most important player in the immune function in the airway
T-lymphocytes
cytotoxic cells of T-lymphocytes
CD8 Tc
helper cells of T-lymphocytes
CD4 Th
what do TH1 cells respond to
infections
what do TH2 cell mediate
allergic inflammation
4 steps of the pathogenesis of asthma
bronchoconstriction
airway edema
airway hyperresponsiveness
airway remodeling
3 contributors to acute bronchoconstriction
exacerbations
IgE-dependent release of mediators
aspirin or NSAIDS - jack up the LOX path
exercise, cold air, stress
what is used as a testing method for airway hyperresponsiveness
methacholine - contractile response
3 main causes of asthma
innate immunity
genetic factors
environmental
3 points of early asthmatic response
peaks at 10-20 min
1.5-3h duration
reversed by b-agonist
3 keys to late asthmatic response
peaks 4-8h after acute response
lasts several days
b-agonists not so effective
what criteria is used for initiating therapy
severity
what criteria is used for monitoring therapy
control
at what step of asthma management do you add a LABA
3
at what step of asthma managment do you add an oral corticosteroid
6
components of intermttent severity 5
symptoms - <2 days/wk
nighttime awakenings - <2x/month
SABA for symptom control - <2days/wk
interference with normal activity - none
lung function - normal
components of mild asthma severity 4
symptoms - >2days/wk but not daily
nighttime awakenings - 3-4X month
SABA for sym. control - >2d/wk, but not daily or more than once a day
interfer with normal activity - minor irritation
components of moderate asthma severity 4
symptoms - daily
nighttime awakenings - >1/wk not nightly
SABA for sym. - daily
interfer with norm activity - some irritation
components of severe asthma severity 4
symptoms - throughout the day
nighttime awakening - often 7x/wk
SABA for sym. - several times/day
interfer with norm activ - extremely limiting
preferred therapy for steps 1-6 of asthma
1. SABA PRN
2. low dose ICS
3. low dose ICS + LABA
4. medium dose ICS + LABA
5. high dose ICS + LABA
6. high dose ICS + LABA + oral corticosteroid
3 quick acting b2-selective adrenergic agonists
albuterol - ventolin, proventil
levalbuterol - xopenex
pirbuterol - maxair
which b2 agonist is not recommended for PRN use and is more for COPD
ipratropium
LABA
potent bronchodilator
sustained activity > 12h
onset 10-20 min
salmeterol - serevent diskus
LABA
potent bronchodilator
onset 5 min
formoterol - foradil
BBW of LABA 4
not to be taken long term (unless uncontrollable)
never used alone, used w/ controller meds
use shortest duraton to achieve control
these don't apply for COPD
polymorphism affects of LABA's
gly/gly - same w/ or w/o LABA
arg/arg - stop LABA improved asthma
moa - inhibits mast cell degranulaton
prophylactic - exercise and antigen asthma, chronic asthma
does not treat ongoing bronchoconstriction
nasal or eye drops
useful for allergic rhinoconjunctivitis
cromolyn sodium - intal
nedocromil sodium - tilade
moa - competitive cysteinyl leukotriene-receptor antagonist
onset hrs
max effect - few days
ind - systemic eosinophilia and vasculitis
montelukast - singulair
zafirlukast - accolate
moa - inhibits production of the cysteinyl leukotrienes by inhibiting 5-lipoxygenase
extended release
monitor hepatic function - chemical hepatitis
zileuton
methyxanthines
theophylline
aminophylline
not recommended
anticholinergic
slower and less intense bronchodilation
use only in pts resistant to LABA or emergency situations (status asthmaticus)
ipratropium bromide - atrovent
ind - moderate and severe persistent asthma when no other drugs work
use when IgE levels are elevated
> 12 yo
moa - binds to IgE preventing binding to the mast cells