Bronchial Asthma

Outline of the Lecture(s)

Bronchial Asthma I
Introduction
Definitions
Epidemiology
Pathogenesis/ Pathophysiology

Bronchial Asthma II
Clinical Features & Investigations
Differential Diagnoses
 Introduction
• Bronchial asthma is one of the most common
chronic illnesses and prevalence is increasing.
• Asthma is probably not one illness, but a
syndrome.
• The disease has different phenotypes with
respect to its course and prognosis and its
association with atopy.
• The diagnosis, assessment of severity and
monitoring of the effects of therapy are
more difficult in young children because it
may not be possible to obtain reliable
objective measurement of airway
obstruction.
 Definitions
Bronchial Asthma:
Asthma is a chronic inflammatory disorder of the
airway in which many cellular elements play a role.

The chronic inflammation causes associated

increase in airways hyperresponsiveness that leads to
recurrent episodes of wheezing, breathlessness, chest
tightness and coughing particularly at night or early in
the morning.

These episodes are usually associated with

widespread or variable airflow obstruction that is
often reversible either spontaneously or with treatments.
 Definitions (contd.)
• Airway responsiveness:
The response of the airways to
provoking stimuli, usually expressed as
the provoking dose (concentration causing
a 20 per cent fall in FEV1) or the slope of
a dose-response curve.
 Definitions (contd.)
• Hyperresponsiveness (Hyperreactivity):
The propensity of the airway to constrict
too easily and too much to allergens.

• Atopy: The ability to develop IgE to

innocuous and ubiquitous environmental
agents such as pollens, mites and molds.
 Definitions (contd.)
• Vital capacity: largest volume a subject
can expire after a single maximal
inspiration.

• Forced vital capacity : The vital capacity

when the expiration is performed as
rapidly as possible.
 Definitions (contd.)
• Forced expiratory volume in one second (FEV1):
Volume expired during first second of Forced Vital
Capacity.

FEV1/FVC=75%

This ratio is reduced in obstructive airway diseases like

asthma, emphysema and bronchitis.

• Peak expiratory flow rate (PEFR): Maximum expiratory

flow rate achieved during a forced expiration.

PEFR is more convenient to measure than FEV1

 Epidemiology
Geographical distribution
• Worldwide
• Prevalence
*Aderele reported 200 hospitalised children
in two and a half years (Archives of disease in childhood
1980…..)
*Sofowora and Clark: 2.4 per cent.
*Okoromah reported 3.0 per cent among 6-13
year old children in Enugu.
*Oviawe reported 0.7 per cent among children in
a rural community.
 Trend in the Prevalence of
Bronchial Asthma in Ibadan,
Nigeria
Falade et al using International Study of Asthma and
Allergies in Childhood (ISAAC) Questionnaire

• ISAAC Phase One(1995)

6-7 year olds : 4.8%
13 -14 year olds:10.7%

• ISAAC Phase Three(2001/2002)

6-7 year olds :5.6%
13-14 year olds:13%
 Epidemiology(contd.)
*Highest prevalence in the UK, Australia
and New Zealand (ISAAC, 1998): 20% -
36.8%.
 Epidemiology (contd.)
• Gender distribution
M:F=1.3:1
 Risk Factors
• Host

• Environmental factors
 Risk Factors (contd.)
• Host factor
Twins study: effect of genetic factors about 35 to 70%

No gene or genes involved in the heritability of atopy or

asthma has been identified with any certainty.

Results suggest involvement of multiple genes and

chromosomal regions likely to harbour asthma
susceptibility genes identified.
 Environmental Factors
• Allergens

• Air pollution

• Viral respiratory infections

 Environmental Factors (contd.)
• Allergens
Outdoor: Pollen (tree, grass and
flower), moulds (Aspergillus fumigatus and
others)

Indoor: Mites (Dermatophagoides

pteronyssinus, D. farina), Animals (cats,
dogs,birds), cockroaches.
 Environmental Factors (contd.)
• Air pollution

Outdoor: Ozone (High ozone level where cars

are many), SO2(High SO2 level in industrialized
areas due to oil and coal combustion)

Indoor: Tobacco smoke, moulds, contaminants

from indoor gas combustion(NO2), fumes,
perfumes, wood smoke.
 Environmental Factors (contd.)
Viral respiratory infections
• Mainly RSV

• Others are: Rhinovirus, Parainfluenza

virus
• Inducers (Precipitating factors)

• Inciters (Triggers)
 Pathogenesis
• Chronic Eosinophilic Inflammation
• CD4+ TH2 Lymphocytes
• Interleukins
• IgE antibodies (Allergen specific)
• Mast Cell (and other effector cells)
• Sensitization
• Early response
• Late response
Pathogenesis (contd.)
 The Allergic Cascade

Sensitization
• CD4+ Th2 cells and B cells interact and produce allergen
specific IgE

• Interactions between CD4+ T Cells and B Cells are important

in IgE synthesis.

• IgE antibodies synthesized bind to high-affinity IgE receptors

on the surface of mast cells in tissue or peripheral-blood
basophils, and low-affinity IgE receptors on the surface of
lymphocytes, eosinophils, platelets, and macrophages.

• This process is known as sensitization.

Pathogenesis (contd.)
 Specimen of bronchial mucosa from a subject
without asthma (Panel A) and a patient with mild
asthma (Panel B) (Hematoxylin and Eosin, x40).
• In the subject without asthma, the
epithelium is intact; there is no
thickening of the sub-basement
membrane, and there is no
cellular infiltrate. In contrast, in
the patient with mild asthma,
there is evidence of goblet-cell
hyperplasia in the epithelial-cell
lining. The sub-basement
membrane is thickened, with
collagen deposition in the
submucosal area, and there is a
cellular infiltrate. Photographs
courtesy of Nizar N. Jarjour, M.D.,
University of Wisconsin
Inflammation and
remodeling in the
asthmatic airway. There
is impressive
inflammation (I), mucus
plugging (MP),
subepithelial fibrosis (SF),
myocyte hypertrophy and
hyperplasia (MH), and
neovascularization (N) in
this autopsy lung section
from a teenage asthmatic
individual.
 Allergic Cascade (contd.)

Early Phase Response

When a sensitized individual comes in contact
with the same allergen again, there is molecular
bridging of the receptors.

• This occurs when allergen interacts with

receptor-bound IgE molecules, causes activation
of the cell and the release of preformed and
newly generated mediators including histamine,
prostaglandins, leukotrienes, and cytokines
among others.
 Early Phase Response (contd.)

• Once present in various tissues, mediators

may produce various physiological effects,
depending on the target organ.

• The early response involves mucosa

oedema and bronchospasm producing the
airway obstruction.
Late Phase Response
If no intervention, there is an influx of
inflammatory cells mainly eosinophils and
neutrophils,

• Further worsening the airway narrowing

and consequently the airflow obstruction.
 The airway obstruction is due to: a) The swelling of the airway mucosa due to
inflammation; b) Mucus clogs in the airways; c) Bronchospasm of the muscles
around the airways
 Airway Remodeling in Asthma

• Remodeling entails thickening of the airway

walls, with increases in submucosal tissue, the
adventitia, and smooth muscle.

• Preventing the progressive loss of lung function

in childhood may require recognition and
treatment of the disease during the first five
years of life.
 Bronchial Asthma II
Clinical Features
Investigations
Differential Diagnoses
 Clinical Features
Symptoms
• One or more of the following three:
Cough

Attacks of wheeze, and

Breathlessness
 Clinical Features (contd.)
• Repeated wheeze

• Recurrent or persistent cough

• Night time disturbance by wheeze or cough

• Symptoms precipitated by viral URTI; exercise or

excitement; family emotional disturbances; potential
allergens such as those associated with pets, pollens,
dust, or feathers; cigarette smoke.

• Presence of collateral allergy e.g., allergic rhinitis and

atopic dermatitis
 Clinical Features (contd.)
• Past medical history of infantile eczema
(atopic dermatitis)

• Family history of atopy

• Also therapeutic response to a

bronchodilator makes the diagnosis more
likely.
 Investigations
• Demonstration of reversible airway
obstruction

Pulmonary function test: FEV1 or

PEFR before and after β2-agonist
administration

An improvement of greater than 12%

after 10 minutes
 Other Tests

a) Bronchial provocation test,

b) Laboratory evaluation
*Full blood count and absolute eosinophil count,
*Specific IgE antibody measurements:
-In vivo i.e., skin prick tests,
-In vitro i.e., radioallergosorbent test (RAST)

c) Chest radiography.
 Differential diagnoses
Differential diagnosis of wheezing during early
life
Very common
Asthma
Viral bronchiolitis

Common
Foreign body in trachea or bronchus
Endobronchial tuberculosis(TB)
Enlarged TB nodes
 Differential diagnoses contd.
Uncommon
Vascular rings
Bronchiectasis
Laryngotracheomalacia
Chlamydia trachomatis infection
Obliterative bronchiolitis
Bronchopulmonary dysplasia
Aspiration from swallowing mechanism dysfunction
or cardioesophageal reflux
 Differential Diagnoses contd.
Rare
Tumour
Laryngeal webs
Tracheostenosis or bronchiostenosis
Alpha-1-antitrypsin deficiency
Cystic fibrosis
 Bronchial Asthma (III)
• Management
 Therapy
• Acute therapy

• Long term management

 Acute Therapy
Exacerbation:

• Usually reflects exposure to inciters

(triggers)

• May reflect failure of long–term

management/poor compliance with
outpatient treatment
 Goals of Therapy
• To reduce wheeze and cough
Relieve airflow obstruction and
hypoxaemia as rapidly as possible

• Reduce the risk and number of acute

exacerbations
Plan prevention of future relapses
 Goals of Therapy (contd.)

• Minimize adverse effects of treatments,

sleep disturbances, and absences from
school
Close monitoring of patients condition and
response to treatments crucial for successful
treatment

• Treatment is tailored to the severity of

asthma
 Management of Acute Exacerbations of
Asthma

• Short History

• Assess severity

Acute exacerbations of asthma may be

classified as mild, moderate or severe /life
threatening

• Follow flow chart (algorithm) for acute

therapy
Short history
 Assessment of Severity
• Table 1: Classification of Acute exacerbation of
Bronchial Asthma
Classification of Acute Exacerbation of
Bronchial Asthma (contd.)
Recognition of acute severe asthma
• Too breathless to talk

• Too breathless to feed

• Tachypnoea

• Tachycardia
Classification of Acute exacerbation of
Bronchial Asthma (contd.)
Life threatening features
• Cyanosis, a silent chest, or poor
respiratory effort

• Fatigue or exhaustion

• Agitation or reduced level of

consciousness
Pharmacotherapy
 Beta2 Agonists

• Short acting β2-agonists e.g., salbutamol (rather

than theophylline)
• Bronchodilators used intermittently for the relief
of symptoms rather than as regular maintenance
therapy
• No oral or intravenous beta2 agonists in the
treatment of acute asthma
• The inhaled method is the route of choice
 Bronchodilators
• Oral steroids given early during an acute
asthma exacerbation (i.e., within 45 minutes of
the onset of symptoms)
• Oral corticosteroids more effective than inhaled
or nebulized corticosteroids
• Children on oral steroids: extra care should be
taken during episodes of increased stress e.g.
surgery
• Subcutaneous adrenaline (0.01 ml/kg), 1:1000, a
maximum of 0.3 ml
• Repeated maximum of 2 times after 20 minutes,
i.e., 3 doses in 1 hour
 Management at Home

• Mild acute exacerbation

Inhaled or nebulised beta2 agonist (3ce

in 1 hour)
 Management at Emergency Room

• Mild/Moderate/Severe
Moderate acute exacerbation
*Inhaled or nebulized beta2 agonist(3ce in 1 hr,
and every hr after)

*Oxygen to achieve SaO2 95% or more

*If no immediate response or patient recently

took oral steroid – oral prednisolone 1-2 mg/kg
Severe acute exacerbation
• Humidified O2

• Short-acting β2 agonist via oxygen driven

nebuliser(3ce in 1 hr.)
 Severe acute exacerbation
bronchial asthma (contd.)
If no response after 15 – 30 minutes
• Oxygen
• Oral prednisolone
• Nebulized salbutamol every 30
mins./continuously
• Add Ipratropium bromide
 Severe acute exacerbation
bronchial asthma (contd.)
If no response
• Aminophylline drip

If no response
• Admit ICU
 The very severe asthma attack

• Children who present in extremis with a

very severe attack of asthma should
immediately be given 100% oxygen and
adrenaline 0.3 ml subcutaneously,
followed by intravenous salbutamol if they
are unable to use a nebuliser. They should
be admitted immediately to a high-care
facility or ICU for intensive treatment
 The very severe asthma attack
(contd.)
• Humidified oxygen
• Short-acting β2 agonist nebulisation
• IV aminophylline 5mg/kg stat and
aminophylline drip 1mg/kg/hr
• IV Hydrocortisone sodium succinate
• Ipratropium bromide 0.25 mg to nebulised
beta2 agonist
 The very severe asthma attack
(contd.)
If no response
• Intubation and mechanical ventilation
Flowchart I
Flowchart II
 Unnecessary therapy

• Antibiotics, cough syrups, mucolytics,

antihistamines, mist tents, lung lavage,
ionisers and physiotherapy (breathing
exercises)
 Supplemental Oxygen

• 100% Oxygen for hypoxaemia(SaO2 < 90

%)
• Face mask or nasal prongs at 3-4
liters/min, or with
• Nasopharyngeal catheter at 1-2 liters/min.
• This will supply about 40% oxygen
 Anticholinergics

• Ipratropium bromide
 CORTICOSTEROIDS

• Oral vs. IV/Inhaled

 THEOPHYLLINE

• It is not recommended for routine use

 Radiographs

• Should be individualized
 Follow-up

• Observed for at least 24 hours before discharge.

• Discharged with sufficient medication for at least 3 days.
• Instructed on the use of the Metered Dose Inhaler
(MDI), spacer or nebuliser.
• PEFR measurements should be made at least 3 times a
day until they are reassessed within 3 days of discharge
to assess PEFR deterioration.
• It is important that trigger factors (inciting agents) of the
acute attack should be identified
• A written plan of action should be given to the patient.
 Immunotherapy

• Immunotherapy can be used as an adjunct

to standard drug therapy in allergic
asthmatic children.
 Long Term Management
• Long term management focuses on
controlling asthma by treating the
underlying airway inflammation.
 CORTICOSTEROIDS

• Inhaled corticosteroids are the agent of

choice in preventive care
 LEUKOTRIENE MODIFIERS

• Very useful
 NEDOCROMIL AND CROMOLYN

• Not as useful as corticosteroid

 LONG-ACTING BETA2 AGONIST

• Useful
 ORAL THEOPHYLLINE

• In summary, its use in children cannot be

recommended because of the potential for
serious side effects, such as cardiac
arrhythmias or convulsions, if therapeutic
blood levels are exceeded
 Classification of Severity for Long
Term Management
• Intermittent

• Mild persistent

• Moderate persistent

• Severe persistent
Table: Classification of Severity for
Long Term Management
PREVENTERS CONTROLLERS RELIEVERS
(Anti-inflammatory action Sustained bronchodilator quick relief of symptoms
to prevent asthma action but weak or
and for use in acute
attacks) unproven anti-
attacks as PRN dosage
inflammatory action.
only
Inhaled corticosteroids Long-acting β2 agonists Short-acting β2
Beclomethasone, 1)Salmeterol agonists
budesonide, fluticasone, Salbutamol, terbutaline,
flunisolide, triamcinolone fenoterol etc
2)Formoterol

Oral corticosteroids Sustained release AntiI-cholinergics

theophylline tablets.
1.Prednisone
2.Prednisolone Leukotriene antagonists: Short-acting
3.Methylprednisone 1) Montelukast theophyllines
2) Zarfirlukast
4.Methylprednisolone
Long term management
 IMMUNOTHERAPY

• Immunotherapy can be used as an adjunct

to standard drug therapy in allergic
asthmatic children

• Sublingual (allergy drops) and injectable

(allergy shots) therapies have been shown
to reduce the presence of asthma and the
overall use of asthma medication
 Other Interventions

• EDUCATION

• Reducing asthma triggers

The control of allergens has not been

demonstrated to work as monotherapy. A recent
study showed that house dust mite allergen
avoidance and dietary fatty acid modification in
the first few years of life do not prevent asthma,
eczema, or atopy in children with a family history
of asthma [Guy et al Allergy,2006]
 Early Interventions Don't Prevent Asthma in
High-Risk Children
• House dust mite allergen (HDM) avoidance and dietary fatty acid modification in the first few years of life do not
prevent asthma, eczema, or atopy in children with a family history of asthma, new research shows.

• Sensitization to HDM and consumption of diets with a low omega-3 to -6 fatty acid ratio have been linked to
asthma. Guy et al studied 616 children who were randomized to receive HDM avoidance, a diet with an increased
omega-3 to -6 fatty acid ratio, both interventions, or no intervention during the first 5 years of life. Of these
children, 516 were available for evaluation at 5 years.

• The HDM avoidance measure involved the use of allergen-impermeable linens and regular washing with an anti-
HDM detergent. With the diet intervention, parents were encouraged to prepare their child's meals using canola-
based oils and tuna oil capsules to achieve a high omega-3 to -6 fatty acid ratio.

• Although HDM avoidance measure reduced bedding allergen levels by 61%, it had no effect on the occurrence of
asthma, wheeze, or atopy. In fact, eczema was actually more common in the HDM avoidance group than in
controls: 26% vs. 19%.

• Similarly, while the diet intervention did succeed in increasing the omega-3 to -6 fatty acid ratio, it did not prevent
asthma, wheezing, eczema, or atopy.

• Despite the null findings of the present study, previous reports support the view that, under certain circumstances,
asthma can be prevented. However, the most effective, practical forms of early life environmental modification and
the circumstances under which it will be appropriate to implement them remain to be established.
.
 Newer therapy of chronic asthma

• Omalizumab and Sublingual Immunotherapy

 Omalizumab

• Omalizumab is a recombinant DNA-derived humanized

IgG monoclonal antibody that selectively binds to human
immunoglobulin E (IgE).

• It inhibits the binding of IgE to the high-affinity IgE

receptor on the surface of mast cells and basophils,
limiting release of allergic mediators.

• Omalizumab is approved for use in children 12 years

and older with moderate to severe persistent asthma
who have a positive skin test or in vitro reactivity to a
perennial aeroallergen and whose symptoms are
inadequately controlled with inhaled corticosteroids .
 Sublingual Immunotherapy

• Sublingual immunotherapy is a newer,

more convenient option than injectable
immunotherapy
 The Take Home Message

• Don't call recurrent viral induced lower

airway obstruction "bronchitis" or
"pneumonia," or RAD, and just give
antibiotics or just bronchodilators
The Take Home Message (contd.)
• Recognition that the viral URIs cause
acute exacerbations, they are not
responsive to antibiotics.
 The Take Home Message (contd.)

• Limit maintenance medication to chronic

or prolonged seasonal allergic symptoms
choose the simplest effective and safe
measures.
 The Take Home Message (contd.)
• Recognize and instruct that maintenance
medication won't prevent viral respiratory
infection-induced exacerbations, and there
needs to be consistency in instructions. This is a
problem for large groups, because you may do
things one way, your partner who is on call the
next weekend may have very different
instructions, for a chronic problem, that makes it
very difficult to provide any kind of consistency,
and just causes confusion for the patient.
The Take Home Message (contd.)
• Eliminate tobacco smoke exposure,
continuing on timely intervention for acute
exacerbations.

• Simplest age-appropriate method for

inhaled bronchodilator delivery on hand
and instructed
The Take Home Message (contd.)
• Early recognition of bronchodilator
subresponsiveness.
The Take Home Message (contd.)
• Oral corticosteroids on hand, and started
the day prior to the need for urgent care.
The Take Home Message (contd.)
• And we've got to develop a mentality of
having zero tolerance for poor control.
There is no such thing as successful
treatment of asthma in the hospital - they
are all failures. It's damage control, that's
all it is. Successful treatment is preventing
that from happening again.