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Adult Asthma for UPCM LU4

Aileen David – Wang MD MSc FPCCP


Clinical Associate Professor
Learning Objectives
At the end of the session, the student should be
able to:
• define asthma
• describe the local prevalence, epidemiology, and
natural history of asthma
• recognize the risk factors for asthma
development and persistence
• recognize its characteristic symptomatology
Learning Objectives

At the end of the session, the student should be


ble to:
recognize diseases that may mimic asthma
enumerate and interpret laboratory tests that
support or confirm the diagnosis of asthma
classify asthmatics according to their level of
chronic severity and control, and give
recommendations on the appropriate drug therap
become familiar with asthma pharmacotherapy
Recent Asthma Guidelines

 Global Initiative for Asthma (GINA) Update


 December 2008
 www. ginasthma .org
 NAEPP Expert Panel Report Update by US
NHLBI
 NIH Publication No. 02 -5075; July 2007
 www.nhlbi.nih.gov/guidelines/asthma
 Philippine Consensus Report on the Dx and
Mx of Asthma
 2004 Evidence -Based Update; 2009 Update
soon to be released
Definition of Asthma
Definition of Asthma
• Asthma, irrespective of the severity, is
a chronic inflammatory disorder of the airways
in which many cells and cellular elements play
a role.
• The chronic inflammation causes an associated
increase in airway hyperresponsiveness that
leads to airflow limitation and respiratory
symptoms
Global Initiative for Asthma (GINA 2004)

Mechanisms behind Asthma Symptoms
Environmental Risk Factors (Causes)

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

Widespread, variable and often reversible


Asthma
AECOPD

• Hypoventilation
• Respiratory acidosis
• Pneumothorax
• Hypotension
Severe Asthma Exacerbation
Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MD


Inflammatory Mediator Soup in Asthma

Source: Peter J. Barnes, MD


Asthma Symptoms

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

 In a recent survey of Filipinos living in urban


communities, about 22% of adults, 33% of
adolescents and 27% of children aged 6 to 7
years have asthma and asthma-like symptoms
National Asthma Epidemiology Study: Urban Focus 2003
Risk Factors for Asthma
Factors that Influence Asthma
Development and Expression

Host Factors Environmental Factors


 Genetic  Indoor allergens

- ATOPY  Outdoor allergens

- BHR  Occupational sensitizers


 Gender  Tobacco smoke
 Obesity  Air Pollution
 Race/ Ethnicity  Respiratory Infections
 Diet


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

Note: Gender and breastfeeding were not


significant
Risk Factors for Persistence
of Asthma Symptoms (Triggers)

House Dust Mite (Dermatophagoides pteronyssinus)


Risk Factors for Persistence
of Asthma Symptoms (Triggers)


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

B. 50 y.o./F, sole complaint of on


and off cough for the past 2
years, treated with various
antibiotics
C. 15 y.o. athlete who develops
SOB after running

D. 48 y.o. smoker with progressive


SOB x 4 y and recent active
hemoptysis
E. All can be considered asthmatics
Triad of Asthma

• 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

“Not all that wheezes is asthma,


not all asthma wheezes”
 Differential Diagnosis of Asthma
 Foreign body aspiration esp. in children
 Tracheal, laryngeal and bronchial lesions/
tumors
 Extrinsic obstruction of the airways
 Other chronic obstructive airways diseases
– COPD, bronchiectasis, diffuse
panbronchiolitis, cystic fibrosis
 Pulmonary embolism
 “Cardiac asthma” – CHF, mitral stenosis
 Vocal cord dysfunction
 Confirmatory Tests for Asthma
 Measurements of airflow limitation, its reversibility and its variability are
critical in establishing a clear diagnosis
 Bronchoprovocation Test
 measures non-specific BHR
 Methacholine/ Histamine Inhalation Challenge
 high sensitivity but low specificity
 a negative test can be useful to exclude a diagnosis of persistent
asthma
Can be positive in recent viral URTI, COPD, bronchiectasis, allergic
rhinitis, etc.
Bronchoprovocation
0
Test
5
Normal
% Fall FEV1

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

PC20 FEV1 – concentration of bronchoprovoking


agent
that causes the FEV1 to fall by 20%
 Confirmatory Tests for Asthma
 Spirometry
 FEV1/FVC < 75% Obstructive Airways Disease
 Acute Bronchodilator Response (Reversibility):
> 12 % increase + absolute increase of 200 ml in FEV1 and/or
FVC

GINA 2004
 Forced expiratory volume
in 1 second (FEV1)
– 4.0 L
 Forced vital capacity FEV1
(FVC)
– 5.0 L FVC
 FEV1/FVC = 80%

Since asthma is an episodic disease, the spirometry


can be normal during a mild or asymptomatic perio
0
F
E
V
L 1 1
i Asthma:
t
e FEV1 > 12%
r 2
COPD:
s FEV1 <
Obstructive 12%
pattern

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 }

Not specific for asthma


Asthma Pharmacotherapy
Drugs Available for Asthma

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

• quick relief bronchodilators


• “rescue” medicine
• use as-needed
• relieve bronchoconstriction and
the accompanying symptoms
• no effect on airway inflammation
and BHR
• frequent need for rescue is a sign
of poor asthma control
 Short Acting Beta2 Agonists

• drug of choice for treatment of


acute asthma exa’s and episodes
• useful as prophylaxis against EIA
• stimulate beta-adrenergic receptors
and activate G proteins to
produce cAMP
• decrease release of mediators
• improve mucociliary transport
• Salbutamol (Albuterol), Levalbuter
Terbutaline, Fenoterol
 Anticholinergics
• slower in onset and of modest
potency compared to SABAs
• reliever of choice for beta-
blocker induced asthma
• additive effect when combined
with SABA
• Ipratropium bromide
Controllers

• used daily on a long-term basis


to achieve and maintain control
of persistent asthma
• act on airway inflammation
and BHR


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

5-LO Inhibitor 5-Lipoxygenase FLAP


e.g. Zileuton

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

STEP 4 Continuous <60% predicted Multiple


Severe Frequent
Limited physical Variability >30% Controllers
persistent activity, freq exa
b
STEP 3 Daily symptoms and >60% - <80%
β 2-agonist use >1 X a week predicted > 2
Moderate Attacks affect Controllers
persistent activity Variability >30%

STEP 2 > 1 a week >2 X a month >80% predicted One


Mild but <1 x a day
Variability 20-30% Controller
persistent But < 1 x a week

STEP 1 <1 a week >80% predicted No


Asymptomatic and <2 X a month
Intermittent normal PEF between Variability <20% Controllers
Needed
attacks
GINA, 2005
Asthma as an Evolving Concept:
Shift in Paradigm of Asthma
Treatment 
from Severity to Control
AW
Remodelling

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

The choice of treatment should be guided by:


 Level of asthma control
 Current treatment
 Pharmacological properties and availability of the
various forms of asthma treatment
 Economic considerations
Cultural preferences and differing health care
systems need to be considered
Assessing Level of Asthma
Control 
(GINA 2008)
Controlled
Characteristi Partly controlled Un-
(All of the (Any present in any
c week)
controlled
following)
None (2 or less / More than
Daytime Sx’s week) twice / week
Activity limitation None Any
3 or more
Nocturnal Sx’s None Any
features of
partly
/ awakening
controlled
Need for None (2 or less / More than asthma present
week) twice / week in any week
“reliever” Rx
Lung function < 80% predicted or
Normal personal best (if
(PEF or FEV1) known) on any day

Exacerbation None One or more / year 1 in any week*


REDUCE
LEVEL OF CONTROL TREATMENT OF ACTION

maintain and find lowest controlling


controlled
step
consider stepping up to
partly controlled gain control

INCREASE
uncontrolled step up until controlled

exacerbation treat as exacerbation

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

 Exacerbations of asthma (asthma attacks) are


episodes of rapidly progressive (in minutes to
hours to days) increase in shortness of breath,
cough, wheezing, or chest tightness, or some
combination of these symptoms.

GINA 2004


Asthma Severity and Exacerbations

 Severe asthmatics tend to have the most


severe and the most frequent
exacerbations
 The more severe the underlying
inflammation, the more difficult and
dangerous the exacerbation
 Even mild asthmatics can have severe,
life- threatening exacerbations!

Acute Exacerbation of Asthma

= Failure of
Chronic
Management
+
Trigger
 Acute Exacerbation of Asthma

= Indicator of
Poor Asthma
Control
Asthma Management and Prevention Program
Component 4: Manage Asthma Exacerbations

Primary therapies for exacerbations:


 Repetitive administration of rapid-acting inhaled β2-
agonist
 Early introduction of systemic glucocorticosteroids

 Oxygen supplementation

Closely monitor response to treatment with serial


measures of lung function