CHRONIC OBSTRUCTIVE

PULMONARY DISEASE

Prof. Dr. Sajid Abbas Jaffri

Department of Medicine
Bahria University Medical & Dental College
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
PREVALENCE
COPD is projected to be the third
biggest killer by 2020
1990 2020
Ischemic heart disease
CVD disease
Lower respiratory infection 3rd
Diarrhoeal disease
Perinatal disorders
COPD 6th
Tuberculosis
Measles Stomach cancer
Road traffic accident HIV
Lung cancer Suicide

Murray & Lopez 1997

 HISTORY
A 65-year-old man, smoker since last 40 years, smoked 2 packs
daily, presents to the emergency department with progressively
worsening shortness of breath. He usually uses 2L/min of oxygen at
home and is able to walk around the house without limitation, but
over the past 4 days he had increasing dyspnea on exertion. He has
also noticed an increase in his chronic cough, which is again
productive of thick green sputum.
On examination, he is tachycardic, has a respiratory rate of 28
breaths/min, and has bilaterally decreased breath sounds with
diffuse wheezing. His arterial ABG measurement show respiratory
acidemia from a partially compensated respiratory acidosis.
Pulmonary function tests demonstrated a decreased FEV1 and
FEV1/FVC ratio.
 DEFINITION OF COPD
ATS/ERS

• A disease state characterized by the presence of

airflow limitation that is not fully reversible.

• The airflow limitation is usually progressive may be

accompanied by airway hyperactivity and is
associated with an abnormal inflammatory response
of the lungs to noxious particles or gases, primarily
caused by cigarette smoking.

• Although COPD affects the lungs, it also produces

significant systemic consequences.
 ESSENTIALS OF DIAGNOSIS
History of cigarette smoking.
Chronic cough dyspnea and sputum
production.
Ronchi, decreased intensity of breath
sounds and prolonged expiration on
physical examination.
Airflow limitation on pulmonary function
testing.
GENERAL CONSIDERATIONS
Airflow obstruction due to chronic
bronchitis or emphysema, most patients
have features of both.
Obstruction
– Is progressive
– May be accompanied by airway
hyperreactivity
– May be partially reversible
 ETIOLOGY
Cigarette smoking is the most important cause
– About 80% of patients have had a significant
exposure to tobacco smoke.
Air pollution, airway infection, familial factors and allergy
have been implicated in chronic bronchitis.
Occupational chemicals: Coal, cotton, cement, dust,
glass, marble dust, wood dust and cadmium
α-Antitrypsin deficiency has been implicated in
emphysema.
PATHOGENESIS OF COPD
Noxious particles
and gases
Host factors

Lung inflammation
Anti-oxidants Anti-proteinases

Oxidative stress Proteinases

Repair mechanisms

COPD pathology
 Inflammation in
INFLAMMATION IN COPD
COPD

Small airway disease Parenchymal destruction

Airway inflammation Loss of alveolar attachments
Airway remodeling Decrease of elastic recoil

AIRFLOW LIMITATION
PATHO-PHYSIOLOGICAL FATURES
IN COPD

Airflow
Inflammation Structural
Limitation Changes

Bronchoconstriction Oxidative stress Alveolar destruction

Mucus hypersecretion  Neutrophils Glandular hypertrophy
Loss of elastic recoil  Macrophages Airway fibrosis
Airway narrowing  CD8+ lymphocytes Blood vessels
Dynamic hyperinflation  IL-8 and TNF-
during exercise Protease/antiprotease
imbalance

Adapted from Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis,
Management, and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. Bethesda,
Md: NIH,NHLBI; 2001. NIH publication no. 2701.
 Non-Smoker Smoker

 Smoking causes 80-90% of COPD.

 50% of smokers develop chronic bronchitis
 15-20% of smokers develop clinical airflow obstruction
 Appearance of autopsied lung from smoker with
advanced COPD emphysema

normal
alveoli

emphysema
alveoli
Inflammatory Small Airways Disease (Bronchiolitis)
In Smokers and COPD Patients

Normal bronchiole Bronchiolitis in a smoker

Mucosal inflammation, mucus gland hypertrophy,
and alveolar wall damage in COPD

Normal Small Airway COPD Small Airway

 CHRONIC BRONCHITIS
The Blue Bloater Phenotype

Chronic bronchitis is characterized by

excessive mucous secretions with
productive cough for 3 months or more in
at least 2 consecutive years.
•More profound hypoxemia at
rest
•Elevated PaCO2 with chronic
respiratory acidosis
•Cor pulmonale with right heart
failure.
 BLUE BLOATER
A "blue bloater" is a person where the primary underlying lung
pathology is chronic bronchitis. As, chronic bronchitis is caused
by excessive mucus production with airway obstruction resulting
from hyperplasia of mucus-producing glands, goblet cell
metaplasia, and chronic inflammation around bronchi.  Unlike
emphysema, the pulmonary capillary bed is undamaged. Instead,
the body responds to the increased obstruction by decreasing
ventilation and increasing cardiac output. There is a dreadful
ventilation to perfusion mismatch leading to hypoxemia and
polycythemia.  In addition, they also have increased carbon
dioxide retention (hypercapnia).  Because of increasing
obstruction, their residual lung volume gradually increases (the
"bloating" part).  They are hypoxemic/cyanotic because they
actually have worse hypoxemia than pink puffers and this
manifests as bluish lips and faces--the "blue" part.
CYANOSED TONGUE

CYANOSED HANDS

BLUE BLOATER
CHRONIC BRONCHITIS
 EMPHYSEMA
The Pink Puffer Phenotype

Emphysema is abnormal enlargement of

air spaces distal to terminal bronchiole,
with destruction of bronchial walls without
fibrosis.
 PINK PUFFER
A "pink puffer" is a person where emphysema is the primary
underlying pathology. As emphysema results from destruction
of the airways distal to the terminal bronchiole--which also
includes the gradual destruction of the pulmonary capillary bed
and thus decreased inability to oxygenate the blood.  So not
only there is less surface area for gas exchange, there is also
less vascular bed for gas exchange--but less ventilation-
perfusion mismatch than blue bloaters.  The body then has to
compensate by hyperventilation (the "puffer" part).  Their
arterial blood gases (ABGs) actually are relatively normal
because of this compensatory hyperventilation.  Eventually,
because of the low cardiac output, people affected with this
disease develop muscle wasting and weight loss.  They actually
have less hypoxemia (compared to blue bloaters) and appear to
have a "pink" complexion and hence "pink puffer".  
PINK PUFFER
EMPHYSEMA
SYMPTOMATIC COMPARISON BETWEEN
CHRONIC BRONCHITIS & EMPHYSEMA
SYMPTOMS AND SIGNS OF COPD
PRESENTATION:
– Usually at 40 to 50 years of age
– Cough
– Sputum production
– Shortness of breath
Dyspnea initially occurs only with heavy exertion, progressing to
symptoms at rest in severe disease.
Exacerbation of symptoms beyond normal day to day variation,
often including increased dyspnea , an increased frequency or
severity of cough, increased sputum volume, or change in sputum
character.
Infections (viral more commonly than bacterial) precede
exacerbations in most patients.
 SYMPTOMS AND SIGNS OF COPD

• Late stage COPD characterized by:

• Hypoxemia
• Pneumonia
• Pulmonary hypertension
• Cor-Pulmonale
• Respiratory failure
 DIFFERENTIAL DIAGNOSIS
Asthma
Bronchiectasis
Bronchopulmonary mycosis
Central air flow obstruction
Cystic fibrosis (usually seen in children
and young adults).
Severe α-Antitrypsin deficiency
 DIFFERENCE BETWEEN
COPD and ASTHMA

COPD ASTHMA

• Onset in mid-life • Onset early in life (often childhood)

• Symptoms slowly progressive • Symptoms vary from day to day
• Long smoking history • Symptoms at night/early morning
• Dyspnea during exercise • Allergy, rhinitis, and/or eczema also
• Largely irreversible airflow present
limitation • Family history of asthma
• Largely reversible airflow limitation
 LABORATORY FINDINGS
Complete Blood Count.
– Hb, TLC, ESR
Arterial Blood Gases.
– Decreased PH, Increased PaCO2, Decreased PaO2
ECG
– Sinus tachycardia, P-Pumonale, RVH, RAD
Sputum examination.
– Streptococcus pneumonia, Haemophilus influenzae,
Moraxella catarrhalis.
 LABORATORY FINDINGS
Spirometry:
– FEV1 and FEV1 / FVC are reduced later in
the disease.
– FVC is reduced in severe disease
– Lung volume measurements show an
increase in total lung capacity(TLC), residual
volume (RV) and elevation of RV/ TLC
indicating air trapping.
 EXPOSURE TO RISK
SYMPTOMS FACTORS
cough tobacco
sputum occupation
dyspnea indoor/outdoor pollution


SPIROMETRY
SPIROMETRY
SPIROMETRY
 SPIROMETRY:
Normal and in Patients with COPD
ASSESSMENT OF SEVERITY
Assessment of severity is based on the FEV1,
as measured by spirometry, which is
compared to the predicted value based on
age, sex and height and expressed as
percentage ( FEV1% ).
• STAGE 1 ( MILD) > 80%
• STAGE 2 ( MODERATE ) 50-79%
• STAGE 3 (SEVERE) 30-49%
• STAGE 4 ( VERY SEVERE) <30%
 IMAGING
Radiographs of patients with chronic bronchitis typically
show only non specific peribronchial and perivascular
markings.
Plain radiographs are insensitive for the diagnosis of
emphysema; they show hyperinflation with flattening of
the diaphragm or peripheral arterial deficiency in about
half of cases.
Computed tomography(CT) of the chest of the chest is
more sensitive and specific than plain radiographs for the
diagnosis of emphysema.
Doppler echocardiography provides a non invasive
estimate pulmonary pressure.
CHRONIC BRONCHITIS
EMPHYSEMA
EMPHYSEMA WITH BULLAE
Far-Advanced Emphysema
on Chest Radiograph
EMPHYSEMA ON CT CHEST
 MANAGEMENT OF COPD
Management of patients with COPD is based
on:
• An accurate diagnosis.
• Assessment of severity of symptoms.
• Degree of airflow obstruction.
• Smoking status.
• The extent of disability and ensuring optimal
medical therapies.
( NICE guidelines on chronic obstructive pulmonary disease,
June 2010 ).
 MANAGEMENT OF COPD
Treatment strategies for COPD are varied and a
multidisciplinary approach to the patient is offered.
A treatment plan should consider:
• Smoking cessation
• Patient education
• Optimizing pharmacological therapies
• Pulmonary rehabilitation
• Nutritional and psychological support
• Treatment of acute exacerbation
• Treatment of Cor- Pulmonale, if present
• Home oxygen therapy and home non- invasive ventilation if
indicated.
 MEDICAL TREATMENT
Supplemental Oxygen(15 hours of nasal
oxygen per day is required).
Bronchodilators (β2- agonists and
anticholinergics)
Oral Theophylline
Corticosteroids
Antibiotics
Mucolytic agents
 SURGICAL TREATMENT
• Bullectomy: In carefully selected patients, this
procedure is effective in reducing dyspnea and
improving lung function.
• Lung Volume Reduction Surgery
• Lung Transplantation: In appropriately
selected patients, improves quality of life and
functional capacity.
• Criteria for referral:
• FEV1<35% predicted PaO2<55-60mm Hg,
PaCO2>50 mm Hg, and secondary pulmonary
hypertension
 OTHER PHARMACOLOGIC
TREATMENT
• Vaccines: Influenza vaccine reduces serious
illness and death in COPD patients by 50%.
Pneumococcal vaccine is recommended every
5 years although data in COPD patients is
lacking.
• Other anti-inflammatory agents: Cromolyn,
nedocromil, and leukotriene inhibitors have
not been adequately tested in patients with
COPD
• Alpha-1 Antitrypsin Augmentation Therapy:
young patients with severe deficiency and
established emphysema
 OTHER PHARMACOLOGIC
TREATMENT
• Antibiotics: Are not recommended other than
in treating infectious exacerbations
(Doxycycline, Amoxicillin, Macrolide,
Fluoroquinolones)
• Mucolytic agents: Not recommended
• Antioxidants (N-acetylcysteine): May reduce
the frequency of exacerbations
• Antitussives: Contraindicated in stable
COPD because cough is protective.
PULMONARY REHABILITATION IN
STABLE COPD
• All COPD-patients benefit from exercise
training programs, improving with respect
to both exercise tolerance and symptoms
of dyspnea and fatigue.
• The minimum length of an effective rehab
program is 2 months; the longer the
better.
• Comprehensive pulmonary rehabilitation
program includes exercise training,
nutrition counseling, and education.
 Management of Stable COPD:
Bronchodilators
• Bronchodilator medications are central to the
symptomatic management of COPD. They
are given on as-needed basis or on a regular
basis to prevent or reduce symptoms.
– Alleviate symptoms
– Improve exercise tolerance
– Improve quality of life
– Decrease the incidence of exacerbations
– Decrease hyperinflation
• Inhaled therapy is preferred
 Management of Stable COPD:
Bronchodilators
• Beta2-agonists: Increase cyclic adenosine
monophosphate levels and promote airway
smooth-muscle relaxation
– Short acting: Albuterol, Salbutamol, Terbutaline
– Long acting: Salmeterol (Serevent), Bambuterol
(Bambec) and Formoterol fumarate (Foster).

Anticholinergics: Block muscarinic

receptors
– Short acting: Ipratropium bromide (Atrovent)
– Long acting: Tiotropium bromide (Spiriva)
Combination: (Combivent)
 Management of Stable COPD:
Bronchodilators
Phosphodiesterase Inhibitors: (Theophylline,
Aminophylline) Increase intracellular cyclic
adenosine monophosphate levels within
airway smooth muscle
– 3rd line agent
– Improves respiratory muscle function, stimulates
the respiratory center, decreases dyspnea, and
enhances activities of daily living
– Toxic side effects: tachyarrhythmias, nausea,
vomiting, seizures
– Monitoring should include intermittent serum
level measurements: target range 8-12mcg / ml
 Inhaled Steroids (ICS) in Stable
COPD
• Glucocorticoids act at multiple points within
the inflammatory cascade.
• Regular treatment with ICS does not modify
the long-term decline in FEV1.
• Appropriate for symptomatic COPD patients
with an FEV1 < 50% and repeated
exacerbations (Stage III and IV).
• ICS reduce frequency of exacerbations and
improve health status .
• ICS combined with long-acting 2-agonist
more effective than individual components.
 Steroids in Stable COPD
GOLD guidelines: Recommends a trial of
6 weeks to 3 months of ICS to identify
subset of patients who may benefit.
Short course of oral steroids is a poor
predictor of long-term response to ICS.
Long-term treatment with oral steroids is
NOT recommended :
– No evidence of long-term benefit
– Major side effects: skin damage, cataracts,
diabetes, osteoporosis, secondary infection,
psychosis, fluid retention
 Management of Stable COPD:

OXYGEN:
The long-term administration of oxygen (>
15 hours per day) to patients with chronic
respiratory failure (Stage IV) has been
shown to increase survival.
Oxygen administration reduces
hematocrit, pulmonary artery pressures,
dyspnea, and rapid eye movement related
hypoxemia during sleep.
 OXYGEN THERAPY
• The goal is to prevent tissue hypoxia by maintaining arterial
oxygen saturation (Sa,O2) at >90%.
• Main delivery devices include nasal cannula and venturi mask.
• Arterial blood gases should be monitored for arterial oxygen
tension (Pa,O2), arterial carbon dioxide tension (Pa,CO2) and
pH.
• Arterial oxygen saturation as measured by pulse oximetry
(Sp,O2) should be monitored for trending and adjusting oxygen
settings.
• If CO2 retention occurs, monitor for acidemia.
• If acidaemia occurs, consider mechanical ventilation.
 Therapy at Each Stage of COPD
I: Mild II: Moderate III: Severe IV: Very Severe

FEV1/FVC < 70%

FEV1 < 30% predicted
FEV1/FVC < 70% FEV1/FVC < 70%
or FEV1 < 50%
FEV1/FVC< 70% predicted plus
FEV1 > 80% 50% < FEV1 < 80% 30% < FEV1 < 50%
chronic respiratory
predicted predicted predicted
failure
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
Add regular treatment with one or more long-acting
bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if
repeated exacerbations
Add long term
oxygen if chronic
respiratory failure.
Consider surgical
treatments
 PHARMACOTHERAPY IN COPD
COPD severity

Mild……….……..  SABD1 prn

 Tiotropium or LABA2 + SABD prn

Moderate…………. Tiotropium + LABA + SABA3 prn

 Tiotropium + LABA (+ theophylline) + SABA prn

Dyspnea
&
disability
Severe……..……  Tiotropium + LABA/ICS4 + theophylline + SABA prn
1. SABD : Short-acting bronchodilator (beta2-agonist or anticholinergic)
1. LABA : Long-acting beta2-agonist (e.g.
Appe
formoterol or salmeterol)
2. SABA : Short-acting beta2-agonist (e.g. salbutamol) ndi
3. LABA/ICS : Long-acting beta2-agonist combined with inhaled x
corticosteroid in one preparation
Can Respir J Vol 10 No 4 May/June 2003, pg. 184
 COPD EXACERBATION
Definition Elements Severity

Worsening dyspnea Severe - all 3

Increased sputum elements
purulence Moderate - 2
Increase in sputum elements
volume
Mild - 1 element
plus:
URI in past 5 days
Fever without
apparent cause
Increased
wheezing or cough
Increase (+20%) of
Modified from Anthonisen et al. Ann Int Med 106:196, 1987 respiratory rate or
heart rate
 Assessment of severity of
exacerbation
Peak flow <100 L/min or FEV1 <1.0 L
indicates severe exacerbation
ABG
CXR
EKG
D-dimer, spiral CT
Sputum culture
 COPD EXACERBATION
PATHOPHYSIOLOGY
Pathophysiology - Current Hypothesis

Chronic Inflammation
Viral Unknown
Infection 20%
25%

Bacterial Air
Infection Acute Pollution
50% 5%
Inflammation

Exacerbation
 The Clinical Course of COPD:
Consequences of Exacerbations

Reduced Accelerated
health-related decline
quality of life in FEV1

Exacerbations

Increased Increased health

mortality with resource
exacerbation utilization and
hospitalizations direct costs
 Management of Exacerbations:
Key Points
Inhaled bronchodilators
(Beta2-agonists and/or
anticholinergics), and
systemic, preferably oral,
glucocortico-steroids are
effective for the
treatment of COPD
exacerbations (Evidence
A).
80% of AECB are
infectious.
Environmental factors
and medication
nonadherence are 20%.
 Role of Infection in COPD
Exacerbation
Up to 60% of exacerbations are due to
respiratory infections.
Bacterial Infections: H. infleunza, M.
catarrhalis, S. pneumoniae.
Acquisition of new strains vs. colonization
Viral Infections: Influenza, Parainfluenza,
Coronavirus, Rhinovirus.
Coinfection is common
 Antibiotic Therapy for COPD
Exacerbation
Placebo-controlled studies demonstrated
that antibiotics improve clinical outcome
in many patients with COPD exacerbation.
A recent meta-analysis demonstrated
improved Survival in moderate -to-
severe COPD treated with antibiotics
compared to placebo (Puhan et al. 2007)
Indications for Antibiotics in COPD
Exacerbation
Increased sputum purulence with increased
SOB of sputum volume.
Need for hospitalization.
Need for mechanical ventilation.
Risk factors for poor outcome:
Comorbidities
Severe underlying COPD (FEV-1<50%)
Frequent exacerbations (> 3/year)
Recent antibiotic use (within the past 3 months)
 COMPLICATIONS
Otherwise stable COPD may be made worse by:

Acute Bronchitis.
Pneumonia.
Pulmonary Thromboembolism.
Atrial dysrthmias, such as atrial fibrillation, atrial flutter, multifocal
atrial tachycardia.
Concomitant left ventricular failure.
Pulmonary hypertension, Cor Pulmonale and chronic respiratory
failure are common in advanced disease.
Spontaneous Pneumothorax occurs in a small fraction of
emphysematous patients.
Hemoptysis may result from chronic bronchitis or bronchogenic
carcinoma.
 PREVENTION
Largely preventable by eliminating chronic
exposure to tobacco smoke.
Smoking cessation slows the decline in
FEV 1 in middle age smokers with mild
airway obstruction.
Vaccination against influenza and
pneumococcal infection.
 PROGNOSIS
Median survival of patients with FEV1 <1L is 4
years.
Degree of dysfunction at presentation is the
most important predictor of survival.
A multidimentional index ( the BODE index),
which includes body mass index, airway
obstruction(FEV1), dyspnea(Medical Research
Council dyspnea score) and exercise capacity,
predicts death and hospitalization better than
FEV1.
 PROGNOSIS
• In severe disease this is poor, with considerable
symptomatic discomfort as the disease progress
and lung function become more severe.
• No single therapy changes the natural course of
the disease.
• In milder disease the importance of smoking
cessation cannot be overemphasized.
• It will not repair damaged lung tissue but the rate
of decline in FEV1 with time will revert to that of a
non smoker.
THANK YOU FOR
ATTENTION