CHAPTER III

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

(COPD)

Definitions (American Thoracic Society):

Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by the
presence of airflow obstruction due to chronic bronchitis or emphysema. The airflow obstruction
is generally progressive, may be accompanied by airway hyper-reactivity, and may be partially
reversible.
Chronic bronchitis is characterized by excessive secretion of bronchial mucus, and is manifested
by productive cough for 3 months or more in at least 2 consecutive years, in the absence of any
other disease that might account for this symptom.
Emphysema denotes abnormal, permanent enlargement of air spaces, distal to the terminal
bronchiole, with destruction of their walls and without obvious fibrosis.
* Note that chronic bronchitis is defined in clinical terms, whereas emphysema is defined in
morphologic terms !

Incidence: 4-6% in men, and 2-3% in women; the 4th cause of death in USA.

Risk factors for COPD:

SMOKING
 Cigarette smoking is the most commonly identified. It correlates with both chronic bronchitis and
emphysema.
 Prolonged cigarette smoking impairs ciliary movement, inhibits function of alveolar
macrophages, leads to hypertrophy and hyperplasia of mucus-secreting glands, and causes
polymorphonuclear leukocytes to acutely release proteolytic enzymes.
 Inhaled cigarette smoke can produce an acute increase in airways resistance due to vagal
mediated smooth-muscle constriction, presumably by stimulating submucosal irritant receptors.
 Obstruction of small airways is the earliest demonstrable mechanical defect in young cigarette
smokers, and the obstruction may completely disappear after cessation of smoking-in less severe
stages of disease- but the reversibility is not complete in more pronounced obstruction.

AIR POLLUTION
 Statistically is well established the direct relation between the high incidence and mortality rates
of both chronic bronchitis and emphysema and industrialised urban areas. Air pollution with
particulate matter and sulphur dioxide (SO2) is especially involved.

OCCUPATION
 Professional exposure to either inorganic or organic dusts or to noxious gases is in direct relation
to the incidence and gravity of chronic bronchitis and accelerating decline in lung function. The
most affected are workers in plastics plants (toluene diisocyanate) and carding room workers in
cotton mills.

17
INFECTION
 Chronic infection with viruses, mycoplasma, and bacteria may lead to chronic obstruction
predominantly in small airways. Rhinovirus is found more often during exacerbations.

FAMILIAL and GENETIC FACTORS

 Familial aggregation may be related to familial smoking habits and indoor home air pollution. It
is well established that familial influence is present in smoking parents`children, generally in
passive smokers, or in relation with indoor air pollution due to the use of natural gas for cooking.
 Some studies of monozygotic twins have suggested some genetic predisposition to the
development of emphysema such is alpha1-antitrypsin deficiency. Normal population has two M
genes, designated as protease inhibitor type MM, and has serum 1AT levels in excess of 2.5g/l.
Individuals who have other genes (Z or S), specially those who are homozygous ZZ or SS have
serum levels often near 0 but always less than 0.5 g/l and develop severe panacinar emphysema in
the third and fourth decades of life, predominantly in the lung bases. (Stauffer 1998).

Pathology and Pathophysiology:

Generalised airflow obstruction is the dominant feature of both diseases.
 In chronic bronchitis it is chiefly due to swelling of the bronchial mucosa and the
accumulation of tenacious mucus within the air passages.
 In emphysema, the main factor in the production of airflow obstruction is extramural
bronchial compression and collapse caused by over-distended alveoli in which air has been
“trapped” during expiration. This phenomenon is aggravated by bronchopulmonary infection.
The most consistent pathological finding in chronic bronchitis is hyperactivity of the mucus-
secreting glands of the medium and large bronchi. In time, this process leads to hypertrophy and
hyperplasy of the large airways (bronchial) mucus-producing glands, found in the submucosa.
REID index is the ratio of the thickness of the submucosal glands to that of the bronchial wall. In
normal persons, Reid index is 0.44 +/- 0.09, and in chronic bronchitis patients is about 0.52 +/- 0.08.
It is now very well established (post-mortem studies) that in COPD type B, the major site of
airflow obstruction is the region of small airways. This initial inflammation of the small airways is
reversible if smoking is stopped in the early stages of disease. The changes often found in the small
noncartilaginous airways (bronchioles) are (fig. III-1):

 Goblet-cell hyperplasia; intraluminal mucus plugs.

 Mucosal and submucosal inflammatory cells.
 Edema.
 Peribronchial fibrosis.
 Increased number of smooth muscle cells (hyperplasia)
and hypertrophy.

Fig. III-1: Morphological aspect of the terminal bronchioles in

type B COPD.

The vast excess of so produced mucus coats the bronchial walls and clogs the bronchioles.
Mucosal edema further reduces the caliber of the air passages and as the degree of obstruction is
greater while breathing out, air is “trapped” in the alveoli.

18
 Emphysema pathogenesis may be due excessive lysis of elastin and other structural proteins in the
lungs matrix by elastase and other proteases derived from lung neutrophils, macrophages, and
mononuclear cells. The result consists of destruction of the alveolar walls, loss of the elastic recoil of
the lung, and, in extreme form, the lung becomes a mass of bullae (fig. III-2).

Fig. III-2: Morphological aspect of the terminal

bronchioles in type A COPD.

Emphysema can be classified according to the site of

damage, in: a) centri-acinar emphysema (just the alveoli
around the respiratory bronchioles are damaged), b) pan-
acinar emphysema (involvement of the whole acinus), and
c) irregular emphysema (the destructive process affects the
lung parenchyma patchily, without particular regard for
acinar structure).

Diagnosis features:

1) History and symptoms. Although chronic bronchitis and emphysema are pathologically
distinct, they frequently coexist, and the relative proportion and importance of each condition may be
difficult to determine in the individual case.
COPD can be regarded as forming a spectrum, with “pure”, chronic bronchitis at one end and
“pure” emphysema at the other. In table III-1 are presented the differences and the relationships
which exist between the two types of COPD, in terms of clinical features:

Predominant Emphysema Predominant Bronchitis

“PINK PUFFERS” “BLUE BLOATERS”
Age of time of diagnosis (years) 60  50 
Dyspnea Severe, constant, progressive Mild to moderate, intermittent
Sputum Scanty, mucoid Copious, purulent
Cough After dyspnea starts Before dyspnea starts. Persistent.
Bronchial infections Less frequent More frequent
Respiratory insufficiency Often terminal Repeated
episodes
Cor pulmonale Rare (“in the last year of life”) Common (early in evolution)
Predominant history Dyspnea Cough (heavy smokers)
Face & skin color Pink-normal color (no cyanosis) Central cyanosis
Body built Asthenic (weight loss) Overweight

Table III-1: Major historical and clinical differentiation features, between the two types of COPD.

Symptoms can be worsened by factors such as cold, foggy weather and atmospheric pollution. In
patients with COPD there is a progressive increase in respiratory disability, but the timing and the
tempo of deterioration widely varies from one case to another.

2) Physical examination in COPD varies very much with severity of disease, but much more
due to the two polar opposite types of fully developed COPD: predominant emphysema &
predominant bronchitis. Most patients have some characteristics of each type. Summary of typical
physical signs of these two polar types are presented in the following tables:

19
 Predominant Emphysema
INSPECTION  Increase in the anteroposterior diameter of the chest relative to the lateral diameter.
 Movement of the chest wall symmetrically diminished in amplitude.
 Obvious use (hypertrophied) of accessory muscles of respiration (sternomastoid and
scalene) with each inspiration.
 Tachypnea.
 The neck veins distended (jugular venous filling) during expiration & collapse briskly
with inspiration.
 The lower intercostal spaces retract with each inspiration.
 Excavation of the suprasternal and supraclavicular fossae during inspiration.
PERCUSSION  Important diffuse hyper resonance.
AUSCULTATION  Breath sounds: diminished vesicular.
 No rhonchi or minor high-pitched rhonchi heard toward the end of expiration.
 Prolonged expiration.
Table III-2: Main physical examination features in type A COPD (predominant emphysema).

Predominant Bronchitis
INSPECTION  Usually, normal chest.
 Respiratory rate is normal or slightly increased.
 No apparent usage of accessory muscles of respiration.
PERCUSSION  Normally resonant or minor hyperresonant.
AUSCULTATION  Breathe sounds: normal vesicular.
 Prolonged expiration.
 Coarse rhonchi & wheezes that change in location and intensity after a deep and
productive cough.

Table III-3: Main physical examination features in type B COPD (predominant bronchitis).

3) Radiological Examination:
 In type A (predominant emphysema) COPD:
 Hyperinflation of the lungs:
 Unusually translucent lung fields, with loss of peripheral vascular markings.
 Flat and low diaphragm, which poorly moves on radioscopy ( < 2 cm).
 Large retrosternal translucency on lateral chest radiographs.
 Bullous changes: parenchyma bullae or subpleural blebs.
 Small, vertical heart: cardiac silhouette is lengthened and narrowed.
 In type B (predominant bronchitis) COPD (no characteristic abnormality on the
radiograph):
 Thickened bronchial walls, looking like tubular or “tramline” shadows.
 Generalized increase in bronchovascular markings (“dirty lungs”)
 Large, horizontal heart: the cardiac silhouette may become more prominent
due to right atrial and right ventricular chamber enlargement.
4) Pulmonary Function Tests:
 In type A (predominant emphysema) COPD:
 Total Lung Capacity (TLC) & Residual Volume (RV) -- invariably increased.
 The maximal expiratory flow rates are diminished.
20
  The elastic recoil: severely decreased.
 Diffusing capacity: decreased (the capacity of lung to transfer CO2)
 In type B (predominant bronchitis) COPD:
 TLC is often normal and RV is mild elevated.
 The maximal expiratory flow rates are invariably diminished (very much
decreased). The forced expiratory volume in 1 second (FEV 1) is reduced, and ratio of
FEV1 to forced vital capacity (FVC) is also subnormal. In advanced states, the FEV 1
may be less than 1 liter, and the FEV1/FVC ratio may be as low as 30%.
 The elastic recoil: normal to slightly impaired (decreased).
 Diffusing capacity: normal to slight decreased
5) Blood Analysis:
 In type A (predominant emphysema) COPD:
 Chronic PaCO2: 35-40 mmHg (normocapnia)
 Chronic PaO2: 65-75 mmHg (mild decreased)
 Hematocrit: <55 %
 In type B (predominant bronchitis) COPD:
 Chronic PaCO2: 50-60 mmHg (hypercapnia)
 Chronic PaO2: 45-60 mmHg (very much decreased)
 Hematocrit: >60 % (secondary polycythemia, due to hypoxemia)
6) Sputum examination: During exacerbations of illness, examination of the sputum may reveal
Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
7) ECG may show:
 Sinus tachycardia. Supraventricular or ventricular arrhythmias.
 Right atrial & right ventricular hypertrophy (cor pulmonale).

Differential Diagnosis:
It is important to distinguish COPD from a variety of other pulmonary conditions. COPD
cannot be diagnosed simply because of a history of heavy cigarette smoking, and the sole finding of
obstructive pulmonary dysfunction on spirometry does not establish a diagnosis of COPD.
Clinical, roentgenographic, and laboratory findings should enable the clinician to distinguish
COPD from other obstructive pulmonary disorders such as:
 bronchial asthma (difficult differentiation when the asthmatic patient has continuous
dyspnea);
 bronchiectasis (recurrent pneumonia and hemoptysis, digital clubbing, and radiographic
abnormalities);
 cystic fibrosis (children and younger adults);
 bronchopulmonary aspergillosis;
 central airway obstruction (flow-volume loops);
 severe alpha 1-antiprotease deficiency (panacinar emphysema early in life, usually in the
third or fourth decade; hepatic cirrhosis and hepatocellular carcinoma may occur).

Complications:
1. Recurrent respiratory infections (acute bronchitis, pneumonia).
2. Pulmonary hypertension and cor pulmonale are the inevitable end-results of COPD, if
other life-threatening complications doesn’t occur previously.
3. Chronic respiratory failure and hypercapnic encephalopathy are common in advanced
COPD.

21
 4. Spontaneous pneumothorax occurs in a small fraction of patients with emphysema, due to
severe coughing attacks, or pulmonary bullae rupture).
5. Secondary polycythemia (increased erythropoietin production, due to hypoxia; white cells
and platelets are unaffected and there is no splenomegaly).
6. Hemoptysis may result from chronic bronchitis or may signal bronchogenic carcinoma.

References:
1. Ferguson GT, Cherniack RM: Management of chronic obstructive pulmonary disease. N. Engl. J. Med. 328:1017,
1993
2. Gherasim L (red), Medicina interna vol I, Ed. Medicala, Bucuresti, 1995.
3. Honig EG, Ingram RH jr.: Chronic Brochitis, Emphysema and Airways Obstruction, in Harrison`s Principles of
Internal Medicine, McGraw Hill Publ., 14th ed., New York 1998.
4. Jansen HM et all: Predisposing conditions to bacterial infection in chronic obstructive pulmonary disease.
Am.J.Respir.Crit.Care.Med. 151:2073,1995
5. Kumar P.J., Clark M.L. Clinical Medicine. 2nd ed. Balliere Tindall, London, 1990, 627-640.
6. Macleod J., ed., Davidson`s Principles and Practice of Medicine –13th ed. Churchill Livinstone, London 1981.
7. Stauffer JL: Chronic Obstructive Pulmonary Disease, in CURRENT Medical Diagnosis & Treatment, 37th edition,
ISBN 0-8385-1524-X, 1998.

22