Chapter 281 - Asthma Flashcards
Prevalence of asthma in adults
10-12%
Prevalence of asthma in children
15%
Increasing prevalence of asthma in developing countries is due to
increased urbanization
Most patients with Asthma in affluent countries are due to
Atopy
Peak age of Asthma
3 years old
Prevalence of asthma according to sex
Children: 2:1
Adults: 1:1
The severity of asthma does not vary significantly within a given patient
True
Major risk factors for asthma deaths
- poorly controlled disease with frequent use of bronchodilator inhalers
- lack of or poor compliance with ICS therapy
- previous admissions to hospital with near-fatal asthma.
These are environmental factors which worsen asthma in a patient with established asthma
Triggers
Major risk factor for Asthma
Atopy
Allergic rhinitis is found in how many percent of asthmatic patients
> 80%
How many percent of the population in affluent countries are atopic
40-50%
Most common allergen to trigger asthma
Dermatophagoides pteronyssinus
Severity of Asthma is genetically determined
true
Most consistent finding in gene polymorphism of which chromosome
chromosome 5q
Th2 cells in asthma secrete these interleukins which are associated with atopy
IL-4
IL-5
IL-9
IL-13
Novel genes associated with Asthma but their function in disease pathogenesis is not yet clear
ADAM 33
DPP 10
ORMDL3
genetic polymorphism associated with reduced response to B2 agonists
Arg-Gly-16 variant in the B2 receptor
Epigenetic mechanisms associated
DNA methylation
Histone modification
Virus implicated in the development of asthma
RSV
What is the Hygiene hypothesis
Lack of infections in early childhood: preserves Th2
exposure to infectionsL shift to protective Th1
Infection with which intestinal parasite is associated with a reduced risk of asthma
Hookworm
Dietary factors associated with an increased risk of asthma
Low in antioxidants (Vit C, Vit A, Mg, Se, omega 3 PUFA)
High in Na and Omega 6 PUFA
Air pollutants triggering asthma symptoms
Diesel
Ozone
Sulfur dioxide
Rigorous allergen avoidance have shown reduced risk of asthma development
False
Which domestic pet has been associated with allergic sensitization
Cats
Which chemicals lead to sensitization independent of atopy
Toluene diisocyanate
Trimellitic anhydride
Asthma occurs more frequently in obese which which BMI?
> 30
Other factors implicated in asthma etiology
Low birth weight Low maternal age Duration of breastfeeding Prematurity Inactivity
How many percent of asthmatic patients have negative skin tests to common inhalant allergens and normal serum concentration of IgE
10%
Characteristic of Intrinsic asthma
non atopic adult onset aspirin sensitive nasal polyps more severe, persistent asthma
pollens usually trigger allergic rhinitis than asthma.But when disrupted, pollen grains may be released and can trigger what kind of asthma
Thunderstorm asthma
Most common triggers of acute severe exacerbation of asthma
URTI by rhinovirus, RSV, coronavirus
Mechanism of beta blockers causing asthma exacerbation
increased cholinergic bronchoconstriction
All beta blockers would be avoided including selective and topical BB
True
ACE-I induced cough is no more frequent in asthmatics than in non asthmatics
true
Mechanism of asthma in Exercise
Hyperventilation, resulting in increased osmolality, triggering mast cell release
Exercise induced asthma occurs when?
begins AFTER exercise has ended and recovers SPONTANEOUSLY within 30 mins
Sports commonly associated with asthma
cross country running in cold weather
overland skiing
ice hockey
EIA is best prevented how?
regular treatment with ICS
Mechanism of asthma in cold air and hyperventilation
increased osmolality triggering mast cell release
Food additive that may trigger asthma through the release of sulfur dioxide gas in the stomach
metabisulfite
How many months should a person be removed from he work exposure before complete recover in occupational asthma
within the first 6 months
Mechanism of premestrual worsening of asthma
fall in progesterone
Mechanism of stress induced asthmas
bronchoconstriction through cholinergic reflex
Degree of inflammation is poorly related to disease severity
true
Characteristic finding in Remodeling
thickening of the basement membrane due to subepithelial collagen deposition
Pathology of asthma is remarkably uniform in different phenotypes of asthma
true
Physiologic abnormality of asthma
airway hyperresponsiveness
Indistinguishable pattern of inflammation seen in intrinsic asthma
Neutrophilic pattern
Characteristic feature of asthmatic airways
Eosinophilic infiltration
Interleukin associated with eosinophilic inflammation
IL-5
Interleukin associated with increased IgE formation
Il-4 and 13
Major sources of mediators that drives chronic inflammation in asthmatic airways
Structural cells– epithelial cells, fibroblasts, airway smooth muscle cells
Th2 cytokines that mediate allergic inflammation
IL-4
IL-5
IL-9
IL-13
Th2 cytokines that amplify the inflammatory response and play a role n a more severe disease
TNF-a
IL-1B
Anti-inflammatory cytokines that are deficient in asthma
IL-10
IL-12
Oxidative stress in asthma is provided by the increased concentration of which product ?
8-isoprostane
Increased oxidative stress is related to disease severity, it may amplify the inflam- matory response, and may reduce responsiveness to corticosteroids.
true
Diagnostic test used in the diagnosis and monitoring of asthmatic inflammation
Fractional excretion of NO
How does Epithelial damage contribute to AHR?
- loss of its barrier function
- loss of enzymes inflammatory mediators
- loss of a relaxant factor
- exposure of sensory nerves
Subepthelial fibrosis n th basement membrane is associated with deposition of which collagen types
III and V
Which interleukin is associated with with increased number of goblet cells contributing to mucus hypersecretion
IL-13
Characteristic structural changes in asthma
- increased airway smooth muscle
- fibrosis
- angiogenesis
- mucus hyperplasia
Direct bronchoconstrictors
histamine
methacholine
Most triggers for asthma symptoms appear to act INDIRECTLY
True
includes allergens, exercise,, hyperventilation, fog, irritant dusts, sulfur dioxide
Prodromal symptoms of an asthma attack
- itching under the chin
- discomfort between the scapulae
- inexplicable fear (impending doom)
Airflow limitation in simple spirometry shows what findngs
reduced FEV1
reduced FEV1/FVC ratio
reduced peak expiratory flow
How is reversibility demonstrated in asthma
> 12% AND 200-mL increase in FEV1 15 min after an inhaled SABA (albuterol 400 μg) or after a 2–4 week trial of OCS (prednisone or prednisolone 30–40 mg daily)
What does the Flow volume loops show
reduced peak flow
reduced maximum expiratory flow
Whole body plethysmography show which findings (although rarely necessary)
increased airway resistance
increased total lung capacity
increased residual volume
increased AHR is normally mea- sured by methacholine or histamine challenge with calculation of the provocative concentration that reduces FEV1 by how much?
20%
FEV1/FVC ratio diagnostic of asthma and copd
<70%
Typical appearance of the flow volume loop indicating a widespread airflow obstruction
scalloped appearance
CXR in asthma
normal
but may show hyperinflated lungs in more severe patients
noninvasive test to measure eosinophilic airway inflammation and may be useful in demonstrating compliance with ICS therapy
FeNO
How many percent of COPD patients have features of asthma ?
15%
Bronchodilator therapies in asthma
B2 agonists
Anticholinergics
Theophylline
Aims of asthma therapy
- Minimal chronic symptoms, including nocturnal
- Minimal exacerbations
- No emergency visits
- Minimal use of a required β2-agonist
- No limitations on activities, including exercise
- Peak expiratory flow circadian variation <20%
- (Near) normal PEF
- Minimal adverse effects
Mode of action of B2 agonists
- relax airway smooth muscles
- inhibition of mast cell release
- reduction in plasma exudation
- inhibition of sensory nerve activation
Duration of action of LABA (salmeterol and formoterol)
12 h
LABA given on a once a day dosing
Indacaterol
Olodaterol
Vilanterol
How is bronchodilator tolerance by mast cells reduced?
concomitant administration of ICS
muscarinic receptor antagonists are less effective than B2 agonists
True
they inhibit only the cholinergic reflex component of bronchoconstriction, whereas β2-agonists prevent all bronchoconstrictor mechanisms
Side effects of antimuscarinics
dry mouth
urinary retention
glaucoma
Bronchodilator which acts by inhibiting the phosphodiesterase in airway smooth muscles
Theophylline
anti-inflammatory effect of theophylline is mediated through which mechanism?
activation of HDAC2
Theophylline level associated with an additional bronchodilator effect in severe asthma
10-20 mg/L
Theophylline level associated with additive effects to ICS in severe asthma
5-10 mg/L
Side effects of theophylline are rarely observed at plasma concentrations of what?
<10 mg/L
Most effective anti-inflammatory agent in asthma therapy
ICS
reduces inflammatory cell numbers, eosinophils, activated T lymphocytes, surface mast cells
Increases/Decreases clearance of theophylline
Rifampicin
Increase
Increases/Decreases clearance of theophylline
Phenobarbitone
increase
Increases/Decreases clearance of theophylline
Ethanol
Increase
Increases/Decreases clearance of theophylline
Smoking
Increase
Increases/Decreases clearance of theophylline
High protein, low carbohydrate diet
increase
Increases/Decreases clearance of theophylline
Barbecued meat
increase
Increases/Decreases clearance of theophylline
Childhood
increase
Decreases clearance of theophylline
cimetidine erythromycin ciprofloxacin allopurinol, zafirlukast Congestive heart failure Liver disease Pneumonia Viral infection and vaccination High carbohydrate diet Old age
Side effects of ICS
hoarseness and oral candidiasis
How many percent of asthma patients may require maintenance treatment with OCS
1%
asthma therapy that blocks activation of cys-LT1-receptors which causes microvascular leakage and increase eosinophilic inflammation
Antileukotrienes
Asthma therapy that inhibits mast cell and sensory nerve activation therefore effective in blocking trigger induced asthma such as EIA and allergen/sulfure dioxide induced symptoms
Cromones
Methotrexate, cyclosporin A, azathioprine, gold, and IV gamma globulin have all been used as steroid-sparing therapies, but none of these treatments has any long-term benefit
True
blocking antibody that neutralizes cir- culating IgE without binding to cell-bound IgE and, thus, inhibits IgE-mediated reactions
omalizumab
SQ every 2-4 weeks
Drugs that block IL-5
mepolizumab
reslizumab
Drug that blocks the IL-5 receptor
Benralizumab
Nonpharmacologic treatments, including hypnosis, acupuncture, chiropraxis, breathing control, yoga, and speleotherapy lacks efficacy
true
bronchoscopic treatment using thermal energy to ablate airway smooth muscle which reduce exacerbations and improve asthma control in patients not controlled on maximal inhaler therapy
Bronchial thermoplasty
drug that blocks against the common receptor for IL-4 and IL-13 (IL-4Ra) showing promise in reducing exacerbations and improving asthma control
Dupilumab
Partly controlled asthma
daytime symptoms >2x/wk any limitation of activities any nocturnal sx/awakening need for reliever >2x/wk FEV1 <80% predicted
How many features are needed for uncontrolled asthma
3 or more
in acute severe asthma, what is the goal oxygen saturation?
> 90%
treatment of acute severe asthma
high doses SABA neb/MDI IV B2 agonists Anticholinergics neb/IV MgSO4 IV/neb Prophylactic intubation Antibiotics NOT routine unless there are signs of pneumonia
How many percent of patients are refractory to treatment despite animal inhaled therapy
5%
most common reason for poor asthma control
poor adherence with ICS
Corticosteroid resistant asthma is defined as?
failure to respond to a high dose of oral prednisone/ prednisolone (40 mg once daily over 2 weeks)
Asthma showing a persistent pattern of variability and may require OCS or, at times, continuous infusion of β2-agonists
type 1 brittle asthma
asthma showing a generally normal or near-normal lung function but precipitous, unpredictable falls in lung function that may result in death
type 2 brittle asthma
Treatment of choice for type 2 brittle asthma
epinephrine SQ
Phenotype of asthma prided by perennial rhinitis and nasal polyps in non atopic patients with a late onset of the disease
Aspirin-sensitive asthma
In aspirin-sensitive asthma, All nonselective COX inhibitors should be avoided, but selective COX2 inhibitors are safe
true
Patterns of asthma during pregnancy
1/3 improve
1/3 deteriorate
1/3 unchanged
Drugs allowed during pregnancy
ICS
SABA
Theophylline
In asthma in pregnancy, prednisone is preferred over prednisolone
true
how many percent of asthmatics smoke?
20%
Which can affect the response to antileukotrienes?
Repeats of an Sp1 recognition sequence in the promoter region if 5-Lipoxygenase
Which bacteria have been implicated in the mechanism of severe asthma development?
Mycoplasma and Chlamydophila
How many percent of young adults are affected by occupational asthma
10%
Acetaminophen consumption in childhood increases risk of developing asthma through which mechanism?
Increased oxidative stress
Which cytokine released from epithelial cells in asthmatic patients instructs dendritic cells to release chemokines that attract Th2 cells into the airways ?
Thymic stromal lymphopoietin
Which chemokine is selectively attractant to eosinophils vis CCR3
Eotaxin
Which chemokines attract Th2 cells via CCR4
CCL17 (TAR )
CCL22(MDC)
How is the diurnal variation in air flow obstruction confirmed?
PEF twice daily
Increased AHR is measured by methacholine or histamine challenge with calculation of the provocative concentration that reduces FEV1 by how much?
20%
What test is done to demonstrate post exercise bronchoconstriction if there is a predominant history of EIA?
Exercise testing
Upper airway obstruction is a differential diagnosis of BA that is confirmed how?
Flow volume loop showing reduction in inspiratory and expiratory flow.
Theophylline at high concentrations cause cardiac arrhyrhmias, epileptic seizures, death through which mechanism
Adenosine A1-receptor antagonism
How is hoarseness and oral candidiasis reduced in patients using ICS
Use of a large volume spacer device
Intranuscular triamcinolone acetonide is a depot preparation used in NON COMPLIANT patients but what is the major problem with this therapy?
Proximal myopathy
Incidence of steroid resistant asthma
<1 in 1000 patients
4 mechanisms of corticosteroid resistant asthma
- increase in GR-B
- Abnormal pattern of histone acetylation
- defect in Il-10 production
- reduction in HDAC2 activity
Proportion of asthmatics who become worse with aspirin and other COX inhibitors
1-5%
Which set of patients require a boost of OCS prior to surgery?
patients with FEV1 <80%