The Acute & Maintenance Treatment of Asthma via Aerosolized Medications

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 Ultra Short-acting Epinephrine Racemic Epinephrine (SABA)

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 Short-acting Albuterol Levalbuterol (SABA)

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. Chest 2015;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. (Kerstjens HA et al. Engl J Med 2012;367:1198-207)

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