The Acute & Maintenance Treatment of Asthma via ......The Acute & Maintenance Treatment of...

The Acute & Maintenance

Treatment of Asthma via

Aerosolized Medications

Douglas S. Gardenhire, EdD, RRT-NPS, FAARC

Associate Professor and Chairman

Department of Respiratory Therapy

Objectives

Define Asthma.

Determine aerosolized agents used to treat acute

asthma.

Determine aerosolized agents used to maintain

asthma control.

Utilize guidelines to treat acute asthma.

Utilize guidelines to maintain asthma control.

Definition of Asthma

Asthma is a heterogeneous disease, usually

characterized by chronic airway inflammation. It

is defined by the history of respiratory

symptoms such as wheeze, shortness of breath,

chest tightness and cough that vary over time

and in intensity, together with variable

expiratory airflow limitation.

GINA, 2016

Question 1

Is Racemic Epinephrine or Epinephrine

available over-the counter to treat asthma?

Yes

No

Short-Acting b Adrenergic Agents

(SABA) Ultra Short-acting

Epinephrine

Racemic Epinephrine

Question 2

Does Step 1 in GINA and NAEPP guidelines

recommend a SABA for the treatment of

asthma?

Yes

No

Short-Acting b Adrenergic Agents

(SABA) Short-acting

Albuterol

Levalbuterol

Use in Asthma

a – agonists are not routinely used for treatment of

asthma

Epi v. Terbutabline, No difference detected (n=38)

Adoun, M et al. J Crit Care, Vol 19, No 2 (June), 2004:

pp 99-102

SABA main bronchodilator of choice (NAEPP, 2007)

Use as needed

Regularly scheduled use is not recommended

Use of at least 1 week decreases tolerance, associated

with poor disease control. Salpeter, Ann Intern Med.

2004;140:802-813

Downregulation

From Gardenhire, DS Rau’s Respiratory Care Pharmacology, 2016 Mosby, St. Louis, MO

GINA <5 years old

GINA 6-11 years old

GINA 12 years old- Adult

Question 3

Corticosteroids assist beta agonists in working

better?

Yes

No

Upregulation

Corticosteroids

Increase the proportion of beta receptors on the cell

membrane

Increase affinity of beta receptors

Inhibit the release of inflammatory mediators

Corticosteroids

From Gardenhire, DS Rau’s Respiratory Care Pharmacology, 2016 Mosby, St. Louis, MO

GINA <5 years old

GINA 6-11 years old

GINA 12 years old- Adult

Long-Acting b Adrenergic Agents

(LABA)

Salmeterol

DPI

50mcg/actuation

4 years old +

Black Box Warning

Problems with Long-term

Bronchodilators SMART Chest 2006

Led to regulatory warning

Salapeter et al. Annu Intern Med 2006

Long-acting Beta2 agonists increases the risk of asthma hospitalizations and deaths compared to placebo

Nelson et al. Chest 2006 Increase in death rate while using salmeterol

Mann et al. Chest 2003

Increased exacerbations in patients receiving Formoterol

Use in Asthma

Addition of Salmeterol or Formoterol for uncontrolled

asthma when not controlled on low/med-dose

ICS…Reduce exacerbations/use of SABA (Greenstone

et al. Cochrane Database Syst Rev 2005)

Should not be used as monotherapy

Daily use should not exceed

100 mcg salmeterol

24 mcg formoterol

Consideration for increasing ICS before adding LABA

(NAEPP, 2007)

GINA <5 years old

GINA 6-11 years old

GINA 12 years old- Adult

Fixed Drug Combinations

From Gardenhire, DS Rau’s Respiratory Care Pharmacology, 2016 Mosby, St. Louis, MO

Question 4

As a respiratory care practitioner do you see the

use of anticholinergics such as ipratropium

bromide used regularly in your daily practice?

Yes

No

Question 5

Are anticholinergics regularly used in the

treatment of asthma?

Yes

No

Anticholinergic Agents

Ipratropium Bromide

Tiotropium Bromide

1.25 mcg via Respimat

Complementary Effect

From Gardenhire, DS Rau’s Respiratory Care Pharmacology, 2016, Mosby, St. Louis, MO

GINA 12 years old- Adult

Use in Asthma

Not superior to beta agonists (NAEPP, 2007;

GINA, 2016)

Asthmatic patients treated with Beta blockers

Alternative to theophylline

Acute, severe exacerbations not responding to

beta agonists (Weber. Ann Allergy, 1990)

Cont.

Ipratropium added lowered hospitalization rate of children with acute moderate to severe asthma (Qureshi et al. N Engl J Med 1998)

Adding multiple doses of ipratropium to beta agonist

Improved lung function

Avoided hospital admission (1 in 11)

(Plotnick & Ducharme, Br Med J 1998)

Cont.

Add-on tiotropium by mist inhaler improves lung function and increases the time to severe exacerbation (Rodrigo GJ et al. Chest2015;147:388-96)

In patients selected for uncontrolled symptoms and persistent airflow limitation despite moderate-high dose ICS and LABA, add-on tiotropium, improved lung function and increased time to first exacerbation. (KerstjensHA et al. Engl J Med 2012;367:1198-207)

Adding multiple doses of ipratropium to beta

Xanthines

Theophylline

Aminophylline

Oxtriphylline

Dyphylline

Use in asthma

Small therapeutic index

Less asthma control than ICS (Dahl et al. Respir Med

2002)

Non-preferred alternative, cost consideration for

inhaled meds (NAEPP, 2007, GINA 2016)

IV aminophylline and theophylline should not be used

in the management of exacerbations (Nair P et al.

Cochrane Database Syst Rev 2012;12:CD002742)

Theophylline does not improve outcomes compared

with SABA alone. Nair P et al.Cochrane Database Syst

Rev 2012;12:CD002742)

Mast Cell Stabilizer and

Leukotriene Modifiers

From Gardenhire, DS Rau’s Respiratory Care Pharmacology, 2016 Mosby, St. Louis, MO

Use in asthma

Cromolyn has favorable safety profile but low efficacy

(Guevara JP et al. Cochrane Database Syst Rev

2006:CD003558)

Leukotriene receptor antagonists (LTRA) are less effective

than ICS (Chauhan BF et al. Cochrane Database Syst Rev

2012;5:CD002314)

Limited evidence for LTRAs in acute asthma. Small studies

have demonstrated improvement (Ramsay CF et al. Thorax

2011;66:7-11)

Regular treatment with LTRA in young children modestly

reduced symptoms and need for oral corticosteroids

(Bisgaard H et al. Am J Respir Crit Care Med 2005;171:315-

22)

Monoclonal Antibodies

Omalizumab (Xolair)

Anti-IgE

12 years and older

Positive skin test to aeroallergen

Mepolizumab (Nucala)

Interleukin-5 antagonist

12years and older

Eosinophilic phenotype

Reslizumab (Cinqair)

Interleukin-5 antagonist

18 years and older

Eosinophilic phenotype

GINA <5 years old

GINA 6-11 years old

GINA 12 years old- Adult

Treatment of

Exacerbation

GINA 2016

GINA 2016

Summary SABA first line agents

Corticosteroids first agent to consider in uncontrolled asthma

LABA are effective, work best with corticosteroids

Xanthines have unwanted side effects

Cormolyn and Antileukotriens are safe, but not always effective

Ipratropium can be considered but not routine

Tiotropium add-on treatment only

Each patient is different, EDUCATE!

Questions, Comments,

Happy Thoughts?

dgardenhire@gsu.edu

Twitter

@RTPharmacology