By/

Dr. Wadia Alruqayb, PharmD, MSc, PhD

Dr. Ola Nafea, M.D., P.h.D
 Age of onset Usually, <4o years

Smoking history Uncommon

Sputum production Uncommon

Allergies Common

Symptoms Intemittent and variable

Disease process Stable,does not worsen

overtime

Exacerbations A common complication

Inhaled
First-line treatment
corticosteroids
Learning Objectives
By the end of the lecture the student should be able to:
• Recognize the etiology and pathophysiology of COPD.
• Describe the clinical presentation, diagnosis and
assessment of COPD.
• List treatment goals of COPD.
• Design a therapeutic plan for treatment for COPD and
acute exacerbations.
• Recognize the key differences between asthma and
COPD.
 Overview

v Chronic obstructive pulmonary disease (COPD) is the third leading cause of death

worldwide, causing 3.23 million deaths in 2019.

v COPD is not curable but symptoms can improve if one avoids smoking and

exposure to air pollution and gets vaccines to prevent infections.

v Global prevalence was 10.3% in 2015 and expected 600 million in 2050.

v It can also be treated with medicines, oxygen and pulmonary rehabilitation

v Medical cost: 24 billion (US, 2020), 6% of health budget (Europe, 2021), a\nd
 DEFINTION
●Chronic obstructive pulmonary disease (COPD) is a common lung disease
characterized by airflow limitation that is not fully reversible. COPD is both chronic
and progressive and is associated with an abnormal inflammatory response of the

lungs to noxious particles or gases.

• Some patients present with structural lesions (emphysema) and/or physiological
abnormalities (e.g., low or normal FEV1) without airflow obstruction (FEV1/FVC ≥

0.7 post-bronchodilation). These patients are called “Pre-COPD”

* COPD is preventable and treatable and causes significant extrapulmonary effects

that contribute to disease severity in some patients.
 EITOLOGY
Risk Factors

● Cigarette smoking is the most common risk factor and accounts for

most cases of COPD (95%).

● Other factors:

Ø Exposure to tobacco smoke, occupational dust, chemicals, and

air pollution, Low birth weight, recurrent lung infections

Ø Genetic: e.g., α1-antitrypsin (AAT) deficiency.

 EITOLOGY
● α1-antitrypsin (AAT):
q It protects the lung from damage by elastase enzyme which is
released by the neutrophils.
q AAT Deficiency (AATD):
o Elastase is uninhibited.
o Destroy lung matrix and alveolar structures
o Accelerated decline in lung function.
q Patients developing COPD at an early age or those with a strong
family history of COPD should be screened for AAT deficiency.
(Treatment: Augmentation therapy: weekly pooled human AAT
transfusion).
COPD pathophysiology
 PATHOPHYSIOLOGY
● Inflammation:
Exposure to noxious gas and particles ➝ chronic inflammatory
changes (neutrophilic) involving airways, pulmonary vasculature, and
lung parenchyma (alveoli and pulmonary capillaries) ➝ destructive
tissue changes and chronic airflow limitation.
● Oxidative stress:
Oxidants ➝ tissue damage. Oxidants promote inflammation directly
and exacerbate the protease–antiprotease imbalance by inhibiting
antiprotease activity.
 CLINICAL PRESENTAION
● Symptoms

• Chronic cough—may be intermittent; may be unproductive

• Chronic sputum production
• Dyspnea—worse with exercise; progressive over time

● Signs

• Shallow breathing (Drawing small amounts of air into your lungs, not
using their full capacity)
• Increased resting respiratory rate (N=12 to 18 B/M).
• Use of accessory respiratory muscles (neck, back, & abdomen).
• Cyanosis of mucosal membranes (seen in later stages of disease).
 DIAGNOSTIC TESTS
Pulmonary function tests (Spirometry) is performed to:

1. Diagnosis (Measure post bronchodilator spirometry to confirm the

diagnosis).

2. Assessment of severity of airflow obstruction.

3. Follow up assessment (monitor progression).

• Therapeutic decision.

• Identification of rapid decline.

 DIAGNOSTIC TESTS
● Pulmonary function tests (Spirometry):
to determine disease severity:
Ø The post-bronchodilator FEV1 determines disease severity ➝ The
GOLD guidelines (Global Initiative for Chronic Obstructive Lung
Disease)
Ø Patients with all levels of severity of COPD exhibit the hallmark
finding of airflow obstruction; specifically, a reduction in FEV1/FVC
ratio to less than 70% (0.70).
Ø A postbronchodilator FEV1/FVC < 70% (0.70) confirms a
diagnosis of COPD.
 THE COPD ASSESSMENT TEST (CAT)

CAT is a questionnaire for people with COPD. It is designed to measure the impact of
COPD on a person's life, and how this changes over time.
 Severity of Post-Bronchodilator Airflow Limitation

In patients with FEV1/FVC <70% (0.70)

GRADE SEVERITY FEV1 (% predicted)

GOLD 1 Mild ≥ 80

GOLD 2 Moderate 50-79

GOLD 3 Severe 30-49

GOLD 4 Very severe <30

FEV1 is the total volume of air exhaled in 1 second. FVC is the total volume of air exhaled
after maximal inhalation.
 mMRC (MODIFIED MEDICAL RESEARCH COUNCIL) DYSPNEA
SCALE

GRADE SEVERITY

0 Dyspnea only with strenuous exercise

1 Dyspnea when hurrying or walking up a slight hill

2 Walks slower than people of the same age because of dyspnea or has to stop
for breath when walking at own pace

3 Stops for breath after walking 100 yards (91 m) or after a few minutes

4 Too dyspneic to leave house or breathless when dressing

Score of <2 means less symptoms

Score of ≥2 means more symptoms
! ! COMBINED ASSESSMENT OF COPD SEVERITY
(GOLD RISK GROUP) ! !

Patient Exacerbations in
Description CAT mMRC
Group Last Year

A Less symptoms; low risk 0-1 <10 0-1

B More symptoms; low risk 0-1 ≥10 ≥2

C Less symptoms; high risk ≥2 <10 0-1

D More symptoms; high risk ≥2 ≥10 ≥2

a. Less severe (low risk): 0 or 1 exacerbation (not leading to hospital admission)

b. More severe (high risk): 2 or greater or 1 or greater leading to hospital admission
 TREATMENT: GOALS
• Relieving Symptoms
• Improve Exercise Tolerance
• Improve overall Health Status
Reduce
Symptoms

AND

• Prevent disease progression

• Prevent and treat exacerbations Reduce
• Prevent and treat complications Risk
• Reduce morbidity and mortality
 Treatment options for
COPD
A. Non-
B. Pharmacological
Pharmacological

Smoking
Anti-
cessation
Vaccination LTOT Surgery
Bronchodil inflammatory Antimicrobial
ator agents
 NONPHARMACOLOGICAL TREATMENT

1. Smoking cessation

2. Vaccinations

3. Long-Term Oxygen Therapy

4. Surgery
 NONPHARMACOLOGICAL TREATMENT
1. Smoking cessation
v Since a significant proportion of people with COPD continue to smoke despite
knowing they have the disease, Smoking cessation represents the single most
important intervention in preventing the development, as well as progression, of
COPD.
v It was found that smoking cessation improved QoL and lung function and lower the
risk of motality.1,2

2. Treatment options:
A. Nicotine replacement therapy.
B. Varenicline.
C. bupropion (antidepressant).
1. Smoking cessation
 NONPHARMACOLOGICAL TREATMENT
2. Vaccinations
● Vaccinations reduce the risk of respiratory infections, hospitalizations due to serious
respiratory illness and the risk of mortality.
For Example:
• Annual influenza vaccine,
• COVID-19,
• Pneumococcal vaccinations
• Tdap [tetanus, diphtheria, and whooping cough (pertussis)] if not received as
part of childhood vaccinations.
 NONPHARMACOLOGICAL TREATMENT
3. Long-Term Oxygen Therapy; after optimization of pharmacotherapy.
• LTOT increases survival and improves the quality of life.
• Approximately 1.5 million patients in the United States receive LTOT.
• It is indicated for stable patients who have (GOLD, 2023):
Ø PaO2 at or below 55 mmHg or SaO2 at or below 88%, with or without
hypercapnia (↑CO2) confirmed twice over a three-week period; or
Ø PaO2 between 55 mmHg and 60 mmHg, or SaO2 of 88%, if there is evidence
of pulmonary hypertension, peripheral edema suggesting congestive cardiac
failure, or polycythemia (hematocrit > 55%).
• Re-evaluation 60 to 90 days with repeat arterial blood gas (ABG) or oxygen
saturation measurements to decide oxygen is still indicated or not.
 NONPHARMACOLOGICAL TREATMENT
4. Surgery
Only small number of COPD patients will benefit from surgery

bullectomy lung volume reduction surgery lung transplantation

• A surgical procedure that
can remove giant bullae
which occupy greater than
one third of the right or left
chest.
(LVRS)
• Remove the upper portion of
both lungs.
• Sometimes removes some good
air sacs as well.
• Replaces one or both of your
lungs with a lung or lungs from
an organ donor
• Best who have no other major
health problems, and have
such severe lung disease that
the benefits of surgery
outweigh the risks
 COPD treatment

COPD

Stable Unstable

Symptoms are well Experiencing frequent

managed and or severe exacerbations
pulmonary decline is and a faster decline in
minimized. pulmonary function
 ! ! PHARMACOLOGICAL TREATMENT: Stable COPD ! !
Patient
Symptoms and Exacerbations Recommended Recommended
Group First Choice Treatment Intensification

A Continue, discontinue, or
Few symptoms (CAT score < 10) Bronchodilator try alternative class of
No hospitalizations (short- or long-acting) bronchodilator
< 1 exacerbation in the past year

B
Many symptoms (CAT score ≥ 10) LAMA + LABA
No hospitalizations LABA or LAMA
< 1 exacerbation in the past year

C LAMA + LABA
Few symptoms (CAT score < 10) or
≥ 1 COPD-related hospitalization or LAMA (LABA + ICS if eosinophils
≥ 2 exacerbations in the past year ≥ 300 cells/mcL)

D (LAMA + LABA + ICS if

LAMA eosinophils ≥ 100
or cells/mcL)
Many symptoms (CAT score ≥ 10) (LAMA + LABA if highly or
≥ 1 COPD-related hospitalization or symptomatic CAT > 20) (add roflumilast if
≥ 2 exacerbations in the past year or eosinophils < 100
(LABA + ICS if eosinophils > cells/mcL) ± azithromycin
300 cells/mcL) (if eosinophils < 100
cells/mcL and former
smoker)

Single inhaler à more convenient and improve adherence.

 PHARMACOLOGICAL TREATMENT: KEY POINTS
1. Inhaled medications
• Choice of inhaler device should be individualized for optimal efficacy, access,
cost, patient preference, and ability to properly use.
• Assessment of inhaler technique and adherence prior to therapy modification.
2. Bronchodilators
• Bronchodilators are first-line for all diagnosed with COPD.
• Inhaled bronchodilators are recommended over oral bronchodilators.
•Long-acting agents (LABA, LAMA) are preferred over short-acting (SABA, SAMA),
EXCEPT in those with only occasional dyspnea and when immediate relief is
needed in those on long-acting maintenance therapy
• Combination of [LAMA + LABA] is preferred when starting treatment with long-
acting bronchodilators; patients not controlled on a single long-acting
bronchodilator should be escalated to dual (more effective).
• Combination of [SABA + SAMA] is more effective than either alone.
• LAMAs provide greater exacerbation risk reduction than LABAs.
•Theophylline is not recommended unless other bronchodilators are either
unavailable or unaffordable for long-term treatment.
PHARMACOLOGICAL TREATMENT: KEY POINTS (CONTINUE)
3. Anti-inflammatory agents
•Long-term monotherapy with ICS/oral steroids is not
recommended; low efficacy, increases risk for side effects (e.g.,
pneumonia)
•ICS improves symptoms and reduces exacerbations in those with
signs of inflammation [INDICATIONS; e.g., comorbid asthma, blood
eosinophilia ≥300 (a marker of inflammation) or present with an
exacerbation history].
•Addition of PDE4 inhibitor (Roflumilast→ reduce lung inflammation)
to [LABA + LAMA (±ICS)] may be considered in those with severe to
very severe airflow limitation, chronic bronchitis, and exacerbations.
•In those with exacerbations despite appropriate therapy: macrolides
(azithromycin) may be considered
• Roflumilast and azithromycin, which are used in only the most severe
cases.
AECOPD: ACUTE EXACERBATIONS OF COPD
● Definition: an event characterized by dyspnea and/or cough and sputum that
worsen over < 14 days, which may be accompanied by tachypnea and/or
tachycardia.
● Cause: COPD exacerbations can be caused by respiratory tract infections (viral
or bacterial), increased air pollution or unknown factors.

● Classification:
Treatment
Dyspnea RR HR SaO2 CRP
Recommendation
≥ 92
Mild VAS < 5 <24 < 95 < 10 SABD only
(≤ 3% if known)
SABDs &oral
≥ < 92
Moderate VAS ≥ 5 ≥ 24 ≥ 10 corticosteroid ±
95 (≥ 3% if known)
Antibiotics
< 92
(≥ 3% if known) +
VAS ≥ 5 ≥ Hospitalization and
Severe ≥ 24 Hypercapnia and ≥ 10
95 emergency room visit
acidosis (PaCO2 > 45/
PH<7.35)
Visual analogue scale A visual analogue scale (VAS) or a category-
ratio scale may be used to assess dyspnea
AECOPD: ACUTE EXACERBATIONS OF COPD
● Treatment:
1. Goal: to minimize the negative impact of the current exacerbation and to prevent
subsequent events (e.g., acute reparatory failure).
2. Intensification of short-acting bronchodilators (a SABA, with or without a SAMA)
(no difference in route) PLUS initiation of systemic corticosteroids (oral/ IV).
3. Antimicrobials (for 5 -10 days) are indicated if :
ü All three of the following cardinal symptoms are present (↑ ↑ purulent
sputum, ↑ ↑ sputum production , ↑ ↑ dyspnea)
ü ↑ ↑ purulent sputum PLUS one of the cardinal symptoms
ü A need for mechanical ventilation regardless of symptoms present
4. Non-invasive mechanical ventilation à with acute reparatory failure (rapid
breathing, fast HR, coughing blood…).
5. Recovery time varies, taking up to 4-5 weeks.
 Pulmonary Rehabilitation

It is defined as “a comprehensive intervention based on thorough patient assessment

followed by patient-tailored therapies that include, but are not limited to, exercise
training, education, self-management intervention aiming at behavior change,
designed to improve the physical and psychological condition of people with chronic
respiratory disease and to promote the long-term adherence to health-enhancing
behaviors.”
 Pulmonary Rehabilitation
Goals:
• Increase exercise tolerance and reduce dyspnea.
• Increase muscle strength and endurance.
• Improve health related quality of life.
• Increase independence in daily functioning.
• Increase knowledge of lung condition and promote self management.
• Promote long term commitment to exercise.
Benefits:
• Decrease hospitalization , and respiratory (breathlessness) and psychological
(depression) symptoms.
• Increase quality of life, physical activity, exercise tolerance, knowledge, and
independence.
 Pulmonary Rehabilitation
Indications:
•Remain symptomatic with dyspnea, fatigue, exercise intolerance
and/or have difficulty performing ADL
•Having difficulty dealing with or managing their disease.

Contraindications:
• Absolute: Unstable angina, bone fracture, and psychiatric condition.
• Relative: Severe cognitive impairment, severe uncontrolled anemia,
and progressive neuromuscular disease.

Outcome assessment:
1. Disease-specific health-related quality of life (HRQoL).
• Patients’ feedback. Such as Chronic respiratory disease
questionnaire.
2. Exercise testing, such as Cardiopulmonary exercise testing (CPET).
 Pulmonary Rehabilitation

Education

General
Psychological
Exercise
Support
Training

PR Multidisciplinary
Components
Team
Nutritional Breathing
Advice Retraining

Outcome
Assessment
 COPD Complications
1. COPD exacerbation.
2. Acute respiratory failure.
3. Decrease energy and activities of daily living.
4. Poor oxygenation.
5. Increase risk of lung cancer.
6. Problems with sleep.
7. Depression and anxiety.
8. Increased risk of VTE
 COPD MONITORING
ü Assess symptomatic benefit of therapy after initiation (i.e,

mMRC or CAT score)

ü Assess exacerbation history

ü Assess inhaler technique regularly

ü Assess technique and adherence before modifying therapy

ü Assess tobacco cessation readiness, if continued smoking

ü Assess immunization status (influenza, pneumococcal)

KEY DIFFERENCES OF COPD VS. ASTHMA
ITEM COPD ASTHMA
Age of onset Usually, <4o years
Usually, >4o years?

Smoking history
Usually, > 10 years Uncommon
Sputum Common Uncommon
production
Allergies Uncommon Common

Symptoms
Persistent Intemittent and variable

Disease process Progressive, Stable,

worsen overtime does not worsen overtime

Exacerbations A common complication

A common complication

First-line
Inhaled
treatment ! Bronchodilators
corticosteroids
Types of lung diseases
 Further readings
• DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. Pharmacotherapy Handbook. 12th edition
(2023), McGraw-Hill Professional, New York. Available at
https://accesspharmacy.mhmedical.com/book.aspx?bookID=3097.

• Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and
PreventionofChronicObstructivePulmonaryDisease(2023Report).https://goldcopd.org/2023-gold-report-2/.
Quick quiz
1. Which of the following is considered the most effective
method for confirming the diagnosis of COPD?
A. Chest X-ray
B. Spirometry
C. Arterial blood gas (ABG) analysis
D. High-resolution computed tomography (HRCT)
--------------------------------------------------------------------------------
2. Which of the following is a recommended non-
pharmacological intervention for managing stable COPD?
A. Short-acting beta-agonists (SABAs)
B. Long-acting muscarinic antagonists (LAMAs)
C. Oxygen therapy
D. Inhaled corticosteroids (ICS)
3. Which of the following medications is specifically indicated for COPD patients with a
history of frequent exacerbations and eosinophilic inflammation?
A. Tiotropium
B. Salmeterol
C. Roflumilast
D. Mepolizumab
-------------------------------------------------------------------------------------------------------------------
4. Which of the following cell types plays a significant role in the inflammatory
response observed in COPD?
A. Eosinophils
B. Neutrophils
C. Lymphocytes
D. Mast cells
-------------------------------------------------------------------------------------------------------------------
5. What is the underlying mechanism responsible for the airflow limitation observed in
COPD?
A. Constriction of bronchial smooth muscles
B. Increased production of surfactant
C. Thickening of the airway epithelium
D. Loss of elastic recoil in the lung tissue
6. RS is a 70-year-old male patient with a long history of smoking. He presents to his
primary care physician with increasing dyspnea on exertion, chronic cough, and
sputum production. Physical examination reveals decreased breath sounds and
prolonged expiratory phase. Spirometry confirms the diagnosis of moderate COPD
with an FEV1/FVC ratio of 55%.
6.1 Based on the spirometry results, RS's COPD is classified as:
A. Mild
B. Moderate
C. Severe
D. Very severe
6.2 Which of the following medications would be the most appropriate initial
pharmacologic treatment for RS's moderate COPD?
A. Long-acting muscarinic antagonist (LAMA)
B. Short-acting beta-agonist (SABA)
C. Inhaled corticosteroid (ICS)
D. Long-term oxygen therapy(LTOT)
6.3 In addition to pharmacologic treatment, which of the following interventions
would be beneficial for RS's COPD management?
A. Smoking cessation counseling
B. Oxygen therapy
C. Pulmonary rehabilitation
D. Antibiotic therapy