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Management of Asthma and COPD Exacerbations

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Sarah Milkovich

on 5 November 2014

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Transcript of Management of Asthma and COPD Exacerbations

Management of
Asthma and COPD Exacerbations


Sarah Milkovich, PharmD, RPh
PGY-1 Clinical Pharmacy Resident
Fairview Hospital
November 5th, 2014

Objectives
Review common risk factors and triggers for both asthma and COPD exacerbations
Discuss pharmacotherapy for inpatient and outpatient management of both asthma and COPD exacerbations
Discuss maintenance therapy for asthma and COPD
Demonstrate the use of maintenance therapy

Asthma and COPD
COPD Prevalence 2011
Asthma affects 1 in 11 children and 1 in 12 adults in the US
In the US, approximately 6% of the population diagnosed with COPD
Both asthma and COPD account for significant morbidity, mortality, and healthcare costs
Asthma vs. COPD
Asthma
COPD
Mediated by
Eosinophils
Mast cells
CD4 T-lymphocytes
Bronchoconstriction
Smooth muscle activation
Basal membrane thickening
Characterized by inflammation
Mediated by
Neutrophils
Macrophages
CD8 T-lymphocytes
Reduced airway caliber
Bronchiectasis
Cell damage
Airway narrowing
Goblet cells
Hypersecretions
Clinics 2012; 67(11): 1335-1343
Centers for Disease Control and Prevention, 2011
NHLBI, 2012
Signs and Symptoms
Asthma Exacerbation
Shortness of breath
Wheezing
Cough
Chest tightness
Fatigue
Reduction of 20% or more of personal best peak expiratory flow
Emerg Med J. 2014 Oct;31(e1):e40-5.
Asthma Exacerbation Triggers
Allergens: dander, pollen, mold
Respiratory infection
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Nonadherence
National Asthma Education and Prevention Program Expert Panel, 2007
Asthma Exacerbation Risk Factors
Previous severe exacerbation
Asthma-related hospitalization or ED visit
Three or more ED visits for asthma in past year
No inhaled glucocorticoid maintenance therapy
Frequent use of short-acting beta agonists
Poor adherence to medications or action plan
Difficulty perceiving asthma symptoms
Goals of Outpatient Management
GINA, 2012
Relieve airflow limitation
Prevent or reverse hypoxemia
Initiate or optimize controller therapy
Short-Acting Beta Agonist (SABA)
Albuterol
Levalbuterol
SABA Dosing: Albuterol
After 1st hour, dosing depends on severity
Mild exacerbation
Responds to 2 to 4 puffs every 3 to 4 hours
Nebulizer: 2.5 to 10mg every 1 to 4 hours
More severe exacerbation
May require 6 to 8 puffs every 1 to 2 hours
Nebulizer: 10 to 15mg per hour continuously
MDI: 2 to 6 puffs every 20 minutes x 1 hour
Nebulizer: 2.5mg every 20 minutes x 1 hour PRN
Repeat peak flow after 1st hour
Initial dosing
MDI = 90 mcg/puff
Nebulizer solution

0.63mg/3mL
1.25mg/3mL
2.5mg/3mL
5mg/mL
SABA Response
Good response
Symptoms resolve
Repeat peak flow returns to 80% and above
Incomplete response
Continued symptoms
Personal best peak flow 50 to 80%
Urgent medical attention
Severe symptoms despite initial therapy
Personal best peak flow (PEF) less than 50%
Outpatient Treatment: Therapy Adjustment
Good response
Continue current therapy
Increase dose of inhaled glucocorticoids
Initiate short-course of oral glucocorticoids
Outpatient Treatment: Therapy Adjustment
Incomplete response
Initiate oral glucocorticoids according to action plan
Timely administration essential to reduce ED visits and hospitalizations
Acute Exacerbations: Inhaled Glucocorticoids
Inhaled glucocorticoids not a substitute for oral glucocortcoids

Increased inhaled glucocorticoid dose early in exacerbation may decrease the need for oral therapy
Dose quadrupled in patients with
mild exacerbations
RR 0.43; 95% CI 0.24-0.78

Doubling inhaled glucocorticoid dose worsened asthma symptoms compared to placebo
No difference in need for systemic glucocorticoid therapy between groups
Am J Respir Crit Care Med 2009; 180:598
Thorax 2004; 59:550
Goals of Inpatient Management
Rapid reversal of airflow limitation
Correct severe hypercapnia or hypoxemia
Supplemental Oxygen
To be administered to all hospitalized patients
Titrate to maintain oxygen saturation of 90% and higher
SABA Therapy
Albuterol dosing
Nebulizer
Initial: 2.5 to 5mg every 20 minutes x 3 doses
Followed by 2.5 to 10mg every 1 to 4 hours
Continuous (ICU): 10 to 15mg/hour
MDI
Initial 4 to 8 puffs every 20 minutes x 3 doses
Followed by 1 puff every 2 to 4 hours
Inhaled Anticholinergics
Recommended combination therapy with inhaled albuterol
Combination therapy increases bronchodilation in severe airway obstruction compared to SABA alone
Ipratropium dosing
Nebulizer: 500mcg every 20 minutes x 3 doses, then as needed
MDI: 4 to 8 puffs every 20 minutes as needed for up to 3 hours
Am J Respir Crit Care Med 2000; 262:1862
National Asthma Education and Prevention Program Expert Panel, 2007
Systemic Glucocorticoids
Early administration is essential for asthma exacerbations refractory to bronchodilator therapy
Reduces airway inflammation and mucus plugging
Severe: PEF less than 40, give immediately
Moderate: PEF 40 to 69%
Lack of full correction in PEF after SABA
Supplement doses for patients on chronic glucocorticoids
National Asthma Education and Prevention Program Expert Panel, 2007
Glucocorticoids: IV vs. PO
Typical dosing: oral
Prednisone 40 to 60mg daily
Prednisolone 0.5 to 1mg/kg daily
Methylprednisolone 32 to 48mg daily
Duration: 5 to 14 days
Identical effects
Typical dosing: IV
ICU: methylprednisolone 60 to 80mg every 6 to 12 hours
Inpatient: methylprednisolone 40 to 60mg every 12 to 24 hours
Duration: 5 to 10 days
Chest 1995; 107:1559
Magnesium Sulfate
Life-threatening or severe exacerbations
PEF below 40
Dosing
Magnesium sulfate 2g IV over 20 minutes
Mechanism
Bronchodilator activity in acute asthma
Calcium influx into airway smooth muscle cells
No benefit in routine use
National Asthma Education and Prevention Program Expert Panel, 2007
Asthma
COPD
Signs and Symptoms
COPD Exacerbation
Change in 1 or more cardinal symptoms
Cough increases in frequency and severity
Sputum production increases in volume and/or changes character
Dyspnea increases
COPD Exacerbation Triggers
COPD Exacerbation Risk Factors
Advanced age
Productive cough
Duration of COPD
History of antibiotic therapy
COPD-related hospitalization in past year
Chronic mucus hypersecretion
Theophylline therapy
Comorbidities
Respiratory infections: 70%
Bacterial
Viral
Other etiologies: 30%
Environmental pollution
Pulmonary embolism
Unknown
ECLIPSE Trial
Prospective study to predict surrogate endpoints of COPD
Evaluated 2138 patients
Moderate to severe COPD
GOLD stages 2, 3, 4
Best predictor: history of prior exacerbations
Low risk: 0 to 1 exacerbation in previous 12 months
GOLD 1 or 2
High risk: 2 or more exacerbations in previous 12 months
GOLD 3 or 4
Other predictors
GERD and pulmonary hypertension
GOLD Staging
GOLD, 2014
Respiration 2000; 67:495
N Eng J Med 2010; 363:1128
Stage 1
FEV1 = 80% and higher than predicted
Stage 2
FEV1 = 50 to 79% of predicted
Stage 3
FEV1 = 30 to 49% of predicted
Stage 4
FEV1 = less than 30% predicted
Outpatient Management of COPD
Intensification of bronchodilator therapy
Initiation of oral glucocorticoids
Oral antibiotics, if appropriate
SABA Therapy
Rapid onset
Bronchodilation
Administered via MDI or nebulizer
Both types of administration are equally efficacious
SABAs used alone or in combination with short-acting anticholinergic
Anticholinergic Agents
Usual dosing
Bronchodilator
MDI: ipratropium 2 puffs every 4 to 6 hours
Combination product
Ipratropium/albuterol 20/100mcg
Combivent Respimat

Caution in BPH or urinary retention
Ipratropium and tiotropium may increase risk of acute urinary retention
Short-acting: ipratropium
Long-acting: tiotropium
Oral Glucocorticoids
Prednisone 40mg daily x 5 days
Certain patients may benefit from a higher dose or longer course if previously taking glucocorticoids
Dosing
Antibiotics
Only recommended for patients most likely to have bacterial infection or most ill
GOLD
For moderately to severely ill patients who have increased cough and sputum purulence
Antimicrobial coverage
Haemophilus influenzae
Moraxella catarrhalis
Streptococcus pneumoniae
Length of therapy: 10 to 14 days
Other Outpatient Therapy
Smoking cessation
Nutrition support
Supplemental oxygen therapy
Inpatient Management of COPD
Reversing airflow limitation with bronchodilators and glucocorticoids
Treating infection
Adequate oxygenation
Preventing intubation and mechanical ventilation
SABA Therapy and
Anticholinergic Combination Therapy
Albuterol dosing
MDI: 4 to 8 puffs every 1 to 4 hours as needed
Nebulizer: 2.5mg every 1 to 4 hours as needed
Ipratropium dosing
Nebulizer: 500mcg every 4 hours as needed
MDI: 18mcg = 1 puff
MDI: 2 to 4 puffs every 4 hours as needed
Glucocorticoid Therapy
Improve symptoms and lung function
Significant reduction in the following with glucocorticoids
Treatment failure rate at 30 and 90 days
At 30 days, 23% vs. 33%
Length of hospital stay
LOS: 8 vs. 10 days
Glucocorticoid Therapy
Oral
GOLD: prednisone 40mg or equivalent daily
Prednisone 30 to 60mg daily
Duration: 5 to 14 days
IV
Methylprednisolone 60 to 125mg IV 2 to 4 times daily
REDUCE Trial
Antibiotic and Antiviral Therapy
Antibiotic therapy
Indicated for moderate to severe COPD exacerbations requiring hospitalization
Duration: 5 to 10 days
Antiviral therapy
Recommended for patients with influenza infection who are hospitalized for COPD exacerbation
Preferred: oseltamivir (Tamiflu)
Zanamivir has risk of brochoconstriction with inhalation
Supportive Care
Supplemental oxygen
Smoking cessation
Thromboprophylaxis
Nutrition support
Randomized, multicenter noninferiority trial
Investigated short-term versus conventional glucocorticoid therapy in patients with COPD exacerbation
Intervention: prednisone 40mg daily for 5 or 14 days
Results
Short-term treatment was noninferior to conventional therapy in regards to re-exacerbation in 6 months
Re-exacerbation rates: 37.2% vs. 38.4%
Difference -1.2%
JAMA 2013; 309(21):2223-2231
Maintenance Therapy for Asthma and COPD
Short-Acting Beta Agonists
Albuterol
(Ventolin, Proair, Proventil)
Levalbuterol (Xopenex)
Products
Demonstration - albuterol inhaler
SABA Take Home Points
Inhaler must be primed prior to first dose
Prime inhaler if not used for 14 days or if dropped
Shake well
Remove cap
Breathe out (as much as possible)
Place mouthpiece to mouth and close lips
Push canister down while breathing in through mouth
Close mouth and hold breath up to 10 seconds
Then breathe normally
GSK, 2014
GOLD, 2014
Rescue inhaler for quick relief
Prime inhaler according to package instructions
Shake well before each puff
Wash actuator in warm water once weekly
Wait 1 minute between sprays
Patients should not need to refill every month (PRN only)
May be less effective in patients on beta-blockers
Inhaled Corticosteroids
Products
Beclomethasone (QVAR)
Budesonide (Pulmicort)
Fluticasone (Flovent)
Mometasone (Asmanex)
Many others
Demonstration: mometasone
Hold inhaler upright
Twist cap counterclockwise
Remove cap (loads dose)
Breathe out fully
Place mouthpiece to mouth
Firmly close lips
Take a fast, deep breath
Wipe mouthpiece dry
Recap
Inhaled Corticosteroid Take Home Points
Maintenance therapy - 1st line for long-term asthma control
Reinforce adherence to prevent exacerbations
Not a rescue medication
Rinse mouth out with water after dose, then spit out water
Prime according to package instructions
Follow dose counter to plan for refills
Recommend calcium and vitamin D due to long-term fracture risk
Short-Acting Anticholinergics
Products
Ipratropium (Atrovent HFA)
Combination therapy
Ipratropium/albuterol (Combivent Respimat)
Demonstration - Combivent Respimat
Specific instructions for assembling inhaler prior to first use
Hold inhaler upright
Turn inhaler base toward white arrows until it clicks (half turn)
Flip cap open
Breathe out slowly
Close lips around mouthpiece without covering vent
Point inhaler toward back of throat
While taking a slow, deep breath, press button and continue to breathe in slowly
Hold breath for 10 seconds if possible
Recap inhaler
Boehringer Ingelheim, 2014
Long-Acting Anticholinergics
Products
Tiotropium
(Spiriva)
Aclidinium (Tudorza Pressair)
Demonstration video - tiotropium
Anticholinergic Take Home Points
Short-acting: rescue therapy
Long-acting: maintenance therapy
Can worsen myasthenia gravis, BPH, urinary retention, and narrow-angle glaucoma
Avoid spraying in eyes
Do not swallow tiotropium capsules
Side effects
Dry mouth
Cough
Bitter taste
Nasopharyngitis
Side effects
Thrush
Dysphonia
Cough
Side effects
Tachycardia
Tremors/shakiness
Cough
Hyperglycemia
GSK, 2014
Merck, 2014
Merck, 2014
Boehringer Ingelheim, 2014
Long-Acting Beta Agonist and Corticosteroid Combinations
Products
Salmeterol/fluticasone (Advair)
Fomoterol/budesonide (Symbicort)
Vilanterol/fluticasone (Breo Ellipta)
Demonstration - Advair Diskus
Rotate cap of diskus
Move tab to the left until click to load dose
Put diskus to mouth and close lips around mouthpiece
Inhale slowly for a few seconds
Hold breath for up to 10 seconds
Replace cap on diskus
GSK, 2014
Long-Acting Beta Agonist and
Corticosteroid Combinations
Demonstration - Breo Ellipta
Each time cover is opened, 1 dose of medication is loaded
Wait until ready to take dose, then open cover until it clicks
Breathe out fully
Put mouthpiece to lips and close lips firmly around it
Take one long, steady, deep breath in through mouth
GSK, 2014
Long-Acting Beta Agonist and Anticholinergic Combination
Product
Vilanterol/Umeclidinium (Anoro Ellipta)
Take home points
Maintenance therapy only
Must be taken daily to prevent exacerbations
Black box warning: increase in asthma-related deaths
Side effects
Anticholinergic effects
Tachycardia
Tremor/shakiness
Long-Acting Beta Agonist Combination
Take Home Points
Black box warning: increase in asthma-related deaths
Only to be used in asthma patients who are not adequately controlled on chronic medication
Maintenance therapy
Reinforce adherence
Bronchodilators used as needed to reduce symptoms
Rinse mouth after use and spit out if product contains a corticosteroid
Side effects
Tachycardia
Tremor/shakiness
Cough
Palpitations
Hyperglycemia
Hypokalemia
GSK, 2014
GOLD, 2014
GOLD, 2014
GOLD, 2014
N Eng J Med 1999; 340:1941
GOLD, 2014
Summary
SABA therapy is preferred in asthma exacerbations
Combination SABA and short-acting anticholinergic therapy preferred in COPD exacerbations
Oral glucocorticoids are considered based on severity
Antibiotics are considered in more severe patients
Questions?
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