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Bronchial
Airflow Symptoms
Hyper-
Limitation
Responsiveness
TRIGGERS
Bronchial Hyperresponsiveness (BHR)
or Airway Hyperresponsiveness
(AHR)
Airways narrow too easily and too
much in response to exogenous or
endogenous stimuli
Allergens
Sensitizers Genetically
Viruses Sw it c Predispose
Air pollutants h d
”
“on
Airway
Chronic Hyperresponsiveness
Inflammat
ion Triggers:
Allergens
Symptoms: Exercise Cold
cough air SO2
dyspnea Particulates
wheezing
Adapted from: Peter J. Barnes, MD
Laitinen 1992
Airway Inflammation in Asthma
Normal Asthmatic
P Jeffery, in: Asthma, Academic Press 1998
Normal
Denuded
mucosa
Thickened
basement
membrane
Inflammatory cells
Wall edema
Hypertrophied
airway sm muscles
Airflow Limitation in Asthma
TRIGGER
BHR
1. Acute bronchoconstriction/spasm
2. Swelling of the airway wall
3. Chronic mucus plug formation
4. Airway wall remodelling
Airflow Limitation in Asthma
TRIGGER
BHR
Asthma
AECOPD
• Hypoventilation
• Respiratory acidosis
• Pneumothorax
• Hypotension
Severe Asthma Exacerbation
Asthma Inflammation: Cells and Mediators
Inflammation
Airway
Hyperresponsiveness
Airway
Remodeling
Prevalence and Natural Hx
of Asthma
Asthma Epidemiology
Asthma is a very common disease
Found in all countries
Prevalence seems to be increasing
Occurs at all ages but predominantly in early life
About half develop before age 10 and another
1/3 before age 40
Asthma Epidemiology
Can begin in the elderly
In childhood, 2:1 male/female preponderance;
difference disappears after age 10
During puberty and thereafter, more females
develop asthma than males
Asthma Epidemiology
Disappears in 30 to 50% of children at puberty, but often reappears in adult life
Risk Odds p-
Factors Ratio 95% C.I. value
Smoker in the household when the child 1.81 1.17 - 2.80 0.007
was 1-3 years old
Severe Respiratory Infection 4.92 2.81 - 8.62 <0.001
Allergy 3.74 2.49 - 5.61 <0.001
Family History
Father 4.27 2.33 - 7.82 <0.001
Mother 4.12 2.21 - 7.70 <0.001
Other Relatives 2.07 1.29 – 3.31 0.002
Risk Factors for Persistence
of Asthma Symptoms (Triggers)
Indoor Allergens – house dust mite,
cockroach, animal allergens (cats,
dogs), fungi, molds, yeasts
Outdoor Allergens- Pollens
Tobacco Smoke
Air Pollution
Factors that Precipitate Asthma
Exacerbations
Respiratory Infections esp. viral- most common
Weather changes
Indoor and outdoor allergens/ air pollutants
Exercise
Drugs – aspirin, beta-blockers, coloring agents
Food
Irritants- household sprays, paints, fumes
Extreme emotional expression/ stress- laughter
Diagnosis of Asthma
Who is unlikely to be an
asthmatic?
A. 18 y.o./F, on and off dyspnea and chest
tightness for the past 10 years
• Dyspnea
• Cough
• Wheeze
Pulmonary Pearls:
Diagnosis of Asthma
Episodic or Intermittent Symptoms
Usually triggered by exogenous factors
Seasonal variability
Typical early morning symptoms
Typical atopic history
Family history of asthma
Positive response to bronchodilators
Is it Asthma?
Recurrent episodes of wheezing
Troublesome cough at night
Cough or wheeze after exercise
Cough, wheeze or chest tightness after
exposure to airborne allergens or pollutants
Colds “go to the chest” or take more than 10
days to clear
Pulmonary Pearls:
Diagnosis of Asthma
No pathognomic manifestation
10
15
20
25 Asthma
30
35
b
0 0.125 0.25 0.5 1 2 4 8 16 32
PC20of Methacholine (mg/ml)
Concentration
PC20
GINA 2004
Forced expiratory volume
in 1 second (FEV1)
– 4.0 L
Forced vital capacity FEV1
(FVC)
– 5.0 L FVC
FEV1/FVC = 80%
3
Asthma COPD
Normal
4
1 2 3 4 4
6 Seconds
Confirmatory Tests for Asthma
Bronchodilator
Reversibility
% = post-BD FEV1 - pre-BD FEV1 x 100
pre-BD FEV1
GINA 2004
Confirmatory Tests for Asthma
Peak Flow Monitoring
Acute BD Response: > 15%
increase in PEF
Diurnal variability > 10% (if no
BD) or > 20% (if on BD)
Drop of >15% with 6-minute
running/exercise
GINA 2004
Confirmatory Tests for Asthma
Peak Flow Diurnal Variability
> 20%
DV = PEFevening - PEFmorning x
100
½ (PEFevening + PEFmorning )
GINA 2004
Other Laboratory Tests in Asthma
Chest Radiograph
no role in making a diagnosis of asthma
usually normal, but may show hyperinflation
useful in excluding other causes of wheezing and detecting
complications of asthma exacerbations (e.g., pneumothorax)
and concomitant conditions (e.g., pneumonia)
Sputum/ Blood Eosinophilia }
Allergy skin tests/ IgE }
ASTHMA MEDICATIONS
TRIGGER
BHR
CONTROLLER RELIEVER
(Maintenance) (As Needed)
Current Asthma Medications
Relievers Controllers
Short acting Beta Cromolyn Sodium
agonist + Anti – Nedocromil Na
cholinergics Corticosteroids
Systemic Long Acting
Steroids Theophylline
Short acting Long Acting Beta
Theophyllines agonists
Anti-Leukotrienes
Anti-IgE
Inhalational is superior to oral therapy.
Relievers
Controllers: Inhaled
Steroids
• Most potent and most effective
anti-inflammatory medications
currently available
• Budesonide, Fluticasone,
Beclomethasone, Flunisolide,
Triamcinolone
• Preferred Rx for all levels of
persistent asthma
• Most common side effects:
dysphonia, oral thrush
gargle after use
Clinical Effects of Inhaled
Corticosteroids on Asthma
improved BHR
reduced symptoms
reduced frequency and severity of exacerbations
reduced oral steroid rescues
reduced prn SABA use
improved lung function
decreased ER visits and hospitalization
improved quality of life
reduced relapse after an acute attack
LEVEL OF EVIDENCE: A
(GINA 2006)
Effects of Corticosteroids on
istopathologic Characteristics in Asthma
Histopathologic
• Decreased cellularity usually resulting from decreases in
eosinophils, mast cells, and lymphocytes
• Decreased numbers of dendritic cells and HLA-DR expression
• Decreased numbers of cells expressing mRNA for IL-4 and IL-5
• Increased numbers of cells expressing mRNA for IFN-γ
• Increased area of ciliated epithelium
• Decreased thickness of basement membrane
• Decreased tenasein in basement membrane
Fish. J Allergy Clin Immunol 1999; 104: 509-516
Systemic
Steroids
• Considered as “relievers” for treatment of moderate to
severe exacerbations, in short-courses of moderate
to high daily dose
• Onset of action > 4 -6 h
• Also used as “controllers” for chronic severe asthma,
in low dose daily or alternate-day therapy
• Long term use is limited by systemic side effects
including adrenal suppression
Inhaled Long Acting Beta2
Agonists (LABA)
Same effects as SABAs
May modulate mediator release from mast cells
and basophils
Activity persists for > 12 h
Provide long-term protection against broncho-
constrictor stimuli and for EIA
The preferred add-on therapy for asthmatics who
remain symptomatic despite the use of inhaled
steroid
Should never be used as sole controller in asthma
Inhaled Long Acting Beta2
Agonists (LABA)
Formoterol – onset of action similar to
Salbutamol
Salmeterol
Fixed dose combination inhaled steroid – LABA
are now available
Budesonide – Formoterol (Symbicort)
Fluticasone – Salmeterol (Seretide)
Theophylline and
derivatives
As a bronchodilator: Weak
phosphodiesterase inhibition, adenosine
antagonism
Use as add-on therapy in moderate to severe
Asasthma esp. nocturnal
a controller: Weak Antisymptoms
- Inflammatory Properties
Eosinophil infiltration of airways
T - lymphocytes in alveolar epithelium
mucociliary clearance
Alternative but not preferred controller in mild
persistent asthma (Philippine Guidelines)
Oral preparation
2002 NHLBI guidelines
Anti-Leukotrienes
Arachidonic Acid
Cysteinyl-LT
Antagonist
LTA4 e.g. Zafirlukast,
Montelukast
LTB4 LTC4
Bronchoconstriction
Mucus secretion
LTD4 Oedema
Chemotaxis Hyperresponsiveness
Immunomodulation Eosinophilia
LTE4
Anti-Leukotrienes
Monotherapy as
alternative first-line
controller
Second-Line
Controller
Add-On
Steroid Sparing
Effect
Drug of choice for
aspirin induced
asthma
Cromones
Mast cell stabilizers: inhibit degranulation
Alternative but not preferred controller in
mild
persistent asthma, esp. in children
Also useful for EIA prophylaxis
4 to 6 week therapeutic trial may be
required to determine efficacy
Oral preparation
Cromolyn sodium, Nedocromil sodium
Classification of Asthma
Classification of Asthma
• Traditional
classification into
Endogenous vs
Exogenous Asthma:
classification clinically
not useful
• Classification Based on Chronic Severity
Assessment vs. Control of asthma
• Severity assessed at the initial consult
• Control assessed on follow up
Classification of Chronic Asthma Severity
Clinical features before treatment
Daytime Night-time PEF or FEV1
Symptoms symptoms Meds to control
Airway
Inflammation
Bronchospasm
1975 1980 1985 1990 1995 2000
Asthma as an Evolving Concept:
Shift in Paradigm of Asthma
Treatment
from Severity to Control
• Asthma severity involves both the
severity of
the underlying disease AND its
responsiveness to treatment
• Asthma severity may change over
months or
years
• Thus, for ongoing Mx of asthma,
classification GINA 2007
by level of control is more relevant and
GINA 2007 Asthma Management and Prevention Program
Assess, Treat and Monitor Asthma
INCREASE
uncontrolled step up until controlled
REDUCE INCREASE
TREATMENT STEPS
STEP STEP STEP STEP STEP
1 2 3 4 5
Treating to Maintain Asthma
Control
When control has been achieved, ongoing
monitoring is essential to:
- maintain control
- establish lowest step and least drug/dose
treatment necessary to maintain
control
If control is maintained for at least 3
months, consider step down to the next
lower step
Asthma episode versus exacerbation
GINA 2004
Asthma Severity and Exacerbations
= Failure of
Chronic
Management
+
Trigger
Acute Exacerbation of Asthma
= Indicator of
Poor Asthma
Control
Asthma Management and Prevention Program
Component 4: Manage Asthma Exacerbations
Oxygen supplementation