Asthma Flashcards
Describes what occurs during an asthma attack
Hyper-responsiveness of the bronchia triggers reversible airway narrowing
eosinophils and other inflammatory cells trigger bronchoconstriction —> wheezing, chest tightness, shortness of breath, and chronic cough
Which immune cells are largely responsible for the hyper responsiveness of the airway seen in asthma attacks?
eosinophils
What are the characteristics symptoms of an asthma attack?
wheezing, chest tightness, shortness of breath, and chronic cough
what are four clinical and pathologic features of asthma?
- Intermittent, reversible airway obstruction
- chronic bronchial inflammation with eosinophils
- bronchial smooth muscle cell hypertrophy and hyperreactivity.
- increased mucus secretion
What is the most common type of asthma and describe how it is characterized?
atopic (“extrinsic”) asthma: Type I IgE-mediated hypersensitivity reaction
usually begins in childhood, attacks preceded by allergic rhinitis, urticaria, or eczema and triggered by allergens
skin test with antigen results in immediate wheal and flare reaction, can also be diagnosed based on serum test that identify the presence of IgEs is that recognize specific allergens
often strong family history
what kind of hypersensitivity reaction is a atopic asthma?
Type I IgE-mediated hypersensitivity reaction
aka “extrinsic” asthma
What does the hygiene hypothesis say about the development of asthma?
exposure to microbes during childhood may protect against development of asthma, by shifting the immunologic profile of helper T cells towards Th1 phenotype vs Th2
Th1: produce IFNy
Th2: produce IL4/5/13 and TNF which are associated with allergic diseases/asthma
how do patients with non-atopic forms of asthma present?
A.k.a. intrinsic/non-immune asthma, do not have evidence of allergen sensitization, and skin test results usually are negative
Family history not common, mostly occurs in adults
ex: aspirin sensitivity asthma (abnormality in prostaglandin metabolism via inhibition of cyclooxygenase) or occupational asthma (fumes, dusts, gases, etc)
also caused by virus-induced respiratory infections (rhinovirus, parainfluenza, RSV), air pollutants, exercise, cigarette smoke
Patient is a 45-year-old male presenting with recurrent rhinitis, nasal polyps, urticaria and bronchospasm. Past medical history is unremarkable except for headaches for which the patient takes aspirin as needed. Skin testing for allergen sensitization is negative. What is likely going on?
likely aspirin sensitivity, causing non-atopic (“intrinsic”) asthma
aspirin inhibits cyclooxygenase, which likely disrupts prostaglandin metabolism
which immune cells respond to allergens in allergen-induced (atopic) asthma?
inhaled antigens are processed by dendritic cells (APC) which present antigenic material to T lymphocytes.
Th2 cells release IL4 in IL13, which signal B lymphocytes to produce antigen specific IgE antibodies
atopic (extrinsic) asthma is associated with excess Th2 cell activation
in atopic asthma, Th2 cells are over-active, producing the following cytokines - what is the effect of each?
a. IL4
b. IL5
c. IL13
a. IL4 —> activate B cells, enhance IgE synthesis
b. IL5 —> chemoattractant for eosinophils
c. IL13 —> stimulates IgE and mucus production
what happens when an asthmatic person with IgE antibody against a particular antigen encounters that antigen?
antibody binds high-affinity IgE receptors on mast cells and basophils
when antigen is inhaled, in binds/cross-links the IgE antibody —> mast cells/basophils activated —> preformed and newly synthesized allergic mediators released
contrast the early phase reaction and late phase reaction caused by mast cell activation in asthma attacks
early phase reaction: bronchoconstriction, increased mucus production, and vasodilation with endothelial leakage and local edema (via histamine, prostaglandin D2, leukotrienes LT C4/D4/E4)
late phase reaction: inflammatory mediators stimulate chemokine production that recruits Th2, eosinophils, basophils, neutrophils
(neutrophils increase airway remodeling)
which allergic mediators are responsible for the bronchoconstriction seen in the early phase reaction of asthma attacks? (5)
mast cell derived mediators - histamine, prostaglandin D2, leukotrienes LT C4/D4/E4
LTC4 and LTD4 are very potent bronchoconstrictors
Describe the airway remodeling that occurs with repeated bouts of mast cell-mediated inflammation due to asthma
hypertrophy of bronchial smooth muscle and mucus glands, increased vascularity, deposition of a subepithelial collagen
airways in asthma are much thicker with lots of mucus, thicker smooth muscle, more mucus glands/goblet cells and immune cells present (esp. eosinophils and lymphocytes)
Describe how inhaled irritants such as cigarette smoke, inorganic dusts, and environmental pollutants trigger asthma
stimulate irritant receptors located in the walls of the larynx, trachea and large bronchi —> inducing bronchoconstriction
describe how exercise can provoke bronchoconstriction in asthma patients
heat movement from the airway wall results in cooling/drying of the airway, which provokes bronchoconstriction in patients with hyperreactive airways
what are Curschmann spirals, Charcot-Leyden crystals, and Creola bodies associated with? what is contained in each of these?
severe asthma
Curschmann spirals: mucous plugs containing whorls of shred epithelium (occlude bronchi/bronchioles)
Charcot-Leyden crystals: made of eosinophils protein galectin-10 (due to breakdown of eosinophils)
Creola bodies: ciliated columnar cells shed from bronchial mucosa
do asthma patients have greater difficulty with airflow on expiration or on inspiration and why?
asthma is obstructive pulmonary disease – lumen size larger during inspiratory phase, therefore, there is greater difficulty with airflow on expiration (esp. forced expiration - positive pleural pressure promotes airway narrowing/closure/air trapping)
describe dynamic hyperinflation as experienced by asthma patients during acute asthma attacks
dynamic hyperinflation: more time is required for expiration when airways are obstructed, and patients do not have sufficient time before the next breath to fully exhale the volume from the previous breath.
air is trapped in lungs, RV and FRC are increased —> more work is required to breathe due to larger volume
what is the mechanism for hypoxemia in asthma? how will this affect partial pressures of oxygen and CO2?
V/Q mismatch - ventilation of respiratory units is nonuniform (some are at higher resistance than others)
—> low PO2 accompanied by low PCO2 (respiratory alkalosis due to increased ventilation seen in exacerbations)
HYPERcapnia is bad sign - indicates progressive airway obstruction, muscle fatigue, and failing alveolar ventilation
pure shunt is unusual
what does asthmatic wheezing sound like and what is it caused by?
asthmatic wheezing - multiple pitches, starting/stopping at various points with various durations
(in contrast to monophasic wheezing of local bronchial narrowing)
mucus hypersecretion + smooth muscle contraction = airway caliber reduction and turbulent airflow —> wheezing sounds
*intensity does not correlate with severity - extreme airway obstruction may completely diminish wheezing/breath sounds
which of these is NOT a non-pulmonary manifestation seen in asthma?
a. allergic rhinitis
b. nasal polyps
c. finger clubbing
d. eczema
a. allergic rhinitis, b. nasal polys, and c. eczema are common non-pulmonary manifestations of asthma
finger clubbing is NOT seen with asthma
How will the partial pressure of carbon dioxide change from mild to moderate asthma to severe attacks?
Ventilation is normal or increased in mild to moderate asthma so the arterial PCO2 is either normal or decreased
in severe attacks airway obstruction may worsen and respiratory muscle fatigues —> alveolar hypoventilation, hypercapnia and respiratory acidosis
how is DLCO affected by asthma exacerbations?
during asthma attacks, expiratory airflow is reduced - air is trapped, which increases RV and causes hyperinflation (increased TLC)
DLCO is increased as consequence of increased lung/lung capillary volume
What are two agents that are used for provocation testing of bronchial hyperresponsiveness as seen in asthma? when is this testing most useful?
- methacholine
- histamine
used in patients with normal PFTs (pulmonary function tests) in whom asthma is suspected - causes bronchoconstriction via direct stimulation of airway smooth muscles —> measure FEV1 with increasing concentrations (positive result shows steeper slope of dose-response curve)
high negative predictive power - mores useful for RULING OUT asthma
Contrast control agents with relief medication used in the pharmacological management of asthma
control agents: inhaled corticosteroids, long-acting bronchodilators (beta agonists, anticholinergics), theophylline, leukotriene modifiers, anti-IgE (omalizumab) and anti-IL-5
relief medications: short acting bronchodilators, systemic corticosteroids, Ipratropium
what is the preferred controller medication for children and adults with asthma?
Inhaled corticosteroids
what laboratory test can be done to measure allergen specific serum IgE levels in asthma patients?
RAST: radio-allergo-sorbent test
how can exhaled nitric oxide be used to assess asthma patients?
indirect method of assessing airway inflammation – increased levels shown to correlate with asthma, exacerbation, and eosinophilic information
can also be used to measure adherence to inhaled corticosteroids
Bronchial thermoplasty
thermal energy applied to the bronchial wall to reduce the increased mass of airway smooth muscles in asthma patients
what kind of drugs are albuterol and terbutaline and what are they used for?
short acting beta agonists (SABAs) - relieve bronchoconstriction and protects against exercise and cold air induced asthma
ipratropium bromide
asthma medication, helps dry up bronchial secretions
additive effects with beta agonists like albuterol or terbutaline
terbutaline
short acting beta-agonist (SABA) to treat asthma
relieves bronchoconstriction and prevents exercise/cold induced asthma
what kind of drugs are fluticasone, mometasone, and budesonide, and what are they used for?
inhaled corticosteroids (ICS) for asthma - reduce frequency of symptoms/exacerbations, decrease airway hyper-responsiveness, anti-inflammatory
also up-regulate beta-adrenergic receptor function - enhance effects of beta agonists (albuterol, terbutaline)
what kind of drugs are formoterol and salmeterol, and what are they used for?
long-acting beta agonists (LABAs) used in treatment of asthma
improve symptoms/ reduce exacerbations when used in combination with inhaled corticosteroids (ICS) - should NOT be used without ICS
what kind of drugs are montelukast and zileuton, and what are they used for?
leukotriene receptor antagonists (LTRAs) used as alternative asthma medication for chronic management
how is Cromolyn used in the management of asthma?
Cromolyn: mast-cell stabilizer, typically used in younger patients for exercise-induced bronchospasm
omalizumab
anti-IgE antibody used in moderate to severe persistent allergic asthma
dupilumab
anti-IL-4 antibody used in management of severe eosinophilic asthma
what kind of drugs are mepolizumab, benralizumab, and reslizumab, and what are they used for?
anti-IL-5 antibody used in management of severe eosinophilic asthma
