ASTHMA

DR ISEKO I.I
UCH POSTGRADUATE
SEMINAR
MAY, 2010.
 INTRODUCTION
• Asthma is a serious global health
problem and constitutes a
significant burden in terms of
• Healthcare costs
• Loss of productivity
• Reduced participation in family/social
life
• There has remarkable
pharmacological improvements in
asthma care and a subsequent
change in the paradigms of
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 INTRODUCTION
• Asthma is defined based on
pathological, physiological and
clinical features.
• Asthma is an inflammatory disorder
of the airways which involve
several inflammatory cells and
multiple mediators that result in
characteristic pathophysiological
changes . of largely reversible
airway narrowing.
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 INTROUCTION
 Asthma 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 hyperresponsivenessthat leads to
recurrent episodes of wheezing, breathlessness,
chest tightness, and coughing, particularly at night
or in the early morning
 These episodes are usually associated with
widespread but variable airflow obstruction that is
often reversible either spontaneously or with
treatment

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 EPIDEMIOLOGY
§ Prevalence rates in Nigeria:
§ Sofowora & Clark - 2.4% in a school survey at
Ibadan.
§ Falade et al using ISAAC Questionnaire found
16.7% (13-14yrs) and 7.2% (6-7yrs) in
Ibadan.
§ Okoromah reported 3% in Enugu (6-13yrs)
§ Oviawe - 0.7% in a rural community at Edo
§ Highest prevalence reported from UK, New
Zealand, and Australia (Isaac)
• A O Faniran- Wheeze and persistent cough were
less prevalent in Nigeria (10.2% and 5.1%,
respectively)

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 EPIEMIOLOGY
• Asthma is one of the most common
chronic diseases globally and
currently affects ~300 million people.
• The prevalence of asthma has risen in
affluent countries over the last 30
years but now appears to have
stabilized, with ~10–12% of adults
and 15% of children affected by the
disease.
• In developing countries where the
prevalence of asthma had been much
lower, there is a rising incidence that
appears to be associated with
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increased urbanization.
 AETIOLOGY

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 AETIOLOGY
• Asthma is a heterogeneous disease
• Genetics is an important determinant
of asthma
• Environmental causes undoubtedly
contribute to its expression.

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 HOST FACTORS

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 Risk Factors that Lead to Asthma
Development
Causal Factors
• Indoor Allergens C o n trib u tin g
– Domestic mites F a cto rs
– Animal Allergens lR e sp ira to ry in fe ctio n s
– Cockroach lS m a llsize a t b irth
Allergens
– Fungi lD ie t
• Outdoor Allergens lA ir p o llu tio n
– Pollens –O u td o o r
– Fungi p o llu ta n ts
• Occupational –In d o o r p o llu ta n ts
Sensitizers lS m o kin g
–Pa ssive S m o kin g
–A ctive S m o kin g

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 The Underlying
Mechanism
R isk F a cto rs ( fo r d e v e lo p m e n t o f
a sth m a )

INFLAMMATION

A irw a y
H y p e rre sp o n siv e n e A irflo w
ss L im ita tio n

S y m p to m s -
R isk F a cto rs ( shortness of
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( for exacerbations
Iseko I.I b) re a th , co u g h ,
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 HYGEINE HYPOTHESIS
• Proposes that lack of infections in
early childhood preserves the TH2
cell bias at birth,
• Exposure to infections and endotoxin
results in a shift toward a
predominant protective TH1
response.

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 PATHOLOGY AND
PATHOPHYSIOLOGY

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 PATHOPHYSIOLOGY
• Clinical spectrum is variable but the
presence of inflammation is
consistent
• There’s inappropriate response of the
specific immune system to
harmless antigens
• Results in Th2-mediated chronic
inflammation
• No good correlation between the
severity of inflammation and the
severity of asthma
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 Fig u re 3 A sth m a a n d a irw a y in fla m m a tio n

Clinical Science www.clinsci.org Clin. Sci. (2002) 103, 201-211

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 CELLS INVOLVED IN ASTHMA
PATHOPHYSIOLOGY

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 Fig u re 1 A sth m a a s a d ise a se o f T h 2 - m e d ia te d ch ro n ic a irw a y in fla m m a tio n

Clinical Science www.clinsci.org Clin. Sci. (2002) 103, 201-211

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 AIRWAY NARROWING
• Airway Smooth Muscle
Contraction- in response to
bronchoconstrictor mediators and
neurotransmitters
• Airway Edema- due to inflammatory
mediators and vascular
permeability(acute exacerbations)
• Airway Thickening- aka
remodelling due to structural
changes (not fully reversible).
• Mucus HyperSecretion
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 STRUCTURAL AIRWAY
CHANGES
• Subepithelial Fibrosis – collagen &
proteoglycan deposition
• Smooth Muscle- Hyperplasia &
Hypertrophy
• Blood Vessels – proliferate under
influence of VEGF
• Mucus Hypersecretion- from
goblet cell hyperplasia &
submucosal gland hypertrophy
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 Asthma: Pathological
changes

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IS IT ASTHMA?

Clinical Evaluation
 CLINICAL EVALUATION
• The diagnosis of asthma is a clinical
one
• there is no standardized definition of
the type, severity or frequency of
symptoms, nor of the findings on
investigation
1.presence of symptoms :>1 of
• wheeze,
• breathlessness,
• chest tightness,
• cough) and of
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 Clinical Features that Increase
the Likelihood of Asthma
• More than one of the following
symptoms: wheeze, cough, difficulty
breathing, chest tightness,
particularly if these symptoms:
– are frequent and recurrent
– are worse at night and in the early
morning
– occur in response to, or are worse after,
exercise or other triggers, such as
exposure to pets, cold or damp air, or
with emotions or laughter
– occur apart from colds
• Personal history of atopic disorder
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 Clinical Features that Increase
the Likelihood of Asthma
• Family history of atopic disorder
and/or asthma
• Widespread wheeze heard on
auscultation
• History of improvement in symptoms
or lung function in response to
adequate therapy
• Otherwise unexplained low FEV1 or
PEF (historical or serial readings)
• Otherwise unexplained peripheral
blood eosinophilia
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Clinical Features that Decrease
the Likelihood of Asthma
• Chronic productive cough in the
absence of wheeze or breathlessness
• Repeatedly normal physical
examination of chest when
symptomatic
• Voice disturbance
• Symptoms with colds only
• Significant smoking history (ie >20
pack-years)
• Cardiac disease
• Normal PEF or spirometry when
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 CLINICAL EVALUATION
• A normal spirogram/spirometry when
not symptomatic does not exclude
the diagnosis of asthma.
• Repeated measurements of lung
function are often more informative
than a single assessment.
• Spirometry is the preferred initial test
to assess the presence and severity
of airflow obstruction.
•
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 CLINICAL EVALUATION
• With a thorough history and
examination, an individual child can
usually be classed into one of three
groups
– High probability – diagnosis of asthma
likely
– Low probability – diagnosis other
than asthma likely
– Intermediate probability – diagnosis
uncertain.
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 CLINICAL EVALUATION

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 CLINICAL EVALUATION-
FURTHER
1.THOSE WITH
OBSTRUCTION(FEV1/FVC-
<70%)
• Offer patients with airways
obstruction and intermediate
probability of asthma a reversibility
test and/or a trial of treatment for a
specified period:
– if there is significant reversibility, or if
a treatment trial is clearly beneficial
treat as asthma
– if there is insignificant reversibility
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and a treatment
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trial is not
 CLINICAL EVALUATION-
FURTHER
2.THOSE WITHOUT
OBSTRUCTION(FEV1/FVC-
>70%)
• In patients without evidence of
airways obstruction and with an
intermediate probability of asthma,
– arrange further investigations before
commencing treatment.

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 CLINICAL EVALUATION
1.TESTS OF AIRWAY HYPER-
RESPONSIVENESS
– Metacholine Test- ≥20% reduction in FEV1
after <8ng/ml
– Indirect provocation tests (mannitol,
exercise)
2.TEST OF EOSINOPHILIC AIRWAY
INFLAMMATION-
– sputum differential eosinophil count>2% or
– exhaled nitric oxide concentrations (FENO)-
>25ppb AT 50ml/sec.
3.TESTS OF ATOPY
– Positive skin tests,
– blood eosinophilia ≥4%, or
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 CLINICAL EVALUATION
TREATMENT TRIALS AND


REVERSIBILITY TESTING
• Assess FEV1 (or PEF) and/or symptoms:
– before and after 400 mcg inhaled
salbutamol in patients with diagnostic
uncertainty and airflow obstruction
present at the time of assessment
– in other patients, or if there is an
incomplete response to inhaled
salbutamol, after either inhaled
corticosteroids (200 mcg twice daily
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I.I for 6-8
 CLINICAL EVALUATION
TREATMENT TRIALS AND REVERSIBILITY


TESTING
• A >400 ml improvement in FEV1 to
either β2 agonists or corticosteroid
treatment trials strongly suggests
underlying asthma.
• >15% improvement in PEF

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“All that wheezes is not
asthma”
--Chevalier Jackson, MD (1865-
1958).
Boston Medical Quarterly,
16:86,1965
 Other Causes of
Wheezing
• Aspiration
• Certain drugs
• Chronic obstructive pulmonary disease
• Endobronchial tumors
• Endotracheal tumors
• Inhaled irritants
• Tracheal stenosis
• Viral tracheobronchitis
• Vocal cord dysfunction
• Pulmonary edema (CHF)
•
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 DIFFERENTIAL DIAGNOSIS

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 Classification Types
1.Symptom-based
– Chronic (mild, moderate, severe)
– Acute severe asthma
– Brittle asthma- wide PEF variability,
sudden severe attacks on a
background of apparently well
controlled asthma
– Nocturnal
– Exercise-induced

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 Classification Types
2.Aetiological
– Extrinsic (atopic)
– Intrinsic (non-atopic)
– Virally induced
– Occupational
3.Pathological
– Eosinophilic
– Neutrophilic
– Fixed airflow obstruction (airway
remodelling
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 Components of Therapy
1.Develop Patient/Doctor Patnership
2.Identify and Reduce Exposure to Risk
Factors
3.Assess, Treat and Monitor Asthma
4.Manage Asthma Exacerbations
5.Special Conditions

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 1. Develop Patient-Doctor
Partnership
• Aim of partnership is guided Self-
Management
• The patient and healthcare professional
discuss and agree on:
– Goals of treatment
– Develop a personalized written self-
management plan including self
monitoring
– Periodically review patient’s treatment
and level of asthma control
• Personal Action Plans to help the
individual make changes to treatment
in response to changes in asthma
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 Develop Patient-Doctor
Partnership
• Written action plans for patients to
follow during exacerbations have
been shown to:
 (Cochrane review of 25 studies)
– Decrease emergency department
visits
– Decrease hospitalizations
– Improve lung function
– Decrease mortality in patients
presenting with an acute asthma
exacerbation
– NAEPP recommends a written action
 Develop Patient-Doctor
Partnership
• Patients should learn to:
– Avoid risk factors
– Take drugs correctly
– Know the difference between
‘controller’ and ‘reliever’
medications
– Recognize signs that asthma is
worsening and take action
– Monitor their status using symptoms
and PEF if applicable
– Seek hospital care
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 2. Identify and Reduce
Exposure to Risk Factors
• Early identification of occupational
sensitizers and removal of the sensitized
patient from further exposure helps
occupational asthma
• Reducing patient’s exposure to some
categories of risk factors reduces the need
for medications
• Reduce exposure to indoor allergens
• Avoid tobacco smoke
• Avoid vehicle emission
• Explore role of infections on asthma development,
especially in children and young infants
•
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 3. Assess, Treat and Monitor
Asthma
• The goal is to achieve and maintain
clinical control
• Treatment should be adjusted
continuous cycle driven by
patient’s status
• At each treatment step, reliever
medications should be provided for
fast symptomatic relief
• Ongoing monitoring is essential to
indentify the lowest step and dose
of treatment to minimize cost and
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Various severities of asthma
• Step-wise pharmacotherapy
treatment program for varying
severities of asthma
– Mild Intermittent (Step 1)
– Mild Persistent (Step 2)
– Moderate Persistent (Step 3)
– Severe Persistent (Step 4)
• Patient fits into the highest category
that they meet one of the criteria
for
 C la ssifica tio n o f S e ve rity

CLASSIFY SEVERITY
Clinical Features Before Treatment
Nocturnal
Symptoms Symptoms FEV1 or PEF

STEP 4 Continuous ≤ 60% predicted

Severe Limited physical Frequent Variability > 30%
Persistent activity

STEP 3 Daily 60 - 80% predicted

> 1 time week Variability > 30%
Moderate Attacks affect
Persistent activity

STEP 2 > 2 times a month ≥ 80% predicted

> 1 time a week
Mild but < 1 time Variability 20 -
Persistent a day 30
30%%

< 1 time a week

STEP 1 ≤ 22 times ≥ 80% predicted
Asymptomatic and times aa
Intermitten normal PEF month
month Variability < 20%
t between attacks
The presence of one feature of severity is sufficient to place patient in that
category.
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 Mild Intermittent Asthma
• Day time symptoms < 2 times q
week
• Night time symptoms < 2 times q
month
• PEF or FEV1 > 80% of predicted
• PEF variability < 20%
– PEF and FEV1 values are only for
adults and for children over the age
of 5
–
 Mild Persistent Asthma
• Day time symptoms > 2/week, but <
1/day
• Night time symptoms < 1 night q
week
• PEF or FEV1 > 80% of predicted
• PEF variability 20%-30%
Moderate Persistent Asthma
• Day time symptoms q day
• Night time symptoms > 1 night q
week
• PEF or FEV1 60%-80% of predicted
• PEF variability >30%
 Severe Persistent Asthma
• Day time symptoms: continual
• Night time symptoms: frequent
• PEF or FEV1 < 60% of predicted
• PEF variability > 30%
 Pharmacotherapy for Adults and
Children Over the Age of 5 Years
• Step 1 (Mild intermittent asthma)
– No daily medication needed
– PRN short-acting bronchodilator
(albuterol) MDI
– Severe exacerbations may require
systemic corticosteroids
– Although the overall diagnosis is
“mild intermittent” the
exacerbations themselves can still
be severe

 Pharmacotherapy for Adults and
Children Over the Age of 5 Years
• Step 2 (Mild persistent)
– Preferred Treatment
• Low-dose inhaled corticosteroid daily
– Alternative Treatment (no particular
order)
• Cromolyn
• Leukotriene receptor antagonist
• Nedocromil
• Sustained release theophylline to
maintain a blood level of 5-15
mcg/mL
 Pharmacotherapy for Adults and
Children Over the Age of 5 Years
• Step 3 (Moderate persistent)
– Preferred Treatment
• Low-to-medium dose inhaled
corticosteroids
• WITH long-acting inhaled beta2-
agonist
– Alternative Treatment
• Increase inhaled corticosteroids within
the medium dose range
• Add leukotriene receptor antagonist or
theophylline to the inhaled
corticosteroid
 Pharmacotherapy for Adults and
Children Over the Age of 5 Years
• Step 4 (Severe persistent)
– Preferred Treatment
• High-dose inhaled corticosteroids
• AND long-acting inhaled beta2-
agonists
• AND (if needed) oral corticosteroids
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 Part
Part 44: Long
Long-term
term Asthma
Asthma Management
Management
Pharmacologic Therapy
Controller Medications:
lInhaled glucocorticosteroids
lSystemic glucocorticosteroids

lCromones

lMethylxanthines

lLong-acting inhaled β2-agonists

lLong-acting oral β2-agonists

lLeukotriene modifiers
lAnti-IgE

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 Part
Part 44:: Long
Long--term
term Asthma
Asthma Management
Management
Pharmacologic Therapy

Reliever Medications:
lRapid-acting inhaled β2-agonists
lSystemic glucocorticosteroids
lAnticholinergics
lMethylxanthines

lShort-acting oral β2-agonists

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 Pharmacotherapy
• Long-acting beta2-agonists (LABA)
– Beta2-receptors are the predominant
receptors in bronchial smooth
muscle
– Stimulate ATP-cAMP which leads to
relaxation of bronchial smooth
muscle and inhibition of release of
mediators of immediate
hypersensitivity
– Inhibits release of mast cell mediators
such as histamine, leukotrienes, and
prostaglandin-D2
– Beta1-receptors are predominant
 Pharmacotherapy
• Long-acting beta2-agonists (LABA)
– Salmeterol (Serevent)
– Salmeterol with fluticasone (Advair)
– Should only be used as an additional
treatment when patients are not
adequately controlled with inhaled
corticosteroids
– Should not be used as rescue
medication
– Can be used age 4 and above with a
DPI
– Deaths associated with inappropriate
 Pharmacotherapy
• Salbutamol
– Short-acting beta2-agonist
• ATP to cAMP leads to relaxation of
bronchial smooth muscle, inhibition
of release of mediators of immediate
hypersensitivity from cells, especially
mast cells
– Should be used prn not on a regular
schedule
• Prior to exercise or known exposure to
triggers
• Up to every 4 hours during acute
 Pharmacotherapy
• Inhaled Corticosteroids
– Anti-inflammatory (but precise MOA
not known)
– Act locally in lungs
• Some systemic absorption
• Risks of possible growth retardation
thought to be outweighed by
benefits of controlling asthma
– Not intended to be used as rescue
medication
– Benefits may not be fully realized for
1-2 weeks
 Pharmacotherapy
• Mast cell stabilizers
(cromolyn/nedocromil)
– Inhibits release of mediators from
mast cells (degranulation) after
exposure to specific antigens
– Blocks Ca2+ ions from entering the
mast cell
– Safe for pediatrics (including infants)
– Should be started 2-4 weeks before
allergy season when symptoms are
expected to be effective
 Pharmacotherapy
• Leukotriene receptor antagonists
– Leukotriene-mediated effects include:
• Airway edema
• Smooth muscle contraction
• Altered cellular activity associated
with the inflammatory process
– Receptors have been found in airway
smooth muscle cells and
macrophages and on other pro-
inflammatory cells (including
eosinophils and certain myeloid
stem cells) and nasal mucosa

 Pharmacotherapy
• Leukotriene receptor antagonists
– No good long-term studies in
pediatrics
– Montelukast as young as 2;
zarfirlukast age 7
– Alternate, but not preferred
medication in persistent asthma and
as addition to ICS
– Showed a statistically significant, but
modest improvement when used as
primary medication
 Pharmacotherapy
• Theophylline
– Narrow therapeutic index/Maintain 5-
20 mcg/mL
– Variability in clearance leads to a
range of doses that vary 4-fold in
order to reach a therapeutic dose
– Mechanism of action
• Smooth muscle relaxation
(bronchodilation)
• Suppression of the response of the
airways to stimuli
• Increase force of contraction of
diaphragmatic muscles
 Part
Part 44: Long
Long-term
term Asthma
Asthma Management
Management
Allergen-specific Immunotherapy
 Greatest benefit of specific
immunotherapy using allergen extracts
has been obtained in the treatment of
allergic rhinitis
Specificimmunotherapy should be
considered only after strict
environmental avoidance and
pharmacologic intervention have failed
to control asthma
 Perform only by trained physician
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 Part
Part 44:: Long
Long--term
term Asthma
Asthma Management
Management
Stepwise Approach to Asthma
Therapy
The choice of treatment should be guided
by:
Severity of the patient’s asthma
Patient’s 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.
05/31/10 73
 4. Manage Asthma
Exacerbations
• Acute exacerbation of asthma is
generally referred to as an acute
asthmatic attack
Treatment of exacerbations depends on:

§ The patient
§ Experience of the health care professional
§ Therapies that are the most effective for the
particular patient
§ Availability of medications
§ Emergency facilities
•
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• Oxygen to alleviate the hypoxia that
results from extreme asthma attacks
(but not the asthma attack itself).
• Nebulized salbutamol or terbutaline
(short-acting beta-2-agonists), often
combined with ipratropium (an
anticholinergic).
• Systemic steroids, oral or intravenous
(prednisone, prednisolone,
methylprednisolone, dexamethasone,
or hydrocortisone). A non tapered 5 -
10 day course seems to be sufficient.
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• Other bronchodilators that are
occasionally effective when the
usual drugs fail
– Intravenous salbutamol
– Nonspecific beta-agonists, injected or
inhaled (epinephrine, isoetharine,
isoproterenol, metaproterenol)
– Anticholinergics, IV or nebulized, with
systemic effects (glycopyrrolate,
atropine, ipratropium)
19/05/2010 – MethylxanthinesIseko I.I(theophylline,
 – Inhalation anesthetics that have a
bronchodilatory effect (isoflurane,
halothane, enflurane)
– The dissociative anaesthetic ketamine,
– Magnesium sulfate intravenous treatment
has been shown to provide a
bronchodilating effect when used in
addition to other treatment in severe
acute asthma attacks.
– Intubation and mechanical ventilation, for
patients in or approaching respiratory
arrest.
– Heliox, a mixture of helium and oxygen,
may be used in a hospital setting. It has a
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more laminar flow than ambient air and
 E m e rg e n cy D e p a rtm e n t M a n a g e m e n t
Acute Asthma
Initial Assessment
History, Physical Examination, PEF or FEV1

Initial Therapy
Bronchodilators; O2 if needed

Good Response
Incomplete/Poor Response Respiratory Failure

Observe for Add Systemic Glucocorticosteroids

at least 1
hour
Good Response Poor Response
If Stable,
Discharge to Discharge Admit to Hospital Admit to ICU
Home
 Managing Severe Asthma
Exacerbations

§ Severe exacerbations are life-threatening

medical emergencies


§ Care must be expeditious and treatment is

often most safely undertaken in a
hospital or hospital-based emergency
department



 In this case
Silence is Not Golden
 CELEBRITIES WITH
ASTHMA…

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 REFERENCES

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 THANK YOU

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