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Dr. Sameh Ahmad Muhamad abdelghany
Lecturer Of Clinical Pharmacology
Mansura Faculty of medicine
Bronchial
asthma
Management

2
ASTHMA
INTRODUCTION
CLASSIFICATION
RISK FACTORS
Diagnosis
Treatment & Prevention
CONTENTS

4
Introduction
 Asthma is a chronic inflammatory disorder
of the airways that is characterized:
o clinically by recurrent episodes of wheezing,
breathlessness, chest tightness, and cough,
particularly at night/early morning.
o physiologically by widespread, reversible
narrowing of the bronchial airways and a
marked increase in bronchial
responsiveness.

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Introduction
 In 2015, 358 million people globally had
asthma, up from 183 million in 1990.
 It caused about 397,100 deaths in 2015,
most of which occurred in the developing
world.
 Asthma was recognized as early as Ancient
Egypt.
 The word "asthma" is from the Greek
ἅσθμα, ásthma, which means "panting".

7
Classification
 A heterogenous disorder.
 Atopic /extrinsic /allergic ( 70%):
o Most common type
o Environmental agent: dust, pollen,
food, animal dander
o Family history - present
o Serum IgE levels - increased
o Skin test with offending agent –wheal
flare

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Classification
 Non-atopic/ intrinsic /non-allergic( 30%)
 Triggered by respiratory tract infection
 Viruses - most common cause
 Family history uncommon
 IgE level normal
 No associated allergy
 Skin tests NEGATIVE
 Cause- hyperirritability of bronchial tree

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Classification
 Drug induced asthma
 Several pharmacologic agents
 Aspirin sensitive asthma
o Increased bronchoconstrictor leukotrienes.
o sensitive to small doses of aspirin.
o Inhibits COX pathway, without affecting
LPO pathway

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Pathophysiology
I. Chronic inflammation
II. Airway Hyperresponsiveness

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Pathophysiology
I. Inflammation
 Chronic inflammatory state
 Involves respiratory mucosa from trachea
to terminal bronchioles, predominantly in
the bronchi.
 Activation of mast cell , infiltration of
eosinophils & T-helper type 2 (Th2)
lymphocytes

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Pathophysiology
I. Inflammation
 Exact cause of airway inflammation is
unknown.
 Thought to be an interplay between
endogenous and environmental factors.
 Endogenous factors
 Atopy
 Genetic predisposition to IgE mediated
type I hypersensitivity
 The major risk factor for asthma
 Genetics

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Pathophysiology
I. Inflammation
 Environmental factors
 Viral infections: RSV, Mycoplasma,
Chlamydia
 Air pollution
 Allergens :house dust mite

14
Pathophysiology
II. Airway Hyperresponsiveness (AHR)
 The excessive bronchoconstrictor response
to multiple inhaled triggers that would
have no effect on normal airways.
 Characteristic physiologic abnormality of
asthma.

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Risk factors
 Host factors:
 predispose individuals to, or protect
them from, developing asthma
i. Genetic
o Atopy
o Airway hyperresponsiveness
ii. Gender
iii. Obesity

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Risk factors
 Environmental factors:
 influence susceptibility to development of
asthma in predisposed individuals,
precipitate asthma exacerbations, and/or
cause symptoms to persist
o Indoor allergens , Outdoor allergens
o Occupational sensitizers
o Tobacco smoke , Air Pollution
o Respiratory Infections
o Diet

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Triggers
 Asthma Triggers
 Allergens
 Virus Infections
 Drugs
 Exercise
 Food
 Air pollutants
 Physical factors
 GERD
 Stress
 Occupational factors

22
Clinical manifestations
 Symptoms
 Wheezing, dyspnea and cough.
 Variable – both spontaneously and with
therapy.
 Symptoms worse at night.
 Nonproductive cough
 Limitation of activity

23
Clinical manifestations
 Signs
 ↑ respiratory rate, with use of accessory
muscles
 Hyper-resonant percussion note
 Expiratory rhonchi
 No findings when asthma is under control or
b/w attacks

24
Classification for asthma severity
Grade Symptoms Night-time
Symptoms
Mild
intermittent
Symptoms ≤ 2
times/week
≤ 2 times/month
Mild
persistent
Symptoms ≥ 2
times/week
but ≤ 1/day
≥ 2 times/month
Moderate
persistent
Daily Symptoms ≥ 1/week
Severe
persistent
Continued Symptoms
Limited physical activity
Frequent

26
Laboratory diagnosis
 Pulmonary function
tests:
 Using Spirometry
 estimate degree of
obstruction
 ↓FEV1, ↓FEV1/FVC,
↓PEF.

27
Laboratory diagnosis
 CXR :
 hyperinflation,emphysema
 Arterial blood-gas analysis
 hypoxia & hypocarbia
 Skin hypersensitivity test
 Sputum & blood eosinophilia
 Elevated serum IgE levels

29
Management
I. Non-Pharmacological
II. Pharmacological

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Non-Pharmacological
 Reduce exposure to indoor allergens
 Avoid tobacco smoke
 Avoid vehicle emission
 Identify irritants in the workplace
 Explore role of infections on asthma
development, especially in children and
young infants

31
Non-Pharmacological
 Influenza Vaccination
o should be provided to patients with asthma
when vaccination of the general population is
advised
o routine influenza vaccination of children and
adults with asthma does not appear to protect
them from asthma exacerbations or improve
asthma control

32
Pharmacological treatment
 Classification of drugs
 Bronchodilators : rapid relief, by relaxation of
airway smooth muscle
 β2 Agonists
 Anticholinergic Agents
 Methylxanthines
 Controllers : inhibit the inflammatory process
 Glucocorticoids
 Leukotrienes pathway inhibitors
 Cromones
 Anti-IgE therapy

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 β2 Agonists in asthma
 Potent bronchodilators.
 Usually given by inhalation route.
 Effects:
o Relaxation of airway smooth muscle
o Inhibition of mast cell mediator release
o Reduction in plasma exudation
o Increased mucociliary transport
o Inhibition of sensory nerve activation
 No effect on airway inflammation

34
a) Short-Acting β2 Agonists
 E.g salbutamol , terbutaline
 Convenient,rapid onset,without significant
systemic side effect
 Bronchodil. of choice in acute severe asthma
 Used for symptomatic relief
 Only treatment required for mild, intermittent
asthma.
 Use >2 times a week indicates need of a regular
controller therapy.

35
b) Long-Acting β2Agonists
 E.g salmeterol, formoterol
 Duration of action - >12 hrs.
 Used in combination with inhaled corticosteroid
therapy.
 Improve asthma control and reduce frequency
of exacerbations.
 Should not be used as monotherapy (increased
mortality).
 Not effective for acute bronchospasm.

36
 Anticholinergic agents
 E.g Ipratropium bromide, tiotropium.
 Prevent cholinergic nerve induced
bronchoconstriction.
 Less effective than β2 agonists.
 Response varies with existing vagal tone.
 Use in asthma
o Intolerance to inhaled β2 agonist.
o Status asthmaticus –additive effect with β2
agonist

37
 Anticholinergic agents
 Ipratropium:
o slow,bitter taste
o precipitate glaucoma
o paradoxical bronchoconstriction
 Tiotropium:
o longer acting, approved for treatment of COPD.
o Dryness of mouth

38
 Methylxanthines
 Medium potency bronchodilator
 E.g Theophylline, theobromine, caffeine
 Recently interest has declined in this class of
drugs:
o Side effects
o Need for plasma drug levels
o Pharmacokinetics
o Availability of other effective drugs
 Still widely used drugs especially in developing
countries due to their lower cost.

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 Methylxanthines
 Adverse effects
o Anorexia, nausea, vomiting, abdominal
discomfort
o headache, and anxiety
o Seizures or arrhythmias
o Diuresis
 Doxyphylline
o long acting,oral

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 Corticosteroids in asthma
 Effective drugs for treatment of asthma.
 Development of inhaled corticosteroids is a
major advance in asthma therapy.
 Used prophylactically as a controller therapy.
 Reduce the need for rescue β2 agonist.
 Benefit starts in 1week but continues up to
several months.
 If asthma not controlled at low dose of ICS then
addition of long acting β2 agonist is more
effective than doubling steroid dose.

41
 Effects: Broad anti-inflammatory effects:
o Marked inhibition of infiltration of airways by
inflammatory cells.
o Modulation of cytokine and chemokine
production
o Inhibition of eicosanoid synthesis
o Decreased vascular permeability.
o Potentiate effect of β2 agonist.

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 Inhaled corticosteroids( ICS)
o Use of β2Agonists >2 times a week indicates
need of a ICS
o E.g Beclomethasone , Budesonide , Fluticasone

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 Inhaled corticosteroids( ICS)
 Adverse effects:
o Oropharyngeal candidiasis, dysphonia
o Decreased bone mineral density.
o Skin thinning, purpura
o Growth retardation in children

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 Systemic steroids in asthma
 Indication
1. Acute exacerbation(lung function <30%
predicted)
2. Chronic severe asthma
 A 5-10 day course of prednisolone 30-
45mg/d is used.
 1% of patients may require regular
maintenance therapy.

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 Leukotrienes pathway inhibitors
a) Inhibition of 5-lipoxygenase, thereby
preventing leukotriene synthesis. Zileuton.
b) Inhibition of the binding of LTD4 to its
receptor on target tissues, thereby preventing
its action. E.g Zafirlukast, montelukast.
 Oral route.
 Adverse effects
o Liver toxicity
o vasculitis with eosinophilia

46
 Leukotrienes pathway inhibitors
 They are less effective than ICSs in
controlling asthma
 Use in asthma
o Patients unable to manipulate inhaler devices.
o Aspirin induced asthma.
o Mild asthma – alternative to ICS.
o Moderate to severe asthma – may allow
reduction of ICS dose

47
 Cromones
 E.g Cromolyn sodium & nedocromil sodium
 On chronic use (four times daily) reduce the
overall level of bronchial reactivity.
 have no effect on airway smooth muscle tone
and are ineffective in reversing asthmatic
bronchospasm; they are only of value when
taken prophylactically.
 Inhalation route

48
 Cromones
 May act by stabilization of Mast cells with
inhibition of mediator release
 Uses
o Asthma - Prevention of asthmatic attacks in
mild to moderate asthma
 Adverse effects
o Well tolerated drugs
o Minor side effects- throat irritation, cough, and
mouth dryness, rarely, chest tightness, and
wheezing

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 Anti-IgE therapy:
 Omalizumab
 recombinant humanized monoclonal antibody
targeted against IgE.
 Action:
o IgE bound to omalizumab cannot bind to IgE
receptors on mast cells and basophils, thereby
preventing the allergic reaction at a very early
step in the process.

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 Anti-IgE therapy:
 Use in asthma
o Persons >12 years of age with moderate-to-
severe persistent asthma.
 Omalizumab is not an acute bronchodilator and
should not be used as a rescue medication or as
a treatment of status asthmaticus.
 Expensive drug
 Has to be given under direct medical
supervision due to the risk of anaphylaxis

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Status asthmaticus
(severe acute asthma)
 Severe airway obstruction
 Symptoms persist despite initial standard
acute asthma therapy.
o Severe dyspnea & unproductive cough
o Sweating , central cyanosis ,tachycardia

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Status asthmaticus
 Treatment of Status asthmaticus
 High conc. of oxygen through facemask
 Nebulised salbutamol in oxygen given
immediately
 Ipratopium bromide + salbutamol
nebulised in oxygen,who don’t respond
within 15-30 min

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Status asthmaticus
 Treatment of Status asthmaticus
 Terbutaline s.c. or i.v.
 excessive coughing or too weak to inspire
adequately.
 Hydrocortisone hemisuccinate i.v. ,
followed by infusion.
 Endotracheal intubation & mechanical
ventilation if above ttt fails

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Prophylaxis
 Preservation of the environment, healthy
life-style (smoking cessation, physical
training) – are the basis of primary asthma
prophylaxis.
 These measures in combination with
adequate drug therapy are effective for
secondary prophylaxis.

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thanks
F o r W a t c h i n g

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