This document defines bronchial asthma and discusses its epidemiology, etiology, pathology, clinical features, diagnosis, classification of severity, and treatment. Some key points: - Asthma is a chronic inflammatory disorder characterized by airway hyperresponsiveness leading to reversible airflow obstruction. It affects 300 million people globally. - Both genetic and environmental factors contribute to asthma development, including atopy, air pollution, allergens, and occupational sensitizers. - Pathologically, it involves eosinophilic inflammation and thickening of the airway walls. Clinically, it presents with wheezing, coughing, and shortness of breath. - Diagnosis involves lung function tests showing reversibility and

1. BRONCHIAL ASTHMA
DR D M KILLINGO

2. DEFINITION
 Clinical syndrome defined physiologically by episodic
reversible airway narrowing and hyper responsiveness
of the airways to a variety of stimuli.
 Defined pathologically by presence of certain
recognizable microscopic features i.e. Infiltration of the
airways with eosinophils, hypertrophy and hyperplasia of
the airway smooth muscle, mucous secretory apparatus
and overall thickening of the airway wall.
 Chronic relapsing inflammatory disorder characterised
by hyperreactive airways leading to episodic reversible
bronchial obstruction owing to increased
responsiveness of the tracheobronchial tree to various
stimuli

3. EPIDEMIOLOGY
 Affects ~ 300million people globally.
 Men = Women in adulthood. In childhood 2:1
 Prevalence 8-30% in developed countries and 0-
5% in developing countries
 Kenyan: urban 10%, rural 3%
 Commoner in those <20years. Peak age 3 years

4. ETIOLOGY/ RISK FACTORS
 Interplay between genetic and environmental
factors
 Endogenous factors
 Genetic predisposition
 25 genes assoc with asthma
 Atopy
 Allergic rhinitis present in 80% of asthmatic patients
 Airway hyperresponsiveness

5. ETIOLOGY CONTINUED
 Environmental factors
 Indoor allergens i.e. house dust mite, domestic pets.
 Outdoor allergens e.g. air pollution by sulphur dioxide,
ozone, diesel particulates trigger symptoms
 Occupational sensitizers
 Hygiene hypothesis – exposure to infections and
endotoxin, helminthic infections
 Occupational exposure, chemicals e.g. toluene
diisocyanate, trimellitic anhydride

6. PATHOLOGY
 Associated with specific chronic inflammation of the
mucosa of the lower airways. Lung parenchyma
spared
 Degree of inflammation poorly related to disease
severity. Infiltration by T lymphocytes, activated
eosinophils and mast cells.
 Thickening of the basement membrane due to sub
epithelial collagen deposition
 Airway narrowed, reddened, wall thickened and
edematous
 Occlusion of airway by mucous plug

7. PATHOPHYSIOLOGY
 Limitation of airflow due to;
 Bronchoconstriction
 Airway edema
 Vascular congestion
 Luminal occlusion with exudate
 FEV1, FEV/FVC, PEF all reduced and an increase in airway
resistance
 Early closure of peripheral airway results in (air trapping) lung
hyperinflation, and increased residual volume
 Early phase reaction(within minutes) due to immediate
hypersensitivity reaction. Mediated by histamine,
prostaglandin D2 and leukotrienes C4,D4,E4
 Late phase reaction(4-6 hours) coincides with influx of
inflammmatoey cells mediated by T lymphocytes( eosinophils
and basophils)

8. INFLAMMATORY CELLS
 Inflammation assoc with airway hyper
responsiveness
 Mast cells
 Initiate bronchoconstrictor response to allergens or
stimuli e.g. hyperventilation, exercise, fog
 Activated by allergens through IgE dependent
mechanism
 Release brochoconstrictor mediators eg histamine,
cysteinyl-leukotrienes, cytokines, chemokines, growth
factors and neurotrophins

9.  Eosinophils
 Linked to dev of airway hyperresponsiveness
 Presence related to disease severity
 Release oxygen radicals and basic proteins
 Release growth factors involved in airway remodelling
 Recruitment involves
 adhesion to vascular endothelial cells via adhesion molecules
 migration to submucosa via chemokines
 Activation and prolonged survival
 Neutrophils
 Role unknown
 Resistant to anti-inflammatory effect of corticosteroids

10.  T lymphocytes
 Co-ordinate inflam response in asthma
 Release cytokines for recruitment and survival of
eosinophils
 Maintain mast cell population
 TH2 response predominant;
 Release IL-5 thus eosinophilic inflammation
 Release IL-13, IL-4 thus increased IgE production
 Structural cells i.e. epithelial cells, fibroblasts, and
smooth muscle cells release cytokines and lipid
mediators.
 Major source of mediators driving chronic inflammation

11. ASTHMA TRIGGERS
 Allergens
 Include pollen, fungal spores, allergens from
domestic pests, roaches, ragweed
 Viral infections
 URTIs esp rhinovirus, RSV, corona virus.
 Pharmacological agents
 Β adrenergic blockers
 ACE inhibitors
 aspirin

12.  Air pollution
 Increased ambient levels of sulphur dioxide, ozone
and nitrogen oxides
 Occupation factors
 Workplace sensitizing agents. Reversal if removed
within 6 months. Later irreversible airway changes
 Hormonal factors
 Premenstrual worsening assoc with fall in
progesterone
 Thyrotoxicosis and hypothyroidism worsen asthma

13. CLINICAL FEATURES
 Wheezing , dyspnea, coughing
 Symptoms worse at night or early morning
 Increased mucus production difficult to expectorate
 Prodromal symptoms; chin itch, impending doom,
discomfort between scapula
 Expiratory and inspiratory rhonchi
 If well controlled no symptoms

14. DIAGNOSIS
 Lung function tests
 Spirometry: reduced FEV, FEV1/FVC ratio, PEF
 Reversibility; > 12% and 200ml incr in FEV1 15 min
after an inhaled short acting β2 agonist or after a 2
week trial with glucocorticoids
 Measure of PEF twice daily confirms diurnal
variation
 Airway responsiveness
 Methacholine or histamine challenge ;FEV reduced
by 20%

15.  Hematologic
 Total serum IgEs and specific IgEs to inhaled
allergens
 Imaging
 CXR normal or hyperinflation
 Skin tests
 Positive in allergic asthma, negative in intrinsic
asthma.
 Allergen testing for occupational exposure

16. DIFFERENTIAL DIAGNOSIS
 Upper airway obstruction
 Left ventricular failure
 Eosinophilic pneumonias
 Systemic vasculitis
 COPD
 Pulmonary tuberculosis
 Tracheomalacia
 Vocal cord palsy

17. Severity
Symptom
frequency
Nighttime
symptoms
Peak expiratory
flow rate or FEV1
of predicted
Variability of
peak expiratory
flow rate or FEV1
Intermittent
Less than once a
week
Less than twice
per month
More than 80%
predicted
Less than 20%
Mild persistent
More than once
per week but less
than once per day
More than twice
per month
More than 80%
predicted
20–30%
Moderate
persistent
Daily
More than once
per week
60–80% predicted More than 30%
Severe persistent Daily Frequent
Less than 60%
predicted
More than 30%
Clinical classification of asthma severity

18. Sign/Symptom Mild Moderate Severe Pending arrest
Alertness May show agitation Agitated Agitated Confused/Drows
Breathlessness On walking On talking Even at rest
Talks in Sentences Phrases Words
Wheeze Moderate Loud Loud Absent
Accessory muscle Usually not used Used Used
Respiratory rate
(/min)
Increased Increased Often >30
Pulse rate (/min) 100 100-120 >120 <60 (Bradycardia
PaO2 Normal >60 <60 ,possible cyanosis
PaCO2 <45 <45 >45
Severity of asthma attack

19. TREATMENT
 Aims of therapy
 Minimal chronic symptoms
 Minimal exacerbations
 No emergency visits
 Minimal use of as required β2 agonist
 No limitation of activity
 PEF circadian variation <20%
 Near normal PEF
 Minimal drug side effects

20.  Bronchodilator therapies
 Reverse bronchoconstriction by acting on smooth
muscle cells
 Little or no effect on underlying inflamm process
 Β2 agonists
 Activate β2 adrenergic receptors. These are coupled through
a G protein to adenyl cyclase resulting in incr intracellular
cAMP thus smooth muscle cell relaxation
 Inhibit mast cell mediator release
 Reduce plasma exudation
 Inhibit sensory nerve exudation
 Decreased cough
 Incr eased mucociliary clearance
 Increased mucus secretion

21.  Anticholinergics
 Prevent cholinergic nerve induced
bronchoconstriction and mucus secretion
 Slower onset of bronchodilation
 Less effective than β2 agonists
 Theophylline
 Inhibit phosphodiesterases in airway smooth
muscle cells thus increase cAMP
 Anti-inflammatory effects at lower doses via
activation of nuclear enzyme histone deacetylase-2
which switches off activated inflammatory genes

22.  Controller therapies
 Inhaled corticosteroids
 Most effective anti-inflammatory agents in asthma
 Switch off transcription genes that encode inflam
proteins
 Inhibit transcription factors NFkB and AP-1.
 Recruit histone deacetylase-2 to inflamm gene complex
thus reverses histone acetylation (assoc with incr gene
transcription)
 Reduce ; no. of inflammatory cells
; activation of inflammatory cells
; eosinophils in the airway and sputum
;activated T ymphocytes
;surface mast cells

23.  Systemic corticosteroids
IV for severe asthma
 Antileukotrienes
 Montelukast and zafirlukast
 Block cys-LT-1 receptors
 Add on therapy
 Cromones
 Cromolyn sodium and nedocromil sodium inhibit
mast cell and sensory nerve activation
 Block trigger induced asthma e.g. EIA

24.  Anti IgE
 Omalizumab
 Blocking Ab, which neutralizes circulating IgE

26. TREATMENT OF ACUTE SEVERE ASTHMA
 Give SABA (inhaler + spacer, nebulised) up to 3
treatments in 1 hour (variable delivery to lower airways!)
 O2 to achieve saturations of >90%
 IV β2 agonists may be given in impending resp failure
 Observe at least 3 hours
 If symptoms return in <3hrs, or fail to improve
 add inhaled anticholinergic to SABA
 add oral/IV corticosteroid
 If still no improvement, admit to hospital
 give humidified oxygen (nasal cannula)
 continue SABA+anticholinergic,
 continue systemic corticosteroid
 consider IV methylxanthines (monitor levels)
 IV or nebulised magnesium sulphate
 monitor closely
 In resp failure, intubate and ventilate