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Asthma
J.B. Handler, M.D.
Physician Assistant Program
University of New England
1
Abbreviations
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SOB-shortness of breath
ASA- aspirin
P.E.- physical exam
EOS- eosinophils
RR- respiratory rate
ABG- arterial blood gas
Nl- normal
CxR- chest x-ray
SaO2- saturation of
oxygen
OP- out patient
V/Q- ventilation/perfusion
DM- diabetes mellitus
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ß- beta
EIA-exercise induced
asthma
PRN- as needed
HTN- hypertension
D/C- discontinue
SO2- sulfate
NO2- nitrate
GERD- gastroesophageal
reflux disease
PO- by mouth
Alt- alternative
NSAID- non-steroidal antiinflammatory drug
2
Definition
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A clinical syndrome of unknown etiology
with three components:
1. Recurrent episodes of airway
obstruction that resolve spontaneously
or following treatment.
2. Exaggerated bronchoconstrictor
response to stimuli that have little/no
effect on non-asthmatics.
3. Inflammation of the airways.
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Case 1
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A 45 y/o white male presents with
paroxysms of severe coughing lasting up
to 1 hour, resolving spontaneously. He
had a recent URI. No prior history of
pulmonary problems. No hx of smoking.
Currently feels well.
P.E: Healthy appearing male, NAD;
Vesicular breath sounds throughout both
lung fields without wheezing, ronchi or
crackles.
What is your differential diagnosis?
4
Differential Diagnosis
New/superimposed respiratory
infection- bronchitis, pertussis, etc.
 Asthma
 Allergies
 Toxin or pollutant exposure
 Early signs of new disease
 Psychogenic cough – dx only of
exclusion
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Epidemiology
5% of child/adult U.S. population
 Can develop any time in life (often
<25 y.o.)
 500,000 hospitalizations, 5,000
deaths/yr.
 15 million OP visits/yr.
 >6 billion dollars/annually
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Pathogenesis
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Genetic predisposition.
Inflammatory infiltrates (lymphocytes,
neutrophils, eosinophils, mast cells).
Injury to airway epithelium; denudation.
Thickened airway wall from:
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Inflammation, collagen deposition, smooth
muscle hypertrophy.
Hypertrophy and hyperplasia of airway
glands.
Airway hyperresponsiveness.
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Pathogenesis
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Episodic airway narrowing: smooth
muscle constriction, thickening of
airway epithelium and mucus secretion
into the airway lumen; mucus inspissates.
Local release of bioactive mediators or
neurotransmitters during attacks
contributes to airway constriction.
End result is acute, reversible
obstruction of the airway lumen to
airflow.
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Pathophysiology
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Airway resistance; medium and small
airwayswork of breathing.
Diffuse airway obstruction.
Airway reactivity to variety of stimuli.
V/Q mismatch: low V/Q contributes to
hypoxemia when present.
Tachypnea results in PCO2. If PCO2,
ominous sign of ventilatory failure.
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Airway Obstruction
AllRefer Health
Asthma Microscopic
Images.google.com
Asthma: Mucous Plugging
Mediators: Acute Response
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Acetylcholine: neurotransmitter released
via intrapulmonary branches of vagus
nerve increases bronchial smooth
muscle contraction bronchoconstriction.
Histamine: endogenous
bronchoconstrictor in mast cells,
basophils, lungs. Vasodilator properties
promote capillary leakage in presence of
inflammation.
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Mediators: Acute Response
Kinins- bradykinin activated by
enzymes (kallikreins) released by
mast cells- bronchoconstrictor.
 Leukotrienes: biochemical mediators
released by mast cells, EOS and
macrophages-potent smooth muscle
constriction; increase mucus
secretion and activate airway
inflammatory cells.
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Asthma Triggers
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“Atopy” association of allergies- inhaled
allergens can trigger attacks- dust mites,
cats, seasonal pollens, hay fever, etc.
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Single largest risk factor for developing
asthma.
Non-specific triggers: URI’s, sinusitis,
tobacco smoke, ozone, GERD, weather,
stress, exercise, SO2, NO2, and others.
Aspirin allergy- cross reactivity with other
NSAIDs, but not selective COX-2 agents.
Absence of triggers not unusual as well.
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Clinical Presentation
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History: “attacks” of coughing, wheezing,
SOB, anxiety, chest tightness.
Associations- allergies, irritants, ASA.
Highly variable presentation.
Episodes often at night and early AM
when airway reactivity is highest.
P.E*: P & RR, secretions, expiratory
phase, wheezing, mucosal swelling.
Note: with severe asthma, wheezing
may decrease or stopdecreased airflow.
*During asthma episode/attack
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Pulmonary Function Testing
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Spirometry easily obtainable – FVC, FEV1,
FEV1/FVC.
PEFR-Peak expiratory flow rate-(L/min)varies with age, gender, height; handheld device good for following asthma
severity as an adjunct to PFT’s.
Spirometry or PEFR following
bronchodilator: assess responsiveness to
treatment.
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Spirometry of Asthmatic
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Lung volumes: TLC, FRC, RV; FVC
normal or slightly
Lung flow:; FEV1, FEV1/FVC (<70%
means obstruction), PEFR.
DLCO- normal
Spirometry in between asthmatic attacks
may or may not be normal; depends on
asthma severity/classification (see
below).
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Case 1
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One year ago, he had a similar episode
which responded to antibiotics.
In the last year he has noted episodic
coughing when using a dictaphone or
speaking for extended periods of time.
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Some episodes with exercise- no pattern.
PFT’s done on 2 occasions when
asymptomatic have been entirely
normal.
Symptoms rapidly respond to short
courses of oral prednisone.
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Pulmonary Testing
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Provocative testing (If spirometry nl)Methacholine challenge to induce Sx and
decrease in FEV1 (by 20% or more). If
negative, asthma very unlikely.
Arterial blood gases (ABG’s)- measure
pH, PCO2, PO2. Respiratory Alkalosis
with PCO2 is common during attack.
If PCO2 is normal or high during an attack
 impending respiratory failure. PO2
indicates severe V/Q mismatch.
CxR- Often normal vs hyperinflation.
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Case 1
During methacholine challenge
testing, he has abrupt onset of
severe coughing with a >20% drop
in FEV1 and FEV1/FVC.
 Treatment with inhaled ß-agonist
aborts the attack.
 PFT’s return to normal following
albuterol.
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Asthma Complications
Infection including pneumonia
 Exhaustion, dehydration
 Oxygenation failure
 Ventilation failure – lose drive to
inflate alveoli
 Death
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Classification of Severity
Applies to clinical features of
chronic, stable asthma.
 Mild intermittent asthma
- Symptoms  2x/week
- No symptoms and normal PEFR
between attacks
- Night symptoms  2x/month
- FEV1 and PEFR  80% predicted*
- PEFR variability 20%
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*In between attacks
Current, Chapter 9 23
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Mild persistent asthma
- Symptoms > 2x/week, <1x/day
- Night symptoms > 2x/month
- FEV1 or PEFR  80% predicted*
- PEFR variability 20-30%
*In between attacks
Current, Chapter 9
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Moderate persistent asthma
- Daily symptoms; daily use of
inhaled short acting ß2 agonists
- Night symptoms >1x/week
- FEV1 or PEFR >60% to <80% *
predicted
- PEFR variability >30%
*In between attacks
Current, Chapter 9
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Severe persistent asthma
- Symptoms daily and frequent- may be
continuous
- Frequent night symptoms
- FEV1 or PEFR 60% predicted*
- PEFR variability >30%
Note: Exacerbations of symptoms are
common in patients with asthma and
often limit activities in moderate to
severe forms.
*In between attacks
Current, Chapter 9
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Long Term Treatment Goals
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Minimize chronic symptoms that impair
normal activity.
Minimize exacerbations/hospitalizations.
Limit side effects of medications.
Cornerstone treatment of persistent
asthma- daily anti-inflammatory therapy
with inhaled corticosteroids.
Stepped care approach (Current, table 93).
Long term control vs. quick relief
meds.
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Quick Relief: Beta Adrenergic
Agents
Most efficacious brondchodilators for
acute symptoms.
 Also used to prevent exercise
induced asthma (EIA).
 2 agonists selectively relax
bronchial smooth musclebronchodilate while limiting cardiac
stimulation.
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Quick Relief: Beta Adrenergic
Agents
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Albuterol, others: Rapid onset of action
(<5”); most effective agents for acute
bronchospasm. Use of a spacer may
improve delivery.
MDI 1-2 puffs (0.18mg) up to 6+ puffs
q6hr; delivery may improve with spacer.
Nebulizer doses (2.5 mg) are 14x more
potent than MDI (2 inhalations)- more
effective for severe asthmatic
exacerbations (ED, hospitalized).
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Inhalers and Spacers
AllRefer Health
Quick Relief: Anticholinergic
Meds
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Reverse vagally mediated
bronchoconstriction and mucus
production.
Ipratropium bromide (Atrovent) via
inhaler 2-4 puffs (18mcg/puff) q6h as an
alternative or adjunct (in moderate to
severe exacerbations) to short acting Bagonists; not as effective.
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Not useful for EIA or allergy induced asthma
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Long Term Control: Inhaled
Corticosteroids
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Low to high dose, local Corticosteroids:
most important and effective for long
term control in persistent asthma.
Reduce chronic and acute inflammation;
mild persistent asthma and worse.
Inhaled preparations for prevention;
dose titrated to symptom relief; may take
weeks for optimal efficacy; adrenal
suppression unlikely.
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Inhaled Corticosteroids
Several agents- varying potency
(Fluticasone, Beclomethazone,
Flunisolide et. al.).
 Usually 2x or 3x daily dosing
 Follow by H2O or mouth wash gargle
to avoid local yeast (Candida)
infection.
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Long Term Control: Long
Acting -agonists
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Used for long term (8-12 hrs)
bronchodilation and EIA; not for
acute episodes.
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Especially beneficial for night time
symptoms.
Salmeterol (Serevent): 50mcg
2x/d. Formoterol is new with similar
effects.
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Salmeterol Safety Concerns
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Two large clinical trials salmeterol s
asthma exacerbations and asthma related
deaths (small number of patients, but
statistically significant).
Black-box warning on labeling since 2005
 Little change in prescribing since.
Message: Use with caution. Confine use
only to patients already on inhaled
corticosteroids with ongoing
symptoms.
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Leukotriene Modifiers
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Leukotriene modifiers: Inhibit synthesis
(Zileuton/Zyflow) or action
(Zafirlukast/Accolade) of leukotrienes;
inhibit inflammatory mediators;
decreases need for rescue inhaler. Modest
efficacy for patients with mild persistent
asthma.
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Alternative to low dose inhaled steroids in
treatment of mild persistent asthma.
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Mediator Inhibitors
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Chromolyn, Nedocromil- mild
improvement in airway function in mild
persistent or EIA. Inhibit mast cell
release of mediators of inflammation;
inhibit asthmatic response to allergens.
Alternative to IC for some patients with
mild persistent asthma and allergies.
Limited usefullness.
Excellent safety profile
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Systemic Corticosteroids
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Systemic steroids are used in Rx of
moderate to severe asthma
exacerbations; marked antiinflammatory properties speed (6+
hours) the resolution of airway
obstruction and reduce rate of relapse;
oral or IV dosing.
Long term use may be required in some
patients with severe persistent asthma.
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Systemic Corticosteroids
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Prednisone et. al. (40-60 mgs/daily for
out-patient care); higher doses required if
severity requires hospitalization.
Safe when used for short term
treatment (see below) of moderate to
severe exacerbations.
May occasionally be needed (short term
course) in some patients with mild
asthma during severe exacerbations.
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Systemic Corticosteroids
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Dangers: Supraphysiologic dosing over
time leads to long term risks: Adrenal
suppression, HTN, osteoporosis, glucose
intolerance/DM, easy bruisability, weight
gain, etc.
Goal: Pulse dosing followed by taper and
D/C, overlapping with  dosing of inhaled
agents which have minimal systemic side
effects.
Tapering dose (days to weeks) allows
return of adrenal-pituitary axis.
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Interest Only
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Phosphodiesterase inhibitorsaminophylline, theophylline- less effective
and potentially toxic; adjunctive Rx for
mod to severe persistent asthma.
Toxicity- Low therapeutic/toxic ratio- GI
(nausea, abd. pain), CNS stimulation
(anxiety, HA,tremors, seizures)and
Cardiac (arrhythmias, tachycardia).
Must monitor serum theophylline levels
to maintain therapeutic range (10-20
ug/ml).
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Still Other……IO
Oral -agonists- terbutaline,
albuterol tablets- usually add little to
inhaled agents; may be useful as an
adjunct; terbutaline causes tremors.
 Immunosuppresive agents:
Methotrexate, cyclosporine,
trolandomycin- for patients
unresponsive to other drugs or
where steroids contraindicated.
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Combination Meds
Advair Diskus: Combination inhaler
with Fluticasone in varying strengths
combined with a fixed dose (50mcg)
of Salmeterol, one inhalation b.i.d,
decreases number of inhalers and
inhalations.
 Combivent: Albuterol + ipratropium
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Case 1: Many Years Later
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He remains asymptomatic and has
reduced meds over time. Rare coughing
episodes rapidly respond to albuterol
inhaler.
Meds:
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Fluticasone MDI 220mcg 2x/d
Abuterol MDI (90mcg/puff)- 2-3 puffs prn
Notes breathing is best when teaching PA
students at UNE!
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Mild Persistent Asthma
Long Term Control:
 Daily meds
 Either low dose
inhaled steroid or
Cromolyn/Nedocromil
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Alternative:
Leukotriene modifier
Quick Relief:
 Short acting B2
agonist
 Frequent or
increasing use of B2
agonist suggests need
for additional therapy.
If needed increase
dose of IC’s
Current, Chapter 9 45
Moderate Persistent Asthma
Long Term Control:
 Daily meds
 Low, medium or high
dose inhaled streroid
 If needed, add long
acting bronchodilator
-B2 agonist (esp for
night time Sx)
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Quick Relief:
 Short acting inhaled
B2 agonist
 Frequent or
increasing use of B2
suggests need for
additional therapy
Alt: SR theophylline
Current, Chapter 9
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Severe Persistent Asthma
Long Term Control:
 Daily meds
 High dose inhaled
corticosteroid
 Long acting
bronchodilator
-B2 agonist
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Alt: SR theophylline
Quick Relief:
 Short acting B2
agonist
 Frequent or
increasing use of B2
suggests need for
additional therapy
Oral steroid therapy
often needed for long
periods.
Current, Chapter 9
47
Mild Asthma Exacerbations
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Stepped care incremental therapy
Most are treated at home with quick
response to ’d dose/frequency of short
acting “rescue” ß-agonist.
These drugs may be needed every 3-6
hours for a short course.
Inhaled corticosteroids may need to be
added (*MIA) or dose ’d (x2) if already
taken (*PA); full effect will take weeks.
*MIA- mild intermittent asthma
*PA- persistent asthma
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Mild Asthma Exacerbations
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If already taking an inhaled
corticosteroid, the dose is doubled
during an acute exacerbation until
PEFR return to normal.
If unresponsive, an oral systemic
corticosteroid may be needed for a
short course, then tapered, returning to
inhaled corticosteroids.
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Moderate/Severe Attacks
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Some patients (caution) managed as out
patient- require very close monitoring via
phone.
Most patients warrant
hospitalization.
Supplemental O2 as needed to maintain
SaO2>90%.
Continuous O2 saturation monitoring via
oximetry if hospitalized.
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Moderate/Severe Attacks
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Reversal of airway obstructionrepetitive/continuous use of high
dose ß-agonists usually via nebulizer.
Early administration of systemic
corticosteroids IV; high dose.
Serial measurement of lung function:
PEFR or spirometry to monitor course.
ABG’s often helpful: pH, PO2, PCO2.
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Moderate/Severe Attacks
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Never sedate during acute asthma
exacerbation; will ventilatory drive.
Dropping PO2 <60mm Hg (O2 sat<90%)
and rising PCO2> 42mm Hg are evidence
of impending respiratory/ventilatory
failure and warrant treatment in the ICU.
Intubation may be required- initiate
before patient has respiratory arrest.
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Moderate/Severe Attacks
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Rehydration IV usually warranted- BP will
drop once on ventilator.
Bronchodilators are maintained on
ventilator.
IV Magnesium Sulfate has some
usefulness for bronchial relaxation.
Once improved, discharge considered
once FEV1 or PEFR70% of predicted or
personal best.
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