What is asthma?

● Asthma is a disease characterized by heightened reaction to a stimuli.

● Pt who are hyperallergic (atopic) usually express other allergic
diseases like eczema, allergic rhinitis and food allergies.
● It falls under obstructive lung disease because this stimuli creates an inflammatory
response which creates mucus (mucus plug) and bronchospasm (reversible
bronchoconstriction).
● Normal airway tone is controlled by sympathetic B adrenergic
(relaxation) and parasympatheic muscarinic (constriction)
● And of course, it's spirometry findings fall under the obstructive category. However,
know that the findings can be REVERSIBLE with medication.
 What are the types of asthma?
● Asthma can be classified in many ways. A common way is:
● Extrinsic (allergic)
● Intrinsic (non-allergic)
● In extrinsic allergies, there seems to be an imbalance of immune cells. For
example, there seems to be a large amount of helper TH2 cells. When
presented with a allergen stimuli, it secretes things like IL4, IL5, and IL10
● IL4: Stimulate B cells to class switch to IgE
● IL5: Stimulate IgA and eosinophils.
● IL10: stimulate more TH2!
● IgE causes mast cell degranulation of things like histamine which
can cause inflammation and bronchoconstriction.
● Eosinophils also release a substance called Major Basic
Protein – which again causes inflammation and
bronchoconstriction.
● Later, all these immune cells cause the release of arachnidonic
acid, which releases prostaglandins and leukotrienes!
● Leukotrienes are especially important here because they
cause more bronchoconstriction which can occur
hours later!
 How do we test for asthma?
● We can use a methacholine test – which is a muscarinic
M3 agonist that causes bronchoconstriction, especially if the
pt has asthma.
● So you give it and then do a spirometry test and look for a
20% drop in FEV1.
● If test is negative, it's the best test for ruling out asthma.
 What are some findings of asthma?
● Physical exam: chest tightness, SOB, wheezing, pulsus paradoxus
● CXR shows hyperinflated lungs and thicken walls and lead to “peribronchial
cuffing” - donut shaped consolidation.
● Microscopic findings include:
● Curschmann spirals: spiral mucus plugs
● Charcot- Leyden crystals: needle shaped breakdown of Major
Basic protein. Indicate eosinophilic activation and is NOT specific
(seen in other eosinophilic attacks like in parasites)
 What is intrinsic asthma?
● AKA non-allergic asthma. Because non-allergic/atopic, pt may
not have eosinophilia or high levels of IgE
● Usually adult onset and bronchoconstriction due to a variety of
things:
● Exercise
● Occupational exposure
● Viruses
● Aspirin: Aspirin inhibits cyclooxygenase (COX) which
prevents the synthesis of prostaglandins. This can move
towards a leukotriene pathway and cause
bronchoconstriction. Nasal polyps. In a kid with nasal
polyp, think CF
Asthma Drugs – Quick Recap
 Drugs
● Omalizumab:
● Monoclonal anti-IgE antibody. Binds to IgE and blocks it's
binding to FceRI.
● Cromolyn
● Stabilize mast cells
● Corticosteroids
● Limit inflammatory reaction. Oral SE include candida.
● Zileuton:
● Inhibit 5-lipoxygenase. SE is hepatotoxicity
● Montelukast, zafirlukast:
● These are selective antagonist to leukotrine receptors
(CysLT1).
B2 Agonists and Muscarinic Antagonists
● We want to maximize our airways by dilating them (B2 agonists) and
stopping constriction (Muscarinic antagonists)
● B2 agonists:
● Short acting: albuterol or levalbuterol. SE: these include
hypokalemia, tachy and palpitations due to some B1
effect. Levalbuterol is more B2 selective.
● Muscarniic antagonists:
● End in "-Tropium"
 What are methylxanthines?
● Methylxanthines include theophylline. Causes
bronchodilation by increase cAMP by
● Blocking phosphodiesterase (which breaks down
cAMP)
● Also is an adenosine antagonist. Adenosine
usually decreases cAMP, thus as an antagonist it +
cAMP.
● Toxicity treated with B BLOCKERS.
● It can also increase contraction force of the diaphragm
by increasing Ca2+ intake into the muscle
● SE: tremor, nausea, vomiting and arrhythmia. They have a
narrow therapeutic index.