This document provides an overview of bronchial asthma, including its classification, pathophysiology, risk factors, diagnosis, and treatment. It begins with an introduction defining asthma as a chronic inflammatory airway disease characterized by wheezing and reversible airway obstruction. It then covers asthma's classification into allergic and non-allergic types, risk factors like genetics and environment, and diagnostic tests like spirometry and allergy testing. The bulk of the document focuses on treatment approaches, including non-pharmacological methods and a wide range of pharmacological options targeting inflammation and bronchodilation. It concludes with guidance on managing severe exacerbations and the goals of prophylaxis.
4. 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.
5. 5
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. 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
8. 8
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
9. 9
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
11. 11
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
12. 12
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
14. 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.
18. 18
Risk factors
Host factors:
predispose individuals to, or protect
them from, developing asthma
i. Genetic
o Atopy
o Airway hyperresponsiveness
ii. Gender
iii. Obesity
19. 19
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
22. 22
Clinical manifestations
Symptoms
Wheezing, dyspnea and cough.
Variable – both spontaneously and with
therapy.
Symptoms worse at night.
Nonproductive cough
Limitation of activity
23. 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
30. 30
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. 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. 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
33. 33
Pharmacological treatment
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. 34
Pharmacological treatment
β2 Agonists in asthma
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. 35
Pharmacological treatment
β2 Agonists in asthma
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. 36
Pharmacological treatment
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
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Pharmacological treatment
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. 38
Pharmacological treatment
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.
39. 39
Pharmacological treatment
Methylxanthines
Adverse effects
o Anorexia, nausea, vomiting, abdominal
discomfort
o headache, and anxiety
o Seizures or arrhythmias
o Diuresis
Doxyphylline
o long acting,oral
40. 40
Pharmacological treatment
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. 41
Pharmacological treatment
Corticosteroids in asthma
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.
42. 42
Pharmacological treatment
Corticosteroids in asthma
Inhaled corticosteroids( ICS)
o Use of β2Agonists >2 times a week indicates
need of a ICS
o E.g Beclomethasone , Budesonide , Fluticasone
43. 43
Pharmacological treatment
Corticosteroids in asthma
Inhaled corticosteroids( ICS)
Adverse effects:
o Oropharyngeal candidiasis, dysphonia
o Decreased bone mineral density.
o Skin thinning, purpura
o Growth retardation in children
44. 44
Pharmacological treatment
Corticosteroids in asthma
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.
45. 45
Pharmacological treatment
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. 46
Pharmacological treatment
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. 47
Pharmacological treatment
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. 48
Pharmacological treatment
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
49. 49
Pharmacological treatment
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.
50. 50
Pharmacological treatment
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
51. 51
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
52. 52
Status asthmaticus
(severe acute asthma)
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
53. 53
Status asthmaticus
(severe acute asthma)
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
54. 54
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.