COPD Management Pearls:for Ambulatory and

Long Term Care Patients

Pamela L. Stamm, PharmD, CDE, BCPSAssociate Professor of Pharmacy Practice

Auburn UniversityJune 25, 2012

Where do you provide care?

a) Community pharmacy

b) Long term care pharmacy

c) Hospital

d) Academia

e) I am retired!!!!!!!

Objectives

1. Differentiate COPD from other respiratory diseases2. Outline an algorithm for chronic COPD treatment3. Compare and contrast tiotropium and ipratropium’s

safety and efficacy in COPD4. Describe the role of inhaled corticosteroids in COPD5. Assist patients in avoiding inhaler misuse6. Minimize the risk of adverse effects of COPD therapy7. Identify medications which could interfere with

respiration in the patient with COPD

OVERVIEW OF COPD

Basic Stats

• 24+ million in the US have COPD• 50% are undiagnosed

• 13% of all nursing home residents have COPD

• 40% chance will enter the nursing home

• 4th leading cause of death• >100,000 die annually from COPD

Which are COPD Risk Factors?

a) Smoking

b) Air pollution

c) Gender

d) History of childhood respiratory infections

e) Occupational dusts and chemicals

Which of the following persons have COPD?

Recognizing COPD / Hallmark Symptoms

Hallmark COPD Symptoms

• Dyspnea (progressive, persistent, worse w/ exercise)

• Cough (dry, productive, or intermittent)• Sputum production

Other patient characteristics:• Exposure to risk factors• Family History

Diagnosis

• Via spirometry: • Postbronchodilator only• Reduced FEV1:FVC ratio < .7

• Reversibility

OVERVIEW OF COPDTREATMENT GUIDELINES

Four Components of COPD Management

Four Components of COPD Management

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

4. Manage exacerbations

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

4. Manage exacerbations

How to reduce disease progression?

a) Smoking cessationb) Add albuterolc) Add antimuscarinicd) Pulmonary rehabilition

Data suggests Long Acting Bronchodilators and Inhaled Corticosteroids may reduce progression

Benefit of Cessation

• ASK Identify tobacco users at all visits.

• ADVISE Strongly urge users to quit.

• ASSESS Determine willingness to quit

• ASSIST Aid quitting

• ARRANGE Schedule follow-up contact.

Strategies to aid cessation

Cessation Therapy

• Comparing monotherapies

• Combined therapy vs monotherapy

• Extended therapy

Monotherapy vs. Placebo

Tønnesen P. Health Policy. 2009. 91; Suppl 1: S15-S25

Treatment OddsRatio

95% Confidence Interval

NRT (any form) 1.73 (1.62−1.85)

Bupropion SR 1.97 (1.67−2.34)

Varenicline 3.22 (2.43−4.27)

5

Table 2

Piper M. Archives of General Psychiatry. 2009;66(11):1253-1262.

7 Day Point Prevalence Abstinence Rates:Comparison of 5 cessation therapies

(Open Label, Intent-to-treat (ITT), n=1346)

16.8 17.719.9

26.929.9

Bup Patch Lozenge Patch + Bup + Lozenge* Patch*

5

Table 2

Smith S, et al. Archives of Internal Medicine. 2009; 169(22):2148-2155.

Comparison of 5 cessation therapies(Randomized, Double-Blind, Placebo Controlled, ITT, n=1504)

40.1

22.2

31.833.2 33.5 34.4

0

5

10

15

20

25

30

35

40

45

6 Month Point Prevalence Abstinence Rates

Placebo Bup Bup + Lozenge Patch Patch + Lozenge

Lozenge

Combining bupropion and varenicline?

% Abstinence at 6 months

7 day point prevalence (n=22)

58

Prolonged abstinence (n=20)

53

Ebbert JO, et al. Nicotine & Tobacco Research 2009 11(3):234-239.

Triple therapy vs Patch: 6 month Cessation Rates

Steinberg MB. Ann Intern Med. 2009;150:447-454.

Treatment Abstinence Odds Ratio (95% CI)

NRT Patch 12/64 (18.8)

2.33 (1.03–5.25)

NRT patch, inhaler, and bupropion

22/63 (34.9)

2.57 (1.05–6.32)

p = .04

Triple therapy vs Patch:Time to Relapse

Steinberg MB. Ann Intern Med. 2009;150:447-454.

Cessation Therapy

• Nicotine Replacement Therapy for 8 weeks

• Varenicline for 12 weeks

• Bupropion for 7-12 weeks plus 12 week extension

Should bupropion be extended?

Wk Placebo Bupropion P value

OnTreat-ment

5 69.3 84.8 .003

17 54 67.8 .003

29 47 57 .036

45 42.3 55.1 .008

Off 71 37.7 47.7 .034

97 40 41.6 > .05

Hays J.et al. Ann Int Med 2001; 135:423-33.

Should varenicline be extended?

Carbon monoxide confirmed continuous abstinence (%)

Week Varenicline extended (n=603)

Varenicline + Placebo 12

(n=607)

P- value

13 95.5 88.5

24 70.5 49.6 <.001

36 50.7 42.3

52 43.6 36.9 .02

Tonstad SS, et al. JAMA 2006;296(1): 64-70

Should NRT therapy be extended?

Scholl RA, et al. Ann Int Med 2010;152:144-51

Carbon monoxide confirmed point prevalence abstinence

Week NRT 8 wks NRT 24 wks P- value

8 95.5 88.5

24 70.5 49.6 <.001

52 50.7 42.3 .95

Which statement is true?

a) Pharmacotherapy doesn’t increase cessationb) Most data supports extended NRT treatment c) Cessation rates drop once treatment in

stoppedd) 6 month data suggests combining patch and

lozengee) Both C and D are true

Importance of Counseling in Cessation

Counseling by health professionals significantly increases quit rates

Brief (3-minute) counseling urging cessation results in 5-10% cessation

Pharmacotherapy is recommended when counseling is insufficient

Four Components of COPD Management

Four Components of COPD Management

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

4. Manage exacerbations

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD

4. Manage exacerbations

• Pharmacologic• Non-

pharmacologic• Education

STAGING and

BRONCHODILATOR THERAPY

IV: Very Severe

III: Severe II: Moderate

I: Mild

Therapy at Each Stage of COPD

Add one or more scheduled long-acting bronchodilators AND pulmonary rehabilitation

Add inhaled glucocorticosteroids if repeated exacerbations (3 or more / year)

Add oxygen if chronic respiratory failure. Consider surgical treatments

Reduce risk factor(s); influenza vaccination; pneumococcal vaccinationShort-acting bronchodilator (when needed)

FEV1 > 80% predicted

FEV1

<30% pred. or 50% and

respiratory failure

FEV1

50 to < 80% predicted

FEV1 30% to < 50%

predicted

GOLD Guidelines . 2011. http://www.goldcopd.org/

Approach to selecting therapy

• Step 1: Assess impact of symptoms

• Step 2: Assess risk of exacerbations

• Step 3: Combine results of steps 1 and 2

• Step 4: Select drug therapy

COPD Assessment Test (CAT): http://catestonline.org• 8-item measure of health status impairment in COPD

0-10 Low 10-20 Medium21-30 High31-40 Very High

Breathlessness Measurement using the Modified British Medical Research Council (mMRC) Questionnaire:

• Relates well to other measures of health status and predicts future mortality risk.

Step 1: Assess Symptoms

I never cough 0-5 I cough all the timeI have no phlegm (mucous) in my chest at all

0-5 My chest is completely full of phlegm (mucous)

My chest does not feel tight at all

0-5 My chest feels very tight

When I walk up a hill or one flight of stairs I am not breathless

0-5 When I walk up a hill or one flight of stairs I am very breathless

I am not limited doing any activities at home

0-5 I am very limited doing activities at home

I am confident leaving my home despite my lung condition

0-5 I am not at all confident leaving my home because of my lung condition

I sleep soundly 0-5 I don't sleep soundly because of my lung condition

I have lots of energy 0-5 I have no energy at all

Modified MRC (mMRC)Questionnaire

0 □ I only get breathless with strenuous exercise1 □ I get short of breath when hurrying on the

level or walking up a slight hill

2 □ I walk slower than people of the same age on the level because of breathlessness, or I have to stop for breath when walking on my own pace on the level

3 □ I stop for breath after walking 100 meters or after a few minutes on the level

4 □ I am too breathless to leave the house or I am breathless when dressing or undressing

Assess Symptoms Assess Risk of Exacerbations

Patient CAT mMRC Spirometric Classification

Exacerbations per year

Characteristic

A < 10 0-1 FEV1 > 50 0-1 Low Risk Less Symptoms

B ≥ 10 > 2 FEV1 > 50 0-1 Low RiskMore Symptoms

C < 10 0-1 FEV1 < 50 > 2 High Risk Less Symptoms

D ≥ 10 > 2 FEV1 < 50 > 2 High RiskMore Symptoms

Combined Assessment of COPD

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Pharmacologic Therapy

Patient Characteristics First choice Second choice

ALess Symptoms

Low Risk

PRN Short Acting

Single Long Actingor

Combination Short Acting

BMore Symptoms

Low RiskTiotropium,

Formoterol, or Salmeterol

Combination Long Acting

CLess Symptoms

High Risk

ICS + LABAor

TiotropiumCombination Long Acting

D More SymptomsHigh Risk

ICS + LABAor

Tiotropium

ICS and LAMA orICS + LABA and LAMA or

ICS+LABA and PDE4-inh. orLAMA and LABA or

LAMA and PDE4-inh.

Other Pharmacologic Treatments

Theophylline: option when expense is an issue

Antibiotics: for infectious exacerbations of COPD

Antioxidant agents: No effect of n-acetylcysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids

Mucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD

JA, a 58 yo male, c/o increasing SOB…

• Newly diagnosed COPD

• Reports he can walk a block on flat ground but gets SOB if he walks up a hill. He can keep up with his friends as long as the ground is flat.

• No h/o exacerbations

How would you classify this patient?

A B C D

What inhaler(s) is(are) recommended per the GOLD Guidelines?

a) PRN short acting agentb) Start salmeterol sched.c) Start ICS and salmeterol

sched.

• Diagnosed with COPD 4 years ago

• Takes albuterol / ipratropium as needed

• He can keep up with his friends as long as the ground is flat.

• 3 exacerbations over 12 months

How would you classify this patient? A B C D

What inhaler(s) is(are) recommended per the GOLD Guidelines?

a) Change to sched tiotropiumb) Change to sched salmeterolc) Change to sched ICS &

salmeterol

DS a 65 yo male with SOB

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Non-pharmacologic

Patient Essential Recommended Depending on local guidelines

ASmoking cessation (can include pharmacologic

treatment)Physical activity

Flu vaccinationPneumococcal

vaccination

B, C, DSmoking cessation (can include pharmacologic

treatment)Pulmonary rehabilitation

Physical activityFlu vaccinationPneumococcal

vaccination

When is Pneumococcal vaccination indicated for pts with COPD?

a) Pneumococcal if > 65yoa only

b) Pneumococcal if < 65 yoa and FEV1 <40%

c) Pneumococcal once before age 65 and once after age 65 w/ at least 5 yrs between

d) Pneumococcal in all and booster every 5 years

Pneumococcal Vaccine

• Should receive if– Smoker between ages of 19-64 years– COPD between ages of 19-64 years– At age 65 years as long as 5 years have occurred

since previous vaccination

• No more than 2 vaccinations recommended

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5934a3.htm#tab

Inhaler Safety

Safety of COPD Treatments

Study Comparison ResultsTORCHNEJM 2007; 356(8): 775-89.

LABA + ICS vsLABA vs ICS

↓ risk of death combo (adj)↓ risk of death vs ICS↔ risk of death vs LABA↑ risk of pneumonia w/ ICS

INSPIREAm J Resp Crit Care Med 2008;177:19-26.

LABA + ICS vs tiotropium

↓ mortality in LABA + ICS↑ risk of pneumonia w/ ICS

Lee TA, et alAnn Int Med 2008;149: 380-90.

Ipra, ICS, THP vs SABA

↓ risk of death w/ ICS↔ risk of death w/ THP, LABA↑ risk of death w/ ipra (CV)

Safety of COPD Treatments

Study Comparison ResultsSingh S, et alJAMA 2008:300:1439-50.

Meta-analysis of antichol trials

↔ risk of total death↑ risk of CV events w/ ipra, tio in long term trials↑ risk of CV events w/ ipra only in short term trials

Tashkin DP, et alNEJM 2008;359:143-54

RCT Tiotropium vs placebo

↔ risk of death, MI, or stroke

UPLIFTNEJM 2008; 359(15): 1543-54.

Tiotropium + usual care vs. usual care

↔ risk of death

INHALER TECHNIQUE……… again and again and again and a…

Importance of Education

For Pressurized MDIs, Plaza and colleagues • No education group 72% made errors• Education group 48% made errors

Verbal education is better than reading a patient package insert (PI)• Reading PI 89% made errors• Verbal instruction 48% made errors

Respiration 1998;65:195-8. Thorax 2000; 55 (Suppl 3):A61.

Importance of Education

• Knowledge of technique does not guarantee ability (make them show you)

• Ability varies by day

• Pediatrician study showed 26% (10 of 38 ) demonstrated all steps correctly

Ann Allergy Immunol. 1996; 76 (2): 145-148(4)

How Do Pharmacists Fare?

CHEST 1993 ; 104( 6): 1737-1742

Why is Good Technique So Difficult?

• Frequency of errors increases with age and COPD severity

• Patients don’t think it through especially when feeling symptoms

• Cannot inhale forcefully enough due to disease

• Multiple devices with different techniques• It works for them…or so they think

Select the appropriate inhaler for the following steps

pMDI DPI Both

• Shake the inhaler• Prime the inhaler• Remove the cap• Inhale fast and deeply• Hold breath up to 10 seconds (4-10)• Exhale through mouth• Rinse and spit• Clean once weekly by running under water

pMDI DPI

• Shake the inhaler (5 sec)• Remove the cap / inspect

opening• Prime the inhaler (see PI)• Exhale slowly• Open/ closed mouth technique• Inhale slowly and deeply• Hold breath up to 10 seconds

(4-10)• Exhale through mouth• Wait 1 minute between doses• Rinse and spit• Clean once weekly by running

opening under water

• Remove cap (if applicable)

• Activate dose & hold correctly• Exhale slowly• Closed mouth technique only• Inhale fast and deep• Hold breath up to 10 seconds

(4-10)• Exhale through mouth• Wait 1 minute between doses• Rinse and spit• Wipe mouthpiece weekly with

dry tissue

Identifying the Crucial Errors

• Failure to remove cap / cover

• Failure to load dose / prime correctly

• Inhaler held incorrectly (upside down, not level)

• Coordination of inhalation and actuation

• Open mouth technique w/ chamber or DPI

• Inhalation at wrong speed

• Inhalation through nose

What’s wrong with this picture?

Lynn Age 46

• Watch video• Watch for symptoms of COPD• Watch inhaler technique. How does she do?

http://www.youtube.com/watch?v=bt6EC-57sbw

Selecting the Best Inhaler

• Patient dependent, patient preference

• Attempt to select similar inhalers (all DPIs or all pMDIs)

• Provide reminders on device

• Observe patient’s technique

Selecting the Best Inhaler (n=53)

PIF(L/min)

Mild Moderate Severe

Flexhaler(budesonide)

60 54 ± 15 27 ± 6 18

DiskusFluticasone/salm

30 72 ± 17 44 ± 10 37

pMDI 25 107 ± 20 78 ± 22 80

Jarvis S. Age and Ageing 2007;Jan: 1-6

Selecting the Best Inhaler• 2tone • Vitalograph AIM • In-Check Dial

Lavorini F. Primary Care Resp J. 2010; 19: 335-341.http://www.2tonetrainer.net

http://www.clement-clarke.com/products/in-check-dial

http://www.vitalograph.com

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JA, a 58 yo male, c/o increasing SOB…

Recently saw PCP who switched his Oxycodone to an equivalent dose of MS Contin. PMH: COPD, DM, HTN, MI, and Chronic Pain.

Current medications: • glipizide 10mg BID • morphine sulfate SR 30mg Q8 hr• metformin 1000mg BID • morphine sulfate IR 15mg • ramipril 10 mg Qday PRN breakthrough pain• HCTZ 12.5 mg Qday • ASA 81 mg Qday• atenolol 50mg Qday

Which medication(s) could be contributing?

a) Metformin

b) Morphine sulfate

c) Atenolol

d) ASA

Medications that Impair Breathing

• Opioid Agonists• Reduce respiratory drive when in excess• Can reduce dyspnea wo/ significant respiratory

depression • Avoid excessive doses• Monitor for signs of overdose

Medications that Impair Breathing

Beta Antagonists• B1 and B2 receptors in lungs• B2 receptors comprise majority of receptors and

are the only receptors on airway and vascular smooth muscle

• B1 receptors comprise 10-30% at other lung locations

• Theory: antagonism can reduce lung function• Theory: nonselective > selective

Beta Antagonists the Evidence

• FEV1 remains unchanged in patients on BB• Bronchodilator use no different from controls• No difference in ED visits or hospitalizations• Morbidity & mortality benefits in pts w/ cardiac

disease & possibly in those wo/• Should be maintained during acute exacerbations• Reduce mortality in patients w/ concomitant

HTN, & postMIDransfield MT, et al. Thorax 2008; 63:301-305.

Barnett MJ, et al. Pharmacotherapy 2005; 25(11): 1550.Brooks TWA, et al. Pharmacotherapy 2007;27(5): 684-690.

Which are compelling indications for BB use?

a) Migraine prophylaxis

b) HTN

c) Coronary artery disease

d) Heart Failure

e) Post-MI

Paradigm Shift Needed

Beta antagonist use in presence of compelling indications

Without Asthma or COPD

With Asthma or COPD

Heart Failure 85 37

HTN 43 39

MI 55 37

Summary

• Smoking Cessation is key!

• LABA are ok monotherapy in COPD

• Tiotropium appears safe, ipratropium unclear

• Pt specific inhaler selection and repeated education is essential

• Do not avoid Beta Antagonists or opioids just because your patient has COPD