Asthma is a chronic respiratory condition characterized by inflammation and narrowing of the airways, leading to symptoms like wheezing, coughing, shortness of breath, and chest tightness. It can be triggered by various factors including allergens, respiratory infections, exercise, smoke, and pollutants. Management involves medication, identifying triggers, creating an action plan, monitoring symptoms, staying active, maintaining a healthy lifestyle, getting vaccinated, and regular check-ups with healthcare providers. Effective management aims to control symptoms, prevent flare-ups, and improve overall quality of life.

1. Asthma: Etiology and
Pathophysiology
Presented by Dr.Abas Reshi

2. Introduction
• Asthma Facts:
– most common chronic disease in
industrialized world
– increasing in prevalence, incidence has
doubled in US since 1980
– estimated 15 - 20 million in US affected
– 5000 die each year from asthma
exacerbations
– average medical cost to manage a person
with severe asthma = $18,000 annually
– most common cause of lost work days and
lost school days

3. What is Asthma?
• Definition of asthma (as defined in the
NIH Expert Panel Report II)
– a chronic inflammatory disease of the
airways in which many cells/cellular
elements play a role, including, mast cells
eosinophils, T-lymphocytes, macrophages,
neutrophils, and epithelial cells
– airway inflammation causes recurrent
episodes of wheezing, breathlessness,
chest tightness, and coughing, particularly
at night or in the early morning.

4. What is asthma?
• Asthma is a chronic inflammatory
disorder of the airways causes
recurrent episodes of coughing,
wheezing, breathlessness, and chest
tightness.
• These episodes are usually associated
with widespread but variable airflow
obstruction that is often reversible
either spontaneously or with treatment.

5. Signs and Symptoms
• Wheezing due to airstream turbulence and vibration of
mucus
• Rapid breathing and shortness of breath (dyspnea)
• Coughing
• Chest tightness
• Hyperinflation of thorax, voluntary at first to dilate
airways; secondarily as a result of incomplete emptying
• Markedly reduced FEV1 (forced expiratory volume)
• Attacks typically last from a few minutes to several
hours and are often associated with exercise or sleep

6. Etiology of Asthma
• Two types of asthma have been described:
– Extrinsic, or allergic asthma (aka atopic asthma)
• Mediated by IgE
• Usually begins in childhood, less common in adults
• Usually associated with atopy
• Sensitization to allergens is key feature
– increased indoor play and exposure to indoor
allergens?
– Decreased childhood infections inhibits normal
development of immune system leading to increases
in allergic responses?
– Intrinsic, or idiopathic asthma
• More common in adults
• Usually not associated with atopy
• Patients may have nasal polyps, asprin sensitivity,
sinusitis
• Attacks may be precipitated by infection, exercise,
inhaling cold air, emotional factors
• Exercise-induced is most common form of intrinsic asthma

7. Asthma Triggers
• Can be physical, chemical, environmental or
pharmacologic in nature
• Common triggers include:
• mold
• pollen
• house dust mites
• pet dander
• cock roach antigens
• cigarette smoke
• perfume and other chemicals (e.g. cleaners)
• viral infections
• cold air
• exercise
• aspirin

8. Pathophysiology
• Well recognized as an inflammatory
condition
– Chronic airway inflammation results in:
• increased smooth muscle cell proliferation and
hypertrophy leading to thickening of the airway
wall
• increased mucous production
• airway edema
– End result is partial airway obstruction and
difficulty in airflow movement

10. Pathophysiology
• Other features:
– Presence of inflammatory mediators may
increase airway reactivity and induce
bronchospasm
• contraction of smooth muscle surrounding
medium-sized bronchi and bronchioles

11. Pathophysiology
• Inflammatory mediators include:
– histamine
– prostaglandins
– leukotrienes
– platelet-activating factors
– cytokines (interleukins)

12. Pathways Mediating Broncho-
constriction and Bronchodilation
• Bronchoconstriction:
– Cholinergic (vagal)
innervation
– Adenosine A1 receptors
– α-Adrenergic pathways
(not well characterized)
– Irritant receptors
• Respond to noxious
chemicals, particulates,
and histamine
• Histamine is released by
mast cells in response to
allergens
• Leukotrienes are most
potent
bronchoconstrictors
known
• Bronchodilation:
– β-Adrenergic (β2)
• β-Adrenergic
innervation of
bronchi is limited
• Noninnervated β2-
receptors are
prevalent on
bronchial smooth
muscle
– Adenosine A2
receptors

13. Traditional Asthma Theory
• Asthma was traditionally thought of as
resulting from altered adrenergic/cholinergic
balance:
– β2 Agonist drugs (albuterol, etc) give rapid,
effective relief in asthma attacks
– Cholinergic muscarinic antagonists also provide
relief (atropine, ipratropium bromide)
– Asthmatics appear to have partial blockade of β-
adrenergic receptors (or a reduced or defective
population)
• Evidence against the β-blockade theory of
asthma
– β-Blockade in normal subjects does not cause
bronchial hyperreactivity or asthma symptoms

14. Revised Asthma Theory
• Asthmatics have an imbalance of adenosine
receptor subtypes (A1 predominates over A2):
– Inhalation of adenosine in asthmatics but not
in normal subjects causes bronchoconstriction
• Adenosine A2 receptor may be inactive or
underrepresented in asthmatics
– Theophylline, an adenosine receptor
antagonist, is effective in the treatment of
asthma
• Antagonizes both receptor
subtypes, but because A1
predominates, blockade of
its effects (bronchoconstriction)
gives relief

15. Current Asthma Theory
• Inflammatory mediators are responsible
for bronchoconstriction
– Leukotrienes, prostaglandins, cytokines
(IL4, IL5)
• Released by macrophages, mast cells, T
lymphocytes
• Promote the migration and activation of other
inflammatory cells, most notably eosinophils
• Eosinophils also release substances that
damage tissue and promote hyperreactivity
– Current and future therapies are directed
at interfering in these pathways
• Zafirlukast (Accolate) is LTD4 and LTE4 receptor
blocker
• Zileuton (Zyflo) is a 5-lipoxygenase inhibitor that
blocks LTD4 and LTE4 synthesis

17. Asthma: Diagnosis,
Classification and Goals of
Therapy

18. Diagnosis of Asthma
• Made on the basis of spirometry:
– Spirometry measurements (FEV 1 , FVC,
FEV 1 /FVC) taken before and after the
patient inhales a short-acting
bronchodilator
– Helps determine whether there is airflow
obstruction and whether it is reversible over
the short term
– Generally valuable in children over age 4;
however, some children cannot conduct the
maneuver adequately until after age 7

19. Diagnosis of Asthma
• Made on the basis of spirometry:
– Measures the maximal volume of air forcibly exhaled
from the point of maximal inhalation (forced vital
capacity, FVC) and the volume of air exhaled during
the first second of the FVC (forced expiratory volume
in 1 second, FEV 1 )
– Airflow obstruction is indicated by reduced FEV 1 and
FEV 1 /FVC values relative to reference or predicted
values
– Significant reversibility is indicated by an increase of
>12 percent and 200 mL in FEV 1 after inhaling a
short-acting bronchodilator

20. Diagnosis of Asthma
• Key indicators in patient history
suggestive of asthma and need for
diagnostic spirometry include:
– Wheezing—high-pitched whistling sounds
when breathing out—especially in children
– History of any of the following:
• Cough, worse particularly at night
• Recurrent wheeze; recurrent difficulty in breathing
• Recurrent chest tightness
• Reversible airflow limitation and diurnal variation as
measured by using a peak flow meter

21. Diagnosis of Asthma
• Key indicators in patient history
suggestive of asthma and need for
diagnostic spirometry include:
– Symptoms occur or worsen in the
presence of:
• Exercise; viral infection
• Animals with fur or feathers; house-dust mites (in
mattresses, pillows, upholstered furniture, carpets)
• Mold; pollen; smoke (tobacco, wood)
• Changes in weather; Strong emotional expression
(laughing or crying hard)
• Airborne chemicals or dusts; Menses
– Symptoms occur or worsen at night,
awakening the patient

22. Classification of Asthma
• Based on severity:
– Step 1 = intermittent
– Step 2 = mild persistent
– Step 3 and 4 = moderate persistent
– Step 5 and 6 = severe persistent
• Refer to Tables in Asthma Guidelines

23. Goals of Therapy
• Prevent chronic symptoms
• Maintain normal/near normal
pulmonary function
• Maintain normal activity level
• Prevent recurrent exacerbations
• Minimize need of ER/hospital
admissions
• Meet patients’ expectations of and
satisfaction with care

24. Management of Asthma
• 4 Components of Care:
– Environmental Control
– Objective monitoring of lung function
– Pharmacologic therapy
– Patient education

25. Environmental Control
• Identify and reduce exposure to
allergens and irritants
– cockroach antigens
– pet dander
– dust mites
– cigarette smoke
– Air Pollution
– Respiratory viral infections
– Chemical Irritants

26. Objective Monitoring
• Peak expiratory flow rate (PEFR):
– is the maximum flow rate that a person can
generate during a forced expiration
• measured in liters/minute
– three zones described
• green zone - asthma is under control
• yellow zone - warning of pending asthma
exacerbation
• red zone - medical emergency
– monitoring recommended in all patients with
step 3 and 4 asthma
– Refer to section on peak flow monitoring in
Expert Panel III report

27. Objective Monitoring
• Peak expiratory flow rate (PEFR):
– Should record peak flow daily and
determine “zones” from personal best
– Use personal best and danger zones to
guide self-management of asthma
exacerbations at home
– Use of peak flow and self-management
plans has been documented to decrease
ER visits and hospital admissions
significantly
• See examples of self-management plans in
Expert Panel III report

28. Pharmacologic Therapy
• 3 goals of pharmacologic therapy
– prevent and control asthma symptoms
– decrease frequency/severity of
exacerbations
– reverse airflow obstruction

29. Pharmacologic Therapy
• 2 types of asthma medications:
– “quick relievers”
• short-acting beta 2 agonist inhalers
– “long-term “controllers”
• inhaled corticosteroids
• long acting beta 2 agonist inhalers
• oral beta 2 agonists
• Theophylline
• cromolyn/nedcromil
• leukotriene modifiers

30. Patient Education
• Key in helping patients control their asthma
and stay out of the hospital
• Should teach and reinforce at every
opportunity:
– Basic facts about asthma
– Roles of medications
– Skills: inhaler/spacer/holding chamber use, self-
monitoring
– Environmental control measures
– When and how to take rescue actions