ASTHMA
Pathophysiology & Interventions for Respiratory Care
Practitioners
Myths
• It’s all in your head.
• While stress may play some role in onset of symptoms like wheezing, it is
a chronic inflammatory airway disease
• A poor mother-child relationship.
• Another attempt to explain the condition psycho-socially.
Myths
• Asthma doesn’t kill anymore.
• Accounts for 5,000 deaths per year
• Asthma isn’t serious anymore.
– Affects 14-15 million people in the U.S.
– Probably most under-diagnosed condition.
– Hospitalization and death rates highest for blacks, children, and poorer individuals.
Myths
• Asthma doesn’t require medical treatment.
– About 470,000 hospitalizations each year.
– About 100 million days of restricted activity annually, sick days, etc.
• Children outgrow asthma.
– Most common chronic disease of childhood.
– Asthma is more common in children and young adults, but is present at all ages.
Myths
• Move to Arizona.
• Buy a pet Chihuahua.
– Allergens and triggers myth.
– New allergens in different environments.
– accounts for 8.8% of the Hawaii population
• There is a cure for asthma.
– Not yet.
– Requires compliance of patient and the health care team.
– New medications
– New research into inflammatory process.
Asthma and Urban Environment
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Aeropollutants
Beta-agonist bronchodilators
Poverty
Race and ethnicity
Illicit drug use
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Psychosocial and family dysfunction
Restricted access to health care
Crowding
Indoor allergens and pollutants
Key Points - Changing Views
• Historically, considered a disease of airway smooth muscle
• Characterized by intermittent bronchospams due to variety of specific and
nonspecific stimuli
• Episodic bronchospasm associated with coughing, wheezing, tightness of
chest, difficulty breathing.
• Symptoms wax and wane, lasting couple of days to couple of weeks
Perspective Change
• Treat the disease, not the patient (vs. treat the patient, not the
disease)
• Too much focus on symptoms, but focus on the disease,
inflammation, came from examining lungs of patients who died
from asthma.
• Saw cellular changes in airway
Changes. . .
• Structural changes of bronchi
– Epithelium changes
– Basement membrane changes
– Smooth muscle growth
– Goblet cell proliferation
– Presence of eosinophils, mast cells, etc., in both atopic and nonatopic
persons with asthma and even in people with mild disease
Current Understanding
• Airway inflammation
• Many different cells and cellular elements involved, e.g., mast cells,
eosinophils, T-lynmphocytes, macrophages, neutrophis, and epithelial
cells
• Inflammation causes recurrent episodes of wheezing, chest tightness,
coughing.
• Airflow obstruction, often reversible with treatment
• Subset of COPD, but reversibility is key
Inflammation - Bi-phasic
• Working definition of asthma (1995, NHLBI)
– Asthma is a chronic inflammatory disorder of the airways in which
many cells & cellular elements play a role (mast cells, eosinophils, T
lymphocytes, macrophages, neutrophils, & epithelial cells).
– In susceptible individuals , inflammation causes recurrent episodes
of wheezing, breathlessness, chest tightness, and coughing, particularly
at night/early morning. These episodes are associated with variable
airflow obstruction often reversible spontaneously/treatment
Inflammation
• Bi-phasic, early and late phase
• Inflammation causes increase in existing bronchial responsiveness to variety of
stimulants, i.e., hyperresponsiveness
• Episodic “attack” is an acute event, early phase, lung function can return to normal
• Recurrent “attacks” are essentially the continuation of the early phase—but now
second, or late phase response—chronic inflammation
• This inflammation modifies the biology of the airway to cause bronchial
hyperresponsiveness
General Aspects of Inflammation
• Redness
– Due to dilatation of small blood vessels in damaged area
• Heat
– Due to increase blood flow through region
• Swelling
– From edema, accumulation of fluid in extra vascular spaces
Pain
stretching and distortion of tissues due to edema
Early Phase
• Inhalation of allergen or some trigger
• Immediate, 5-30 minutes, signs of inflammation.
• Due to release of chemical mediators from mast cells
Exocytosis of Mast Cell
Histamine Release
Early Phase
• Signs
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Smooth muscle contractions—leading to bronchospasm (wheezing)
Mucus secretion
Cough
Edema of the airway and further narrowing of bronchial tree
Resolves within 1 hour, with or without therapeutic intervention
Inflammation - Bi-phasic
Arachidonic Acid Pathways
Arachidonic Acid
• A fatty acid produced from the membrane of mast cells
• Helps to synthesize:
– Cyclooxygenase pathway which produced prostaglandins (PG)
– Lipoxygenase pathway which produced leukotrienes (LT)
PG and LT
All of the chemical reactions, chemical mediators used to be referred to as
SRS-A, slow release substances of anaphylaxis
Now known as either PG, LT
• Prostaglandins are potent muscle constrictors
• Leukotrienes are potent muscle constrictors
• Both are mediating agents/chemicals of the inflammatory process.
LT and PG Pathways
Late Phase State
Late Phase Features
• 6-10 hours later, and then may continue for indefinite period of
time (months)
• Attraction and accumulation of inflammatory cells-all types of
WBC
– From degranulation of original mast cell chemical mediators
– These are cytokines and chemotactic cytokines-(chemokines) proteins
that attract WBCs
Late Phase Features
• Eosinophils and T lymphocytes (T cells)
• Eosinophils migrate from blood to airway; and release more
inflammatory mediators like leukotrienes.
• T cells (Th2) produce Interleukins (IL) another chemical
mediator (activates more T cells)
Late Phase Signs
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Bronchospasm
Further inflammation
Airway edema
Mucus production (hyperproduction)
Obstructive airflows
Increase airway hyper-responsiveness
Signs of the Late Phase
• Airway hyper-responsiveness to various stimuli—cold air,
sneezing, fumes, stress (?)
• This is smooth muscle dysfunction – “twitchy” airways, narrow
too easily and too much
• Loss of airway elasticity
Inflammatory Pathway
Airway Inflammation
• Increase thickening of airway wall due to edema
• Increased numbers of eosinophils, neutrophils, epithelial cells
• Airway lumen filled with mucus from enlarged goblet cells
Why a problem for some patients?
• Key points
– Chronic inflammatory disorder of the airways
– Histopathologic features
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denudation of airway epithelium
collagen deposition beneath basement membrane
edema
mast cell activation
– Immune system features
• inflammatory cell infiltration
– Neutrophils (sudden, fatal asthma)
– Eosinophils
– Lymphocytes
• Airway inflammation (AI) contributes to hyperresponsiveness,
airflow limitation, symptoms & chronicity
• AI causes types of airflow limitation:
– Bronchoconstriction, edema, mucus plug formation, airway wall
remodeling
• Atopy is strongest predisposing factor for developing asthma
– Atopy is the inherited propensity to produce abnormal amounts of IgE
against common environment antigen
Airway Inflammation & Lung Function May Vary
• The cells that influence &/or regulate inflammation results in
different types of AI:
– Acute - early recruitment of cells
– Subacute - cells activated to cause more persistent inflammatory
pattern
– Chronic - persistent level of cell damage & repair. Abnormal changes
may be permanent
Obstructive Defect
• Airflow limitation
– Acute bronchoconstriction
• IgE -dependent mediator release from mast cell (leukotrienes, histamine,
tryptase, prostaglandins)
• aspirin /NSAID
• non-IgE response (cold air, exercise, irritants)
Chronic Airflow Limitation
• Airflow limitation
– Chronic mucus plug formation
• secretions & inspissated plugs
• persistent airflow limitation in severe intractable asthma
– Airway remodeling
• irreversible component of airflow limitation secondary to structural airway
matrix changes
• Airflow limitation
– Airway remodeling
• attributed to chronic, severe airway inflammation
• early intervention with anti-inflammatory therapy suggests prevention of
permanent airflow limitation
Chronic Inflammation
• Asthma is a reversible airway disease
• However, chronic inflammation may result in irreversible airflow
limitations AND
• Airway remodeling - an altered pulmonary tree
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Smooth muscle over-development
New vessels formation
Goblet cells proliferation
Thickening of basement membrane
Chronic Inflammation
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Inflammation is in peripheral airways primarily
But may affect central airways and even the alveoli
Inflammatory cells seem to have a prolonged life in asthma
Irreversible airflow may develop in some patients
Presentation
Complaining of. . .
• “S” (subjective symptoms)
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Cough, esp. late at night
Recurrent wheezing
Recurrent shortness of breath
Recurrent chest tightness
Occurs at night, early morning
Symptoms occur or worse with irritants
PE
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Chest-wheezing on exhalation, sometimes on inhalation
crackles
I:E ratio-prolonged expiratory phase
Increased AP diameter, especially during exacerbation
Unable to complete full sentences
Use of inspiratory accessory muscles
PE
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Cough
Sputum-clear,stringy, translucent
Sternal retractions, intercostal retractions
Dehydrated
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Increased meteabolism
Increased insensible water loss
Decreased fluid intake
vomiting
PE
• Increased respiratory rate
• Increased pulse rate
• Increased blood pressure
– All signs of hypoxemia
PE
• Pulsus paradoxus
– >10 mmHg fall in systolic blood pressure on inspiration. 15-20 mmHg
drop is severe
– Mechanism: increased intrapleural pressures (thorax) promoting
increased venous return & increased RV filling, decreased LV filling
on contraction
• If frequent ER visitor:
– Has inhaled medications
– Has no primary physician
– No other inhaled medications, e.g., inhaled steroids, anti-inflammatory
medications
Diagnostic Exams
• Pulse oximetry
• Arterial blood gas analysis
– Alkalemia, hypoxemia, hypocapnea
• Calculate PA02, P(A-a)02, and Pa02/Fi02
• Bedside spirometry
– Peak flow rates decreased
• Chest film
– Hyperinflation, hyperlucent, flat diaphragms, large AP diameter
Pa02 and Relative Shunt
• Hyperinflation or air trapping
• Causes changes in V/Q, ie. mismatch
• A decreased V to Q ratio, leading to:
– Drop in PA02 and subsequent drop in Pa02
• As air trapping increases, lungs are less compliant
• FRC increases
• More (negative) intrapleural pressures needed to change AP diameter of
chest cage
Compliance and RR
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As lung compliance decreases, ventilatory rate increases
This increases patient’s minute ventilation (VE)
PaC02 drops (<40mmHG)
pH increases (alkalemia)
This is a good sign.
The patient is still attempting to ventilate.
Danger signs—when the RR decreases; PaC02 begins to look normal (toward 40
mmHG)