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COPD Treatment: Using
Evidence-based Practice
to go for the GOLD
DR. ROSEMARY HENRICH, DNP, FNP-BC
DR. AMELIA SCHREIBMAN, DNP, ANP-BC
Objectives

1. Compare pharmacokinetics of 4 types of inhaled medication systems.

2. Name 4 factors that improve the effectiveness of inhaler systems.

3. List 3 patient-centered factors that may impact pharmacokinetics of an
inhaler and need to be considered by the prescriber.

4.Consider 2 tools that are used to assess the effectiveness of a treatment
plan for COPD.

5. Describe an EBP pathway for initiating and then adjusting
pharmaceutical agents in treating COPD/Asthma/ACOS (SABAs, LABAs,
SAMAs, LAMAs, ICS, combination inhalers, oral steroids, anti-leukotrienes,
oxygen, PDE4 Inhibitor, anti-biotics).
Levels of Evidence: EBP
© 2017 Global Initiative for Chronic Obstructive Lung Disease
COPD IS:

A non-curable disease that is usually the result of exposure to noxious
substances,

costing $32 billion annually in the USA, (Lopez-Campos, Tan, & Soriano, 2016),

impacting 210 million people world wide, 24 million in the USA

impacting 6.2% of New Mexico’s population.

Suspected when there is excessive chronic cough and mucous production

Must be diagnosed by post-bronchodilator FEV1/FEVC; + when result is <70%

Goals of treatment are reduction of symptoms/exacerbations and to improve
the quality of life.

Treated using systems that deliver medications to the airways and lungs.
Why Inhaled Medications?
 1.
Deliver medications directly to the
airways and lungs
 2.
Reduce the dose of medication
needed to treat the disease
 3.
Reduce unwanted side effects
associated with systemic medications.
Delivery Systems:
Inhaled Rx
1.
METERED DOSE INHALER
(MDI)
2.
DRY POWDER INHALER
(DPI)
3.
NEBULIZER
4.
SOFT MIST INHALER (SMI)
Pharmacokinetics
4 Phases
Absorption – Disintegration
Metabolism – Liver and GI enzymes
Distribution – Via bloodstream
Elimination – Mainly renal
* A CERTAIN AMOUNT OF AEROSOLIZED DRUG WILL ALWAYS IMPACT THE
NASAL AND ORO-PHARYNX AND BE SWALLOWED!
MDI vs DPI
Pharmacokinetics
Nebulizer Pharmacokinetics

1. Only 5% of the medications used are deposited in the airways and lungs.

2. Efficacy dependent on patient’s breathing patterns (Mouth Inhalation
needed) and equipment.

3. Much of the drug settles in the reservoir.

4. Much also deposits on the rest of the equipment/tubing, patient’s face.

5. Only recommended when other types of inhaled delivery systems
cannot be used!

https://www.degruyter.com/downloadpdf/books/9783110468007/9783110
468007-016/9783110468007-016.pdf
Soft Mist Inhaler (SMI)
PROS:
1.
37% to 53% of the drug reaches the
lower airways.
2.
Ideal size of drug molecule 1-7Micron.
3.
No propellants needed (Mechanical).
4.
Overall, lower dose of drug is effective
5.
Slower delivery system – less oral
intake.

Panos, R. 2013
CONS:
1.
Expensive! Not all plans will cover
2.
Limited number of drugs available
3.
More complicated and ‘differs’ from
current MDIs.
Factors that Improve
Pharmacokinetics
Increase Delivery to the Lung

1. Improved delivery systems

2. Use a reservoir device-spacer
Improve ratio of lung vs GI Absorption
Reduce Swallowed Drug

1. Use drugs with high first pass
metabolism (Swallowed but quickly
metabolized)

2. Rinse mouth and throat after use
(Reduces amount of drug available to
swallow)
Patient-Centered Factors
Co-morbidity
1. Recent MI <4
months
2. CHF NYHA Stage
III or IV
3. Unstable angina
BODE Score
Age
Body mass index
1. Functional
deterioration
2. Mental Capacity
Obstruction
degree
Dyspnea
Exercise
*Individualized care
GOLD Initiative 2017
Smoking Cessation
► Smoking cessation has the greatest capacity to influence
the natural history of COPD.
► If effective resources and time are dedicated to smoking
cessation, long-term quit success rates of up to 25% can
be achieved.
© 2017 Global Initiative for Chronic Obstructive Lung Disease
Subjective Measurements:
Associated With Increased
Exacerbations
mMRC: Dyspnea Scale
Dyspneic (breathlessness)on
CAT SCORE

1. Energy

1. strenuous exercise (0)

2. Sleep quality

2. walking a slight hill (0)

3. Mucous

3. walking on level ground, stops (1)

4. Chest tightness

4. walking 100yds, must stop (2)

5. Cough

5. dressing, self-care (3)

6. Activity
GOLD Category Changes: 2017
Category A
Category B

1. FEV 1 - <0.7 (+ COPD)

1.
FEV 1- <0.7 (+COPD)

2. CAT <10; or mMRC 0-1

2. CAT >10; mMRC or >2

3. 0-1 Exacerbation over past
year with no hospitalizations
for COPD

3. 0-1 exacerbation over the
past year no hospitalization for
COPD.
2017 Global Initiative for Chronic
Obstructive Lung Disease
GOLD CATEGORY Changes: 2017
Category C
Category D

1. COPD Diagnosis
confirmed

1. COPD Diagnosis
confirmed

2. CAT <10; mMRC 0-1

2. CAT >10; mMRC >2

3. Exacerbations: 2 or more
this year or one
hospitalization.

3. Two or more
exacerbations or one
hospitalization for COPD
2017 Global Initiative for Chronic Obstructive
Lung Disease
Treatment for Stable COPD: Only
Occasional Dyspnea
1.
Short Acting Beta Agonist (SABA) Improve Symptoms /FEV1(Evidence A)
Relax smooth muscles in the airways. Adverse: Sinus tachycardia at rest/tremor
Duration: 4-6 Hours
2. Short Acting Muscarinic Agent (SAMA) - Improves Symptoms /FEV1(Evidence
A) Block Broncho constrictors in the airway. Adverse: Dry mouth
Duration: 6 to 8 hours
3. Combination (SABA/SAMA) - Combo most effective (Evidence A)
Duration: 6 to 8 hours
2017 Global Initiative for Chronic Obstructive Lung Disease
Treatment Escalation Needed
More Frequent Dyspnea
1. Long Acting Beta Agonist (LABA) Evidence A
2. Long Acting Muscarinic Agent (LAMA) Fewer exacerbations Evidence A
Fewer Hospitalizations Evidence B
3. Switch to Combination Agent (LABA/LAMA) if dyspnea worsens Evidence A
4. Inhaled medications preferred over oral Evidence A
5. Do not use theophylline unless long acting inhalers are unavailable or unaffordable
Evidence B
2017 Global Initiative for Chronic Obstructive Lung Disease
COPD Worsens

1. Consider ICS (Inhaled steroid) but not as a single agent Evidence A

2. Consider long term LABA/ICS combination Evidence A

3. Long term oral steroid use NOT recommended Evidence A

4. If dyspnea persists LABA/LAMA or LABA/ICS, consider PDE 4 inhibitor
Roflumilast to reduce exacerbations improve lung function Evidence A

5. In former smokers consider long term macrolide Evidence B
One year, increased bacterial resistance/hearing worsens: Fewer exacerbations
Evidence A
2017 Global Initiative for Chronic Obstructive Lung Disease
Severe/Very Severe COPD:
Additions to Inhalers
Consider
1. PDE4 Inhibitor Roflumilast: Chronic bronchitis - is effective Evidence A
*Side effects result in significant drop out rate (GI, Headaches)
Cost $200/month
2. Macrolides for former smokers – is effective over one year Evidence A
Increased bacterial resistance and hearing loss.
•
Rogliani, P., Calzetta, L., Cazzola, M., & Matera, M. G. (2016)
Managing COPD Exacerbations
Oxygen: Goal for saturation 88% to 92%.
Bronchodilators: Short acting beta-agonists
with or with out anti-muscarinic preferred.
Systemic Corticosteroids: 40mgs daily for 5
days. Some authors up to 60mgs.
*2017 GOLD INITIATIVE FOR COPD
Hypoxemia and Oxygen

1. Hypoxemia
at rest: Long-term Oxygen (>15hours a day) indicated and prolongs life.
(Evidence Level A)

2. De-saturation with exercise or activity: Long term Oxygen NOT indicated. Will NOT
prolong life, increase the time to next hospitalization, improve performance on a 6 minute
walk. (Evidence Level A)

3. Resting oxygenation at sea level does not preclude the possibility of desaturation
during air travel. (Evidence Level C)
*GOLD Initiative for COPD 2017
Managing COPD Exacerbations:
When to add antibiotics
A. Patients with the three cardinal signs/symptoms:
1.
Increased dyspnea
2.
Increased sputum production
3.
Increased appearance of purulent sputum.
B. Patients who require mechanical ventilation.
*GOLD Initiative for COPD 2017
COPD vs ASTHMA vs ACOS
COPD
ASTHMA
ACOS
1. Onset in mid-life
1. Usually young at
diagnosis
1. Chest tightness present
2. Symptoms worsen
slowly but also
progressively
3. Usually associated
with smoking/2nd
hand smoke
2. Symptoms vary from day
to day
3. Symptoms worse at night
or early AM
4. Usually allergies also
present
5. Family history of asthma
2. Onset after age 40
3. History of smoking or
other exposures
4. ?History of asthma with
airway remodeling.
5. Exacerbations worse and
3 times more frequent.
*Pruitt, B. 2015
Asthma COPD Overlap Syndrome
ACOS

1. Not well understood

2. Could involve up to 25% of compromised respiratory patients

3. Identify symptoms and treat most common presenting symptoms


A. May be COPD dominant

B. May be Asthma dominant
4. Refer to Pulmonologist for diagnosis treatment guidelines.
Pruitt, B., 2015
Asthma: The Untold Story
• Estimated 300 million individuals are affect globally and its numbers are rising,
especially in children
• Huge economic and resource burden on the health care system
• Societal burden regarding loss of productivity
• The number of people diagnosed will increase by 100 million by 2025
• Deaths are estimated at 250,000 annually globally
American Academy of Allergy Asthma & Immunology, 2017
Types of Asthma
Allergic Asthma: most common, begins in childhood, sputum reveals eosinophilic
airway inflammation. These patients respond very well to ICS
Non-Allergic Asthma: found in adults, sputum reveals neutrophilic, eosinophic and
have few inflammatory cells. Respond less favorably to ICS
Late onset Asthma: adults, usually women. Require high doses of ICS
Asthma with fixed airflow limitation: Patients with long term asthma with airway wall
remodeling
Asthma with obesity: prominent symptoms but little eosinophilic airway inflammation
Asthma in Practice
Global Initiative for Asthma: GINA
Sets the bar in the treatment of asthma
2017 revised the approach in the treatment of asthma for adults and children
Making the Asthma Diagnosis
Confirm with:
Detailed history and examination:
• Patient has more than one respiratory symptom and are variable over time and in intensity.
• Symptoms are worse at night or upon waking.
• Symptoms can be triggered by exercise, laughing, allergens and/or cold air and worsen with
viral infections
Making the Asthma Diagnosis
• Spirometry: obtain baseline FEV1and FVC first. Then assess ratio FEV1:FVC
Adults: FEV1:FVC: NORMAL >0.75-0.80 Children: FEV1:FVC: NORMAL >0.90
• Positive bronchodilator reversibility test:
Adults and children : INCREASE in FEV1 of >12% and >200ml-400 ml from baseline
(greater confidence if >15% with a 400ml improvement from baseline)
• Excessive variability in PEF (peak expiratory flow) twice a day over a 2 week period
Adults: variability >10% Children: >13%
• Significant improvement in lung function after anti-inflammatory tx after 4 weeks
SPIROMETRY (PFTs) IS A MUST!!
Goals of Management
Keys to treatment:
•
•
•
•
•
Ensure asthma diagnosis
Monitor symptoms to achieve maximum control
Minimize future risk of air flow limitation
Minimize exacerbation events
Minimize treatment side effects
Treatment of Asthma
GINA Guidelines 2017
Step 1: SABA as indicated; some consideration to low dose ICS
Step 2: Low dose ICS with SABA as indicated; may consider LTRA and Low dose theophylline
Step 3: Medium/high dose ICS/LABA (not for children <12 years old); may consider low dose ICS with LTRA
or theophylline. Continue with as needed SABA or low dose ICS/formoterol (Reliever therapy). For
children referral to pulmonary specialist should begin.
Step 4: Medium/high dose ICS/LABA; may consider adding triotropium or just high dose ICS and LTRA or
theophylline. Continue with as needed SABA or low dose ICS/formoterol (Reliever therapy)
Step 5: May require referral to pulmonary specialist. Add on treatment options like triotropium, anti-Ig E or
anti-IL5, may add low dose OCS (oral corticosteroids). Continue with as needed SABA or low dose
ICS/formoterol (Reliever therapy)
SABA: Short Acting Beta Agonists:
RESCUE MEDICATION
STEP ONE:
• Evidence indicates that SABA are highly effective for quick relief of sx
• When solely using SABAs: For patients with occasional daytime sx less than 2x/month
•
ICS should be used for patients with more frequent sx or increase of exacerbation risks
ICS: Inhaled Corticosteroids
STEP TWO:
Low dose controller meds + prn reliever
ICS: Anti-inflammatory to reduce and prevent swelling and excess mucus in the airway caused
by inflammation.
• The use of ICS at low doses reduces asthma sx, increase lung fxn, reduces exacerbation risk
increases QOL, reduces asthma related hospitalizations and death
• LTRAs can be used for patients who do not want ICS therapy or can not tolerate ICS, but are
less effective (geared to children as young as 6 months old)
• Patients with purely seasonal allergic asthma, with no interval sx, ICS should begin immediately
with sx presentation for 4 weeks and then reassess
• SR Theophylline has only a weak efficacy in asthma and not for children <12 years
ICS: Inhaled Corticosteroids
ICS:
Aerobid® (flunisolide), Aerospan® (flunisolide), Alvesco®® (ciclesonide), Asmanex® (mometasone),
Flovent® (fluticasone), Pulmocort®(budesonide), Qvar® (beclomethasone)
LTRA: Leukotriene Receptor Antagonist
LTRAs work by blocking a chemical reaction that can lead to inflammation in
the airways
LTRAs can be used for patients who do not want ICS therapy or can not
tolerate ICS or increase in ICS, but are less effective (not first choice in
pharmacotherapy)
LTRAs are a class of oral medication that is non-steroidal
(AKA anti-inflammatory bronchoconstriction preventors)
Chewable tablet form with few side effects (N/V)
Examples of LTRAs include:
Singulair®(Montelukast), Accolate® (Zafirlukast)
LABA: Long Acting Beta Agonists
STEP THREE: One or two controllers + prn reliever meds
• Adults/adolescents combo low dose ICS/LABA for maintenance and prn
SABA
OR
• Combo low dose ICS(budesonide or beclomethasone) /formoterol as
maintenance and reliever (Dry powder inhaler or nebulizer)
(Children 6-11 years increase to medium ICS plus prn SABA)
• Used in conjunction with low dose inhaled corticosteroids to prevent
bronchospasm in patients with asthma as reliever medication
• When used regularly every day it decreases the number and severity of
asthma attacks and improves lung function, BUT will not relieve an
asthma attack that has already started when used alone
LABA: Long Acting Beta Agonists
LABAs: VoSpireER Extended-Release Tablets® (albuterol sulfate), Foradil
Aerolizer® (formoterol fumarate inhalation powder), Serevent Diskus®
(salmeterol xinafoate)
COMBINATION ICS/LABA: metered dose and dry powder inhaler
Advair Diskus and HFA®(fluticasone and salmeterol), Breo Ellipta ®
(fluticasone furoate and vilanterol), Dulera® (mometasone and
formoterol), Symbicort® (budesonide and formoterol),
Step 3: Additional considerations
• Assess patient for inhaler technique, exposures to
toxins/allergens, confirm sx are asthma related
• Pharmacotherapy options are age dependent as
are doses
LAMA: Long Acting Muscarinic
Antagonist (old term anticholenergics)
STEP FOUR: Two or more controllers + prn reliever meds
Contingent on how well Step 3 was effective
Adults/adolescence: Combination low ICS/formoterol as maintenance and reliever treatment (for
patients with >1 exacerbations in previous year. Can increase maintenance dose if needed
OR
Combo medium dose ICS/LABA + prn SABA( if asthma is not controlled on low dose ICS/LABA and
prn SABA)
Chldren 6-11 years: refer to expert assessment and advice
Adults/Adolescence: Add on: LAMAs (Triotropium) via mist inhaler for patients with a history of
exacerbation. NOT indicated for patients <12 years
Higher level care indications
STEP 5:
• When persistent sx’s or exacerbations occur despite good adherence and patient technique in Step 4
• Referral to a specialist and add on treatment (this should happen before this stage if indicated)
Types of add on therapies (if not already instituted):
• Triotropium (LAMA)
• Anti-immuoglobulin E (anti-IgE) for patients >6 years
• Anti-interleukin -5 (SQ) for patients >12 years with severe eosinophilic asthma
• Sputum guided treatment (has shown to reduce exacerbations and lower doses of ICS)
• Low dose oral corticosteroids (OCS):<7.5 mg/day may be effective but many side effects. Should only be
considered for poor sx control despite good adherence and proper technique with Step 4 tx (need to
consider osteo, cataracts,
Other considerations
Vitamin D
• Several studies have shown that low serum Vitamin D levels have been linked
with poor lung function
• Very common in children today
• No firm evidence that there is improvement in lung function with Vitamin D
• More studies are underway
Theophylline (Elixophyllin, Theo-24)
• Consider the interaction with other medications and side effects (seizures,
dysrhythmias, HF, HTN, liver dysfunction, PUD){can cause toxicity easily}
• If at this point, pulmonary expertise is indicated
Remember the cycle…...
Assess patient:
Refer to
specialists
Dx, Sx control/lung fxn, inhaler technique
Review Response:
Sx’s, exacerbations, side-effects,
patient satisfaction and lung function
Adjust treatment:
Pharm and non-pharm
strategies and treat
modifiable risk factors like
smoking, second hand
smoke, obesity and co
morbid conditions
CASE STUDY
54 y/o female ex-smoker 12 pack years presents with:
H/O asthma since infancy, allergy to mites, intolerance to NSAIDS and nasal polyps
CC: grade1 dyspnea, cough, wheezing and occasional rhinitis and breathy
OBJECTIVE FINDINGS:
• + obstructive disease with +bronchodilator reversibility test with post BD
FEV1 <80% and >12% and 400 ml from baseline (considered marked reversibility)
• sputum IgE 212 U/ml.
• The patient had one exacerbation treated as an outpatient in the previous
year.
• Fairly stable with ICSs/LABA every 12 hours and anti-leukotrienes (Step 2)
What is the diagnosis?
A. Asthma exacerbation
B. ACOS
C. COPD exacerbation
D. None of the above
ACOS: Asthma COPD Overlap
Syndrome
WHY!?
• Over 40 years of age
• Sx’s since childhood
• H/O asthma, allergies
• Sx’s are reduced but not fully with treatment
• High tx needs
• Eosinophils in the sputum
• C/O dyspnea
• Airflow limitation that is persistent
Treating ACOS
Pharmacotherapy:
ICS: low to moderate
LABA and/or LAMA in conjunction with ICS
May need to increase dosage of current treatment
Other considerations:
Evaluate adherence/technique/environmental situation
Re-evaluate patient in 4 weeks
CASE STUDY

68 y/o male reports to urgent care with an increase in shortness of breath
and phlegm production over past 48 hours. Dyspnea scale = 3, it had
been 1. Base line FEV1 = <56%. History of 50 pk/yr smoking, quit 6 months
ago... mucous is dark grey in color. T 99.3, P 110, R 22 BP 138/88 - O2 Sats
are 86%. Normal COPD medications include a LAMA, with a SABA rescue
inhaler. He has been using his SABA every hour or so he reports. This is
second urgent care visit this year, he was hospitalized 6 weeks ago.

Diagnosis:

GOLD Stage before exacerbation = A, B, C, D

Treatment:

Follow-up:
CASE STUDY

DIAGNOSIS: COPD exacerbation

GOLD Category: C to a D

Treatment: Oxygen, Antibiotics – 5 to7 days, Prednisone - Oral 5 days.

SABA/SAMA nebulizer

Possible admission.

FOLLOW UP: LABA/ICS and LAMA

Continue to evaluate
References
American Academy of Allergy Asthma & Immunology. (2017). Asthma statistics..
Retrieved from http://www.aaaai.org/about-aaaai/newsroom/asthma-statistics
Asthma Society of Canada. (2017). Treatment. Other medicines. Retrieved from http://
www.asthma.ca/adults/treatment/leukotriene.php
Global Initiative for Asthma. (2017). 2017 GINA report, global strategy for asthma
management and prevention. Retrieved from http://ginasthma.org/2017gina-report-global-strategy-for-asthma-management-and-prevention/
Global strategy for the diagnosis, management and prevention of COPD, Global Initiative for
Chronic Obstructive Lung Disease (GOLD) 2017. Retrieved from:
http://www.goldcopd.org/uploads/users/files/AsthmaCOPDOverlap.pdf
MedlinePlus. (2017). Formoterol oral inhalation. Retrieved from https://medlineplus.gov/
druginfo/meds/a602023.html#top
References
Panos, R. J. (2013). Efficacy and safety of eco-friendly inhalers: focus on
combination ipratropium bromide and albuterol in chronic obstructive
pulmonary disease. International Journal of Chronic Obstructive Pulmonary
Disease, 8, 221–230. http://doi.org/10.2147/COPD.S31246
Pruitt, B. (2015). Is it asthma, COPD or both? Respiratory Therapy, Retrieved from:
http://www.rtmagazine.com/2015/04/is-it-asthma-copd-or-both/
Rogliani, P., Calzetta, L., Cazzola, M., & Matera, M. G. (2016). Drug safety
evaluation of roflumilast for the treatment of COPD: a meta-analysis. Expert
opinion on drug safety, 15(8), 1133-1146.
Thorsson, L. (1998). Influence of inhaler systems on systemic availability. Journal of
Aerosol Medications (Supp 3), 829. Retrieved from:
https://media.lanecc.edu/users/driscolln/RT127/Softchalk/Pharmcology_SFTCHLK_
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