Chronic

Obstructive Pulmonary
Disease

Yoshiko Ikeda-Maquiling, MD
Chronic obstructive pulmonary disease (COPD) is defined as a disease state
characterized by airflow limitation that is not fully reversible

Emphysema – an anatomically defined condition characterized by
destruction and enlargement of the lung alveoli

Chronic bronchitis - a clinically defined condition with chronic cough and
phlegm

Small airways disease - a condition in which small bronchioles are narrowed
•  Chronic obstructive pulmonary disease (COPD) is
defined as a disease state characterized by airflow
limitation that is not fully reversible).

•  COPD includes emphysema, an anatomically defined

condition characterized by destruction and
enlargement of the lung alveoli; chronic bronchitis, a
clinically defined condition with chronic cough and
phlegm; and small airways disease, a condition in
which small bronchioles are narrowed.

•  COPD is present only if chronic airflow obstruction

occurs; chronic bronchitis without chronic airflow
obstruction is not included within COPD.
 Risk Factors
Cigarette smoking
Major risk factor for mortality
Pack-years – average number of packs of cigarettes
smoked per day multiplied by the total number of
years of smoking
Most highly significant predictor of FEV1
Environmental and/or genetic factors contribute to
the impact of smoking on the development of
airflow obstruction
•  By 1964, the Advisory Committee to the Surgeon General of
the United States had concluded that cigarette smoking was a
major risk factor for mortality from chronic bronchitis and
emphysema. Subsequent longitudinal studies have shown
accelerated decline in the volume of air exhaled within the
first second of the forced expiratory maneuver (FEV1) in a
dose-response relationship to the intensity of cigarette
smoking, which is typically expressed as pack-years (average
number of packs of cigarettes smoked per day multiplied by
the total number of years of smoking).

•  This dose-response relationship between reduced pulmonary

function and cigarette smoking intensity accounts for the
higher prevalence rates for COPD with increasing age.
•  The historically higher rate of smoking among males
is the likely explanation for the higher prevalence of
COPD among males; however, the prevalence of
COPD among females is increasing as the gender gap
in smoking rates has diminished in the past 50 years.
Although the causal relationship between cigarette
smoking and the development of COPD has been
absolutely proved, there is considerable variability in
the response to smoking. Although pack-years of
cigarette smoking is the most highly significant
predictor of FEV1 (Fig. 260-1), only 15% of the
variability in FEV1 is explained by pack-years. This
finding suggests that additional environmental and/
or genetic factors contribute to the impact of
smoking on the development of airflow obstruction.
 Risk Factors
Airway Responsiveness and COPD
Dutch hypothesis suggests that asthma, chronic
bronchitis, and emphysema are variations of the same
basic disease, which is modulated by environmental
and genetic factors to produce these pathologically
distinct entities
British hypothesis contends that asthma and COPD are
fundamentally different diseases: Asthma is viewed as
largely an allergic phenomenon, while COPD results
from smoking-related inflammation and damage
•  A tendency for increased bronchoconstriction in response to a
variety of exogenous stimuli, including methacholine and
histamine, is one of the defining features of asthma (Chap.
254). However, many patients with COPD also share this
feature of airway hyperresponsiveness. The considerable
overlap between persons with asthma and those with COPD
in airway responsiveness, airflow obstruction, and pulmonary
symptoms led to the formulation of the Dutch hypothesis.

•  This suggests that asthma, chronic bronchitis, and

emphysema are variations of the same basic disease, which is
modulated by environmental and genetic factors to produce
these pathologically distinct entities.
•  The alternative British hypothesis contends that asthma and
COPD are fundamentally different diseases: Asthma is viewed as
largely an allergic phenomenon, while COPD results from
smoking-related inflammation and damage. Determination of the
validity of the Dutch hypothesis vs. the British hypothesis awaits
identification of the genetic predisposing factors for asthma and/
or COPD, as well as the interactions between these postulated
genetic factors and environmental risk factors. Of note, several
genes related to the proteinase-antiproteinase hypothesis have
been implicated as genetic determinants for both COPD and
asthma, including ADAM33 and macrophage elastase (MMP12)
as described below.
•  Longitudinal studies that compared airway responsiveness at the
beginning of the study to subsequent decline in pulmonary
function have demonstrated that increased airway
responsiveness is clearly a significant predictor of subsequent
decline in pulmonary function. Thus, airway hyperresponsiveness
is a risk factor for COPD.
 Risk Factors
Respiratory Infections

Occupational Exposures
Coal mining, gold mining, and cotton textile dust,
have been suggested as risk factors for chronic
airflow obstruction

Ambient Air Pollution
Biomass combustion – significant risk factor for
COPD among women

•  The impact of adult respiratory infections on decline in
pulmonary function is controversial, but significant long-term
reductions in pulmonary function are not typically seen
following an episode of bronchitis or pneumonia. The impact
of the effects of childhood respiratory illnesses on the
subsequent development of COPD has been difficult to assess
due to a lack of adequate longitudinal

•  Increased respiratory symptoms and airflow obstruction have
been suggested to result from general exposure to dust and
fumes at work. Several specific occupational exposures,
including coal mining, gold mining, and cotton textile dust,
have been suggested as risk factors for chronic airflow
obstruction.
•  Although nonsmokers in these occupations developed some
reductions in FEV1, the importance of dust exposure as a risk
factor for COPD, independent of cigarette smoking, is not certain
for most of these exposures. However, a recent study found that
coal mine dust exposure was a significant risk factor for
emphysema in both smokers and nonsmokers. In most cases, the
magnitude of these occupational exposures on COPD risk is likely
substantially less important than the effect of cigarette smoking.
•  Some investigators have reported increased respiratory
symptoms in those living in urban compared to rural areas, which
may relate to increased pollution in the urban settings. However,
the relationship of air pollution to chronic airflow obstruction
remains unproved. Prolonged exposure to smoke produced by
biomass combustion—a common mode of cooking in some
countries—also appears to be a significant risk factor for COPD
among women in those countries. However, in most populations,
ambient air pollution is a much less important risk factor for
COPD than cigarette smoking.
 Risk Factors
Passive or second-hand smoking exposure
Maternal smoking results to reduced lung
growth in children

Genetic considerations
α-1 antitrypsin deficiency – associated with
early-onset COPD

•  Exposure of children to maternal smoking results in
significantly reduced lung growth. In utero tobacco smoke
exposure also contributes to significant reductions in
postnatal pulmonary function. Although passive smoke
exposure has been associated with reductions in pulmonary
function, the importance of this risk factor in the
development of the severe pulmonary function reductions in
COPD remains uncertain.
•  Although cigarette smoking is the major environmental risk
factor for the development of COPD, the development of
airflow obstruction in smokers is highly variable. Severe 1
antitrypsin ( 1AT) deficiency is a proven genetic risk factor for
COPD; there is increasing evidence that other genetic
determinants also exist.
•  The effects of cigarette smoking on pulmonary
function appear to depend on the intensity of
smoking exposure, the timing of smoking exposure
during growth, and the baseline lung function of the
individual; other environmental factors may have
similar effects.

•  Most individuals follow a steady trajectory of

increasing pulmonary function with growth during
childhood and adolescence, followed by a gradual
decline with aging. Individuals appear to track in
their quartile of pulmonary function based upon
environmental and genetic factors that put them on
different tracks.
•  The risk of eventual mortality from COPD is closely associated
with reduced levels of FEV1. A graphic depiction of the
natural history of COPD is shown as a function of the
influences on tracking curves of FEV1 in Fig. 260-2. Death or
disability from COPD can result from a normal rate of decline
after a reduced growth phase (curve C), an early initiation of
pulmonary function decline after normal growth (curve B), or
an accelerated decline after normal growth (curve D).
•  The rate of decline in pulmonary function can be modified by
changing environmental exposures (i.e., quitting smoking),
with smoking cessation at an earlier age providing a more
beneficial effect than smoking cessation after marked
reductions in pulmonary function have already developed.
Genetic factors likely contribute to the level of pulmonary
function achieved during growth and to the rate of decline in
response to smoking and potentially to other environmental
factors as well.
 Pathophysiology
Airflow obstruction
Reduced FEV1, FEV1/FVC
Compared to asthma, FEV1 will not improve
with inhaled bronchodilators



•  Persistent reduction in forced expiratory flow rates is
the most typical finding in COPD. Increases in the
residual volume and the residual volume/total lung
capacity ratio, nonuniform distribution of ventilation,
and ventilation-perfusion mismatching also occur.

•  Airflow limitation, also known as airflow obstruction,
is typically determined by spirometry, which involves
forced expiratory maneuvers after the subject has
inhaled to total lung capacity. Key parameters
obtained from spirometry include FEV1 and the total
volume of air exhaled during the entire spirometric
maneuver [forced vital capacity (FVC)]. Patients with
airflow obstruction related to COPD have a
chronically reduced ratio of FEV1/FVC.
•  In contrast to asthma, the reduced FEV1 in COPD seldom shows large
responses to inhaled bronchodilators, although improvements up to 15%
are common. Asthma patients can also develop chronic (not fully
reversible) airflow obstruction. Airflow during forced exhalation is the
result of the balance between the elastic recoil of the lungs promoting
flow and the resistance of the airways limiting flow. In normal lungs, as
well as in lungs affected by COPD, maximal expiratory flow diminishes as
the lungs empty because the lung parenchyma provides progressively less
elastic recoil and because the cross-sectional area of the airways falls,
raising the resistance to airflow.

•  The decrease in flow coincident with decreased lung volume is readily

apparent on the expiratory limb of a flow-volume curve. In the early
stages of COPD, the abnormality in airflow is only evident at lung volumes
at or below the functional residual capacity (closer to residual volume),
appearing as a scooped-out lower part of the descending limb of the
flowvolume curve. In more advanced disease the entire curve has
decreased expiratory flow compared to normal.
 Pathophysiology
Hyperinflation
•  In COPD there is often "air trapping" (increased
residual volume and increased ratio of residual
volume to total lung capacity) and progressive
hyperinflation (increased total lung capacity)
•  Hyperinflation of the thorax during tidal
breathing preserves maximum expiratory airflow
to a certain extent
•  It pushes the diaphragm into a flattened position
decreasing the zone of apposition between the
diaphragm and the abdominal wall
 Pathophysiology
Gas Exchange

•  PaO2 usually remains near normal until the FEV1 is decreased to
~50% of predicted
•  Elevated PaCO2 is not expected until the FEV1 is <25% of
predicted
•  Pulmonary hypertension severe enough to cause cor pulmonale
and right ventricular failure due to COPD typically occurs in
individuals who have marked decreases in FEV1 (<25% of
predicted) and chronic hypoxemia (PaO2 <55 mmHg)
•  Nonuniform ventilation and ventilation-perfusion mismatching are
characteristic of COPD, reflecting the heterogeneous nature of the
disease process within the airways and lung parenchyma.


•  Although there is considerable variability in the relationships
between the FEV1 and other physiologic abnormalities in
COPD, certain generalizations may be made. The PaO2 usually
remains near normal until the FEV1 is decreased to ~50% of
predicted, and even much lower FEV1 values can be
associated with a normal PaO2, at least at rest. An elevation
of arterial level of carbon dioxide (PaCO2) is not expected
until the FEV1 is <25% of predicted and even then may not
occur.
•  Pulmonary hypertension severe enough to cause cor
pulmonale and right ventricular failure due to COPD typically
occurs in individuals who have marked decreases in FEV1
(<25% of predicted) and chronic hypoxemia (PaO2 <55
mmHg); however, recent evidence suggests that some
patients will develop significant pulmonary hypertension
independent of COPD severity (Chap. 250).
•  Nonuniform ventilation and ventilation-perfusion
mismatching are characteristic of COPD, reflecting the
heterogeneous nature of the disease process within the
airways and lung parenchyma. Physiologic studies are
consistent with multiple parenchymal compartments having
different rates of ventilation due to regional differences in
compliance and airway resistance.
•  Ventilation-perfusion mismatching accounts for essentially all
of the reduction in PaO2 that occurs in COPD; shunting is
minimal. This finding explains the effectiveness of modest
elevations of inspired oxygen in treating hypoxemia due to
COPD and therefore the need to consider problems other
than COPD when hypoxemia is difficult to correct with
modest levels of supplemental oxygen in the patient with
COPD.
 Pathology
Large Airway

•  Cigarette smoking often results in mucous gland
enlargement and goblet cell hyperplasia leading to cough
and mucus production that define chronic bronchitis
•  Bronchi also undergo squamous metaplasia, predisposing
to carcinogenesis and disrupting mucociliary clearance
•  Although not as prominent as in asthma, patients may have
smooth-muscle hypertrophy and bronchial hyperreactivity
leading to airflow limitation
•  Neutrophil influx has been associated with purulent
sputum of upper respiratory tract infections

 Pathology
Small airways

•  The major site of increased resistance in most individuals
with COPD is in airways 2 mm diameter
•  Characteristic cellular changes include goblet cell
metaplasia, infiltration of mononuclear phagocytes and
smooth-muscle
•  Reduced surfactant may increase surface tension at the air-
tissue interface, predisposing to airway narrowing or
collapse
•  Loss of bronchiolar attachments as a result of extracellular
matrix destruction may cause airway distortion and
narrowing in COPD.
 Pathology
Lung Parenchyma
•  Emphysema is characterized by destruction of gas-exchanging air
spaces
•  Macrophages accumulate in respiratory bronchioles of essentially
all young smokers.
•  Centriacinar emphysema, the type most frequently associated with
cigarette smoking, is characterized by enlarged air spaces found
(initially) in association with respiratory bronchioles. It is most
prominent in the upper lobes and superior segments of lower lobes
and is often quite focal.
•  Panacinar emphysema refers to abnormally large air spaces evenly
distributed within and across acinar units. Panacinar emphysema is
usually observed in patients with 1AT deficiency, which has a
predilection for the lower lobes.

•  The dominant paradigm of the pathogenesis of
emphysema comprises four interrelated events (Fig.
260-3):
•  (1) Chronic exposure to cigarette smoke may lead
to inflammatory cell recruitment within the
terminal air spaces of the lung.
•  (2) These inflammatory cells release elastolytic
proteinases that damage the extracellular matrix of
the lung.
•  (3) Structural cell death results from oxidant stress
and loss of matrix-cell attachment.
•  (4) Ineffective repair of elastin and other
extracellular matrix components result in air space
enlargement that defines pulmonary emphysema.
 Clinical Presentation
History
•  The three most common symptoms in COPD are
cough, sputum production, and exertional dyspnea
•  As COPD advances, the principal feature is worsening
dyspnea on exertion with increasing intrusion on the
ability to perform vocational or avocational activities.
In the most advanced stages, patients are breathless
doing simple activities of daily living
•  Patients may also develop resting hypoxemia and
require institution of supplemental oxygen
 Physical Findings
•  In the early stages of COPD, patients usually have an entirely
normal physical examination
•  Current smokers may have signs of active smoking, including an
odor of smoke or nicotine staining of fingernails
•  In patients with more severe disease, PE is notable for a prolonged
expiratory phase and may include expiratory wheezing
•  Signs of hyperinflation include a barrel chest and enlarged lung
volumes with poor diaphragmatic excursion as assessed by
percussion
•  Patients with severe airflow obstruction may also exhibit use of
accessory muscles of respiration, sitting in the characteristic
"tripod” position to facilitate the actions of the
sternocleidomastoid, scalene, and intercostal muscles
 Physical Findings
•  Patients with predominant emphysema, termed "pink puffers," are
thin and noncyanotic at rest and have prominent use of accessory
muscles, and patients with chronic bronchitis are more likely to be
heavy and cyanotic ("blue bloaters”)
•  Advanced disease may be accompanied by systemic wasting, with
significant weight loss, bitemporal wasting, and diffuse loss of
subcutaneous adipose tissue
•  Some patients with advanced disease have paradoxical inward
movement of the rib cage with inspiration (Hoover's sign)
•  Signs of overt right heart failure, termed cor pulmonale, are
relatively infrequent since the advent of supplemental oxygen
therapy. Clubbing of the digits is not a sign of COPD, and its
presence should alert the clinician to initiate an investigation for
causes of clubbing. In this population, the development of lung
cancer is the most likely explanation for newly developed clubbing.
 Laboratory Findings
•  The hallmark of COPD is airflow obstruction
•  PFT shows airflow obstruction with a
reduction in FEV1 and FEV1/FVC. Lung
volumes may increase, resulting in an increase
in total lung capacity, functional residual
capacity, and residual volume. In patients with
emphysema, the diffusing capacity may be
reduced, reflecting the lung parenchymal
destruction characteristic of the disease.
 Laboratory Findings
•  ABG and oximetry may demonstrate resting or exertional
hypoxemia, provide information about alveolar ventilation and
acid-base status by measuring arterial PCO2 and pH.
•  An elevated hematocrit suggests the presence of chronic
hypoxemia, as does the presence of signs of right ventricular
hypertrophy
•  Obvious bullae, paucity of parenchymal markings, or hyperlucency
suggests the presence of emphysema. Increased lung volumes and
flattening of the diaphragm suggest hyperinflation but do not
provide information about chronicity of the changes
•  Computed tomography (CT) scan
•  Recent guidelines recommend measurement of α1-AT level in
subjects with COPD or asthma with chronic airflow obstruction
 Treatment
Stable Phase COPD
Only three interventions—smoking cessation,
oxygen therapy in chronically hypoxemic patients,
and lung volume reduction surgery in selected
patients with emphysema—have been
demonstrated to influence the natural history of
patients with COPD
There is currently suggestive, but not definitive,
evidence that the use of inhaled glucocorticoids
may alter mortality rate (but not lung function)
 Pharmacotherapy
•  Smoking Cessation
•  Bronchodilators
•  Anticholinergic agents
•  Beta-agonists
•  Oral and inhaled glucocorticosteroids
 Pharmacotherapy
•  Theophylline
•  Oxygen
Only therapy demonstrated to unequivocally
decrease mortality rates in COPD patients
Resting O2 saturation 88% or <90% with signs of
pulmonary hypertension or right heart failure
•  Other agents
NAC
α1-AT therapy
 Non-Pharmacologic Therapies
•  General Medical Care
Influenza and pneumococcal vaccine is recommended
•  Pulmonary Rehabilitation
•  Lung Volume Reduction Surgery
Patients are excluded if they have significant pleural
disease, PASP >45 mmHg, extreme deconditioning,
CHF, or other severe comorbid conditions
Patients with upper lobe–predominant emphysema and
a low postrehabilitation exercise capacity are most
likely to benefit from LVRS
 Non-Pharmacologic Therapies
Lung Transplantation
COPD is currently the second leading indication for lung
transplantation
Current recommendations are that candidates for lung
transplantation should be <65 years; have severe
disability despite maximal medical therapy; and be
free of comorbid conditions such as liver, renal, or
cardiac disease
In contrast to LVRS, the anatomic distribution of
emphysema and the presence of pulmonary
hypertension are not contraindications to lung
transplantation.

 COPD Exacerbations
•  Exacerbations are episodes of increased dyspnea and
cough and change in the amount and character of
sputum that may or may not be accompanied by other
signs of illness, including fever, myalgias, and sore
throat
•  The frequency of exacerbations increases as airflow
obstruction increases; patients with moderate to
severe airflow obstruction [GOLD stages III, IV] on
average have one to three episodes per year
•  History of prior exacerbations is a strong predictor of
future exacerbations
 Precipitating Causes and Strategies to
Reduce Frequencies of AECOPD
•  Bacterial and viral respiratory infections
•  Despite the frequent implication of bacterial infection,
chronic suppressive or "rotating" antibiotics are not
beneficial in patients with COPD
•  Chronic oral glucocorticoids are not recommended for
this purpose
•  Inhaled glucocorticoids reduce the frequency of
exacerbations by 25–30% and should be considered in
patients with frequent exacerbations or those who
have an asthmatic component
•  Influenza vaccine has been shown to reduce
exacerbation rates in patients with COPD
 Patient Assessment
•  Establish the severity of the exacerbation as well as
the severity of preexisting COPD
•  PE should incorporate an assessment of the degree
of distress of the patient - tachycardia, tachypnea,
use of accessory muscles, signs of perioral or
peripheral cyanosis, the ability to speak in complete
sentences, and the patient's mental status
•  CXR, ABG
 Management
•  Bronchodilators
•  Antibiotics
Bacteria frequently implicated in COPD
exacerbations include Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella
catarrhalis
•  Glucocorticoids
30-40 mg or oral prednisolone or its equivalent for
10-14 days
 Management
•  Oxygen
Maintain O2 sats of 90%
•  Mechanical ventilatory support
Contraindications to NIPPV include cardiovascular instability, impaired
mental status or inability to cooperate, copious secretions or the
inability to clear secretions, craniofacial abnormalities or trauma
precluding effective fitting of mask, extreme obesity, or significant
burns
Invasive mechanical ventilation is indicated for patients with severe
respiratory distress despite initial therapy, life-threatening hypoxemia,
severe hypercarbia and/or acidosis, markedly impaired mental status,
respiratory arrest, hemodynamic instability, or other complications