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 hyper-
reactivity, airway remodeling

1970’s 1980’s 1990’s present

Bronchospasm Bronchospasm Bronchospasm
+ Inflammation + Inflammation
Dendritic cells
+ Remodeling

Th17

T cell Eosinophil
Th-2
IL-5 / IL-13

CHEST 2013; 144(3):1026–1032.

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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 2014,14:49–54

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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
Assess Physical Exam
severity Peak flow determination

Inhaled Up to 2 treatments
SABA 20 minutes apart

Good Incomplete Poor

response response response
• Peak flow 50- • Peak flow <50%
• Normal peak flow
80% predicted predicted
• Consider brief ER
• Start oral • Start oral
trial of oral Admit
corticosteroids corticosteroids
corticosteroids
• Contact primary • Contact primary
MD MD ©2014 MFMER | slide-10
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 β2-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, dose-
dependent 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

Corticosteroid therapy
Leukotriene inhibitors
2) Control inflammation Anti-IgE therapy
Thermoplasty

3) Provide bronchodilator Short acting beta-agonists

Long acting beta-agonists
for relief 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 life-
threatening 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. ©2014 MFMER | slide-24
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.

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The Nobel Prize in Physiology or Medicine 1950.

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