1

CHRONIC OBSTRUCTIVE PULMONARY DISEASE Swedish hypothesis or Alpha 1 protease inhibitor (A1PI)
deficiency hypothesis
Jessamine Dacanay , MD, FPCP, DPCCP
Rommel Bayot, MD, FPCP  A1PI is a serine protease inhibitor
 The only proven genetic abnormality that predisposes
Note: to COPD
This trans follow Dr. Bayot’s flow of discussion
Green boxes: lecture from Dr. Dacanay and other slides not included in Dr. Bayot’s  Cigarette smoking markedly accelerates loss of lung
lecture. The rest are the same. function in patients with A1PI deficiency as well
Blue boxes: lectures from Dr. Bayot.
Gray text: not mentioned by Dr. Bayot American hypothesis
COPD  Deficient maintenance of lung structure particularly the
alveolar capillaries could lead to emphysema
 Common preventable and treatable disease
characterized by persistent airflow limitation that is Non-Proportional Venn Diagram
usually progressive and associated with an enhanced
chronic inflammatory response in the airways and
the lung to noxious particles or gases
 Exacerbations and comorbidities contribute to the
overall severity in individual patients

Our aim in the treatment of COPD is to control of symptoms and

prevent further decrease in the lung function as well as the
decrease in exacerbation, because the greater the exacerbation,
the greater is the severity of the disease.

Asthma COPD
Inflammatory chronic chronic
response Asthma-COPD overlap syndrome  having clinical features of
Course Resolves with Progressive
both. Most of the COPD patients are either having chronic
medication
bronchitis or emphysema. Whether it is an overlap syndrome or
not, we should always consider emphysematous patients
HYPOTHESIS ON COPD PATHOGENESIS acquiring chronic bronchitis or asthma and vice versa.

Dutch hypothesis However, there are other respiratory pathologies that have
airflow obstruction but may not have COPD, like Cystic fibrosis
 asthma and airway hyperactivity can progress to COPD and bronchiolitis.
 Epidemiologic studies suggest that there is an
accelerated loss of lung function among asthmatics
especially asthmatics who smoke
APPROACH TO COPD PATIENTS
 Functional changes in both the small airways and the
alveolar parenchyma have been reported HISTORY
 Airway hyperresponsiveness as a risk factor remains
controversial  Cough and Dyspnea
 Most frequent symptoms
Asthmatics that smoke developed a fixed airflow limitation  Specially bronchitic patients
where in there is unresponsiveness to bronchodilators. Their
bronchodilator response is always less than 12% and less than  Sputum production
200ml.  (+) Hemoptysis  if there is a component of bronchiectasis
 Abnormal health status (Quality of Life)- St. George
British hypothesis
Respiratory Questionnaire and Chronic Respiratory
 Mucus hyper secretion Disease Questionnaire  correlates poorly with FEV1 but
 mucus in the airways could contribute to the correlated better with exercise performance and survival
development of fixed airflow limitation and airway o High score  poor exercise performance and
remodelling survival
 Exacerbations – ask for the frequency
 No effect on loss of lung function, after correction for
o Exacerbations - Increase cough, sputum,
smoking
dyspnea and fatigue
 Small effect of mucus hypersecretion on COPD
occurrence PHYSICAL EXAMINATION

 Reveals little abnormality especially during quiet

breathing

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 Wheezing is not a consistent finding and does not relate

to the severity of obstruction.

It does not mean that if the patient is not wheezing, FORMS OF COPD
he/she is not in distress. Absence of wheezes could also
signify complete obstruction. 1. Bronchitis
- Inflammation and alteration of airway
structures
 Prolonged expiratory time - Altered airway anatomy  heterogeneity of
o The most consistent findings in patients with airflow distribution within the lung 
symptomatic COPD (longer than the normal 4 ventilation-perfusion imbalance hypoxemia,
seconds) and right heart failure
o The problem in COPD patients is the trapping - “blue bloater” clinical phenotypes
of air inside the lungs, thus prolonging the - MORE ON AIRWAYS
expiratory time. 2. Emphysema
o We encourage patient to do pursed lip - Destruction of the alveolar wall
breathing to exhale more volume of the lungs - Would not caUse hypoxia, although there
during expiratory time. would be decreased airflow
 Severe COPD - “pink puffer” phenotype
o Barrel-shaped chest. - MORE ON ALVEOLAR WALLS
o Pursed lip breathing  to compensate for the
air trapping
o Emaciation especially in patients with DIAGNOSIS OF COPD
emphysema
o inguinal hernias 1. Spirometry
 Patients may observed sitting forward and leaning on  Most important test to diagnose and stage COPD
their elbows or supporting their upper body with  FEV1: low in COPD
extended arms  help in maximizing the volume of air o Most important measurement
passing through o FVC is normal
 Accentuated S2  particularly P2, for those with  Reduction in post bronchodilator FEV1/FVC ratio
pulmonary hypertension (less than 70%)
o Diagnostic of airway obstruction but is
Emphysematous Bronchitic not useful to monitor disease progression
Asthenic Overweight o TIP in the exam: look at POST bronchodilator
Scanty mucoid sputum Copious, purulent sputum PFT not Prebronchodilator
Long history of exertional Less dyspniec  FEV6 is commended for use in most office settings
dyspnea o Easier to perform
Tachypneic with pursed lip Chronic cough o Avoids prolonged exhalation maneuvers
breathing
reducing the chance of syncope during
Barrel chest
the test
Pink puffer Blue bloater
o DRAWBACK: variable
Prominent accessory muscles Non prominent accessory
(hypertrophied SCM) muscles
Decreased breath sounds due (+) Wheezes and crackles 2. Lung Volumes
to air trapping  ↑ TLC (emphysema) – loss of elastic recoil permits
Hyperresonant lungs Resonant lungs the lungs to expand to a greater maximal volume
Cor pulmonare late in the Cor pulmonare early in the  ↑ RV and FRC
course course  ↓ VC – residual volume increases with increasing
respiratory rate
 Dynamic hyperinflation
o Increases in lung volume with increasing
respiratory rate
o Inspiratory capacity increases
 Suggested as a surrogate for the
measurement of dynamic
hyperinflation

Remember: if RV increases, the VC contracts/decreases to

accommodate the total lung capacity.

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3. Diffusing Capacity
 DECREASED in proportion to the severity of
EMPHYSEMA because of the destruction of the
alveoli and the loss of alveolar capillary bed
 Measurement is not sensitive to low grades of
emphysema
 Also reduced in other diseases that destroy the
alveolar capillary bed
 Emphysema – DECREASED DLCO
 Chronic bronchitis – NORMAL DLCO (no
destruction of alveoli, only gland hypertrophy and
narrowing of airway lumen)
4. Arterial Blood Gas
 Early stages
o Mild or moderate hypoxemia without
hypercapnia
 Late stages
o Hypoxemia tends to become severe
o Hypercapnia develops, leading to acidosis
 Abnormalities worsen during acute exacerbations
and may also worsen during exercise and sleep
 Alterations in ABG largely reflect alteration in
ventilation-perfusion relationships
o Hypercapnia is observed with increasing
frequency as values of the FEV1 fall below
1L
5. Chest Radiograph
 Help exclude other pathology in patients with
COPD
 Chronic bronchitis
o Increased thickness of bronchial walls
viewed on end
o Increased prominence of lung markings
o Neither specific nor sensitive
 Emphysema (2 radiographic patterns) – LATE
disease
o Patterns of pulmonary arterial deficiency:
triad of overinflation, oligemia, and
bullae
o Increased markings which resembles the
“dirty chest” appearance
COMPLICATIONS OF COPD
 Overinflation
o Flattening of the diaphragm
o Increase in the width of the retrosternal
air space (less sensitive)
o CAUTION: may also be seen with severe
asthma
Retrosternal
airspace
Widening of the
Intercostal spaces
Flattening of the
diaphragm
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6. Computed Tomography
 Has the resolution needed to delineate and
quantify subtle findings → more sensitive in
emphysema
 Can visualize small blebs and emphysematous
airways
 Small blebs on the subpleural area may rupture
and cause spontaneous pneumothorax usually at
the apex.
 Methods to assess COPD
o CT density – quantify emphysema →
estimates of both severity and extent of
disease
o Analytic methods – distinguish the
pattern of emphysema
7. Laboratory test
 No biomarker have yet affected clinical practice
 Erythrocytosis or anemia may be a feature of
COPD
 Sputum examination
o Stable bronchitis
 Sputum: mucoid
 Microscopy: predominance of
macrophages; bacteria are few
o Exacerbation
 Sputum: grossly purulent
 Microscopy: influx of neutrophils;
number or organisms increases
 Culture: Streptococcus pneumonia
and Haemophilus influenza;
Moraxella catarrhalis
(orophrayngeal commensal flora)
most common pathogens in COPD
 Eosinophils – indicate a greater
likelihood to respond to inhaled
glucocorticoid therapy
 Cultures and Gram stains, however, are rarely
necessary for institution of antimicrobial therapy
unless the patient has sustained an exacerbation
during or soon after receiving a course of antibiotic
therapy.
 Pneumothorax- rupture of a bullae
 Cor pulmonale – any problem in lungs will be
transferred to the right side of the heart  RV
failure leading to cor pulmonale
 Pneumonia
 Sleep abnormalities – concomitant hypoventilation
aggravating hypercapnia
 Giant bullae – prone to rupture
CASTILLO, N.P. 3F
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Systemic Manifestation and Comorbidities RISK FACTORS FOR COPD

Cardiovascular Infarction  Genes

Arrythmia  Exposure to particles
Congestive heart failure o Tobacco smoke – most important risk factor
Aortic aneurysm o Occupational dusts, organic and inorganic
Hypercoagulability Stroke o Indoor air pollution from heating and cooking
Pulmonary embolism with biomass in poorly ventilated dwellings
Deep vein thrombosis o Outdoor air pollution
Atrophy
 Lung growth and development
Systemic Weight loss
 Gender
Osteoporosis
 Age- higher incidence as we grow old
Skin Wrinkling
Anemia  Respiratory infections
Lung Cancer  Socioeconomic status
 Asthma/ bronchial hyperreactivity
 Chronic bronchitis
*Smoking  causes 10-15% of the smoking population to
develop COPD but may have other diseases such as MI, Stroke, Cigarette smoking
lung CA
 Most important risk factor for COPD
BODE Index (predictor of mortality)  Smokers lose lung function in a dose-dependent manner
o This is the reason why we compute for the
pack years
 80% of individuals who have COPD and 80% who die
from COPD in the US are smokers
 There is variable susceptibility to the effects of cigarette
smoke and other factors also contribute to risk

Not all smokers will develop COPD. It is in the interplay of

exposure to noxious substances and inherited genes as a result,
we have different susceptibility in developing the symptoms of
COPD. Some may develop COPD early in life with little exposure
to smoke, some may develop COPD later in life even with very
high exposures to smoke.
6 MWD- 6 minute-walk test

 We measure the distance covered within 6 mins of

walking. Cigarette Smoking Effects on the Natural History of
 Severe COPD  less distance covered COPD:

BODE Index  Reduces maximally attained lung function (lung growth)

 Measures severity of COPD
 Body, Obstruction, Dyspnea, Exercise
 The higher the score, the higher the severity of COPD
EPIDEMIOLOGY OF COPD
 Higher in males than in females
 “Plateau phase” of lung development is reduced in
duration and may be absent causing a rapid decrease in
lung function
 Average decline of about 40 ml/yr (i.e. 2L over 50 years)
is the normal, with smoking, there is further decrease of
lung capacity.
 Smoking cessation in adulthood can slow the rate of
decline among individuals with mild COPD

BURDEN OF COPD

 COPD is the leading cause of morbidity and mortality

worldwide.
 The burden of COPD is projected to increase in coming
decades due to continued exposure to COPD risk factors
and the aging of the world’s population.
 COPD is associated with significant economic burden

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Normally, 10-18 years old, there is normal lung growth then it
plateaus for a few years. Through years, there will be slow and
gradual loss of 1L to 5mL/ year of lung capacity. In an average
smoker, there is a faster rate of decline of FEV1 compared to their
non-smoking counterparts. Highly susceptible smokers, those
with genetic predisposition, experience more decline in lung
function.
Occupational exposures
 Attributes nearly 20% of COPD risk among smokers and
more than 30% among non-smokers
Environmental air pollution (particulates)
 Contribute to accelerated decline in lung function
 Increased mortality
Indoor air pollution
 Smoke from biomass fuels
 Major cause of COPD in the developing world
 Systemic exposures have also been suggested to play a
role.
Early life events
 Maternal smoking may be a risk factor for the
development of COPD
o Has been associated with low birthweight and
increased incidence of respiratory illnesses
o Both Low Birth Weight and childhood
respiratory infections are risk factors for the
1. BRONCHITIS
development of COPD but not uniform
throughout.
Alpha 1- Antitrypsin Deficiency (discussed above)
 Explains the genetic susceptibility of certain patients
 Serpin E2 on chromosome 2  proteinase inhibitor but
is not an elastase inhibitor, another susceptibility gene
Asthma  constant hyperresponsiveness, increase chance of
developing of COPD (Dutch Hypothesis); accelerated loss of lung
function in asthmatics who smoke
Mucus Hypersecretion  recent studies haave shown that this
has small effect only
Gender
 Related to the demographics of exposure to cigarettes
or other inhaled toxins within a population
 Increased prevalence among men
 Equally prevalent among women in many populations
 Women
o Different comorbidities
o Lower prevalence of ischemic heart disease
o Higher prevalence of CHF, osteoporosis and
diabetes
Socioeconomic status
 Morbidity and mortality rates have been shown to be
inversely related to socioeconomic status (not yet
established)
[PULMO] COPD (DR. DACANAY/ DR. BAYOT)
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 Low SES  unable to access early diagnosis, lack of
COPD therapy
NATURAL HISTORY OF COPD
1. Early COPD
 Treatment goals in early disease include alleviation of
symptoms
 Early disease often have no complaints
 ATS guidelines (1995): it was not necessary to diagnose
such individuals
 Mild lung function compromise
o Increased mortality due to acute cardiac
events due to systemic inflammation
2. Advancing COPD
 As FEV1 declines, risk for mortality increases
 Cardiac events (MI)  major cause of death
 Death due to respiratory casues, however, increases
with increasing severity of lung function compromise
 Exacerbations
 Increase in frequency as FEV1 declines
 Less than 50% FEV1
 Times at which individuals are at particular
risk for death
 Mortality is also increased among those who have
recovered from an exacerbation
 Mortality rate: 30-49%
PATHOLOGY OF COPD
 Bronchi
o Submucosal glands  dialted ducts;
hypertrophy and hyperplasia of glandular
elements
o Increased goblet cell frequency
o Patchy areas of squamous metaplasia and
dysplasia may replace normal ciliated
epithelium; persistent smoking  precipitates
squamous metaplasia to overt CA.
o Increased amount of airway smooth muscle
 Reid index or ratio of glandular to bronchial wall
thickness
o Traditional way of measuring glandular
enlargement
 Respiratory bronchioles
o Airways less than 2 mm in diameter
o Primary sites of physiologic airway
obstruction with narrowing
 Airway remodelling processes are similar to those in
larger airways
 Goblet cell metaplasia with mucus plugging,
inflammation, smooth muscles hyperplasia, and fibrosis
 Smoking leads to predominantly mononuclear
inflammatory process particularly CD8 T cells
o In asthma – CD4 T cells
o In bronchitis – CD8 T cells; and BALT in late
stages of COPD
 Destruction of lung parenchyma  loss of alveolar
attachments  small airway collapse
CASTILLO, N.P. 3F
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 Involves the upper and posterior

portions of the lungs more than
the lower portions.

2. Panacinar Emphysema

Normal bronchus vs. Bronchus of Chronic bronchitis. In

Chronic bronchitis, there is airway compromise due to
submucosal hypertrophy and increase in mucus
production.
o Dilatation of all of the respiratory air
Collagen deposition  makes the airway more fibrotic, spaces of the secondary lung lobule
making it hard and unresponsive to bronchodilators o May be either focal or diffuse
(“remodelling of the airways”) o Associated clinical diseases:
2. EMPHYSEMA  Congenital lobar overinflation or
emphysema from bronchial atresia
 Characterized by destruction of gas exchanging air
(apicoposterior segmental bronchus
space including respiratory bronchioles, alveolar ducts
of the left upper lobe)
and alveoli
 Intravenous Ritalin
 Alveolar walls become perforated and later, in the
(methylphenidate tablet) abusers
absence of repair, become obliterated with
coalescence of small distinct air spaces into abnormal
a. Focal Panacinar
and much larger air spaces, forming giant bulla.
 More common at the lung bases than
Types of Emphysema (favorite questions come from here according to Dr. at the apices and are often seen in
Dacanay) older persons

1. Proximal Acinar Emphysema b. Diffuse Panacinar

 Most often associated with A1 PI
deficiency
 the emphysema is usually more
severe at the bases than the apices

3. Distal Acinar Emphysema

o Begin in the respiratory bronchioles

o Scarring and focal dilatation of the bronchioles
and of the adjacent alveoli leading to enlarged
air space or microbulla in the center of the
secondary lung lobule
o Focal emphysema and centriacinar o Also known as paraseptal or subpleural
emphysema
a. Focal emphysema o Localized along fibrous interlobular septa
 A form of centriacinar emphysema or beneath the pleura
 Occurs in persons who have has heavy o Pulmonary function may be normal or
exposure to a relatively inert dust nearly so despite the presence of many
such as coal dust superficial areas of locally severe
 Associated with large numbers of emphysema
pigment laden macrophages o Produces the apical bullae giving rise to
simple spontaneous pneumothorax in
b. Centriacinar Emphysema young persons
 Form of emphysema most frequently
associated with prolonged cigarette
smoking in persons who have had no
unusual dust exposure

[PULMO] COPD (DR. DACANAY/ DR. BAYOT) CASTILLO, N.P. 3F


Bullae
 Areas of marked focal dilation of respiratory air spaces
 Results from:
o Coalescence of adjacent areas of emphysema
o Locally severe panacinar emphysema
o Ball valve effect in the bronchi supplying an
emphysematous area
 May be simple air spaces or may retain the trabeculae of
the emphysema that led to them
 Occurs as a part of widespread emphysema
Blebs
 Intrapleural collections of air
 A form of interstitial emphysema
 Complication of interstitial emphysema in the newborn
period
 Complication of pulmonary barotraumas complicating
mechanical ventilation  high pressures from
mechanical ventilation may cause production of blebs
 Part of the spontaneous pneumomediastinum of adults
 Rupture  cause of spontaneous pneumothorax
Cysts
 Air spaces lined by epithelium, which usually have the
characteristics of bronchial epithelium
 Also known as intrapulmonary bronchogenic cyts
 Occur near the tracheal bifurcation but they may be
seen more peripherally in the lung parenchyma
STRUCTURE-FUNCTION CORRELATION IN COPD
Cause of airway limitation in COPD
 Airflow is not obstructed by bronchial gland
enlargement
 Airflow is reduced by narrowing of airways due to
o Smooth muscle contraction
o Narrowing of airways, particularly the small
airways due to peribronchial fibrosis
o Destruction of the alveolar wall that results in
loss of lung elastic recoil and loss of tethering
of small airways, thus permitting small airway
collapse during expiration
If the attachments of the alveolar walls are destroyed, these
permit the early collapse of the alveoli during expiration. This is
the reason why air is trapped inside the lungs.
Compliance and Lung Volumes in Emphysema
 Increased compliance of the lungs  consistently
decreased elastic recoil pressures
Lungs are easily stretched because of the destroyed tethering
mechanism of alveolar walls.
[PULMO] COPD (DR. DACANAY/ DR. BAYOT)
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Carbon Monoxide Diffusing Capacity (DLCO)
 Loss of internal surface area of the capillary bed of the
lung with emphysema
 Failure to increase in COPD patients (supine or prone
position) possibly due to loss of capillary capacitance of
capillary volume
 Decrease DLCO in emphysema
PATHOGENESIS OF CHRONIC BRONCHITIS
Small Airway Obstruction
 Chronic bronchitis refers to symptoms of chronic sputum
production
 Mainly a manifestation of large airway disease
 Obstruction of bronchioles less than 2 mm diameter is a
major factor in airflow obstruction in COPD
 Cigarette smoke may lead to similar types of injury and
inflammation in the airway as in the airspaces, the
manifestations are distinct
 Major remodeling events include goblet cell hyperplasia
with excessive mucus production, epithelial dysplasia,
smooth muscle hypertrophy, airway fibrosis, and
inflammation including BALT in late GOLD stages
Airway Inflammation
 Characterized by increased numbers of neutrophils,
monocytes, and lymphocytes. No eosinophils!
 CD8+ T cells and B cells, in particular, grow with increasing
severity of COPD
 Oxidants and other particulates in cigarette smoke induce
epithelial cells and constitutive macrophages to release
cytokines and chemokines that activate the innate as well as
adaptive immune response
Goblet Cell Metaplasia
 Structural changes (glandular hyperplasia and
increased number of goblet cells) --increased
mucus production
 Neutrophil elastase not only causes elastin destruction
in the lung parenchyma but also acts as a potent
secretagogue working via cleavage of membrane
tethered transforming growth factor-α (TGF-α) that
activates the epidermal growth factor receptor (EGFR),
leading to expression of the MUC5AC mucin
 Other factors such as oxidants and matrix
metalloproteinases (MMPs) may also induce EGFR-
mediated mucus production.
Epithelial Injury, Repair and Fibrosis
 Insults to airway epithelium result to endoplasmic
reticulum stress and potentially to cell death
 Lung can restore epithelial integrity
 Aberrant repair can fail to “turn off” the
fibroblast response or lead to epithelial
mesenchymal transformation  peribronchial
fibrosis that contributes to expiratory airflow
limitation
CASTILLO, N.P. 3F
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Exacerbations ASTHMA vs. COPD

 Pathogens first encounter innate host defense (mucociliary

clearance, the epithelial barrier, constitutive host
macrophages, and rapidly accumulating neutrophils)

 Tobacco smoking impairs macrophage phagocytosis, and

airway remodeling interferes with mucociliary clearance,
each predisposing to airway colonization and acute
infectious bacteria and viruses
 Chronic infections with a variety of pathogens may lead to
increased chronic inflammation
o Can potentially predispose both to loss of lung
function and to increased risk for acute
exacerbation.
 Acute infections with viruses and bacteria are major
causes of acute exacerbations
o COPD patients are advised to have pneumonia and Proteinase-Antiproteinase Theory in COPD Pathogenesis
influenza vaccines to lessen acute exacerbations  Elastases
o Association of chronic airflow obstruction and
PATHOGENESIS OF EMPHYSEMA
emphysema with deficiency of serum A1PI, the
endogenous inhibitor of neutrophil elastase
o Intratracheally instilled papain, a plant-derived
cysteine proteinase. Into experimental animals,
resulting in a airspace enlargement
(emphysema)
 Emphysema could be induced by proteolytic injury to
the lung extracellular matrix

Elastase-Induced

 Neutrophil elastase
o Increased air space size and lung volumes

Alveolar destruction  Pocrine pancreatic elastase (PPE)

 Brought about by disruption of the ECM by MMPs and o Initial rapid increase in air space size due to direct
Neutrophil Elastases as well as elastolysis with diminution of lung elastin content
 cytotoxic enzymes (performing and granzymes) from at 24 hours
the inflammatory cells causing cell death
 Autoantibodies produced by BALT  Although elastin is critical to the structural integrity of the
Airway fibrosis lung, other matrix components such as collagen must also
 Release of TGF-B activating fibroblasts causing fibrosis be lost for an alveolar space to enlarge
and deposition of collagen.
 A broader concept is the proteinase-antiproteinase
MECHANISMS UNDERLYING AIRFLOW LIMITATIONS IN COPD hypothesis, which states that the balance between matrix-
degrading proteinases and their endogenous inhibitors
determines whether the lung is protected or susceptible to
Small Airways Disease Parenchymal destruction proteolytic injury
 Airway inflammation  Loss of alveolar
 Airway fibrosis, luminal attachments Proteinases
plugs  Decrease of elastic recoil
 Increased airway  Serine proteinases
resistance  Matrix metalloproteinases
 Cysteine proteinases
 Aspartic proteinases
AIRFLOW LIMITATION

Alpha1- Proteinase Inhibitor Deficiency

 Serpin or serine proteinase inhibitor is a

prominent protein in the serum
o Commonly known as alpha1-antitrypsin

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o Produced mainly in the liver; found in high
concentrations in the bloodstream, and permeates
tissues including the lung
o Acute phase reactant, with its serum concentration
rising during pregnancy, during infections, after
severe burns, and in the presence of malignant
tumors
o Smoking elevates the serum A1PI concentration by
about 20%
Assess degree of Airflow Limitation
 use spirometry for grading severity according to
spirometry, using for grades split at 80%, 50% and 30%
of predicted value
Classification of severity of airflow limitation in COPD
In patients with FEV1/FVC <0.70 post bronchodilator:

GOLD 1 Mild FEV1 ≥ 80% Predicted

 M allele – normal
GOLD 2 Moderate 50% ≤ FEV1 < 80% predicted
 Z allele – single amino acid point mutation:
GOLD 3 Severe 30% ≤ FEV1 < 50% predicted
substitution of a lysine for a glutamic acid
GOLD 4 Very Severe FEV1 <30% predicted
 Pi MM – normal (150-350 mg/dl or 20-48
μmol)
 Pi ZZ – severely deficient (2.5-7 μmol) *FEV1/FVC ≥ 0.70 post bronchodilator  does not qualify for
 Pi MZ – A1PI levels intermediate (12-35 μmol) COPD assessment
 The premature development of severe emphysema is the A 65 year old with a 45-pack year smoking history came back
hallmark of homozygous A1PI deficiency with the results of his PFT. PFT result showed the ff:
 Symptoms or signs of pulmonary disease rarely develop
before age 25 years FEV1: 48% predicted
 onset of dyspnea occurs at a median age of 40 years in Pi Z FVC: 90% predicted
smokers and 53 years in nonsmokers FEV1/FVC: 53
 Bronchiectasis has been reported in association with A1PI
deficiency. Post bronchodilator PFT showed:
 Tobacco smoking and the development of pulmonary
disease are strongly associated. Smokers who are type Pi Z FEV1: 49% predicted
have a significantly lower life expectancy than nonsmokers
FVC: 90% predicted
who are type Pi Z.
FEV1/FVC: 54
 Asthma, recurrent respiratory infections, and unidentified
genetic factors have been suggested as possible risk factors
for chronic airflow limitation. Classify the severity of airflow limitation
 Radiographically, Pi Z patients characteristically have more
1. Is this and obstructive ventilatory defect?
definite evidence of emphysema. The finding of basilar
To answer: look at the post bronchodilator FEV1/FVC ratio
emphysema is not constant in Pi Z patients, but when
present, it is strongly suggestive of the diagnosis. FEV1/FVC ratio = 54  obstructive
2. Classify the severity
GLOBAL STRATEGY FOR DIAGNOSIS, MANAGEMENT AND Look at FEV1 post bronchodilator  49% predicted 
PREVENTION OF COPD severe
3. What is its reversibility?
CLINICAL EVALUATION OF COPD Reversibility is 12% and 200ml increasein FEV1 post
bronchodilator and is computed by:
 Clinical evaluation should assess 3 components for guiding
COPD patient’s management:
o Assess symptoms
o Assess airflow limitation
o Assess risk of exacerbations
2% reversibility is not significant. Therefore, this patient
Assess Symptoms of COPD has:
Severe obstructive ventilator defect with no significant
 The characteristic symptoms of COPD are chronic and bronchodilator response. Since there is no significant
progressive dyspnea, cough, and sputum production. bronchodilator response, we can confirm that this is COPD.
 Dyspnea: Progressive, persistent and characteristically
It is not asthma because asthma has a significant
worse with exercise.
bronchodilator response.
 Chronic cough: May be intermittent and may be
unproductive.
 Chronic sputum production: COPD patients Assess Risk of Exacerbations
commonly cough up sputum.
 use history of exacerbations and spirometry
 Use COPD Assessment Test  two exacerbation or more within the last year or an
 mMRC Breathlessness Scale FEV1 <50% of predicted value are indicators of high
risk

[PULMO] COPD (DR. DACANAY/ DR. BAYOT) CASTILLO, N.P. 3F

 10

Exacerbations 3. Use combined assessment

 An acute event characterized by a worsening of the

patient’s respiratory symptoms that is beyond normal
day-to-day variation and leads to a change in
medication.

COMBINED ASSESSMENT OF COPD

When assessing risk, choose the highest risk according to GOLD

grade or exacerbation history. One or more hospitalizations for
COPD exacerbations should be considered high risk.

Patient Characteristic Spirometric Exacerbation/ CAT mMRC

Classification year
A Low risk, Less GOLD 1-2 ≤1 ≤ 0-1
Symptom 10
B Low risk, more GOLD 1-2 ≤1 ≥10 ≥2
symptom
C High risk, less GOLD 3-4 ≥2 <10 0-1
On the left side of the rubric, we assess the risk of airflow symptoms
limitation using spirometry. At the bottom of the rubric, we D High risk, GOLD 3-4 ≥2 ≥10 ≥2
assess the symptoms using COPD assessment test and mMRC. On more
the right, we assess the rate of exacerbation. symptoms

With all the elements complete, we can now classify the patient.
A 60 year old male, known COPD patient consulted because of on
1. Assess symptoms first and off dyspnea especially during walking and has to stop for
breath after walking about 100 meters. It was accompanied by
productive cough with whitish phlegm. History also revealed 2
episodes of exacerbation since last year.

PFT result showed the ff:

 FEV1: 48% pred

 FVC: 90% pred
 FEV1/FVC: 53

Post bronchodilator PFT showed:

 FEV1: 49% pred

 FVC: 90% pred
2. Assess risk of exacerbations next  FEV1/FVC: 54

Combining all the risk assessments, in what group will this

patient belong?

1. Assess symptoms first.

We use the mMRC  stop for breath after walking
about 100 meters.
 Grade 3 : Category B
2. Assess risk of exacerbation
2 episodes of exacerbation since last year  Category B
or D, but we choose D because of his mMRC result.
3. Combine all the risk assessment  Category D

*memorize the mMRC questionnaire found at the last page of this trans..
For CAT no need to memorize, only the score will be given in the exam.

[PULMO] COPD (DR. DACANAY/ DR. BAYOT) CASTILLO, N.P. 3F

 11

TREATMENT Salmeterol and formoterol  12 hours duration

Therapeutic goals include: LAMA

 Prevention of disease progression  Tiotropium – OD 24 hours duratioon

 Relief of symptoms  Glycopyronium – OD 24 hours duration
 Improvement in exercise tolerance
 Improvement in health status 2- Agonist Anticholinergics
 Prevention and treatment of exacerbations  Bronchodilation and  Block action of Ach on
improvement in M3 muscarinic
 Prevention and treatment of COPD- related complications
airflow in some pts receptors, which
 Reduction in mortality w/ COPD induce contraction of
 Increase ciliary airway smooth
Reduction of Risk Factors
beating frequency muscle.
 Smoking cessation  Improve mucus  Tiotropium has a
o Cessation early in the development of COPD can transport prolonged duration of
 Improve endurance action because it
stop the accelerated loss of lung function
of fatigued dissociates from M3
o Cessation later in the course of disease may not be
respiratory muscles receptor extremely
as effective because airway inflammation may slowly
 SABA & LABA
persist  Short-acting” agents
 SABA: rapid onset
o Nevertheless, cessation at any age reduces overall (ipratropium and
after inhalation (5 to
mortality. 15 min) that persists oxitropium):
o Smoking should be regarded as a primary disease for 2 to 4h bronchodilation in
 Behavioral support program appropriate > Salbutamol 10-15 min and last 4-
for the patient > Terbutaline 6h
 Pharmacologic support (bupropion,  Long-acting
varenicline, nortryptiline and clonidine)  LABAs): longer onset (tiotropium,
but bronchodilation glycopyronium):
 Other risk factors for up to 12 hours or slower in onset, peak
o Avoidance of exposures to other noxious dusts and more bronchodilator
>Salmeterol activity after 1-2h, but
fumes (environmental or occupational exposures)
>Formoterol has a markedly
 Slows disease progression prolonged duration.
> Indacaterol
 May have benefit even late in the disease used once daily
>Vinalterol
o Influenza vaccination can reduce mortality among
Mode  M-dose inhaler  Inhalation using an
elderly patients and should be given annually to all (MDI) or a dry MDI or DPI (preferred
COPD patients and prevent exacerbation powder inhaler mode)
o Pneumococcal vaccine is also recommended (less (DPI) – preferred
data support)  Nebulized aqueous
solutions of β-
agonist - unable to
MANAGEMENT OF STABLE COPD: PHARMACOLOGIC generate flow rates
THERAPY needed for effective
use of the above
First Choice and Second Choice Drugs (Memorize and it is expected devices
that we know the examples of each drug classes) 
Nebulizers - effective
in pts too weak to
use inhaler device,
altered mental
status, or in those
whose inspiratory
capacity is too
limited to permit
effective inhalation[
Tx  Improvement in  Improvement in
Effects airflow obstruction airflow obstruction
 Symptom relief  Symptom relief
 Exacerbation  Exacerbation
prevention prevention
 Alteration of dse
progression: trend of
Roflumilast and other PDE-4 Inhibitors  selective long acting; mortality that did
chronic bronchitic patients; add on therapy not reach statistical
significance
Indacaterol and Vinalterol  new LABA drug , 24 hours duration

[PULMO] COPD (DR. DACANAY/ DR. BAYOT) CASTILLO, N.P. 3F

 12

Side  Tremor, palpitations,  Local toxicities: can  Cromolyn Sodium Nedocromil & Leukotriene
Effects anxiety, and precipitate acute Antagonist
insomnia (most attacks of glaucoma o There are no data establishing a role for cromolyn,
common)  Systemic effects: dry nedocromil, or cysteinyl leukotriene antagonists in
 Ventricular mouth and urinary treating COPD
arrhythmias and retention  Expectorants
hypokalemia  Contraindicated in o Role in promoting mucous clearance in COPD
BPH  urinary patients remains controversial
retention o Consensus that agents like guaifenesin and glyceryl
guaiacolate provide little or no benefit in most
patients
Methylxanthines Inhaled Glucocorticoid
 Theophylline - only Physical therapy
methylxanthine o Postural drainage
currently used to treat  Major sputum producers <>30ml/day)
COPD patients  Difficulty coughing up their secretions
Tx  Mild - Modest  Improvement in o Procedure
Effects bronchodilator airflow obstruction:  Bronchodilator should be
activity 50- to 100-mL in administered 20 to 30 minutes before
 Anti-inflammatory FEV1 postural drainage
effects  Symptom relief  Cupped hand chest wall percussion or the
 Modest inotropic and  Exacerbation use of an electromechanical percussor
diuretic effects prevention: risk of  Mucolytics
 May augment skeletal 20% to 25% o Increased mucus production
muscle strength  Alteration of dse  Hypertrophied and hyperplastic airway
progression submucosal glands and goblet cells
 Impaired mucociliary clearance and
 reduced
cough
hospitalization and
o Avoidance of inhaled irritants - most successful
reduced mortality
means of controlling excessive airway mucous secretion
Side Dose-related  Local effects: oral
o No remedy is supported by evidence from rigorous
Effects  Nausea and vomiting, candidiasis
clinical trials
seizures, and (thrush) and
o Clinician must individualize patient management
arrhythmias dysphonia
o N-Acetyl cysteine - active antioxidant, and this may be
 Inhaled Glucocorticoid  Advise px to brush its means of action rather than its properties as a
 Pathogenesis of COPD: or gargle after mucolytic
inflammation treatment o Iodinated glycerol may have had some symptomatic
 Systemic: increased benefits, but removed from marketplace - toxicity
bruising and o Saturated solution of potassium iodide (SSKI)
reduced bone alternative
density
Long term Oxygen Therapy
 Bronchodilators
o Effects may be due to alterations in resting tone o Long-term O2 therapy extends life in hypoxemic COPD
rather than an effect on “bronchospasm” patients
 Modest improvement may be of benefit o 24-h regimen more beneficial than 12-hour regimen
for the compromised COPD patient o Other benefits:
o Improvement in lung volumes, particularly in o Reduction in hematocrit
dynamic hyperinflation, may also occur o Modest neuropsychological improvement
o Bronchodilators are often used in COPD both on a o Some improvement in pulmonary hemodynamics
o Improve dyspnea and work of breathing by reducing airway
chronic basis and also as needed for “rescue”
resistance and decreasing minute ventilation needs
o Patients with COPD most commonly experience
o Can be given in 12 hr duration during daytime.
dyspnea due to increased respiratory demands,
such as occurs with exertion and exercise Indications
o For Prevention of exercise induced bronchospasm:  Resting arterial Po2 55mmHg while breathing air
long active bronchodilators are probably both  Resting arterial Po2 is between 56-59mmHg who
more convenient and more effective demonstrate erythrocytosis/ polycythemia (Hct≥ 55%)
or evidence of cor pulmonale
 Systemic Glucocorticoid
o If at all possible should be avoided associated with Oxygen during Exercise
increased mortality (more likely due to underlying  Pts w/an arterial Po2 of 60mmHg while breathing room air
disease) may develop worsening hypoxemia with exercise
o Randomized study demonstrated  No difference
in FEV1, symptoms, or exacerbation frequency

[PULMO] COPD (DR. DACANAY/ DR. BAYOT) CASTILLO, N.P. 3F


Oxygen during Sleep
 Pts w/COPD typically have a drop in arterial oxygen tension
during sleep, particularly those patients with mild resting
hypoxemia (daytime resting Sao2 less than 95%)
Commercial Air Travel
 Cabins of commercial airlines are pressurized to an altitude
between 5000 and 10000 ft
o Reduced inspired oxygen partial pressure
o Arterial PO2 may fall below 40 mmHg in some
patients with COPD
 Extensive experience has proved that flying without
supplemental oxygen is safe for most subjects with COPD
 Hypercapnic COPD patients should employ supplemental
oxygen while flying
o Patients are advised to have a pre-flight
assessment and CT Scan to detect bullae and blebs.
 In flight desaturation can be measured by a hypoxic
challenge, which correlates well within flight saturation
 Patients with major bullous disease should be warned that
ascent to high altitude can precipitate life threatening
pneumothorax; such a patient should probably not fly.
Pulmonary Rehabilitation
 Attempts to return highest possible functional capacity,
 Essential component in comprehensive care for pts
w/severe COPD
 Benefits: improved independence and quality of life,
hospital days, and improved exercise capacity
 Lung function, assessed by FEV1, is not improved
 Effects on health status (“quality of life”) are generally much
greater than seen w/pharmacologic treatment
 All components contribute to patient well-being.
 exercise training is key
 upper body training to develop the respiratory muscles
Controlled Breathing
 Techniques
o pursed lip breathing and deliberately slow prolonged
expiration, which may be coupled with manual upper
abdominal compression and the standing bent-forward
position, with the outstretched arms and hands
supporting the body
 the main benefit appears to be a decrease in end expiratory
lung volumes as a result of the prolongation of expiratory
time
 increase airway pressure and this prevent dynamic airway
collapse and may transiently improve arteria PO2
 The overall benefit of these techniques, however, remains to
be established.
Nutrition
 Patients with advanced COPD and a predominance of
emphysema often experience progressive weight loss, with
some patients becoming frankly cachectic
o Marked somatic depletion incl a sig reduction in
triceps skinfold thickness
 CAUSE: multifactorial including a 15-25% in resting
energy expenditure, and circulating inflamm cytokines
 Main consequence is muscle strength incl weakness of
both the inspiratory and the expiratory muscles
[PULMO] COPD (DR. DACANAY/ DR. BAYOT)
13
 Improved nutrition can restore respiratory and general
muscle strength and endurance, but such improvement
is realized only after clear-cut weight gain
 Anabolic androgens can improve muscle strength and may
improve body mass, but there is insufficient evidence to
support their routine use
Lung Volume Reduction Surgery
 National Emphysema Treatment Trial (NETT)
o Localized disease and with poor exercise capacity
o LVRS - reduction in mortality and improvements in
HRQOL and exercise capacity
 Advised for patients with multiple bullous emphysema by
removing localized bulla
 Currently available at a limited number of centers and
should be considered for patients likely to meet the selection
criteria
Lung Transplantation
 More difficult than transplantation of other solid organs
 Prone to infection & rejection, and there are special
problems related to its preservation before transplantation
 Single-lung transplant - most common procedure of choice
when transplantation is performed for emphysema
 Bilateral lung transplant may provide better outcomes
ACUTE EXACERBATIONS
 Course of COPD is characterized by episodic periods of
worsening symptoms, termed exacerbations
 Widely used definitions relate sx to need to utilize
healthcare resources
 Two key approaches to exacerbation management:
prevention and acute care
Prevention
 ICS - 20% reduction in exacerbation frequency
 Tiotropium has an effect of similar magnitude
 Ipratropium may have a modest effect
 LABA bronchodilators, used alone, may also reduce
exacerbations and salmeterol may be more effective than
formoterol
o Formoterol- fast acting, long acting, used mainly as
controller
 Influenza vaccination probably reduces the frequency of
influenza-associated exacerbations
Acute Management
 Antibiotics
 Glucocorticoids
 Bronchodilator
 Oxygen
 Ventilator support
1. Antibiotics
 About ½ of acute exacerbations of chronic bronchitis are
assoc w/bacterial infection by pathogens that commonly
colonize Respiratory Tract: H. influenzae, S. pneumoniae, M.
catarrhalis.
 Treatment is usually empirical and not based on sputum
cultures.
CASTILLO, N.P. 3F

 7-10-day course is most often, although 5d is probably
sufficient.
 If systemic symptoms such as fever are prominent, patient
should be regarded as having pneumonia and treated with
broad-spectrum antibiotic coverage as recommended.
2. Glucocorticoids
 IV Systemic corticosteroids demonstrated to reduce
recovery time and to reduce treatment failures when used
to treat acute exacerbations
 Dose required is not clear, but 30-60mg of prednisone or
equivalent appears to be adequate
 Duration also not established, but 2wks treatment appears
sufficient
3. Bronchodilator
 General practice to use rapidly acting bronchodilators and,
for very ill patients, to use nebulizers, because many patients
may not be able to generate flows required to use other
devices during an exacerbation.
 3 doses for every 15 minutes
 IV aminophylline can improve lung function slightly,] but
its overall clinical benefits remain controversial It should be
used only with caution & blood theophylline levels should be
monitored.
Acute Respiratory Failure
 ARF in COPD is defined as development of an arterial
Pco2 above 50mmHg or an arterial Po2 below 50mmHg
in association with recent clinical worsening.
 Most are caused by superimposed acute chest illness such as
an acute exacerbation, but other causes e.g. pneumothorax,
congestive HF, pulmonary embolus and metabolic
derangements like hypophosphatemia or hypokalemia
 Goals of treatment are primarily maintenance of adequate
oxygenation and prevention of respiratory acidosis & 2
complications.
4. Oxygen
 Supplemental oxygen should be given to maintain the Po2
above 60 mm Hg and the Sao2 above 90%
 Rises in arterial Pco2 may occur because of suppression of
hypoxic peripheral chemoreceptor ventilatory drive, the
Haldane effect, in which oxygenated Hgb transports less
carbon dioxide than deoxygenated hemoglobin, and the
worsening of ventilation-perfusion matching in diseased
lungs
o We do not want to exceed ventilation by 80mmHg
because it will suppress CO2 transport. Loss of CO2
will decrease the ventilation drive, thus further
worsening the V/Q mismatch.
 Hypoxic ventilatory drive is not usually suppressed until
arterial Po2 increases to 60mmHg or higher.
5. Ventilatory Support
 A major advance in the treatment of acute exacerbations of
COPD has been the implementation of non-invasive positive-
pressure ventilation Not only can intubations be avoided,
but mortality for severe COPD exacerbations is also
substantially reduced.
[PULMO] COPD (DR. DACANAY/ DR. BAYOT)
14
 There are several contraindications to its use including
respiratory arrest, cardiac instability, high aspiration
risk, and inability to fit the device securely.
 If contraindications are present or if noninvasive ventilation
is inadequate, patients may require intubation and
mechanical ventilatory support
Non-Invasive Ventilation
o Positive pressure is applied
o Given through a mask
o Acts as a pneumatic splint
o Golden period
o Within 1- 2 hours tachypnea should
disappear
o pCO2, respiratory frequency and pH should
normalize
Invasive Ventilation
o applied by using an endotracheal tube
o given when patient becomes unresponsive to non-
invasive ventilation
Indications for NON-invasive Ventilation (at least 2 criteria)
 Moderate to severe dyspnea with use of accessory muscles
and paradoxical abdominal motion
 Moderate to severe acidosis (pH 7.30-7.35) & hypercapnia
(PaCO2 >45-60)
 Respiratory frequency > 25 breaths/min
Contraindications for NON-invasive ventilation
1. Respiratory arrest
2. CV instability (hypotension, arrhythmias, MI)
3. Somnolence, impaired mental status, uncooperative
4. High aspiration risk, copious secretions
5. Recent facial or gastroesophageal surgery
6. Craniofacial trauma, fixed nasopharyngeal abnormality
7. Burns
8. Extreme obesity
Indications for INVASIVE Ventilation:
1. Severe dyspnea w/ use of accessory muscles &
paradoxical abdominal motion
2. Respiratory frequency >35 breaths/min
3. Life-threatening hypoxemia (paO2 <40 or PaO2/FiO2 <200)
4. Severe acidosis (pH<7.25) & hypercapnia (PaCO2 >60)
5. Respiratory arrest
6. Somnolence, impaired mental status
7. Cardiovascular instability
8. Failure of non-invasive ventilation (no improvement after 2
hours on non-invasive ventilation)
CASTILLO, N.P. 3F