Asthma Flashcards
Most common allergen to trigger asthma
Dermatophagoides species
Most common triggers of acute severe exacerbations
RSV,Rhinovirus, Coronavirus
Trigger of asthma that is linked to hyperventilation which results in increased osmolality in airway lining fluid and triggers mast cell mediator release resulting in bronchoconstriction..
Exercise
Asthma trigger that is used as a food preservative which may trigger asthma through the release of sulfur dioxide gas in the stomach
Metabisulfite
Dendritic cells
Specialized macrophage-like cells in the airway epithelium, which are the major antigen-presenting cells.
Which phenotype predominates in asthma? TH2 or TH1?
TH2 phenotype
TH2 cytokines that mediate allergic inflammation
IL-4, IL-5, IL-9, IL-13
Risk Factors and Triggers Associated with Asthma
Inflammation in the airways of asthmatic patients leads to airway hyperresponsiveness and symptoms
Which interleukin induces airway hypersecretion in experimental models of asthma?
IL-13
Limitation of airflow is mainly due to? What is the effect in FEV1/FVC ratio and PEF (peak expiratory flow)?
Bronchoconstriction( from mast cell mediators)
What are the characteristic symptoms of asthma?
Wheezing, dyspnea, and coughing, which are variable, both spontaneously and with therapy
Lung function tests (spirometry) in asthma
reduced FEV1, FEV1/FVC ratio, and PEF
Reversibility is demonstrated by a >12% and 200-mL increase in FEV1 15 min after an inhaled short-acting β2-agonist (SABA; such as inhaled albuterol 400 μg) or in some patients by a 2–4 week trial of oral corticosteroids (OCS) (prednisone or prednisolone 30–40 mg daily
Skin prick tests to common inhalant allergens (house dust mite, cat fur, grass, pollen) are _________in allergic asthma and _________ in intrisic asthma
Positive, Negative
*NOT helpful in diagnosis
What is now used as a noninvasive test to measure eosinophilic airway inflammation?
Fractional exhaled Nitric oxide (FeNO)
These act primarily on airway smooth muscle to reverse the bronchoconstriction of asthma.
Bronchodilators
What are the three classes of bronchodilators?
B2 adrenergic agonists, anticholinergics, theophylline.
What are the aims of asthma therapy?
Mechanism of B2 agonist
B2 Agonists activate B2 adrenergic receptors, which are widely expressed in the airways. B2 receptors are coupled through a stimulatory G Protein to adenylyl cyclase, resulting in AMP, which relaxes smooth muscle cells and inhibit cerain inflammatory cells, particularly mast cells.
What are the other additional non-bronchodilator effects that may be clinicaly useful in B2 agonists?
- Inhibition of mast cell mediator release
- Reduction in plasma exudation
- Inhibition of sensory nerve activation
LABA and frequency of dose
Every 12 hours: SF
Salmeterol
Formoterol
Once daily VIO
Vilanterol
Indacaterol
Olodaterol
Most common side effects of B2 agonists
Muscle tremor and palpitations, seen more commonly in elderly patients
Anticholinergics-Muscarinic receptor antagonists mechanism
Prevent cholinergic nerve-induced bronchoconstriction and mucus secretion
Mechanism of Theophylline
Mechanism of Inflammation in low doses of theophylline
The bronchodilator
effect is due to inhibition of phosphodiesterases in airway
smooth-muscle cells, which increases cyclic AMP.
Mechanism of Inflammation in low doses of theophylline
Theophylline activates the key nuclear enzyme
histone deacetylase-2 (HDAC2), which is a critical mechanism for switching off activated inflammatory genes and may therefore reduce corticosteroid insensitivity in severe asthma.
What are the most common side effects of theophylline?
Nausea, vomiting, and headache.
At high concentrations of theophylline, what are the side effects? Mechanism of death
Cardiac arrythmias
Epileptic seizures
Death due to adenoside A1-receptor antagonism
Molecular mechanism, major effect of corticosteroids?
The major effect of
corticosteroids is to switch off the transcription of multiple activated genes that encode inflammatory proteins such as cytokines,chemokines, adhesion molecules, and inflammatory enzymes
Factors affecting clearance of theophylline
Usual course of OCS
Prednisone/ Prednisolone 30-45 OD for 5-10 days. No need for tapering.
Systemic side effects of corticosteroids
Truncal obesity, bruising, osteoporosis, diabetes, hypertension, gastric ulceration, proximal myopathy, depression, cataracts
Depot Drug that may be used for those who need OCS but are noncompliant.
Intramuscular Triamcinolone Acetonide
Potent bronchoconstrictors, cause microvascular leakage and increase eosinophilic inflammation through the activation of cys-LT1 receptors.
Cysteinyl-leukotrienes
Controller Therapies
Inhaled Corticosteroids
Systemic Corticosteroids
Antileukotrienes
Cromones
Anti-IgE
Anti-IL5
Asthma controller drugs that appear to inhibit mast cell and sensory nerveactivation and are, therefore, effective in blocking trigger-inducedasthma such as EIA and allergen- and sulfur dioxide-induced
symptoms.
Cromolyn sodium and nedocromil sodium
Blocking antibody that neutralizes circulating
IgE without binding to cell-bound IgE. Given as a subcutaneous injection every 2-4 weeks.
OMALIZUMAB
Antibodies that block IL-5,markedly reduce blood and tissue eosinophils and reduce exacerbations in patients who have persistently increased sputum eosinophils despite maximal ICS therapy.
mepolizumab, reslizumab) or its receptor (benralizumab)
Alternative therapies that are nonpharmacologic
Hypnosis
Acupuncture
Chiropraxis
Breathing control
Yoga
Speleotherapy
__________ is an antibody against the common receptor for IL-4 and IL-13 (IL-4Rα) is more promising in reducing exacerbations and improving asthma control in severe asthma.
Dupilumab
Parameters of Asthma control
(DANRL)
Stepwise Approach to Asthma therapy According to the Severity of asthma and ability to control symptoms
Mainstay of treatment of Acute Severe Asthma
High does of SABA given either by nebulizer or via a MDI with a spacer.
True or False. Prophylactic intubation may be indicated
for impending respiratory failure, when the PCO2
is normal or rises.
TRUE
What is the most common reason for poor control of asthma?
Poor Adherence with medication, particularly ICS.
How is adherence to OCS measured?
- Suppression of plasma cortisol
- Expected concentration of prednisone/Prednisolone in the plasma.
True or False. Women may develop severe premenstrual worsening of asthma which is responsive to corticosteroids.
FALSE. Treatment with progesterone or gonadotropin-releasing factors.
Complete resistance to corticosteroids is defined as
Failure to respond to a high dose of oral prednisone/prednisolone 40 mg OD over 2 weeks ideally with a 2 week run-in with matched placebo.
Type of Brittle asthma that has generally normal or near-normal lung function but precipitous, unpredictable
falls in lung function that may result in death
Type II
Most effective treatment for brittle asthma
Subcutaneous epinephrine
________ is a welldefined phenotype of asthma that is usually preceded by perennial rhinitis and nasal polyps in nonatopic patients with a late onset of the disease.
Aspirin-sensitive asthma
results from an allergic pulmonary reaction to inhaled spores of Aspergillus fumigatus and, occasionally, other Aspergillus species.fleeting eosinophilic infiltrates in the lungs, particularly in the upper lobes.
Airways become blocked with mucoid plugs rich in eosinophils, and patients may cough up brown plugs and have hemoptysis.
Bronchopulmonary Aspergillosis
