Asthma Flashcards
anti-inflammatory cytokines;
may be deficient in asthma
IL-10 and IL-12
anti-inflammatory cytokines;
may be deficient in asthma
IL-10 and IL-12
upstream cytokine released from epithelial cells of asthmatics that orchestrates the release of chemokines that selectively attract TH2 cells
Thymic stromal lymphopoietin
selectively attractant to eosinophils via CCR3 and is expressed by epithelial cells of asthmatics
Eotaxin
CCL11
expressed by epithelial cells of asthmatics attract TH2 cells via CCR4
CCL17 (TARC) and CCL22 (MDC)
expressed by epithelial cells of asthmatics attract TH2 cells via CCR4
CCL17 (TARC) and CCL22 (MDC)
Proinflammatory transcription factors activated in asthmatic airways
nuclear factor-B (NF-B)
activator protein-1
Proinflammatory transcription factors activated in asthmatic airways
nuclear factor-B (NF-B)
activator protein-1
transcription factors regulate the expression of TH2 cytokines in T cells
nuclear factor of activated T cells
GATA-3
transcription factors regulate the expression of TH2 cytokines in T cells
nuclear factor of activated T cells
GATA-3
Bronchoconstrictor mediators released in asthma
Chemokines
Histamines
Leukotrienes
Prostaglandin D2
physiologic abnormality of asthma:
Airway hyperresponsiveness
Bronchoconstrictor mediators released in asthma
histamine, prostaglandin D2, Cysteinyl leukotrienes, cytokines, chemokines, growth factors, neutrotropins
physiologic abnormality of asthma:
Airway hyperresponsiveness
Mech for basement membrane thickening in asthmatic patients
subepithelial fibrosis
deposition of types III and V collagen
Mech for basement membrane thickening in asthmatic patients
subepithelial fibrosis
deposition of types III and V collagen
How epithelial damage may contribute to AHR
1) loss of its barrier function to allow penetration of allergens;
2) loss of enzymes (such as neutral endopeptidase) that degrade certain peptide inflammatory mediators;
3) loss of a relaxant factor (so called epithelial-derived relaxant factor);
4) exposure of sensory nerves
How epithelial damage may contribute to AHR
1) loss of its barrier function to allow penetration of allergens;
2) loss of enzymes (such as neutral endopeptidase) that degrade certain peptide inflammatory mediators;
3) loss of a relaxant factor (so called epithelial-derived relaxant factor);
4) exposure of sensory nerves
- Mechanism involved in exercise induced asthma
hyperventilation
results in increased osmolality in airway lining fluid –> triggers mast cell mediator release –>
bronchoconstriction
- Mechanism involved in exercise induced asthma
hyperventilation
results in increased osmolality in airway lining fluid –> triggers mast cell mediator release –>
bronchoconstriction
induce mucus hypersecretion in experimental models of asthma
IL-4
IL-13
mechanism premenstrual worsening of asthma
fall in progesterone
mechanism premenstrual worsening of asthma
fall in progesterone
Mechanism of Exercise-induced asthma (EIA)
prior administration of B2-agonists and antileukotrienes
regular treatment with ICS
Mechanism of Exercise-induced asthma (EIA)
> prior administration of B2-agonists and antileukotrienes
> regular treatment with ICS
may trigger asthma through the release of sulfur dioxide gas in the stomach
Metabisulfite (food preservative)
Increased ambient levels of ____ are associated with increased asthma symptoms
sulfur dioxide, ozone, and nitrogen oxides
reversible occupational asthma
If removed from exposure within the first 6 months of symptoms
PATHOPHYSIOLOGY
Limitation of airflow in asthma
bronchoconstriction, but airway edema, vascular congestion, and luminal occlusion with exudate
PATHOPHYSIOLOGY
lung hyperinflation, (air trapping) and increased residual volume in asthma
Early closure of peripheral airway
PATHOPHYSIOLOGY
lung hyperinflation, (air trapping) and increased residual volume in asthma
Early closure of peripheral airway
direct broncho constrictors Increased bronchoconstrictor responsiveness
histamine
methacholine
MOA of AHR with fog
mast cell activation
MOA of AHR with sulfur dioxide
cholinergic reflex
Diagnosis reversibility of airflow limitation in asthma
> 12% and 200-mL increase in FEV1 15 minutes after an inhaled short-acting 2-agonist or in some patients by a 2 to 4 week trial of oral corticosteroids (OCS) (prednisone or prednisolone 30-40 mg daily)
spirometry findings in asthma
reduced
FEV1
FEV1/FVC ratio
PEF
how to measure increased AHR
methacholine or histamine challenge with calculation of the provocative concentration that reduces FEV1 by 20% (PC20)
noninvasive test to measure eosinophilic airway inflammation; may be a test of compliance with therapy
Exhaled NO;
elevated levels of NO in asthma are reduced by ICS,
MOA ipratropium (anti-cholinergic)
prevent cholinergic nerve-induced bronchoconstriction and mucus secretion
MC adverse effect of ipratropium (anti-cholinergic)
dry mouth
MOA ipratropium (anti-cholinergic)
prevent cholinergic nerve-induced bronchoconstriction and mucus secretion
MC adverse effect of ipratropium (anti-cholinergic)
dry mouth
MOA theophylline
inhibition of phosphodiesterases in airway smooth-muscle (which increases cyclic AMP)
Other effects of B agonists helpful against asthma
inhibition of mast cell mediator release
reduction in plasma exudation
inhibition of sensory nerve activation
SABA duration of action
3-6 hours
soluble salt of theophylline previously used for the treatment of severe asthma
aminophylline
now replaced by LABA– more effective and fewer side effects
soluble salt of theophylline previously used for the treatment of severe asthma
aminophylline
now replaced by LABA– more effective and fewer side effects
Factors Affecting Clearance of Theophylline
Increased Clearance
Enzyme induction (rifampicin, phenobarbitone, ethanol)
Smoking (tobacco, marijuana)
High-protein, low-carbohydrate diet
Barbecued meat
Childhood
(imagine a TB patient, alcoholic, with seizure) smoker drug addict barbecuing meat (for a high protein low carb lunch) for his child
Factors Affecting Clearance of Theophylline
Increased Clearance
Enzyme induction (rifampicin, phenobarbitone, ethanol)
Smoking (tobacco, marijuana)
High-protein, low-carbohydrate diet
Barbecued meat
Childhood
(imagine a TB patient, alcoholic, with seizure) smoker drug addict barbecuing meat (for a high protein low carb lunch) for his child
Factors Affecting Clearance of Theophylline
Decreased Clearance
Congestive heart failure Liver disease Pneumonia Viral infection and vaccination High carbohydrate diet Old age
MOA ICS
switch off the transcription of multiple activated genes that encode inflammatory proteins such as cytokines, chemokines, adhesion molecules, and inflammatory enzymes
Local SE ICS
hoarseness (dysphonia) and oral candidiasis
MOA montelukast and zafirlukast
Antileukotrienes
block cys-LT1-receptors
(activation of cys-LT1-receptors
cause microvascular leakage, and increase eosinophilic inflammation –> bronchoconstriction)
MOA montelukast and zafirlukast
Antileukotrienes
block cys-LT1-receptors
(activation of cys-LT1-receptors
cause microvascular leakage, and increase eosinophilic inflammation –> bronchoconstriction)
MOA Cromolyn sodium and nedocromil sodium (cromones)
inhibit mast cell and sensory nerve activation
Steroid-Sparing Therapies used in asthma
Methotrexate cyclosporin A azathioprine gold IV gamma globulin
blocking antibody that neutralizes circulating IgE without binding to cell-bound IgE and, thus, inhibits IgE-mediated reactions
Omalimumab
duration trial of therapy to show objective benefit: Omalizumab
3 to 4-month
chronic asthma
ICS given twice daily
O2 asthma
face mask to achieve oxygen saturation of >90%
(approximately 5% of asthmatics) are difficult to control despite maximal inhaled therapy
refractory asthma
Rx refractory asthma
OCS
most effective therapy Brittle asthma
subcutaneous epinephrine,
Brittle asthma persistent pattern of variability and may require oral corticosteroids or, at times, continuous infusion of 2-agonists
type I brittle asthma
Brittle asthma normal or near-normal lung function but precipitous, unpredictable falls in lung function that may result in death
type 2 brittle asthma
Hx of OCS treatment impt before surgery
will have adrenal suppression and should be treated with an increased dose of OCS immediately prior to surgery
allergic pulmonary reaction to inhaled spores of Aspergillus fumigatus and, occasionally, other Aspergillus species.
Bronchopulmonary aspergillosis (BPA)
Rx Bronchopulmonary aspergillosis (BPA)
itraconazole
Direct bronchoconstrictors increased in asthma
Histamine
Methacholine
Define reversibility in asthma
> 12% and 200 ml increase in fev1 15 mins after an inhaled short acting B2 agonist
Or 2-4 wk trial of OCS
Non invasive test used to measure airway inflammation
FENO exhaled nitric oxide
Vasculities associated with wheezing
Churg strauss
Polyarteritis nodosa
