Asthma in Adults

Jessica Lo MS3, SUNY Downstate

May 2014
Introduction
1 in 12 people in the U.S. have asthma = 25 million people (CDC 2011)
7 million are children
$56 billion per year in medical costs, missed school days and missed work
days
>3000 deaths due to asthma in the U.S. (2010)
Numbers growing every year

What is Asthma?
Chronic inflammatory disease of the airways causing airflow obstruction
Obstructive lung disease
Bronchial hyperresponsiveness
Symptoms typically wax and wane
REVERSIBLE (at least partially)
Triad of:
Bronchoconstriction
Inflammation and edema of airway walls
Mucus production/plugging


Asthma - Pathophysiology
2 mechanisms
Intrinsic non-immune related, caused by vagal stimulation (e.g. viral
infection, exercise, cold air)
Extrinsic immune-related, caused by mast cell activation and
degranulation (e.g. allergens)
Asthma - Pathophysiology
Extrinsic
Allergens bound by dendritic cells
and presented to T- and B-cells
T-cells secrete cytokines causing B-
cell production of IgE
IgE coats mast cells; cross-linking
causes mast cell degranulation
and release of histamine,
leukotrienes, and inflammatory
cytokines

Asthma - Pathophysiology
2 phases of asthma attack
Early phase
Within several minutes
Allergen exposure by sensitized individual causes mast cell degranulation and release
of histamines, prostaglandins, leukotrienes, etc.
Can also be through vagal stimulation by irritant
Bronchoconstriction via smooth muscle contraction, edema via blood vessel dilation
and increased permeability, and mucus production
Late phase
Hours later
Recruitment of other inflammatory and immune cells, e.g. eosinophils, basophils,
neutrophils, T-cells, monocytes, dendritic cells
Further release of inflammatory mediators
Clinical Features - History
Respiratory symptoms in presence of triggers that resolve with avoidance of
trigger or with asthma medication
E.g. allergens, exercise, cold air, smoke, infection, aspirin
Symptoms
Wheeze
Cough, often worse at night
Dyspnea
Chest tightness
Symptoms typically episodic and often worse at night
Personal or family history of asthma, allergies, or other atopic diseases
History of chronic cough, nighttime cough, or recurrent bronchitis as a child
Clinical Features Physical
Scattered, high-pitched musical wheezes
Commonly expiratory, but can also be inspiratory
Usually varies in tone and duration over time, starts and stops at different points of respiratory
cycle
Severe
Tachypnea
Tachycardia
Prolonged expiration (decreased I:E ratio)
Tripod position
Use of accessory muscles of respiration
Pulsus paradoxus (decrease in SBP >12mmHg during inspiration)
Absence of wheeze may indicate severe bronchoconstriction
Extra-pulmonary
Nares pale, swollen mucosa suggest of allergic rhinitis; nasal polyps suggest aspirin sensitivity
Skin atopic dermatitis

Nasal polyps
Diagnosis of Asthma
History
Physical exam
Spirometry
FEV1/FVC ratio <70%
Increase in FEV1 >12% or 200ml with
administration of short-acting bronchodilator
(e.g. albuterol)
Decrease in FEV1 >20% with
bronchoprovocation test (methacholine or
mannitol inhalation)
Peak expiratory flow
>20% variability over several recordings
Other Studies
CBC with diff may show eosinophilia (>15% or >1500/microL)
CXR
May show pneumonia (possible exacerbating factor)
Also used to rule out other causes of asthma-like symptoms
Poorly controlled asthma may have atelectasis due to mucus plugging
Allergy tests identify triggers
Total serum IgE when considering use of omalizumab as therapy
Classifying Asthma Severity
Intermittent
Symptoms 2 days/week
Nighttime awakenings 2x/month
Use of short-acting beta
2
-agonist 2 days/week
Mild persistent
Symptoms >2 days/week but less than daily
Nighttime awakenings 3-4x/month
Use of short-acting beta
2
-agonist >2 days/week but not daily and not >1x/week
Moderate persistent
Symptoms daily
Nighttime awakenings >1x/week but not nightly
Use of short-acting beta
2
-agonist daily
Severe persistent
Symptoms throughout the day
Nighttime awakenings often 7x/week
Use of short-acting beta
2
-agonist several times a day

Classifying Asthma Severity & Initial
Treatment
Management of Asthma by Severity
Reassessment and Adjusting Therapy
Asthma Medications
Asthma Medications Mechanisms of
Action
Asthma Medications
Short-acting beta
2
-agonists (SABA)
E.g. Albuterol, levalbuterol, pirbuterol, metaproterenol
Use: PRN
Mechanism: bronchial smooth muscle relaxation
Side effects: increase HR, tremors, arrhythmias, irritability
Levalbuterol marketed to have fewer side effects
Long-acting beta-agonists (LABA)
E.g. salmeterol, formoterol, arformoterol
Use: usually added to treatment if moderate persistent asthma or worse.
Used as twice daily controller
Mechanism and side effects same as short-acting


Asthma Medications
Inhaled corticosteroids (ICS)
E.g. beclomethasone, budesonide, flunisolide, fluticasone, mometasone
Use: added for mild persistent or worse. Twice daily controller
Mechanism: decreases inflammation by inhibiting cytokine production
Side effects: dysphonia, thrush, reflex cough
Systemic corticosteroids
E.g. prednisone, prednisolone, methylprednisolone (IV)
Use: moderate to severe exacerbations. Usually given for 3-10 days to avoid
adrenal suppression
Side effects: adrenal suppression, leukocytosis, immune suppression, Cushings
syndrome, neuropsychiatric disturbance, osteoporosis, cataracts
Asthma Medications
Anticholinergics
E.g. ipratropium, tiotropium
Use: in combination with SABA for mild/moderate persistent asthma
Mechanism: inhibit muscarinic cholinergic receptors to reduce vagal tone bronchodilation
Side effects: dry mouth, blurred vision, urinary obstruction
Methylxanthines
E.g. theophylline
Use: add-on or alternative for moderate or severe persistent; used rarely
Mechanism: inhibits phosphodiesterase, leading to increased cAMP smooth muscle relaxation
Side effects: tachycardia, nausea/vomiting, sleep disturbance, arrhythmias and seizures in overdose;
narrow therapeutic index
Leukotriene modifiers
E.g. montelukast, zafirleukast, zileuton
Use: as alternative or add-on to ICS or LABA
Mechanism: leukotriene receptor antagonist (montelukast, zafirleukast) or leukotriene synthesis inhibitor
(zileuton). Leukotrienes responsible for eosinophil infiltration of airways
Side effects: elevated transaminases, hepatotoxicity (zileuton)

Asthma Medications
Mast cell stabilizers
E.g. cromolyn, nedocromil
Use: maintenance/controller. Add-on or alternate to ICS or LABA
Mechanism: prevents activation and degranulation of mast cell by membrane
stabilization (cromolyn) and prevents release of inflammatory mediators by by
neutrophils, eosinophils, monocytes, and macrophages (nedocromil)
Side effects: sore throat, unpleasant taste
Anti-IgE
E.g. Omalizumab
Use: moderate to severe persistent asthma. Good for patients with allergies.
Subcutaneous administration
Mechanism: prevents IgE binding to mast cells
Side effects: anaphylaxis



Urgent Care Setting
Assessment
Physical tachypnea, HR >120, diaphoresis, use of accessory muscles, inability to speak full
sentences, pulsus paradoxus
Peak flow meter PEF <200L/min or <50% of baseline
Pulse oximetry
ABG hypoxemia; normal or increased PaCO2 indicates worsening of exacerbation either
by severe airway narrowing or inspiratory muscle fatigue
Supplemental oxygen, albuterol, ipratropium, inhaled or IV steroids
Maintain O
s
sat >90%
Terbutaline drip or epinephrine
Magnesium sulfate IV if patient unimproved on conventional therapy
Bronchodilation by inhibition of calcium influx into smooth muscle cells
If all else fails - Intubation and mechanical ventilation
Methylxanthines, mast cell stabilizers, omalizumab, and LABAs are NOT effective in acute
exacerbations
References
UptoDate
FirstAid for USMLE Step 1
http://www.cdc.gov/nchs/fastats/asthma.htm
Clinical Guideline for the Diagnosis, Evaluation and Management of Adults
and Children with Asthma New York State Department of Health