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