Asthma Flashcards
____ is the most common chronic disease associated with significant morbidity and mortality,
Asthma
____ is a hallmark of asthma.
Airway hyperresponsiveness
A major therapeutic objective in asthma is to decrease the degree of ____
airway hyperresponsiveness.
Most asthmatics have evidence of chronic inflammation in the airways. Most commonly, this inflammation is ___ in nature.
eosinophilic
In some patients, ___ inflammation may be predominant, especially in those with more severe asthma.
neutrophilic
_____ is an immune response involving the innate and adaptive arms of the immune system to promote barrier immunity on mucosal surfaces.
Type 2 inflammation
It is called Type 2 because it is associated with the type 2 subset of _____, which produce the cytokines interleukin (IL)____
CD4+ T-helper cells
4, IL-5, and IL-13.
IL?
Promotes B-cell isotype switching to IgE production.
IgE binding to mast cells and basophils triggers allergen sensitivity.
IL4
IL?
Regulates eosinophil formation, recruitment, and survival.
IL5
IL13
Induces airway hyperresponsiveness, mucus hypersecretion, and goblet cell metaplasia.
May occur alongside type 2 inflammation or independently
Non Type 2 Inflammation
This type of inflammation is more commonly seen in severe asthma that has not responded to the common anti-inflammatory therapies, such as corticosteroids, that usually suppress type 2 inflammation
Neutrophilic inflammation
Non type 2 inflammation is also commonly seen in ____
reactive airway dysfunction syndrome
____are the major cytokines associated with type 2 inflammation.
IL-4, IL-5, and IL-13
____ have been implicated in non–type 2 inflammation.
IL-6, IL-17, tumor necrosis factor α (TNF-α), IL-1β, and IL-8
It is produced by epithelial cells, especially in response to IL-13, and by stimulated inflammatory cells including eosinophils, mast cells, and neutrophils.
NO
___ Also implicated in type 2 inflammation
IL-9
The cysteinyl leukotrienes (leukotrienes _____ ) are produced by eosinophils and mast cells.
C4 , D4 , and E4
Prostaglandin D 2(PGD 2 ) is produced by ___
mast cells.
___ has a strong genetic predisposition
Asthma
The most consistently identified igenes include
ORMDL3/ GSDMB (in the 17q21 chromosomal region), ADAM33, DPP-10, TSLP, IL-12, IL-33, ST2, HLA-DQB1, HLA-DQB2, TLR1, and IL6R. I
Genetic polymorphisms linked to differential therapeutic responses:
____: Affects response to β-agonists
.
Variants in ____: Impacts corticosteroid response.
β-receptor variant (Arg16Gly in ADRB2)
glucocorticoid-induced transcript 1 gene
____and ____exposure are associated with increased childhood asthma.
Maternal smoking
secondhand smoke
Childhood secondhand smoke exposure increased asthma risk ___
twofold
Active smoking is estimated to increase the incidence of asthma by up to ___ in adolescents and young adults.
fourfold
Incidence and frequency of ____ infections in children are associated with development of asthma
human rhinovirus
respiratory syncytial virus
The evidence is not yet definitive, but ____insufficiency may increase asthma risk in the progeny and supplementation may decrease such risk
vitamin D
Use of ___and ____in pregnancy has been associated with an increased risk of asthma in children
H 2 blockers
proton pump inhibitors
___ and ___ have been associated with increased risk of asthma in the progeny.
Preeclampsia
prematurity
Babies born by ____are at higher risk for asthma.
cesarean section
A subset of women develop asthma around ___. Such asthma tends to involve ___
menopause
non–type 2 mechanisms
A solitary exposure to a high concentration of irritant agents that rapidly (usually within hours) produces bronchospasm and bronchial hyperactivity is known as ___
RADS
So-called allergic bronchopulmonary aspergillosis (ABPA) is characterized by a ______ response to aspergillus with IgE >1000 IU/mL, eosinophils >500/μL, positive skin test to Aspergillus, and specific IgE and IgG antibodies to Aspergillus.
type 2 airway inflammatory