Asthma Flashcards
Major risk factor for asthma?
Atopy
Lack of infections in early childhood preserves the TH2 cell bias at birth, whereas exposure to infections and endotoxin results in a shift toward a predominant protective TH1 immune response?
Hygiene hypothesis
May be suspected when symptoms of asthma improve during weekends and holidays
Occupational asthma
Independent risk factor for asthma, particularly in women, but the mechanisms are thus far unknown
Obesity (body mass index >30 kg/m2)
Consumption of this drug in childhood, which may be linked to increased oxidative stress, predisposes to asthma development
Acetaminophen (Paracetamol)
Most common allergens to trigger asthma?
Dermatophagoides species
Minority have negative skin tests to common inhalant allergens and normal serum concentrations of IgE. These patients usually show later onset of disease (adult-onset), commonly have concomitant nasal polyps, and may be asa sensitive
Intrinsic asthma
Pollen grains are disrupted and the particles that may be released can trigger severe asthma exacerbations
Thunderstorm asthma
Most common viral triggers of acute severe exacerbations
Upper respiratory tract virus infections such as rhinovirus, respiratory syncytial virus, and coronavirus
Inhibit breakdown of kinins, which are bronchoconstrictors; however, they rarely worsen asthma
ACEI
Commonly acutely worsen asthma, and their use may be fatal. The mechanisms are not clear, but are likely mediated through increased cholinergic bronchoconstriction
Beta blockers
Which beta blockers should be avoided in asthma?
All beta blockers, even selective beta 2 blockers or topical application (e.g., timolol eye drops)
Antiplatelet that may worsen asthma in some patients?
Aspirin
How is EIA best prevented?
Regular treatment with ICS, which reduce population of surface mast cells
When does EIA start and end typically?
Exercise-induced asthma (EIA) typically begins after exercise has ended and resolves spontaneously within about 30 min
What type of weather triggers EIA?
EIA is worse in cold, dry climates than in hot, humid conditions. It is, therefore, more common in sports activities such as cross-country running in cold weather, overland skiing, and ice hockey than in swimming
Food preservative that trigger asthma through the release of sulfur dioxide gas in the stomach.
Metabisulfite
How can premenstrual worsening of asthma be improved?
Treat with high doses of progesterone or GnRH
Why is GERD common in asthmatic patients?
GERD is usually increased by bronchodilators
Common pathologic finding in fatal asthma?
Occlusion of airway by mucus plugs
Characteristic finding of asthma is thickening of the basement membrane due to
Subepithelial collagen deposition
Thickening of basement membrane in asthma is also found in what condition?
Eosinophilic bronchitis
T/F These pathologic changes in asthma are found in all airways, but do not extend to the lung parenchyma
True
Characteristic physiologic abnormality of bronchial asthma?
Airway hyperresponsiveness
Infiltration of __ is a characteristic feature of asthmatic airways.
Eosinophils
Increased numbers of __ are found in sputum and airways of some patients with severe asthma and during exacerbations
Neutrophils
Upstream cytokine released from epithelial cells of asthmatics that orchestrates the release of chemokines that selectively attract TH2 cells.
Thymus stimulated lymphopoeitin (TSLP)
Expected spirometry findings in asthma?
reduction in forced
expiratory volume in 1 second (FEV1), FEV1/forced vital capacity
(FVC) ratio, and peak expiratory flow (PEF)
Examples of direct bronchoconstrictors which contract
airway smooth muscle
Histamine, methacholine
Examples of indirect stimuli, which release bronchoconstrictors from mast cells or activate sensory nerves
Allergens, exercise, irritant dusts, sulfur dioxide
Prodromal symptoms that precede an attack?
itching under the chin, discomfort
between the scapulae, or inexplicable fear (impending
doom)
Reversibility in spirometry is demonstrated as:
> 12% and 200-mL increase in FEV1
15 min after an inhaled short-acting β2-agonist
What tests can be done to confirm the diurnal variations in airflow obstruction?
Measurements of PEF twice daily
Noninvasive test to measure airway inflammation. The typically elevated levels in asthma are reduced by ICS, so this may be a test of compliance with therapy
FENO
Examples and duration of action of SABA
Albuterol, terbutaline, 3-6 hours
Examples and duration of action of LABA
Salmeterol, Formoterol, >12 hours
Most common side effects of Beta 2 agonists?
Muscle tremors, palpitations (but not a problem during inhalational route), commonly seen in the elderly
Mild hypokalemia
Less effective than beta 2 agonists in asthma therapy because they inhibit only the cholinergic reflex component of bronchoconstriction
Anticholinergics (Ipratropium, Tiotropium)
Most common side effects of anticholinergics?
Dry mouth (most common), in elderly patients, urinary retention and glaucoma
Reduce corticosteroid insensitivity in severe asthma by activates the key nuclear enzyme histone deacetylase-2 (HDAC2)
Theophylline
MOA of Theophylline
Inhibition of phosphodiesterases in airway smooth-muscle cells, which increases cyclic AMP
Theophylline occasionally used (via slow IV infusion) in patients with severe
exacerbations that are refractory to SABA
IV Aminophylline
Most common SE of theophylline
nausea, vomiting,and headaches and are due to phosphodiesterase inhibition
Diuresis and palpitations may also occur, and at high concentrations,
cardiac arrhythmias, epileptic seizures, and death may occur
due to:
adenosine A1-receptor antagonism
Examples of drugs that block CYP450 causing elevated levels of theophylline
Erythromycin, Allopurinol
most effective anti-inflammatory agents
used in asthma therapy, reducing inflammatory cell numbers and
their activation in the airways.
ICS
Local SE of ICS?
hoarseness (dysphonia) and oral candidiasis
How to reduce SE of ICS?
use of a large volume spacer device
Dose of course of OCS (usually prednisone or prednisolone) used to treat acute exacerbations of asthma; no tapering of the dose is needed.
30–45 mg once daily for 5–10 days
Block cys-LT1-receptors and provide modest clinical benefit in asthma
Antileukotrienes (Montelukast)
controller drugs that appear to inhibit mast cell and sensory nerve
activation and are, therefore, effective in blocking trigger-induced
asthma such as EIA and allergen- and sulfur dioxide–induced
symptoms
Cromolyn sodium
blocking antibody that neutralizes circulating
IgE without binding to cell-bound IgE and, thus, inhibits
IgE-mediated reaction
Omalizumab
Most common reason for poor control of asthma
Non compliance with maintenance medications
failure to respond to a high dose of oral prednisone/prednisolone
(40 mg once daily over 2 weeks), ideally with a 2-week run
Corticosteroid resistant asthma
Type of Brittle Asthma show a persistent pattern of
variability and may require oral corticosteroids or, at times, continuous
infusion of β2-agonists
Type 1
generally normal or near-normal lung function but precipitous, unpredictable
falls in lung function that may result in death
Type 2
Most effective therapy of Brittle Asthma?
SC epinephrine
T/F All COX inhibitors should be avoided
False selective COX2
inhibitors are safe to use when an anti-inflammatory analgesic is
needed
Medications safe for asthma in pregnancy?
SIT
SABA ICS Theophylline
Rule of thirds in asthma in pregnancy?
1/3 improve, 1/3 worsen, 1/3 unchanged
T/F Breastfeeding is contraindicated when taking asthma meds during pregnancy
False
