Asthma

INTRODUCTION

Asthma is a disorder of the respiratory system that leads to

episodic difficulty in breathing.
It is a chronic inflammatory disorder of the airways in which
many cells and cellular elements play a role, in particular, mast
cells,eosinophils,T lymphocytes, macrophages, neutrophils and
epithelial cells.
In susceptible individuals this inflammation causes recurrent
episodes of wheezing,breathlessness,chest tightness and
coughing.
These are usually associates with variable airflow obstruction
that is often reversible.

EPIDEMIOLOGY

The probability of children having asthma like symptom is

estimated to be between 5% and 12% with a higher occurrence
in boys than girls and in children whose parents have an
allergic disorder.
Over 5 million people in the UK have asthma and around 300
million worldwide.
Individuals who develop asthma at an early age,however ,do
have a poor prognosis.

AETIOLOGY

The specific abnormality underlying asthma is hyper reactivity of the

lungs to one or more stimuli.

This can also occur in certain patients with chronic bronchitis and
allergic rhinitis but usually to a lesser extent.

One of the most common trigger factors is the allergen found in the
house dust mite.

Allergens
Pollens,moulds,house dust mite, animals
Industrial chemicals
Isocyanate containing paints, epoxy resins,aluminium,hair sprays.

CONT
Drugs
Aspirin, ibuprofen and other prostaglandin synthetase
inhibitors, beta blockers.
Foods
nuts, fish, sea food, dairy products, food colouring.
Other industrial chemicals
Wood or grain dust, cotton dust, cigarette etc
Miscellaneous
Cold, exercise, hyperventilation ,viral respiratory tract
infections, emotion or stress.

TYPES OF ASTHMA
Extrinsic Asthma

Intrinsic Asthma

Atopic asthma
Hereditary predisposition
Personal history of allergic
Starts early in life
Serum IgE levels
Symptoms may be seasonal or
perennial
Responds to corticosteroids

Idiopathic or cryptogenic
No hereditary predisposition
No history of allergies rhinitis,
atopic dermatitis
Starts late in life
Serum IgE levels are normal
Symptoms are perennial
Responds to corticosteroids

PATHOPHYSIOLOGY

Inhaled allergens cause allergic reactions characterized by activation of

IgE antibodies

Then rapid activation of airway mast cells and macrophages,which

release proinflammatory mediators such as histamines and eicosanoids.

Late phase inflammatory reaction involves activation of eosinophills,T

lymphocytes,basophills,neutrophills,and macrophages.

Eosinophills migrate to airways and release cytotoxic mediators and

cytokines

T lymphocytes activation leads to release of cytokines from type 2 Thelper cells

CONT

Alveolar macrophages release a number of mediators,including

PAF and leukotrienes B4 ,C4, and D4.

The chemotactic agents cause infiltration of the macrophages

into the lumen of airways.

In asthma hypertrophy of bronchial glands and goblet cells

occurs that produce mucus. It plugs the airways.

Mucociliary clearance is also decreased due to inflammation of

epithelial cells. This can result bronchoconstriction

CLINICAL MANIFESTATIONS
Chronic Asthma

Acute Asthma

Episodic dyspnea associated

with wheezing
Chest tightness
Coughing
Whistling sound when
breathing occur with
exercise(spontaneously),allergen
s
Expiratory wheezing on
auscultation
Signs of atopy
Interval between symptoms
may be days,weeks,months

Airway eodema
Excessive mucus acumulation
Complain of severe dyspnea
Chest tightness or burning
Expiratory and inspiratory
wheezing on auscultation
Tachycardia,tachypnea
Pallor or cynanosis

DIAGNOSIS

Blood examination : Eosinophilia (5-15%) is not uncommon.

Leucocytosis indicates presence of infection.

Sputum examination may help in detecting respiratory

infection.

Chest X-ray may show inflated lungs and may help in

detecting chest infection, rib fracture, pneumothorax and
pneumomediastinum

Skin test

CONT

Peak flow meter+spirometry

PEFR+FEV1 Decrease
PEFR+FEV1 Increase >15% after B agonist
inhalation

TREATMENT
Reducing inflammation
Increasing bronchodilation
Restoration of normal airways function
Prevention of severe acute attacks
Avoidance of recognized trigger factors

CHRONIC ASTHMA
The pharmacological management of asthma depends upon the
frequency and severity of patients symptoms.
I.

Sympathomimetics
2 adrenergic receptor stimulation activates adenyl cyclase,
which produce an increase in intracellular cAMP. This cause
relaxation of bronchial smooth muscles and bronchodilation
Short acting agents
Salbutamol 2-4mg
Inh. 100-200g 3-4 times daily
Terbutaline 5-10mg
Long acting agents
Inh. Salmeterol 25g bid
Inh. Formeterol 12-24g bid

II. Methyl xanthines

Produce bronchodilation by inhibition of phosphodiesterase
and inhibition of calcium ion influx into smooth muscles
Theophylline 250-1000mg in 1-2 divided doses
Aminophylline 5mg/kg as a single dose iv inj
III Corticosteroids
Inhalational
Beclomethasone
Budesonide
Systemic
Prednisolone
Hydrocortisone

Prednisolone-40-60mg
Inh. Beclomethasone 100-400g in 2 div doses
Inh. Budesonide 200-800g in 2 div doses
Inh. Fluticasone 200-500g in 2 div doses
IV Anticholinergic
They are competitive inhibitors of muscarnic
receptors:they produce bronchodilation only in cholinergic
madiated bronchoconstriction.
Ipratropium bromide-500mcg repeated as necessary

V leukotriene antagonist

Both having similar action and clinical utility

Block the cys-leukotrienes LTC4.LTD4,LTE4
Alternative for inhaled corticosteroids
Dose montelukast-10mg OD, zafirlukast-20mg BD

VI Mast cell stabilizers

Inhibits degranulation of mast cell by trigger stimuli and prevent the

realese of histamines,LTs,PAF,interleukin etc from mast cell.Inhibition
of mediator release by cromolyn is through blockade of calcium influx
in mast cell.
Sodium cromoglycate,ketotifen

CONT
VII Anti IgE Antibodies

Selectively binds to human immunoglobin E and decrease

binding affinity of IgE to the high affinity IgE receptor on
the surface of mast cell and basophill,reduce allergic
response.
Omalizumab -Doses ranges from 150 to 375mg given
subcutaneously at either 2 or 4 weeks intervals.

TREATMENT STEPS FOR ACHIEVING

CONTROL

Total of 5 steps for control.

steps 1-5provide options for increasing efficacy with exception of
steps 5 where issues of availability and safety influence selection
of treatment
Step 1-inhaled short acting B2 agonist as required
Step 2-is the initial treatment for most patient with persistent
asthma symptoms-PLUS inhaled steroid.200-800mcg/day
Step 3-if symptoms suggest asthma is severly uncontrolled this
step is commenced-PLUS long acting B2 agoinist(LABA)assess

Cont
Step 4-persistent poor control.
increase steroid upto 2000mcg/day-PLUS LRA,sr
theophylline,B2 agoinist tablet.
Step-5-continous of frequent use of oral steroid
Use daily steroids tablet in lowest dose providing adequate
control.

ACUTE ASTHMA
Main aim is to relieve airflow obstruction and hypoxaemia as quickly as
possible and to plan prevention in future relapses.
Immediate management
inhalation 4L/min to maintain spo2>90%
High concentration of oxygen(humidified if possible)
short

acting B2 agoinist (salbutamol 5mg/hr) and ipratropium 0.5mg

Nebuliser driven by oxygen or via a metered dose inhaler through a space
device
1-2 puffs every 2-4 minutes upto 10puffs and repeat every 20-30minutes

Cont
Subsequent management
If patient fail to improve
Inj magnesium sulphate 40mg/kg in 50ml 5%dextrose as slow
infusion over 20 minutes.
Inj aminophylline 5mg/kg slowly followed by 0.8-1.2mg/kg/hr
slow infusion.
If aminophylline is given then monitor the serum concentration of
aminophylline(therapeutic range 10-20ug/ml)

REFERENCES
1.

2.

Roger walker and Cate Whittlesea,Clinical pharmacy and

Therapeutics fifth edition.
Joseph T Dipiro,Robert L.Talbert,Pharmacotherapy,seventh
edition

THANK YOU