BRONCHIAL ASTHMA

PATHOGENESIS, CLINICAL FEATURES

AND
DIAGNOSIS

BRIG S B H ZAIDI
MBBS, MD, FCPS, MRCP
Frequency of Asthma
• Common in industrialized nations such as Canada,
England, Australia, Germany, and New Zealand,
• The prevalence rate of severe asthma in industrialized
countries ranges from 2-10%
• Estimated to affect 300 million persons worldwide.
• Trends suggest an increase in both the prevalence and
morbidity of asthma, especially in children younger than
6 years.
• Factors that have been implicated include urbanization,
air pollution, passive smoking, and change in exposure
to environmental allergens.
Definition of Asthma
• Chronic inflammatory disorder of the airways in which many
cells and cellular elements play a role.

• In susceptible individuals, this inflammation causes recurrent

episodes of wheezing, breathlessness, chest tightness, and
coughing, particularly at night or in the early morning.

• These episodes are associated with widespread but variable

airflow obstruction that is reversible either spontaneously,
or with treatment.

• GINA
• Asthma is a common chronic disorder of the airways that
is complex and characterized by
– variable and recurring symptoms,
– airflow obstruction,
– bronchial hyper responsiveness,
– and an underlying inflammation.

• The interaction of these features of asthma determines

the clinical manifestations and severity of asthma and
the response to treatment.

– 2007 Expert Panel Report 3

 Exercise-induced asthma (EIA),
• An asthma variant defined as a condition in which exercise
or vigorous physical activity triggers acute bronchospasm in
persons with heightened airway reactivity.

• It is observed primarily in persons who have asthma

(exercise-induced bronchospasm in asthmatic persons)

• Also found in patients with normal resting spirometry findings

with atopy, allergic rhinitis, or cystic fibrosis and even in
healthy persons, many of whom are elite athletes (exercise-
induced bronchospasm in athletes).

• Exercise-induced bronchospasm is often a neglected

diagnosis, and the underlying asthma may be silent in as
many as 50% of patients, except during exercise.
Causes of Asthma
• Factors that can contribute to asthma or airway
hyperreactivity may include any of the following:

– Environmental allergens: House dust mites, animal allergens

(especially cat and dog), cockroach allergens, and fungi are
most commonly reported.

– Viral respiratory tract infections

– Exercise; hyperventilation

– Gastroesophageal reflux disease

– Chronic sinusitis or rhinitis

– Aspirin or nonsteroidal anti-inflammatory drug

(NSAID) hypersensitivity, sulfite sensitivity

– Use of beta-adrenergic receptor blockers (including

ophthalmic preparations)

– Obesity: Based on a prospective cohort study of

86,000 patients, those with an elevated body mass
index are more likely to have asthma.
• Environmental pollutants, tobacco smoke

• Occupational exposure

• Irritants (eg, household sprays, paint fumes)

• Various high and low molecular weight compounds:

– A variety of high and low molecular weight compounds are
associated with the development of occupational asthma, such as
insects, plants, latex, gums, diisocyanates, anhydrides, wood
dust
• Emotional factors or stress

• Perinatal factors: Prematurity and increased maternal age

increase the risk for asthma

• Breastfeeding has not been definitely shown to be

protective.

• Both maternal smoking and prenatal exposure to tobacco

smoke also increase the risk of developing asthma
Pathophysiology
• The pathophysiology of asthma is complex
and involves the following components:

– Airway inflammation

– Intermittent airflow obstruction

– Bronchial hyper responsiveness

 The mechanism of inflammation in asthma

• May be acute, sub acute, or chronic,

• The presence of airway oedema and mucus
secretion also contributes to airflow obstruction
and bronchial reactivity.
• Varying degrees of
– mononuclear cell and eosinophil infiltration
– mucus hyper secretion,
– desquamation of the epithelium,
– smooth muscle hyperplasia, and
– airway remodeling are present.
• T lymphocytes play an important role in the regulation of
airway inflammation through the release of numerous
cytokines.

• Fibroblasts, endothelial cells, and epithelial cells,

contribute to the chronicity of the disease.

• Other factors, such as adhesion molecules (eg,

selectins, integrins), are critical in directing the
inflammatory changes in the airway.

• Cell-derived mediators influence smooth muscle tone

and produce structural changes and remodeling of the
airway.
 Airway hyper responsiveness or bronchial
hyper reactivity in asthma
• This 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 nonmyelinated sensory
neurons.

• The degree of airway hyper responsiveness generally

correlates with the clinical severity of asthma.
 Airflow obstruction

• Can be caused by a variety of changes, including

– acute bronchoconstriction,
– airway edema,
– chronic mucous plug formation,
– and airway remodeling.
• 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.
 Pathogenesis of exercise-induced
bronchospasm
• Controversial.

• 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 disease may be mediated by water loss from the

airway, heat loss from the airway, or a combination of
both.
• The abnormal heat and water fluxes in the bronchial tree
result in bronchoconstriction, occurring within minutes of
completing exercise.

• Results from bronchoalveolar lavage studies have not

demonstrated an increase in inflammatory mediators.

• These patients generally develop a refractory period, during

which a second exercise challenge does not cause a
significant degree of bronchoconstriction.
Clinical Evaluation
 History

• Detailed assessment of the medical history should

address

– (1) whether symptoms are attributable to asthma,

– (2) whether findings support the likelihood of asthma

(eg, family history),

– (3) asthma severity,

– (4) the identification of possible precipitating factors

• Asthma symptoms may include the following:
– Cough, worse particularly at night
– Wheezing
– Shortness of breath
– Chest tightness
– Sputum production
– Decreased exercise tolerance

• Asthma symptom patterns can vary as follows:

– Perennial versus seasonal
– Continual versus episodic
– Duration, severity, and frequency
– Diurnal variations (nocturnal and early-morning awakenings)
• Precipitating or aggravating factors for asthma,
– Environmental allergen exposure (dust mites, pet dander,
pollens)
– Occupation
– Medications
– Exercise
– Viral upper respiratory tract infections
– Strong emotional expression
– Menstrual cycles
– Airborne dusts or chemicals
• Family history may reveal the following conditions:
– Asthma
– Allergy
– Sinusitis
– Rhinitis
– Eczema

• Social history may reveal the following conditions:

– Home characteristics
– Smoking
– Workplace or school characteristics
– Educational level
– Employment
– Social support
 General Physical Examination

• Skin:
– Observe for the presence of atopic dermatitis, eczema, or other manifestations of allergic
skin conditions
• 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

• End-expiratory wheezing or a prolonged expiratory

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

• Diminished breath sounds and chest hyperinflation

(especially in children) may be observed during acute
asthma exacerbations.

• The presence of inspiratory wheezing or stridor may

prompt an evaluation for an upper airway obstruction
such as vocal cord dysfunction, vocal cord paralysis,
thyroid enlargement, or a soft tissue mass (eg, malignant
tumor).
Differential Diagnoses
• Airway Foreign Body
Heart Failure
Allergic and Environmental Asthma
Pulmonary Embolism
Alpha1-Antitrypsin Deficiency
Pulmonary Eosinophilia
Aspergillosis
Sarcoidosis
Bronchiectasis
Sinusitis, Chronic
• Bronchiolitis
Tracheomalacia
COPD
URTI
Churg-Strauss Syndrome
Vocal Cord Dysfunction
Cystic Fibrosis
Foreign Body Aspiration
Gastroesophageal Reflux Disease
Laboratory Studies
• Blood eosinophilia greater than 4% or 300-400/µL

• Eosinophil counts greater than 8% may be observed in

patients with concomitant atopic dermatitis.
• This finding should prompt an evaluation for allergic bronchopulmonary
aspergillosis, Churg-Strauss syndrome, or eosinophilic pneumonia

• Total serum immunoglobulin E levels greater than 100 IU are

frequently observed in patients experiencing allergic
reactions, but this finding is not specific for asthma

• British Thoracic Society recommends using sputum

eosinophilia determinations to guide therapy
Imaging Studies

• In most patients with asthma, chest radiography findings

are normal or may indicate hyperinflation.

• Chest radiography should be considered in all patients

being evaluated for asthma to exclude other diagnoses.

• Sinus CT scanning may be useful to help exclude acute

or chronic sinusitis as a contributing factor..
 Pulmonary function testing (spirometry)

• Spirometry assessments should be obtained as the primary test

to establish the asthma diagnosis.

• Spirometry should be performed prior to initiating treatment in

order to establish the presence and determine the severity of
baseline airway obstruction.

• The assessment and diagnosis of asthma cannot be based on

spirometry findings alone because many other diseases are
associated with obstructive spirometry indices.
•
• Spirometry measures the forced vital capacity (FVC), the
maximal amount of air expired from the point of maximal
inhalation, and the FEV1. A reduced ratio of FEV1 to FVC,
when compared with predicted values, demonstrates the
presence of airway obstruction.

• Optimally, the initial spirometry should also

include measurements before and after inhalation of a short-
acting bronchodilator in all patients in whom the diagnosis of
asthma is considered.

• Reversibility is demonstrated by an increase of 12% and 200

mL after the administration of a short-acting bronchodilator
 Methacholine- or histamine-challenge
testing

• Bronchoprovocation testing with either methacholine or histamine is

useful when spirometry findings are normal or near normal, especially
in patients with intermittent or exercise-induced asthma symptoms.

• Bronchoprovocation testing helps determine if airway hyperreactivity

is present, and a negative test result usually excludes the
diagnosis of asthma.

• Methacholine is administered in incremental doses up to a maximum

dose of 16 mg/mL, and a 20% decrease in FEV1, up to the 4 mg/mL
level, is considered a positive test result for the presence of bronchial
hyperresponsiveness.
 Peak-flow monitoring

• Peak-flow monitoring is designed for ongoing monitoring of patients

with asthma because the test is simple to perform and the results
are a quantitative and reproducible measure of airflow obstruction.

• It can be used for short-term monitoring, exacerbation management,

and daily long-term monitoring.

• Peak-flow monitoring should not be used as a substitute for

spirometry to establish the initial diagnosis of asthma.

• Results can be used to determine the severity of an exacerbation

and to help guide therapeutic decisions as part of an asthma action
plan.
• Exercise testing
– Testing involves 6-10 minutes of strenuous exertion at 85-90% of
predicted maximal heart rate and measurement of postexercise
spirometry for 15-30 minutes.
– The defined cutoff for a positive test result is a 15% decrease in
FEV1 after exercise.

• Eucapnic hyperventilation
– Eucapnic hyperventilation with either cold or dry air is an alternate
method of bronchoprovocation testing.
– It has been used to evaluate patients for exercise-induced asthma
and has been shown to produce results similar to those of
methacholine-challenge asthma testing.
THANK YOU