Chronic Obstructive

Pulmonary Disease

Angela S. Stewart, Pharm.D., BCPS

Contact Information

WSU College of Pharmacy

Yakima Extension
509-249-7920
stewas@wsu.edu
Objectives

Understand COPD pathophysiology and

risk factors
Describe the role of spirometry
Compare COPD & asthma treatment
Develop a maintenance regimen for
COPD
Recommend drug therapy for an
exacerbation of COPD
References

www.goldcopd.com 2016 Update

preferred
www.acponline.org ACP 2011
guideline
www.thoracic.org nice online tools

COPD Chapter in Pharmacotherapy text

Outline
Background
Diagnosis and Assessment
Risk Factor Reduction
Stable COPD
Acute Exacerbation of COPD
Case Studies
COPD Definition

A common, preventable, treatable disease

Persistent, progressive airflow limitation

Enhanced chronic inflammatory response

Exacerbations and comorbidities

contribute to severity
Previous Classification

Emphysema Chronic Bronchitis

Pink Puffers Blue Bloaters
Destruction of Chronic, excess
distal air spaces sputum production
Mechanism Mechanism
Inflammation and
Protease activity infection
Loss of elasticity Cell hypertrophy
Loss of capillaries Cartilage atrophy
Global Strategy for Diagnosis, Management and Prevention
of COPD

Risk Factors for COPD

Genes

Infections

Socio-economic
status

Aging Populations
2014 Global Initiative for Chronic Obstructive Lung Disease
 Pathogenesis of
Cigarette smoke COPD
Biomass particles
Particulates
Host factors
Amplifying mechanisms

LUNG INFLAMMATION
Anti-oxidants Anti-proteinases

Oxidative
stress Proteinases

Repair
mechanisms

COPD PATHOLOGY
Source: Peter J. Barnes,
 Global Strategy for Diagnosis, Management and Prevention
of COPD

Mechanisms Underlying Airflow

Limitation in COPD
Small Airways Disease Parenchymal
Airway inflammation Destruction
Airway fibrosis, luminal Loss of alveolar
plugs attachments
Increased airway resistance Decrease of elastic recoil

AIRFLOW LIMITATION
2014 Global Initiative for Chronic Obstructive Lung Disease
Other Physiologic Abnormalities

Mucous hypersection
Gas exchange abnormalities
Pulmonary hypertension
Systemic effects
Exacerbations
Epidemiology

12 million Americans
Prevalence from 4-9%
3rd cause of death, rate increasing
Frequent hospitalizations, phyisican
and emergency visits
Huge economic impact
80-90% from smoking
 Of the six
leading
causes of
death in the
United
States, only
COPD has
been
increasing
steadily since
Source: Jemal A. et al. JAMA
 COPD

Manage Stable COPD: Goals of

Therapy

Relieve symptoms
Improve exercise tolerance Reduce
symptoms
Improve health status

Prevent disease progression

Reduce
Prevent and treat exacerbations
risk
Reduce mortality
2014 Global Initiative for Chronic Obstructive Lung Disease
 Four Components of COPD
Management
1. Diagnosis and Assessment of Disease

2. Reduce risk factors

3. Manage stable COPD

Education
Pharmacologic
Non-pharmacologic

4. Manage exacerbations
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Diagnosis of COPD
EXPOSURE TO RISK
SYMPTOMS FACTORS
shortness of breath
tobacco
chronic cough occupation
sputum indoor/outdoor pollution

SPIROMETRY: Required to establish

diagnosis
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Symptoms of COPD
The characteristic symptoms of COPD are chronic
and progressive dyspnea, cough, and sputum
production that can be variable from day-to-day.

Dyspnea: Progressive, persistent and

characteristically worse with exercise.

Chronic cough: May be intermittent and may be

unproductive.

Chronic sputum production: COPD patients

commonly cough up sputum.
2014 Global Initiative for Chronic Obstructive Lung Disease
Additional Assessments

Detailed Medical History

Exposures
Other lung disease
Family history
Physical Exam
Signs/symptoms lung disease
Spirometry

FEV1
FEV1/FVC ratio
Impaired gas exchange
Not fully reversible
Spirometry: Normal and
Patients with COPD
 Global Strategy for Diagnosis, Management and Prevention
of COPD

Classification of Severity of
Airflow Limitation in COPD*
In patients with FEV1/FVC < 0.70:

GOLD 1: Mild FEV1 > 80% predicted

GOLD 2: Moderate 50% < FEV1 < 80%

predicted

GOLD 3: Severe 30% < FEV1 < 50%

predicted
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of COPD
Assess symptoms
Assess degree of airflow
limitation using spirometry
Assess risk of exacerbations

Assess comorbidities
2014 Global Initiative for Chronic Obstructive Lung Disease
 Assessment of Symptoms

COPD Assessment Test (CAT): An 8-item

measure of health status impairment in
COPD
(http://catestonline.org).

Breathlessness Measurement using the

Modified British Medical Research
Council (mMRC) Questionnaire: relates
well to other measures of health status
 Combined
Assessment of
When assessing risk, choose the highest
COPD
risk according to GOLD grade or
exacerbation history

Patien Characteristic Spirometric Exacerbation mMRC CAT

tC Classificatio s per year
n
Low Risk
A GOLD 1-2 1 0-1 < 10
Less Symptoms
Low Risk
B GOLD 1-2 1 >2 10
More Symptoms
High Risk
C GOLD 3-4 >2 0-1 < 10
Less Symptoms
High Risk 10
D GOLD 3-4 >2 >2
More Symptoms
Risk Factor Reduction

Smoking Cessation
Minimize Occupational Exposures
Address Indoor & Outdoor Air
Pollution
Immunizations
Influenza vaccine
Pneumococcal vaccine
COPD vs Asthma

Often difficult to distinguish

Symptoms & Airflow limitation
Response to beta-agonists
Response to anti-cholinergics
Response to inhaled steroids
Ability to scale back therapy
 ASTHMA COPD
Allergens Cigarette smoke

Y Y
Y

Ep cells Mast cell Alv macrophage Ep cells

CD4+ cell Eosinophil CD8+ cell Neutrophil

(Th2) (Tc1)

Bronchoconstriction Small airway narrowing

AHR Alveolar destruction

Reversible Airflow Limitation Irreversible

Source: Peter J. Barnes,

Pharmacology Pearls

Medications are effective, use them if

symptomatic
Improve symptoms, decrease
exacerbations, improve QOL
Little effect on disease progression
Inhaled route is preferred
Adherence is good
Teaching on inhaler technique
important
Bronchodilator Therapy

Central to Symptom Management

Inhaled Route Preferred
Choice of Therapy is Individualized
PRN versus Scheduled Treatments
Long Acting versus Short Acting
Combination Therapy
Anticholinergic Agents

MOA: smooth muscle relaxation

Safe & well tolerated
Place in therapy
Ipratropium
Quaternary amine
MDI or nebulizer
Duration 4-6 hours
Tiotropium
Dry powder inhaler & soft mist inhaler
Duration 24 hours once daily dosing
Clinical outcomes First Line
Improves symptoms & health status
Reduces exacerbations & hospitalizations
Does not affect disease progression
?? Increased cardiovascular events & death
Several new options see handout
Short-acting Beta-agonists

MOA - bronchodilators
Available agents
Most common is albuterol
No benefit of levalbuterol
Place in therapy
As needed for intermittent symptoms
Mainstay of exacerbation treatment
Long-acting Beta-agonists

MOA bronchodilator
Available agents
Salmeterol, formoterol
Several other new options see handout
Improve symptoms, QOL, exacerbations
Well tolerated
Alternative to long-acting anticholinergic
Combination Bronchodilators

Benefits increased response, fewer

adverse effects
Short Acting
Ipratropium + albuterol
New Long Acting Options
Umeclidinium + vilanterol
Tiotropium + oladaterol
Glycopyrrolate + indacaterol
Theophylline

Place in therapy - controversial

Less effective than inhaled therapy
Risks may outweigh benefits
2nd or 3rd line
Mechanism of action- unknown
Dosing and Administration
Use long acting forms - 300-900 mg daily
Theophylline interactions

Increased clearance
Smoking
Phenytoin
Rifampin
Decreased clearance
Macrolides, quinolones, beta-blockers, CCBs
Heart failure, respiratory failure, liver
disease
Inhaled Corticosteroids

Demonstrated Benefits
Decrease symptoms, exacerbations
Improve function and quality of life
Do not alter progression
Indications
Severe disease, frequent exacerbations
Adverse Effects
Increased fracture risk, pneumonia, others
Increased exacerbation with withdrawal
Combined Steroid + LABA

Place in therapy
May improve adherence if steroid
indicated
More effective than individual agents
alone
Increase risk of pneumonia
Inconclusive data on mortality
Systemic Corticosteroids

Indications in maintenance therapy

Avoid if possible
No evidence of long-term benefit
Adverse Effects serious toxicities
Dosing & Administration
Lowest effective dose
AM, once daily administration
Roflumilast (Daliresp)

Mechanism of Action PD4 inhibitor

Clinical effects
Small decrease in rate of exacerbation
Adverse effects
Nausea, vomiting, weight loss
CNS, psychiatric
Other Drug Therapies

Oral N-acetylcysteine
Cough suppressants avoid
Beta-blockers OK if indicated
Prophylactic antibiotics
 Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: Pharmacologic
Therapy
RECOMMENDED FIRST CHOICE
C D
GOLD 4 ICS +

Exacerbations per year

ICS + LABA 2 or more
LABA or
and/or >1
LAMA
GOLD 3 LAMA leading
to
hospital
A B
GOLD 2 SAMA prn admission
LABA
or or
GOLD 1 SABA prn LAMA 1 (not
0
leading
to
CAT < 10 CAT > 10 hospital
mMRC 0-1 mMRC > 2
2014 Global Initiative for Chronic Obstructive Lung Disease admission)
 Global Strategy for Diagnosis, Management and Prevention of
COPD
Manage Stable COPD: Pharmacologic
Therapy
(Medications in each box are mentioned in alphabetical order, and
therefore not necessarily in order of preference.)
Patient Recommended Alternative choice Other Possible
First choice Treatments
LAMA
SAMA prn or
A or LABA Theophylline
SABA prn or
SABA and SAMA

LAMA
SABA and/or SAMA
B or LAMA and LABA
Theophylline
LABA

ICS + LABA LAMA and LABA or

or LAMA and PDE4-inh. or SABA and/or SAMA
C
LAMA LABA and PDE4-inh. Theophylline

ICS + LABA ICS + LABA and LAMA or

Carbocysteine
and/or ICS+LABA and PDE4-inh. or
D SABA and/or SAMA
LAMA LAMA and LABA or
Theophylline
LAMA and PDE4-inh.
Additional Treatments

Pulmonary Rehabilitation
PT and OT
Oxygen to keep O2 saturation > 90%
Non-invasive positive pressure
ventilation
Surgery and Transplant
Palliative Care when indicated
Acute Exacerbation

Definition and causes

Treatment
Oxygen & ventilator support -
cornerstone
Bronchodilators
Corticosteroids
Antibiotics
Additional Measures
Maximize Inhaled Therapy

Albuterol
2.5-10 mg every 20 min x 3 then every
1-4 hours as needed by nebulizer
Ipratropium
0.5 mg every 6 hours by nebulizer
Inhaled vs nebulizer
Role of LABA
Steroid Therapy in Exacerbation

Moderate Benefit
Improve patient outcomes: recovery time,
lung function, relapse
Monitor for adverse effects
Hyperglycemia, worsening HF
Dosing & Administration
40 mg prednisone daily for 5 days
Emerging role for inhaled steroids
Antibiotic Therapy

Indications still controversial

Dyspnea, sputum volume, sputum purulence
ICU, Mechanical ventilation
Appropriate agents
Amoxicillin/clavulanic acid or ampicillin/sulbactam
Azithromycin
Doxycycline
May need to consider resistant organisms
Duration 5-10 days
Other Interventions

Provide VTE prophylaxis

Heparin 5000 units SQ every 8 hours
Enoxaparin 40 mg SQ daily
Fondaparinux 2.5 mg SQ daily
Maximize therapy for comorbid
conditions
IV fluids, diuretics, nutrition support
Know patients end of life wishes
 Consequences Of COPD Exacerbations

Negative Impact on
impact on symptoms
quality of life and lung
function

EXACERBATIONS
Accelerated Increased
lung function economic
decline costs
Increased
Mortality

2014 Global Initiative for Chronic Obstructive Lung Disease

COPD Complications

Cor Pulmonale
Secondary polycythemia
Respiratory failure
CO2 narcosis
Pulmonary Hypertension in
COPD
Chronic hypoxia

Pulmonary vasoconstriction
Muscularization
Intimal
Pulmonary hypertension hyperplasia
Fibrosis
Cor pulmonale Obliteration

Edema
Death
Source: Peter J. Barnes,
MD