Acute Asthma

An update

Robert Vassallo, MD
Mayo Clinic, Rochester, MN, USA.
Kuwait congress Update in Internal Medicine
February 2014

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Disclosures
I have nothing to disclose with respect to this
presentation.

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Abbreviations used in this presentation

SABA - short acting beta agonist
LABA - long acting beta agonist
NO nitric oxide
IL-5 - Interleukin-5
IL-13 Interleukin-13
Th T-helper cell

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Outline of this presentation

Advances in asthma pathophysiology
Overview of current therapy and acute management in
hospitalized patients.
Use of biomarkers to monitor therapy
Safety concerns with long acting beta-antagonists
A paradigm shift: anti-cholinergic therapy in asthma
Treatment of severe asthma:
Omalizumab (Xolair)
Anti-IL-13 Therapy (Lebrikizumab)
Bronchial thermoplasty

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Asthma pathophysiology

Key components: inflammation, bronchial hyperreactivity, airway remodeling

1970s
Bronchospasm

1980s
Bronchospasm
+ Inflammation

1990s

present

Bronchospasm
+ Inflammation
+ Remodeling

Dendritic cells

Th17

T cell

Eosinophil
Th-2
IL-5 / IL-13
CHEST 2013; 144(3):10261032.

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All of the following cause

obstructive lung disease except:
A) Obliterative bronchiolitis
B) Bronchiectasis
C) Asthma
D) Marked obesity
E) Chronic Obstructive Pulmonary Disease
(COPD)

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Establishing the diagnosis

Not all that wheezes is asthma
The medical history!
Pulmonary function testing with bronchodilator
Reversibility: 12% AND 200 cc change in FEV1
Obstructive physiology on pulmonary function
test (FEV1 reduced much more than FVC)

Bronchoprovocation testing
Methacholine, histamine, exercise
Exhaled nitric oxide (NO)

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Nitric Oxide
Exhaled NO

Exhaled nitric oxide is a biological marker

that correlates with eosinophilic inflammation
in asthma.
Exhaled NO measurement can provide
diagnostic and predictive value for a
corticosteroid response.
More longitudinal studies are required to
clarify the clinical significance of exhaled NO
in asthma.

Kim et al, Curr Opin Allergy Clin Immunol 2014,14:4954

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Treatment of acute severe asthma requiring

hospitalization

Why do patients develop respiratory failure with severe asthma attacks?

Air trapping
Mucus plugging
Increased work of breathing

NHLBI Asthma web educ resources

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Modified from NHLBI EPR3 2007

Acute Asthma

Initial Assessment and Management

History
Physical Exam
Peak flow determination

Up to 2 treatments
20 minutes apart

Normal peak flow

Consider brief
trial of oral
corticosteroids

Peak flow 5080% predicted

Start oral
corticosteroids
Contact primary
MD

Peak flow <50%

predicted
Start oral
corticosteroids
Contact primary
MD

ER
Admit
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Acute Asthma Management

Clinical and Laboratory Assessment

Assess clinically accessory muscle use, tachypnea,
tachycardia, diaphoresis, pulsus paradoxus,
exhaustion.
Assess airflow limitation peak flow measurement.
Assess oxygenation pulse oximetry.
Assess for hypercapnia selected patients especially
if somnolent, fatigued, difficulty with speech, elderly,
concomitant use of sedatives.
Imaging chest X ray
Blood work CBC, glucose.

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Treatment of Acute Severe Asthma

Principles and Primary Goals of care

Relieve airflow limitation: bronchodilator therapy

Treat airway inflammation: steroids.
Treat hypoxemia or hypercapnia if present.
Non-invasive ventilation / mechanical ventilation
in severe cases (clinical judgment).
Selected therapies: magnesium sulphate and
heliox.
Limited or no role for antibiotics and
methylxanthines.
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In the treatment of severe asthma,

corticosteroid therapy would be expected
to cause all of the following, except:
A) Corticosteroids enhance efficacy of 2-adrenergic
agonists (bronchodilator).
B) Corticosteroids may decrease hospital admission
rates in acute asthma if administered early.
C) High dose parenteral steroids may cause
hyperglycemia.
D) Corticosteroids enhance edema in the acute
asthmatic airway.

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Treatment of Acute Asthma

Bronchodilator therapy

Albuterol (or salbutamol) provides rapid, dosedependent bronchodilation.

Continuous administration may be more
effective in severe exacerbations.
Levalbuterol is the R-isomer of albuterol.
Ipratropium bromide is an anticholinergic
bronchodilator with a slow onset of action and
peak effectiveness at 60 to 90 minutes.

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Treatment of Acute Asthma

Corticosteroid therapy

Oral administration of prednisone is often

equivalent to iv methylprednisolone unless there is
nausea.
Give a 5- to 10-day course.
Current evidence is insufficient to permit
conclusions about using inhaled corticosteroids in
acute asthma.
For severe exacerbations unresponsive to the
albuterol and corticosteroid therapy, adjunctive
treatments may be used: iv magnesium sulphate or
heliox.
Expert Panel Report 3: National Heart Lung and Blood Institute 2007
https://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf 2014 MFMER | slide-15

Treatment of Acute Asthma

Heliox
Heliox is a mixture of helium and oxygen
(usually a 70:30 helium to oxygen ratio) that is
less viscous than ambient air.
Heliox improves delivery and deposition of
nebulized albuterol.

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Challenges in severe asthma

Why do patients get hospitalized?

Patient non-adherence to medication.

Continued exposure to triggers (pets etc) or
exposure to second-hand smoke.
Incomplete assessment of co-morbidities like
sleep apnea or GERD.
Inadequate follow-up
Pharmacogenomics and individualized patient
responses to medication.
Aldington S, Beasley R. Thorax 2007; 62: 447-458
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Asthma management
Post-hospital follow up of severe asthma

1) Identify triggers
2) Control inflammation

Corticosteroid therapy
Leukotriene inhibitors
Anti-IgE therapy
Thermoplasty

3) Provide bronchodilator
for relief

Short acting beta-agonists

Long acting beta-agonists
Long acting anti-muscarinic

4) Assess response

Symptom diary, pulmonary

function testing, exhaled NO

5) Modify (escalate/ de-escalate as appropriate) and

educate. Assess for risk factors associated with
higher mortality.
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Risk Factors Associated with Higher

Mortality in Acute Asthma
Previous severe exacerbation (e.g., ICU admission).
Two or more hospitalizations for asthma.
Three or more ED visits for asthma in the past year.
Using >2 canisters of SABA per month.
Difficulty perceiving asthma symptoms or severity of
exacerbations.
Other risk factors:

sensitivity to Alternaria
low socioeconomic status or inner-city residence
illicit drug use
major psychosocial problems

comorbidities like cardiovascular disease, etc .

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Expert Panel Report 3: National Heart Lung and Blood Institute 2007
https://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
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Treatment of severe asthma

Anti-IgE Therapy
Biologic antibody therapy (Omalizumab; Xolair) binds IgE in the
circulation and prevents it from activating mast cells and basophils.
In moderate to severe asthma, anti-IgE therapy reduced
exacerbation rate and reduced steroid dose needed.
Anti IgE therapy is recommended as an add-on to optimized
standard therapy in asthmatics 12 years and older who need
continuous or frequent treatment with oral corticosteroids.
Elevated serum IgE

1. Ann Intern Med. 2011 3;154(9):573-82

2. Lancet Respir Med. 2013;1(3):189-90.
3. Cochrane Database Syst Rev. 2014 13;1
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Tiotropium
Recent double blind trial in asthmatic patients
Addition of tiotropium compared with:
Doubling inhaled steroid
Addition of salmeterol
Tiotropium increased am peak flows more than
doubling inhaled steroids and equivalent to
salmeterol.
Most secondary outcomes favored tiotropium
N Eng J Med 2010;363:1715-26
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Risks with LABA monotherapy

Meta-analyses have shown that LABAs are associated
with increased risk of overall death when used as
monotherapy.
The use of LABAs concomitantly with inhaled
corticosteroids significantly reduces asthma
hospitalizations and is not associated with lifethreatening events and asthma-related deaths.
The evidence appears to support the use of LABAs plus
inhaled steroids in a single inhaler device for patients
with moderate to severe asthma.
Thorax 2012;67:342-349
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Bronchial Thermoplasty

Am J Respir Crit Care Med. 2012 Apr 1;185(7):709-14.

Am J Respir Crit Care Med. 2010 Jan 15;181(2):116-24.

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Treatments for severe asthma in the

pipeline

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New and Emerging Therapies Being Evaluated for Asthma.

Wechsler ME. N Engl J Med 2013;368:2511-2513.

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Anti-IL-13 Therapy (Lebrikizumab)

Bottom line: more studies needed

N Engl J Med. 2011 Sep 22;365(12):1088-98.
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Thank you for your attention.

"In our opinion, the awards
we received belong truly to
all the men and women of
the Mayo Clinic because it
was the spirit of cooperative
endeavor, the fundamental
credo of the institution, which
made possible the work
which resulted in our trip to
Stockholm. Dr Philip Hench,
MD.

The Nobel Prize in Physiology or Medicine 1950.

Nobelprize.org. Nobel Media AB 2013. Web. 30 Jan 2014.
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