COPD

1. Chronic Obstructive
Lung Disease:
GOLD Guidelines

2. COPD - Definition
Global Obstructive Lung Disease Guidelines (GOLD) : 2013
• “A common preventable and treatable disease state
characterized by persistent airflow limitation that is
usually progressive and associated with enhanced
chronic inflammatory response in the airways and the lung
to noxious particles or gasses. “
• GOLD guidelines were recently updated in 2013

3. Extrapulmonary effects : skeletal muscle
wasting, cachexia
Comorbidities: cardiovascular (ischemic heart
disease and heart failure), osteoporosis ,
normocytic anemia, diabetes, metabolic
syndrome and depression, musculoskeletal and
psychological conditions
Chronic obstructive pulmonary disease (COPD)
encompasses several diffuse pulmonary diseases,
including chronic bronchitis, emphysema, chronic
asthma, bronchiectasis, and:
The result is irreversible airflow obstruction.

5. Chronic bronchitis (definition): — Chronic bronchitis is
defined as a chronic productive cough for three months in
each of two successive years in a patient in whom other
causes of chronic cough (eg, bronchiectasis) have been
excluded. It may precede or follow development of
airflow limitation. This definition has been used in many
studies, despite the arbitrarily selected symptom duration.

6. Chronic bronchitis can be categorized as:
1.Non-obstructive chronic bronchitis:
a) simple chronic bronchitis - (mucoid sputum production characterizes
simple chronic bronchitis),
b) chronic mucopurulent bronchitis - (persistent or recurrent purulent
sputum production in the absence of localized suppurative disease, such as
bronchiectasis, characterizes chronic mucopurulent bronchitis).
2. Obstructive chronic bronchitis (chronic bronchitis with obstruction).
Chronic bronchitis with obstruction must be distinguished from chronic infective
asthma. The differentiation is based mainly on the history of the clinical
illness:
• patients who have chronic bronchitis with obstruction present with a
long history of productive cough and a late onset of wheezing, whereas
•patients who have asthma with chronic obstruction have a long history of
wheezing with a late onset of productive cough.

7. Emphysema — Emphysema is defined by abnormal and
permanent enlargement of the airspaces distal to the
terminal bronchioles that is accompanied by destruction of
the airspace walls, without obvious fibrosis (ie, there is no
fibrosis visible to the naked eye). Exclusion of obvious fibrosis
was intended to distinguish the alveolar destruction due to
emphysema from that due to the interstitial pneumonias, etc.
However, many studies have found increased collagen in the lungs
of patients with mild COPD, indicating that fibrosis can be a
component of emphysema. While emphysema can exist in
individuals who do not have airflow obstruction, it is more common
among patients who have moderate or severe airflow obstruction.
The various subtypes of emphysema (eg, centriacinar,
panacinar, distal acinar (paraseptal) are described
below.

8. Asthma — The Global Initiative for Asthma gives the following definition
of asthma.
“Asthma is a chronic inflammatory disorder of the airways in
which many cells and cellular elements play a role.
The chronic inflammation is associated with airway
responsiveness that leads to recurrent episodes of wheezing,
breathlessness, chest tightness, and coughing, particularly at
night or in the early morning. These episodes are usually
associated with widespread, but variable, airflow obstruction
within the lung that is often reversible either spontaneously
or with treatment.”

9. Interrelationships of
COPD subtypes

10. Chronic obstruction as an element, (but not an
essence) of other nosological entities:
•Patients with airflow obstruction due to diseases that have
a known etiology or a specific pathology (eg, cystic fibrosis,
bronchiectasis, obliterative bronchiolitis, tuberculosis) are not
considered to have COPD. However, these exclusions are
loosely defined.

11. PATHOLOGY — The predominant pathologic
changes of COPD are found in the airways, but
changes are also seen in the lung parenchyma and
pulmonary vasculature.
In an individual, the pattern of pathologic changes
depends on the underlying disease (eg, chronic
bronchitis, emphysema, alpha-1 antitrypsin
deficiency), possibly individual susceptibility, and
disease severity.

12. Airways — Airways abnormalities in COPD include chronic
inflammation, increased numbers of goblet cells, mucus gland
hyperplasia, fibrosis, narrowing and reduction in the number of
small airways, and airway collapse due to the loss of tethering
caused by alveolar wall destruction in emphysema.
•Chronic inflammation in chronic bronchitis and emphysema is
characterized by the presence of CD8+ T-lymphocytes, neutrophils,
and CD68+ monocytes/macrophages in the airways. Among patients
with chronic bronchitis who have mucus hypersecretion, an
increased number of goblet cells and enlarged submucosal glands
are typically seen.
•In comparison, the bronchial inflammation of asthma is
characterized by the presence of CD4+ T-lymphocytes, eosinophils,
and increased interleukin (IL)-4 and IL-5.

13. Lung parenchyma — Emphysema affects the structures distal to the terminal
bronchiole, consisting of the respiratory bronchiole, alveolar ducts, alveolar
sacs, and alveoli, known collectively as the acinus. These structures in
combination with their associated capillaries and interstitium form the lung
parenchyma. The part of the acinus that is affected by permanent dilation or
destruction determines the subtype of emphysema.
•Proximal acinar (also known as centrilobular) emphysema refers to
abnormal dilation or destruction of the respiratory bronchiole, the central
portion of the acinus. It is commonly associated with cigarette smoking, but
can also be seen in coal workers’ pneumoconiosis.
•Panacinar emphysema refers to enlargement or destruction of all parts of
the acinus. Diffuse panacinar emphysema is most commonly associated with
alpha-1 antitrypsin deficiency, although it can be seen in combination with
proximal emphysema in smokers.
•In distal acinar (also known as paraseptal) emphysema, the
alveolar ducts are predominantly affected. Distal acinar emphysema
may occur alone or in combination with proximal acinar and panacinar
emphysema. When it occurs alone, the usual association is spontaneous
pneumothorax in a young adult.

14. Pulmonary vasculature —
Changes in the pulmonary vasculature include
•intimal hyperplasia and
•smooth muscle hypertrophy/hyperplasia thought to
be due to chronic hypoxic vasoconstriction of the small
pulmonary arteries.
•Destruction of alveoli due to emphysema can lead to
loss of the associated areas of the pulmonary capillary
bed.

15. COPD - Risk FactorsCOPD - Risk Factors
• Hereditary - Alpha-1 Antitrypsin Deficiency
• Environmental
• Cigarette Smoking
• 15-20% of smokers will develop COPD
• (~1 in 5) - this implies a genetic
predisposition to developing COPD; tends
to cluster in families
• Occupational exposures to dust, chemicals
• Hereditary - Alpha-1 Antitrypsin Deficiency
• Environmental
• Cigarette Smoking
• 15-20% of smokers will develop COPD
• (~1 in 5) - this implies a genetic
predisposition to developing COPD; tends
to cluster in families
• Occupational exposures to dust, chemicals

16. CLINICAL FEATURES
Smoking and inhalational exposure history — The most
important risk factor for COPD is cigarette smoking and the amount
and duration of smoking contribute to disease severity. Thus, a key
step in the evaluation of patients with suspected COPD is to ascertain
the number of pack years smoked (packs of cigarettes per day
multiplied by the number of years), as the majority (80 percent) of
patients with COPD have a history of cigarette smoking. It is useful to
ask the age of starting and the age of quitting, as patients may
underestimate the number of years they smoked. With enough
smoking, almost all smokers will develop measurably reduced lung
function. In the absence of
agenetic/environmental/occupational predisposition,
smoking less than 10 to 15 pack years of cigarettes is unlikely
to result in COPD.
Best variable for predicting which adults will have airflow
obstruction on spirometry is a history of more than 40 pack
years of smoking

17. The chronologically
taken environmental/occupational history may
disclose other important risk factors for COPD,
such as exposure to fumes or organic or inorganic
dusts. These exposures help to explain the 20 percent of
patients with COPD (defined by lung function alone) and
the 20 percent of patients who die from COPD who
never smoked

18. Symptoms and pattern of onset —
The three cardinal symptoms of COPD are:
•dyspnea,
•chronic cough and sputum production and the most
common early symptom is
•exertional dyspnea.
•Less common symptoms include
•wheezing and
•chest tightness.
•However, any of these symptoms may develop
independently and with variable intensity.
•There are three typical ways in which patients
with COPD present:

19. 1. Patients who have an extremely sedentary
lifestyle but few complaints require careful
questioning to elicit a history that is suggestive of
COPD. Some patients unknowingly avoid exertional
dyspnea by shifting their expectations and limiting
their activity. They may be unaware of the extent
of their limitations or that their limitations are due
to respiratory symptoms, although they may
complain of fatigue.

20. 2. Patients who present with respiratory
symptoms generally complain of dyspnea and
chronic cough.
The dyspnea may initially be noticed only during
exertion. However, it eventually becomes noticeable
with progressively less exertion or even at rest.
The chronic cough is characterized by the insidious
onset of sputum production, which occurs in the
morning initially, but may progress to occur throughout
the day. The daily volume rarely exceeds 60 mL.
The sputum is usually mucoid, but becomes purulent
during exacerbations.

21. •3. Patients who present with episodes of
increased cough, purulent sputum, wheezing,
and dyspnea that occur intermittently, with or
without fever.
• Diagnosis can be problematic in such patients.
The combination of wheezing plus dyspnea may lead to
an incorrect diagnosis of asthma.
• Conversely, other illnesses with similar manifestations
are often incorrectly diagnosed as a COPD
exacerbation (eg, heart failure, bronchiectasis,
bronchiolitis).
The interval between exacerbations decreases as
the severity of the COPD increases

22. Approximately 62 percent of patients with
moderate to severe COPD report variability in
symptoms (eg, dyspnea, cough, sputum,
wheezing, or chest tightness) over the course of
the day or week-to-week;
morning is typically the worst time of day.

23. SYSTEMIC SYMPTOMS, etc.
Patients with COPD may experience weight gain
(due to activity limitations), weight loss (possibly
due to dyspnea while eating), muscle weakness,
limitation of activity (including sexual), cough
syncope, or feelings of depression or anxiety.
Weight loss, even cachexia (PP-emphysema)
generally reflects more advanced disease and is
associated with a worse prognosis. However, the
majority of COPD patients are overweight or obese
(BB-bronchitis).

24. Comorbid diseases that may accompany
COPD
include lung cancer, coronary heart disease,
osteoporosis, metabolic syndrome, skeletal
muscle weakness, depression, and cognitive
dysfunction. Patients may also report a family
history of COPD or other chronic respiratory
illness.

25. Physical examination — 1
The findings on physical examination of the chest vary with the severity
of the COPD.
•Early in the disease, the physical examination may be normal, or may
show only prolonged expiration or wheezes on forced exhalation.
•As the severity of the airway obstruction increases, physical
examination may reveal hyperinflation (eg, increased resonance
to percussion), decreased breath sounds, wheezes, crackles at the
lung bases, and/or distant heart sounds.
•Features of severe disease include an increased anteroposterior
diameter of the chest (“barrel-shaped” chest) and a depressed
diaphragm with limited movement based on chest percussion.
Yellow nicotine stains on the fingers are a clue to ongoing and
heavy cigarette smoking.
Clubbing of the digits is not typical in COPD (even with
associated hypoxemia) and suggests comorbidities such as lung
cancer, interstitial lung disease, or bronchiectasis.

26. •Patients with end-stage COPD may adopt positions that relieve
dyspnea, such as leaning forward with arms outstretched and
weight supported on the palms or elbows. This posture may be
evident during the examination or may be suggested by the
presence of callouses or swollen bursae on the extensor surfaces
of forearms. Other physical examination findings include use of
the accessory respiratory muscles of the neck and shoulder
girdle, expiration through pursed lips, paradoxical retraction of
the lower interspaces during inspiration (ie, Hoover's sign),
cyanosis, asterixis due to severe hypercapnia, and an enlarged,
tender liver due to right heart failure. Neck vein distention may
also be observed because of increased intrathoracic pressure,
especially during expiration.
Physical examination — 2

27. EVALUATION — Evaluation for COPD is
appropriate in adults who report dyspnea, chronic
cough, chronic sputum production or have had a
gradual decline in level of peak activity, particularly if
they have a history of exposure to risk factors for the
disease (eg, cigarette smoking, indoor biomass
smoke). All patients are evaluated with spirometry
and selected patients have laboratory testing and
imaging studies.

28. COPD - Prevalence
• Fourth leading cause of mortality
(100,000/year)
• Only major health problem for which
mortality has been increasing for past
20 years
• Results in 500,000 hospitalizations/year
• Second leading cause of missed work
days

29. COPD - Diagnosis
• Symptoms
• chronic cough - intermittent, nonproductive
• cough with sputum production, ‘smoker’s cough’
• dyspnea on exertion, usually progressive and indolent
(slow advancing)
• Spirometry
• Should spirometry screening be performed on the general
population?
• No, but in those with higher risk - i.e. all current and
former smokers over the age of 40 years with any of
the above symptoms of disease

30. The Importance of Screening for
COPD
• The Rule of 50s
• 50% of COPD patients are
undiagnosed (or approximately 12 million
patients in U.S.)
• COPD is evident by age 50
• At time of diagnosis, FEV1 is <50%
predicted
• 50% 5-year survival rate

31. COPD Staging
• Based upon the GOLD Guidelines
• Classified into 4 stages
• Staging is based primarily upon FEV1:
• FEV1 < 80%
• FEV1:FVC < 70% more severe the
disease
• The lower the FEV1 the classification.

32. GOLD Guidelines for Therapy

33. COPD Management and Therapies
• Vaccination - pneumococcal (i.m.) and influenza (s.c.)
• Regular Assessment of lung function - annually
• Cessation of tobacco use
• Drug Therapy:
• short acting (SABA) vs. long acting bronchodilators
(LABA)
• inhaled (ICS) vs. oral corticosteroids (systemic steroids)

34. COPD - Management of Stable Disease
• Smoking cessation: rate of FEV1 deterioration
will slow to near normal (20 ml /yr vs. 65 ml
/yr for active smokers) if patient stops smoking

35. COPD - Drug Therapy
• Therapy recommendations based on their effect on FEV1.
• First Line therapy:
• Beta agonists - short (SABA) and long acting (LABA)
• Anticholinergics - short (SAMA) and long acting (LAMA)
• Second Line therapy:
• Steroids - inhaled (ICS) vs. oral (systemic steroids)
• Supplemental therapies

36. Beta agonists
• Mechanism of Action -
bronchodilate by
stimulating Beta-2
receptors
• Studies show that COPD
patients do not
develop tolerance to
short acting or long
acting beta agonists
• Asthmatics tend to
develop tolerance to
short acting agonists
• Can Salmeterol be used
as monotherapy?
Drug Albuterol Salmeterol
Onset 1 to 3 min 20 min
Duration 4 to 6 hrs 12+ hrs
YES, salmeterol monotherapy had
adverse outcomes in asthma study, note
COPD.

37. Anticholinergics
• Mechanism of action-
bronchodilation by
decreasing airway
smooth muscle tone
• Also reduces
sputum production
• Combination of an
anticholinergic +
β2-agonist produces
greater and more
sustained rise in
FEV1 than either
drug alone.
Drug
Ipratropiu
m
Tiotropium
Onset 20 min ?
Duration 4 to 8 hrs 24 hrs
Selectivity
All
Muscarinic
M1 and M3>
M2

38. Tiotropium (Spiriva)
• Studies show that once
daily tiotropium has
resulted in a lasting increase
in FEV1 out to one year.
• 174 ml above baseline
in good short-term
responders
• 56 ml increase in
poor short-term
responders
Special delivery device.

39. Inhaled Corticosteroids (ICS)
• Have not been shown to slow the progression of
disease or provide long term benefit
• ISOLDE trial - patients with FEV1 of 50%
predicted value had a 25% reduction of
exacerbations
• Combination with salmeterol more effective in
reducing exacerbations than either drug alone
• Unfortunately, recently published trial failed to
demonstrate statistically significant reduction in
mortality with salmeterol/fluticasone combo.

40. New COPD Treatment Data
• compared salmeterol/fluticasone head to
head with tiotropium
• No difference in exacerbation rate
although more in tiotropium group had
higher drop out rate.
• More patients in salmeterol/fluticasone
developed pneumonia.

41. Oral Corticosteroids
• They have no proven benefit in stable
COPD
• Oral steroids are useful for acute
exacerbations
• What is the recommended duration of
therapy?
• Maximum benefit obtained during
first 2 weeks of therapy.

42. Supplemental Therapies
• Supplemental oxygen for hypoxemia (worn
for more than 15 hrs/day) has been shown to
reduce moratality
• What are the qualification parameters
for oxygen therapy?
• PaO2 of 55mmHg or less, or pulse
oximetry of 88% or less
• Pulmonary Rehabilitation
• Lung reduction and lung transplantation
surgeries

43. GOLD Guidelines for Therapy

44. Summary
• Early diagnosis, disease prevention, smoking
cessation and vaccination are important.
• Initiate bronchodilator therapy early in disease
course, combination of albuterol with ipratropium most
effective
• Inhaled corticosteroids may be useful in patients
with severe disease or with objective responses on
spirometry.
• Will likely see inflammatory modulators (TNF-
α) in the future