Bronchial Asthma

Bronchial asthma is a chronic airway disorder which can affect people of all age
group.

Asthma is defined as a chronic inflammatory disorder of the airways which is

associated with airway hyper – responsiveness. The eosinophils, mast cells,
lymphocytes and other cells are involved in the inflammatory process which
results in hyper responsiveness of the bronchi. The mediators and the
cytokines are also involved in the process.

It produces recurrent episodes of wheezing, breathlessness, chest tightness

and coughing particularly at night or in early morning. These episodes are
usually associated with widespread but variable airflow obstruction within the
lungs, which is often reversible either spontaneously or with treatment.

In asthmatic patient, airway inflammation usually persists even during

asymptomatic periods. Though the symptoms and bronchospasm are
intermittent, airway inflammation is persistent. Thus asthma is considered as a
chronic disease, often lifelong but its severity fluctuates and at times there
may be prolonged remissions.

Epidemiology

 More prevalent in developed countries rather than developing

countries.
 More in children (15%) than adults (10-12%)
 More in urban rather than ruler areas (cause is not known)
 The disease can start at any age but in majority it starts before 10 yrs of
age.
 It is twice common in boys than girls but is adults the male, female ratio
is usually equal.

Atopy is the principal associate of asthma in individuals aged 5- 30yrs. It is a

state of disordered immunity in which predominant T-helper lymphocyte type
2 (TH2) immune mechanism drive the production of IgE on exposure to
common environmental antigens or allergens.
Classification

1. Extrinsic Asthma – It applies to those who produce excessive IgE in

response to allergens (atopic)
2. Intrinsic Asthma – It refers to those cases in whom excessive IgE
production cannot be demonstrated (non-atopic)
3. Mixed type.

COMPARATIVE FEATURES OF EXTRINSIC AND INTRINSIC ASTHMA

Extrinsic asthma Intrinsic asthma

Clinical features :
1. Young patient – child or teenager 1. Adult patient over 35 or more
2. History of eczema in childhood 2. No history of eczema in childhood
3. Family history of asthma, eczema 3. Negative family history
or hay fever.
4. Attacks related to specific 4. Attacks related to infection,
antigens. exercise etc
5. Intermittent attacks. 5. Often persistent asthma
6. Attacks are acute but usually self 6. Attacks more fulminant and
– limiting. severe
7. Not aspirin – sensitive, occasional 7. Aspirin – sensitive, nasal polyps
polyps
Investigation :
1. Skin test with allergen extracts 1. Skin test usually negative
usually +ve
2. Inhalation provocation test with 2. Normal or low IgE
allergens positive
Negative or non – specific
reactions to solvents
3. IgE frequently raised
Response to treatment
Good response to beta – agonists and Poor response to beta – agonists,
sodium cromoglycate. variable response to cromoglycate
Prognosis favourable. Prognosis poor
In the other classification asthma is divided into two groups depending on the
aetiology

1. Inducing Factors – The inducing factors induce asthma in susceptible

persons. It is more common in relatives of atopic individuals. The
inducing factors are the genetic factors, obesity, and exposure to
tobacco smoke, maternal smoking during pregnancy or infancy, rhino –
syncytial virus infections and exposure to high concentration of allergens
in infancy can also induce bronchial asthma.
2. Triggering Factors – The triggering factors provoke symptoms in persons
who already have asthma. The triggering factors are allergens, vigorous
exercise, viral infections etc.
3. Some factors such a viral infection and occupational sensitizers act as
both inducers and triggering factors.

Pathology

Gross Appearance

Patient dying from acute episodes of asthma have a bulky and over distended
lungs which fail to deflate when the chest is opened. The airways are thickened
and plugged with sticky secretions.

Microscopic Appearance

marked thickening of basement membrane, bronchial smooth muscle

hypertrophy and damaged epithelium, which is shaded. The bronchial wall
contains inflammatory cells mainly eosinophils. The other cells are neutrophils,
lymphocytes and plasma cells.

The mucus or bronchial secretion of asthmatic patients contain eosinophils,

eosinophil cationic protein, desquamated airway epithelial cells termed as
creola bodies, Charcot-Leyden crystals, and thick thread like sputum called
Curschmann’s spirals. The mucus is often impacted in the small airways in
severe asthma.

Pathogenesis of Asthma
 Initial Sensitisation

The T- Lymphocytes play a key role in asthmatic airway inflammation and

sensitisation. There are two types of T-Lymphocyte helper (TH) cells. Th1
controls the synthesis of IgA and IgM where as Th2 controls IgE production.

Exposure to an inducing factor sensitises T cells of a person with genetic

susceptibility to bronchial asthma and causes Th2 dominance. Once sensitised,
these Th2 cells get into airway mucosa and govern IgE-mediated responses to
allergic reaction.

In a normal individual when a noxious allergic substance enters the airway IgA
is released. However in a sensitised person IgE is released. Once sensitised
even a low dose of same noxious substance provokes asthma.

Environmental factors (Sensitisation) Genetic susceptibility

Allergy, Infection, Smoking, Air Pollution chromosome C5q and C11 q

Antigen Presenting Cell

(Th 1 Cell – IgA, IgM)

Th 2 Cell
IgE

Mast cell Eosinophil cell

(Early response) (Late Response)
 Airway inflammation

Bronchoconstriction and
Airway Hyper – responsiveness
Clinical effect – Asthma, rhinitis, urticaria

Airway remodelling Normal airway mucosa

irreversible airway obstruction Reversible airway obstruction

Provocation of Asthma

When an allergen is inhaled by an asthmatic patient, airway obstruction starts

within minutes and the peak effect is observed within 20-30 minutes. This is an
early phase reaction and is due to direct action of mast cell derived mediators
on the smooth muscles of the airways. When inhaled allergens come in contact
with mast cells located in airway mucosa, then histamine and archidonic acid
derivatives such as leukotrienes and PGF are released.

In some cases the reaction soon terminates and resolution starts with the
decrease in short –lived mediator concentration. Whereas in many cases, a
second phase of airway obstruction occurs in 6-10hrs later. This is called late
phase reaction or late response and it is inflammatory in nature.

Clinical Features

 Episodic breathlessness, wheezing, Cough and chest tightness are

important symptoms of bronchial asthma.
  These symptoms have diurnal variation and are worse at night and early
morning. It leads to disturbed sleep due to cough and wheeze.
 There is an increased mucus production, which is thick, mucoid and
difficult to expectorate.
 History of recurrent episodes of asthma is caused by one or more
triggering factors, which is important for the diagnosis of bronchial
asthma.
 In between the episodes the patient is usually symptom free.
 Asthmatic are frequently associated with other atopic conditions like
eczema, urticaria, allergic rhinitis etc.

Physical Examination

Ronchi are heard as the predominant sign of asthma especially during

expiration.

During the exacerbation phase of asthma there is increase in respirator rate,

flaring of alae nasai, use of accessory muscles of respiration and pulsus
paradoxus.

As asthmatic complaints are more at night and during early morning, the
physical examination done during the day time if normal cannot exclude the
diagnosis of bronchial asthma.

Differential diagnosis

At times it is difficult to differentiate between COPD and Asthma. History of

smoking, exertional dyspnoea and lack of symptoms free period favour
diagnosis of COPD. Nocturnal worsening, chest tightness, episodic pattern and
good response to bronchodilators and steroids favour diagnosis of asthma.

Chronic obstructive pulmonary disease.

COPD Asthma
History
Does not usually begin in Usually begins in childhood
childhood
Allergy or asthma in patient No Yes
‘s family
Cough or sputum Over many years Often recent
Dyspnoea Usually progressive More often paroxysmal
Variable breathlessness Slight Much
Attacks or breathlessness at Uncommon Common
rest
Cough at night Wakes then coughs Awakens coughing
Investigation
Improvement in PEF after Little or none Usually
bronchodilator i.e.
reversible obstruction
Daily variations in PEF Little ‘Morning dip’ plus day to day
Treatment
Effects or oral Negligible Improvement
corticosteroids

Acute left ventricular failure may cause wheezing and dyspnoea especially
at night. Dyspnoea starting 1-2 hrs after sleep, history of heart disease,
inspiratory crepitations and gallop rhythm supports the diagnosis of left
ventricular failure. Early morning dyspnoea and response to bronchodilator are
characteristic of asthma.

Upper airway obstruction with a tumour or lymphadenopathy is occasionally

mistaken for asthma. There is rapid progressive airway obstruction and
inspiratory stridor. Spirometry shows reduced inspiratory flow and the flow
volume curve become flat instead of being curved normally.**********

Hyperventilation syndrome, foreign body aspiration, bronchiectasis,

pulmonary tuberculosis and acute pulmonary thromboembolism have to be
differentiated from asthma. Careful history taking can help us to differentiate
asthma from these conditions.

Diagnosis

Blood examination – Absolute eosinophil count is more than 400. Total serum
IgE and specific IgE are elevated in bronchial asthma.

Sputum examination – In asthmatic patients number of eosinophils are

increased in the induced (administration of hypertonic saline with nebuliser)
sputum.
Airway Hyper responsiveness – Increased airway hyper responsiveness (AHR) is
characteristic of bronchial asthma. It is measured by methacholine or
histamine challenge test. This test is useful in the diagnosis of asthma when
the patient is in remission with normal lung functions

Chest Radiograph – Chest radiograph shows hyperinflation in a patient with

asthma. It may also reveal complications of severe asthma such as rib fracture,
pneumothorax and pneumomediastinum.

Skin Prick Test – Sensitivity to particular antigens can be identified by injecting

a small amount of allergens into the skin. Skin prick test to common inhalant is
usually positive to allergic asthma. Allergens can also be identified by
estimation of specific IgE in the blood through radioallergosorbent test (RAST).
However SPT is cheaper and more sensitive than RAST.

Measurements of Lung Functions – The measurement of Peak expiratory flow

rate (PEFR) by a flow meter and forced expiratory volume in one second (FEV1)
by a spirometer are most useful in making a diagnosis and assessing the
severity of asthma.

Peak expiratory flow rate

Peak expiratory flow rate (PEFR) represents maximal expiratory effort

performed after full inhalation. PEFR is reduced with increasing severity of
airway obstruction. It can be measured with a handy tool called peak flow
meter. PEFR help to assess the severity of the asthma.

In asthma PEFR reversibility is also one of the important index. After a baseline
PEFR, patient is given bronchodilator inhalation or nebulisation. The PEFR
noted after 15 min after the bronchodilator administration, shows the
magnitude of reversibility. More than 20% reversibility is diagnostic of asthma.

Spirometry
Asthma is diagnosed by demonstration of reversible airway obstruction in
spirometry. A ratio of FEV1 and forced vital capacity (FVC) less than 0.7 is
diagnostic of airway obstruction.

After bronchodilator administration, FEV1 increases by more than 12% and

200mL in asthmatic patients. It is called reversibility of airway obstruction
which is characteristic of asthma.

Lung Volume and diffusing capacity

Lung volumes, such as residual volume and total lung capacity, are increased in
a patient with asthma. Carbon monoxide diffusing capacity (DLCO) is either
normal or increased in the asthma patients. Diffusing capacity of the lung for
carbon monoxide is reduced in patients with COPD, therefore it is useful in
differentiating COPD from asthma.

Oximetry
Pulse oximetry helps in assessing the severity of acute asthma. It detects
hypoxaemia in severe asthma. Normally oxygen saturation should be more
than 90%. Pulse oximetry is also helpful in monitoring oxygen therapy.

Arterial Blood gas Analysis

Periodic assessment of arterial blood gases proves useful in monitoring the

patients of acute asthma. Arterial blood gas analysis gives basic information
about pH, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide
(PaCO2) and bicarbonate (HCO3). In severe asthma, PaO2 decreases but PaCO2
remains normal. When PaCO2 starts rising, it is indicated of assisted ventilation

Assessment of Severity

GINA guidelines helps to assess asthma severity on the following basis –

Symptoms, Activity limitation, Lung function test, inhaler use and frequency of
exacerbations. On this basis asthma is characterised into controlled, partly
controlled and uncontrolled.

Parameters to determine the control of asthma

 Day time symptoms less than twice per week

 Short acting beta agonist (SABA) inhaler use less than twice per week
 Without any night time symptoms
 Without limitation of activity
 Normal PEFR and FEV1 values.

Controlled – Asthma is said to be controlled if all indices are fulfilled and

patient did not have an exacerbation in last one year.

Partly Controlled – Asthma is said to be partly controlled if any of the indices is

more than described above or the patient had an exacerbation during the last
one year.
Poorly controlled – Asthma is said to be poorly controlled when more than 3
indices are more severe than described above or the patient had an
exacerbation during the last week.

The severity of Asthma is also classified as under

Management

Patient Education – Patient must be educated to identify and avoid the risk
factors and triggers involvement in asthma. Monitor the severity of the asthma
by symptom score and peak flow meter so that the medicines can be
appropriately administered.

Manage exacerbation – The aim of the treatment during management of an

exacerbation is to relieve bronchospasm and hypoxia as quickly as possible. A
future plan is made to prevent the recurrence of exacerbation.

Drug Therapy

Asthma drugs are administered as injection, tablet, syrup or aerosol form. With
aerosols the dose and the side effects of the drug are much less and the
therapeutic effect is better.

Devices used for administrating inhaled medicines include metered dose

inhaler (MDIs), dry powder inhalation (DPIs) and nebulisation (jet nebulisers
and ultrasonic nebulisers). With steroid MDIs and DPIs, hoarseness of voice
and oral candidiasis are common in some patients. Rinsing of the mouth after
use of inhaler, use of spacer device with MDI and the use of MDIs and DPIs
before food are some of the measures to prevent local adverse effect of
inhaled corticosteroids. When used with spacer, delivery of MDI drug into
airways also improves.

Acute severe Asthma (Status Asthmaticus)

It is the extreme stage of severity of asthma with coughing, wheezing,
shortness of breath, chest wall recession (indrawing in the flesh between the
ribs and the sternum), inability to complete a sentence in one breath, use of
accessory muscles, respiratory rate >25/min, pulse >110/ min and presence of
pulsus paradoxus.

(Pulsus Paradoxus – In normal individual the systolic pressure falls by 2-4mm of

Hg with normal inspiration and it falls by 10mm of Hg with deep inspiration.
When the systolic pressure falls more than 10mm of Hg during inspiration, the
pulse is called pulsus paradoxus)

Presence of pulsus paradoxus indicates presence of severe asthma and PEFR is

less than 60% of their usual value (predicted or the best). Pulsus paradoxus
may also be present in other conditions like cardiac tamponade, constrictive
pericarditis and superior vena cava obstruction.

If the condition worsens the airways become further narrow and the
movement of air decrease. In such situations, wheezing ceases. It indicates
that the airways are extremely narrowed and very little air is moving in and
out. This is called as silent chest type asthma.

Features of life threatening asthma includes – silent chest, cyanosis, feeble

respiratory effort, bradycardia, hypotension and PEFR< 30% of their usual
value (predicted or the best). Patient may be exhausted, confused and lapses
into coma. Arterial blood gas analysis shows normal or high PaCO2 (more than
45mm Hg), severe hypoxia (PaO2 <60 mm Hg) and low pH. Acute severe
asthma may lead to complications, such as dehydration, acute cor pulmonale
and pneumothorax.

Treatment in Acute severe Asthma

The aim of treatment in acute severe bronchial asthma is to save life. Hypoxia
is treated with high concentration of oxygen to maintain oxygen saturation
above 90%.
Usually 40-60% oxygen is administrated. In contrast to chronic obstructive
pulmonary disease, carbon dioxide retention is not aggravated by
administration of higher concentration of oxygen in bronchial asthma.

Short acting bronchodilator is administered via oxygen driven nebuliser. It is

repeated as frequently as every 15- 30 minutes depending on the severity of
the asthma. Intravenous steroids, aminophylline, magnesium sulphate etc are
given depending on the requirement. In any condition the sedative drugs are
contraindicated as they induce respiratory depression.

If any patient does not respond to the treatment one should suspect
pneumonitis or pneumothorax. Chest Radiograph helps in diagnosis.

PEFR is to be monitored every 15- 30 minutes from the starting of the

treatment. Pulse oximetry is done do maintain the saturation above 90%. If
oxygen saturation is less than 90%, an arterial blood gas analysis should be
done and repeated every 2 hours.

Assisted mechanical ventilation is required in patients showing deterioration.

The prognosis of acute severe asthma is good. Mortality is rare and occurs
usually when treatment is delayed or inadequate.

Indications of Mechanical Ventilation

Absolute indication – Cardio – pulmonary arrest, deteriorating consciousness.

Relative indication – Hypercapnia, acidosis, progressive deterioration with

increasing distress or physical exhaustion.

Complications – Hypotension, barotraumas and nasocomial pneumonia.