Asthma

Asthma is a common disease,

affecting approximately 5%
of the population

Men and women appear to

be equally affected
 Definition
• Asthma is characterized by chronic
airway inflammation and increased
airway hyper-responsiveness leading
to symptoms of wheeze, cough, chest
tightness and dyspnea

• Functionally characterized by
presence of airflow obstruction
reversible with treatment
• Episodic or chronic symptoms of airflow
obstruction: breathlessness, cough, wheezing,
and chest tightness

• Symptoms frequently worse at night or in the

early morning

• Prolonged expiration and diffuse wheezes on

physical examination

• Limitation of airflow on pulmonary function

testing or positive broncho-provocation
challenge

• Complete or partial reversibility of airflow

obstruction, either spontaneously or following
bronchodilator therapy
 Factors contributing to
• asthma
Environmental allergens (House dust mites,
animal allergens [especially cat and dog],
cockroach allergens, and fungi are most
commonly reported)

• Viral respiratory infections

• Exercise; hyperventilation

• Gastroesophageal reflux disease (GERD)

• Chronic sinusitis or rhinitis

• Aspirin or nonsteroidal anti-inflammatory drug

hypersensitivity, sulfite sensitivity

• Use of beta-adrenergic receptor blockers

(including ophthalmic preparations)
• Obesity

• Environmental pollutants, tobacco smoke

• Irritants such as household sprays and paint

fumes

• Occupational exposure : insects, plants, latex,

gums, diisocyanates, anhydrides, wood dust,
and fluxes.

• Emotional factors or stress

• Perinatal factors (Prematurity and increased

maternal age increase; maternal smoking and
prenatal exposure to tobacco smoke also
increase the risk of developing asthma)

• "Cardiac asthma" is wheezing precipitated by

 Exercise Induced Asthma
• Exposure to cold or dry air
• Environmental pollutants (eg, sulfur, ozone)
• Level of bronchial hyperreactivity
• Chronicity of asthma and symptomatic control
• Duration and intensity of exercise
• Allergen exposure in atopic individuals
• Coexisting respiratory infection
 Pathophysiology

The pathophysiology of asthma is complex and involves the following components:

(1) airway inflammation

•

(2) intermittent airflow obstruction

•

(3) bronchial hyper-responsiveness

•
 Airway inflammation
• The mechanism of inflammation in asthma may be acute,
subacute, or chronic
• Mononuclear cell and eosinophil infiltration, mucus
hypersecretion, desquamation of the epithelium, smooth
muscle hyperplasia, and airway remodeling are present.
• Some of the principal cells identified in airway inflammation
include mast cells, eosinophils, epithelial cells, macrophages,
and activated T lymphocytes.
• T lymphocytes play an important role in the regulation of
airway inflammation through the release of numerous
cytokines
• Other constituent airway cells, such as fibroblasts,
endothelial cells, and epithelial cells, contribute to the
chronicity of the disease
• Finally, cell-derived mediators influence smooth muscle tone
and produce structural changes and remodeling of the airway
 Airflow obstruction
Airflow obstruction can be caused by a variety of changes:

• Acute bronchoconstriction is the consequence of

immunoglobulin E–dependent mediator release upon exposure
to aeroallergens and is the primary component of the early
asthmatic response

• Airway edema occurs 6-24 hours following an allergen

challenge and is referred to as the late asthmatic response

• Chronic mucous plug formation consists of an exudate of

serum proteins and cell debris that may take weeks to resolve

• Airway remodeling is associated with structural changes due

to long-standing inflammation and may profoundly affect the
extent of reversibility of airway obstruction
 Airway hyper-
responsiveness
• The presence of airway hyperresponsiveness or
bronchial hyperreactivity in asthma is an
exaggerated response to numerous exogenous
and endogenous stimuli

• The mechanisms involved include direct

stimulation of airway smooth muscle and indirect
stimulation by pharmacologically active
substances from mediator-secreting cells such as
mast cells or non-myelinated sensory neurons

• The degree of airway hyperresponsiveness

generally correlates with the clinical severity of
asthma
 Pathogenesis of Exercise Induced
Asthma
• Controversial

• The disease may be mediated by water loss from the

airway, heat loss from the airway, or a combination of
both

• The upper airway is designed to keep inspired air at

100% humidity and body temperature at 37°C (98.6°F).
The nose is unable to condition the increased amount of
air required for exercise, particularly in athletes who
breathe through their mouths

• The abnormal heat and water fluxes in the bronchial

tree result in bronchoconstriction, occurring within
minutes of completing exercise

• Results have not demonstrated an increase in

inflammatory mediators
 Histopathology
• Denudation of airway epithelium
• Collagen deposition beneath the basement
membrane
• Airway edema
• Mast cell activation
• Inflammatory cell infiltration with neutrophils,
eosinophils, and lymphocytes (especially T
lymphocytes)
• Hypertrophy of bronchial smooth muscle and
hypertrophy of mucous glands with plugging of
small airways with thick mucus can occur
• This airway inflammation underlies disease
chronicity and contributes to airway
hyperresponsiveness, airflow limitation, and
respiratory symptoms (including recurrent
episodes of wheezing, breathlessness, chest
tightness, and cough, particularly during the
nighttime and early morning hours).
 There is basement membrane thickening of
bronchus and submucosal infiltrates of eosinophils
with chronic inflammatory cells in Asthmatic
bronchus
 Clinical Findings
Symptoms
• Episodic wheezing

• Difficulty in breathing

• Chest tightness

• Cough
• The frequency of asthma symptoms is highly
variable

• Some patients may have only a chronic dry cough

and others a productive cough

• Some patients have infrequent, brief attacks of

asthma and others may suffer nearly continuous
symptoms

• Asthma symptoms may occur spontaneously or

may be precipitated or exacerbated by many
different triggers as discussed above

• Asthma symptoms are frequently worse at night;

circadian variations in bronchomotor tone and
bronchial reactivity reach their nadir between 3
AM and 4 AM, increasing symptoms of
bronchoconstriction
 Signs
General
• Evidence of respiratory distress manifests
as increased respiratory rate, increased heart
rate, diaphoresis, and use of accessory muscles
of respiration

• Marked weight loss or severe wasting may

indicate severe emphysema

• Pulsus paradoxus: This is an exaggerated fall

in systolic blood pressure during inspiration and
may occur during an acute asthma exacerbation

• Depressed sensorium: This finding suggests a

more severe asthma exacerbation with
impending respiratory failure
 Chest examination

• Chest examination may be normal between

exacerbations in patients with mild asthma

• End-expiratory wheezing or a prolonged

expiratory phase is found most commonly,
although inspiratory wheezing can be heard

• Diminished breath sounds and chest

hyperinflation may be observed during
acute exacerbations
• Wheezing during normal breathing or a
prolonged forced expiratory phase correlates
well with the presence of airflow obstruction.
Wheezing during forced expiration does not

• During severe asthma exacerbations, airflow

may be too limited to produce wheezing,
and the only diagnostic clue on auscultation
may be globally reduced breath sounds with
prolonged expiration
• Upper airway: Some physical findings
increase the probability of asthma, nasal
mucosal swelling, increased nasal
secretions, nasal polyps are often seen in
patients with allergic asthma

• Skin: Eczema, atopic dermatitis, or other

manifestations of allergic skin disorders
may also be present
 Investigations
Pulmonary Function Testing

SPIROMETRY
• Clinicians are able to identify airflow obstruction on
examination, but they have limited ability to assess
it or to predict whether it is reversible

• The evaluation for asthma should therefore include

spirometry (FEV1, FVC, FEV1/FVC) before and after
the administration of a short-acting bronchodilator

• These measurements help determine the presence

and extent of airflow obstruction and whether it is
immediately reversible
• Airflow obstruction is indicated by a reduced
FEV1/FVC ratio (< 75%)

• In severe airflow obstruction with significant

air trapping, the FVC may also be reduced,
resulting in a pattern that suggests a
restrictive ventilatory defect

• Significant reversibility of airflow obstruction

is defined by an increase of 12% and 200
mL in FEV1 or 15% and 200 mL in FVC after
inhaling a short-acting bronchodilator
 Peak expiratory flow (PEF)

• Peak expiratory flow (PEF) meters are handheld

devices designed as home monitoring tools

• PEF monitoring can establish peak flow variability,

quantify asthma severity, and provide both the
patient and the clinician with objective
measurements on which to base treatment
decisions

• Measuring PEF is recommended as part of a

comprehensive approach to asthma management
• A peak flow meter is an inexpensive, pocket-sized device that
measures peak expiratory flow (PEF), or how fast a person can
breathe out

• To measure PEF, the person takes a deep breath and then blows
into a tube on the peak flow meter as hard and as fast as
possible. This can be done at home.
• PEF shows diurnal variation

• It is generally lowest on first awakening and highest

several hours before the midpoint of the waking day

• PEF should be measured in the morning before the

administration of a bronchodilator and in the afternoon
after taking a bronchodilator

• A 20% change in PEF values from morning to afternoon

or from day to day suggests inadequately controlled
asthma

• PEF values less than 200 L/min indicate severe airflow

obstruction

• Inform the patient that a peak flow of less than 80% of

the patient's personal best indicates a need for
additional medication and a peak flow below 50%
indicates severe exacerbation
 Bronchial provocation testing

• Bronchial provocation testing with histamine

or methacholine—or exercise challenge testing
—may be useful when asthma is suspected
and spirometry is nondiagnostic

• Bronchial provocation is not generally

recommended if the FEV1 is less than 65% of
predicted

• A positive test is defined as a decrease in

FEV1 of at least 20% at exposure to a dose of
16 mg/mL or less

• A negative test has a negative predictive value

for asthma of 95%.
 Arterial blood gas measurements

• Arterial blood gas measurements may be normal

during a mild asthma exacerbation, but respiratory
alkalosis and an increase in the alveolar-arterial
oxygen difference (A–a–DO2) are common

• During severe exacerbations, hypoxemia develops

and the PaCO2 returns to normal

• The combination of an increased PaCO2 and

respiratory acidosis is a harbinger of respiratory
failure and may indicate the need for mechanical
ventilation.
 Diagnosis of Asthma
Comparable clinical history with either/ or

• FEV1 ≥ 15% ( and 200ml) increase

following administration of a
bronchodilator/ trial of corticosteroids

• > 20% diurnal variation on ≥ 3 days in a

week for 2 weeks on PEF diary

• FEV1≥15% decrease after 6 minutes of

exercise
 Additional Testing
Chest radiographs:
• Routine chest radiographs in patients
with asthma usually show only
hyperinflation

• Other findings may include bronchial

wall thickening and diminished
peripheral lung vascular shadows

• Chest radiographs are indicated when

pneumonia, another disorder mimicking
asthma, or a complication of asthma
Bronchial asthma
 Asthmatic Lungs
Thee chest is hyper-expaned and the lungs are
large volume
 Measurement of allergic status:
• Increased Eosionophils in blood or sputum
• Increased serum total IgE
• Skin testing or in vitro testing to assess sensitivity to relevant
environmental allergens may be useful in patients with
persistent asthma

Assessment of airway Inflammation:

• The diagnostic usefulness of measurements of biologic markers
of inflammation such as cell counts and mediator titers in blood
and sputum is being investigated

Evaluations for paranasal sinus disease or gastroesophageal

reflux should be considered in patients with pertinent symptoms
and in those who have severe or refractory asthma
 Management
The goals of asthma
therapy
• Minimize chronic symptoms that impair
normal activity (including exercise)
• Prevent recurrent exacerbations
• Minimize the need for emergency department
visits or hospitalizations
• Maintain near-normal pulmonary function

These goals should be met while providing

optimal pharmacotherapy with the fewest
adverse effects and while meeting patients'
and families' expectations of satisfaction with
asthma care
Metered Dose
Inhaler( MDI)
 Stepwise approach for
managing
Long-Term Quick Relief asthma
Education
Control

Step 1:
Mild No daily Short-acting Teach basic facts about
bronchodilator: asthma
intermitte medication
inhaled β2- Teach inhaler/inhalation
nt needed chamber technique
agonists as needed
for symptoms. Discuss roles of
medications
Develop self-
Intensity of treatment
management and action
will depend on
plans
severity of
exacerbation. Discuss appropriate
environmental control
measures
Use of short-acting
inhaled β2-
agonists > 2 times
a week may
indicate the need
for long-term
 Long-Term Control Quick Relief Education
Step 2: One daily medication: Step 1 actions Step 1 actions
plus: plus:
Mild Anti- Use of short- Teach self-
persisten inflammatory: acting inhaled monitoring
either inhaled β 2-agonists on Refer to
t corticosteroid a daily basis, or group
(low doses) or increasing use, education if
cromolyn or indicates the available
nedocromil need for Review and
Less desirable additional long- update self-
alternatives: term control management
sustained-release therapy plan
theophylline or
leukotriene
modifier
 Long-Term Control Quick Relief Education

Step Daily medication:. Step 1 As for step Step 1

3: actions plus: 2 actions plus:

Moderat Either Teach self-

e monitoring
Anti-inflammatory: inhaled
persiste
nt corticosteroid (medium dose) Refer to
or group
education if
Inhaled corticosteroid (low-
available
medium dose) and a long-acting
bronchodilator (long-acting Review and
inhaled β2-agonist, sustained- update self-
release theophylline or long- management
acting β 2-agonist tablets) plan
If needed: Anti-inflammatory:
inhaled corticosteroid
(medium-high dose)
and Long-acting
bronchodilator (long-acting
inhaled β2-agonist, sustained-
 Long-Term Control Quick Relief Education

Step 4: Daily medication: As for step 2 Step 2 and 3

      actions plus:
Severe Anti-inflammatory: Refer to
persisten inhaled individual
t corticosteroid (high education,
dose) and counseling
Long-acting
bronchodilator
(long-acting inhaled
β2-agonist,
sustained release
theophylline or
long-acting inhaled
β2-agonist tablets)
and
Corticosteroid
tablets or syrup
(1–2 mg/kg/d,
generally not to
 Step Down Therapy

Once asthma control is

established the dose of inhaled
or oral corticosteroid should be
titrated to the lowest dose at
which effective control of asthma
is maintained
Asthmatic Exacerbations
Precipitated by
• Infections (viral)
• Moulds ( Alternaria and
Cladosporium)
• Pollen
• Air pollution

Characterized by Increased
symptoms, deterioration in PEF and
increase in airway inflammation
 Approach to Treatment of Asthma
Exacerbations
• Correction of hypoxemia through the use of
supplemental oxygen

• Reversal of airflow obstruction by repetitive

or continuous administration of an inhaled
short-acting β 2-agonist and the early
administration of systemic corticosteroids

• Serial measurement of airflow in the

emergency department

• The post exacerbation care plan is an

important aspect of management
 Approach to Treatment of
Mild Asthma Exacerbations
• Mild asthma exacerbations are characterized by only
minor changes in airway function (PEF > 80%) and
minimal symptoms and signs of airway dysfunction

• Most patients respond quickly and fully to an inhaled

short-acting β2-agonist alone. However, an inhaled
short-acting β2-agonist may need to be continued
every 3–4 hours for 24–48 hours

• For mild exacerbations in patients already taking an

inhaled corticosteroid, the dose is doubled until peak
flow returns to predicted or personal best

• In patients not already taking an inhaled corticosteroid,

initiation of this agent should be considered.
 Immediate assessment of Acute
severe asthma
Acute severe asthma
• PEF 33-50% predicted
• Respiratory rate ≥ 25/ min
• Heart rate≥110/ min
• Inability to complete sentence in one breath

Life threatening feature

• PEF 33-50% predictedSPO2 < 92% or PaO2 < 60mmHg
• Normal PCO2
• Silent Chest
• Cyanosis
• Feeble respiratory effort
• Bradycardia or arrhythmia
• Hypotension
• Exhaustion
• Confusion
• Coma

Near Fatal asthma

• Raised PaCO2 and or requiring mechanical ventilation with
raised inflation pressures
 Approach to Treatment of
Moderate & Severe Asthma
Exacerbations
• Owing to the life-threatening nature of severe
exacerbations of asthma, treatment should be
started immediately once the exacerbation is
recognized

• A brief history pertinent to the exacerbation

can be completed while treatment is given.
More detailed assessments, including
laboratory studies, usually add little in the
early phase of evaluation and management
and should be delayed until after initial therapy
has been completed.
 Oxygen therapy
• Asphyxia is a common cause of death,
and oxygen therapy is therefore very
important

• Supplemental oxygen should be given to

maintain an SaO2 > 90% or a PaO2 > 60
mm Hg

• Oxygen-induced hypoventilation is very

rare, and concern for hypercapnia should
never delay correction of hypoxemia.
Oxygen therapy
 High-dose inhaled short-acting
β2-agonist
• Frequent high-dose delivery of an inhaled
short-acting β2-agonist is indicated and is
usually well tolerated in the setting of
severe airway obstruction

• At least three MDI or nebulizer treatments

should be given in the first hour of therapy

• Thereafter, the frequency of administration

varies according to the improvement in
airflow and associated symptoms and the
occurrence of side effects
 Systemic corticosteroids
• They reduce inflammatory
response and hasten resolution of
exacerbations

• Administered orally, prednisolone

30-60 mg but intravenous
hydrocortisone 200 mg may be
used
 Intravenous Fluids
• Dehydration due to insensible watr
loss

• Hydration therapy given with

potassium supplementation to
compensate for salbutamol induced
hypokalemia
• A small minority of patients will not
respond well to treatment and will show
signs of impending respiratory failure due
to a combination of worsening airflow
obstruction and respiratory muscle fatigue

• Such patients can deteriorate rapidly and

thus should be monitored in a critical care
setting

• Mechanical ventilation is given in selected

patients