfur dioxide,
ozone, and nitrogen oxides are associated
with increased asthma symptoms
Hormonal Factors
 Some women show premenstrual worsening
of asthma, which can occasionally be very
severe
Stress
 Many asthmatics report worsening of
symptoms with stress
 Psychological factors can induce broncho
constriction through cholinergic reflex
pathways
 Paradoxically, very severe stress such as
bereavement usually does not worsen, and
may even improve, asthma symptoms
Diagnosis
 The diagnosis is usually apparent from the
symptoms of variable and intermittent
airways obstruction, but is usually
confirmed by objective measuements of
lung function
Lung Function Tests
 Simple spirometry confirms airflow
limitation with a reduced FEV1, FEV1/FVC
ratio, and PEF
 Reversibility is demonstrated by a >12% and
200-mL increase in FEV1 15 minutes after an
inhaled short-acting beta2-agonist
 > 20% diurnal variation on ≥ 3 days in a
week for 2 weeks on PEF diary
 FEV1 ≥ 15% decrease after 6 mins of exercise
Airway Responsiveness
 The increased AHR is normally measured by
methacholine or histamine challenge test
that reduces FEV1 by 20% (PC20)
 This is rarely useful in clinical practice, but
can be used in the differential diagnosis of
chronic cough and when the diagnosis is in
doubt in the setting of normal LFT
Skin Tests
 Skin prick tests to common inhalant
allergens are positive in allergic asthma and
negative in intrinsic asthma
 Not helpful in diagnosis
 Positive skin responses may be useful in
persuading patients to undertake allergen
avoidance measures
Exhaled Nitric Oxide
 Exhaled NO is now being used as a noninvasive
test to measure eosinophilic airway
inflammation
 The typically elevated levels in asthma are
reduced by ICS
 This may be a test of compliance with therapy
 It may also be useful in demonstrating
insufficient anti-inflammatory therapy
Treatment
 Asthma is a chronic condition but effective
treatment is available for the majority of
patients
 The goal of management should be to
obtain and sustain complete control
 Patients should be made to understand the
nature of the condition, the relationship
between symptoms and inflammation, the
importance of key symptoms such as
nocturnal waking, the different types of
medication
Avoidance of aggravating factors
 Occupational asthma
 Atopic patients where removing or reducing
exposure to relevant antigens, e.g. a pet
animal
A stepwise approach
 Step 1: Occasional use of inhaled shortacting β2-adrenoreceptor agonist
bronchodilators
 For patients with mild intermittent asthma
(symptoms less than once a week for 3
months and fewer than two nocturnal
episodes/month)
Step 2: Introduction of regular ‘preventer’
therapy
 Regular anti-inflammatory therapy
(preferably inhaled corticosteroids (ICS)
such as beclometasone,budesonide,
fluticasone or ciclesonide) should be started
in addition to inhaled β2-agonists taken on
an as-required basis
In any patient who:
 Has experienced an exacerbation of asthma
in the last 2 years
 Uses inhaled β2-agonists three times a week
or more
 Reports symptoms three times a week or
more
 Is awakened by asthma one night per week
 For adults, a reasonable starting dose is 400
μg beclometasone dipropionate (BDP) or
equivalent per day, although higher doses
may be required in smokers
 Step 3: Add-on therapy
 If a patient remains poorly controlled
despite regular use of ICS, a thorough review
should be undertaken focusing on
adherence, inhaler technique and on-going
exposure to modifiable aggravating factors
 In general, add-on therapy should be
considered in adults taking 800 μg/day BDP
(or equivalent)
 Long-acting β2-agonists (LABAs), such as
salmeterol and formoterol, with a duration
of action of at least 12 hours, should be
added
 Fixed combination inhalers of ICS and
LABAs have been developed
 These are more convenient, increase
compliance, and prevent patients using a
LABA as monotherapy alone
 Oral leukotriene receptor antagonists (e.g.
Montelukast 10 mg daily) are generally less
effective than LABA as add-on therapy but
may facilitate a reduction in the dose of ICS
and control exacerbations
 Oral theophyllines may be considered in
some patients but their unpredictable
metabolism, propensity for drug
interactions and prominent side-effect
profile limit their widespread use
 Step 4: Poor control on moderate dose of
inhaled steroid and add-on therapy:
addition of a fourth drug
 In adults, the dose of ICS may be increased
to 2000 μg BDP/budesonide (or equivalent)
daily
 A nasal corticosteroid preparation should
be used in patients with prominent upper
airway symptoms
 Oral therapy with leukotriene receptor
antagonists, theophyllines or a slowrelease
Β2 -agonist may be considered
 Step 5: Continuous or frequent use of oral
steroids
 At this stage prednisolone therapy should be
prescribed in the lowest amount necessary
to control symptoms
 Long-term oral corticosteroids (> 3 months)
will be at risk of systemic side-effects
 Osteoporosis can be prevented in this group
of patients by using bisphosphonates and
calcium
 Steroid-sparing therapies such as
methotrexate, ciclosporin or oral gold may
be considered
 New therapies, such as omalizumab, a
monoclonal antibody directed against IgE,
may prove helpful in atopic patients
Step-down therapy
 Once asthma control is established, the dose
of inhaled(or oral) corticosteroid should be
titrated to the lowest dose at which effective
control of asthma is maintained
 Decreasing the dose of ICS by around 25–
50% every 3 months is a reasonable strategy
for most patients
Asthma in pregnancy
Clinical course
 Unpredictable
 One-third worsen, one-third remain stable
and one-third improve
Safety of drugs in pregnancy





Safe
β2-agonists
Inhaled steroids
Theophyllines,
Oral prednisolone
Oral leukotriene receptor antagonists
 Uncontrolled asthma represents the
greatest danger to the fetus and mother
Breastfeeding
 Medications are safe
Acute severe asthma
Features
 PEF 33–50% predicted (< 200 L/min)
 Respiratory rate ≥ 25/min
 Heart rate ≥ 110/min
 Inability to complete sentences in 1 breath
Life-threatening features
 PEF < 33% predicted (< 100 L/min)
 SpO2 < 92% or PaO2 < 8 kPa (60 mmHg)
 Normal or raised PaCO2
 Silent chest
 Cyanosis
Life-threatening features (contd)
 Feeble respiratory effort
 Bradycardia or arrhythmias
 Hypotension
 Exhaustion
 Confusion
 Coma
Treatment
 Arterial blood gas
 Nebulised salbutamol 5 mg 2–4-hourly
 Oxygen—high-flow/60%
 Hydrocortisone 200 mg i.v.
ADMIT
 Administer repeat salbutamol 5 mg +
ipratropium bromide 500 μg by o2-driven
nebuliser
 Consider i.v. magnesium sulphate 1.2–2.0 g
over 20 mins, or aminophylline 5 mg/kg
loading dose over 20 mins followed by a
continuous infusion at 1 mg/kg/
 Correct fluid and electrolytes
Thank you