Chronic obstructive pulmonary disease (COPD)

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Chronic obstructive pulmonary disease (COPD)

• Definition
• COPD is a disease state characterized by airflow
  limitation that is not fully reversible.
• The airflow limitation is usually both
  progressive and associated with an abnormal
  inflammatory response of the lungs to noxious
  particles or gases.

Epidemiology and aetiology

• COPD is caused by long-term exposure to toxic
  particles and gases.
• In developed countries, cigarette smoking
  accounts for over 90 of cases. However, only
  10-20 of heavy smokers develop COPD, indicating
  individual susceptibility. The development of
  COPD is also related to the number of cigarettes
  smoked per day the risk of death from COPD in
  patients smoking 30 cigarettes daily is 20 times
  that of a non-smoker.
• Climate and air pollution are of less importance
• social class and occupation may also play a part
  in aetiology, but these effects are difficult to
  separate from that of smoking, indoor and outdoor
  air pollutants, and nutritional status.
• Some animal studies suggest that diet could be a
  risk factor for COPD but this has not been
  proven in humans.

Pathophysiology
The most consistent pathological finding is
hypertrophy and increase in number of the
mucus-secreting goblet cells of the bronchial
tree, evenly distributed throughout the lung but
mainly seen in the larger bronchi. In more
advanced cases, the bronchi themselves are
obviously inflamed and pus is seen in the lumen.
Microscopically there is infiltration of the
walls of the bronchi and bronchioles with acute
and chronic inflammatory cells and lymphoid
follicles in severe disease.
The epithelial layer may become ulcerated and,
when the ulcers heal, squamous epithelium may
replace the columnar cells. The inflammation is
followed by scarring and a remodelling process
that thickens the walls and leads to widespread
narrowing in the small airways. The small airways
are particularly affected early in the disease,
initially without the development of any
significant breathlessness. This initial
inflammation of the small airways is reversible
and accounts for the improvement in airway
function if smoking is stopped early.
In later stages the inflammation continues, even
if smoking is stopped. The Lung Parenchyma
developed emphysema which is characterized by
destruction of gas-exchanging airspaces, i.e.,
the respiratory bronchioles, alveolar ducts, and
alveoli. Their walls become perforated and later
obliterated with coalescence of small distinct
airspaces into abnormal and much larger
airspaces.

• a1-Antitrypsin deficiency
• a1-Antitrypsin inhibitor is an antiproteinase
  inhibitor produced in the liver, secreted into
  the blood and which diffuses into the lung. Here
  it functions as an antiprotease that inhibits
  neutrophil elastase, a proteolytic enzyme capable
  of destroying alveolar wall connective tissue.
  More than 75 alleles of the a1-antitrypsin
  inhibitor gene have been described. The three
  main phenotypes are MM (normal), MZ (heterozygous
  deficiency) and ZZ (homozygous deficiency).
• Hereditary deficiency of a1-antitrypsin inhibitor
  accounts for about 2 of emphysema cases. A small
  minority develop liver disease .

Emphysema is classified into distinct pathologic
types Centriacinar emphysema, the type most
frequently associated with cigarette smoking, and
it is most prominent in the upper lobes and
superior segments of lower lobes and is often
quite focal. Panacinar emphysema ,is usually
observed in patients with a1 AT deficiency, which
has a predilection for the lower lobes. N.B,
smoking-related emphysema is usually mixed,
particularly in advanced cases, and these
pathologic classifications are not helpful in the
care of patients with COPD. Irregular
emphysema,there is scarring and damage affecting
the lung parenchyma patchily without particular
regard for acinar structure.
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Centrilobular
Panlobular
Emphysema leads to expiratory airflow limitation
and air trapping. The loss of lung elastic recoil
results in an increase in TLC while the loss of
alveoli with emphysema results in decreased gas
transfer. Other mechanisms that have been
suggested for airflow limitation
are Inflammation and scarring cause the small
airways to narrow. Mucus secretion which blocks
the airways. These all cause narrowing of the
small airways and trapping of air leading to
hyperinflation of the lungs and breathlessness.
Clinical Presentation
History The three most common symptoms in COPD
are cough, sputum production, and exertional
dyspnea. for months or years before seeking
medical attention. Although the development of
airflow obstruction is a gradual process, many
patients date the onset of their disease to an
acute illness or exacerbation. A careful history,
however, usually reveals the presence of symptoms
prior to the acute exacerbation. As COPD
advances, the principal feature is worsening
dyspnea on exertion . Accompanying worsening
airflow obstruction is an increased frequency of
exacerbations . 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. In
patients with more severe disease, the physical
examination is notable for a prolonged expiratory
phase and expiratory wheezing. In addition, signs
of hyperinflation include a barrel chest.
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 sterno-mastoid, scalene, and intercostal
muscles. Patients may develop cyanosis, visible
in the lips and nail beds.
Although traditional teaching is that patients
with predominant emphysema, termed "pink
puffers," are thin and non cyanotic at rest and
have prominent use of accessory muscles, and
patients with chronic bronchitis are more likely
to be heavy and cyanotic ("blue bloaters"),
current evidence demonstrates that most patients
have elements of both bronchitis and emphysema
and that the physical examination does not
reliably differentiate the two entities. Signs of
overt right heart failure, termed cor pulmonale,
are relatively infrequent since the advent of
supplemental oxygen therapy. N.B,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, because the
development of lung cancer is the most likely
explanation .
Complications
Respiratory failure The later stages of COPD are
characterized by the development of respiratory
failure(type 2). For practical purposes this is
said to occur when there is either a Pao2 of less
than 8 kPa (60 mmHg) or a Paco2 of more than 7
kPa (55 mmHg) . Cor pulmonale The persistence of
chronic alveolar hypoxia and hypercapnia leads to
constriction of the pulmonary arterioles and
subsequent pulmonary arterial hypertension.
Cardiac output is normal or increased but salt
and fluid retention occurs as a result of renal
hypoxia leading to Cor pulmonale .??
Investigations
Pulmonary function tests show evidence of airflow
limitation .The ratio of the FEV1 to the FVC is
reduced and the PEFR is low. In many patients the
airflow limitation is reversible to some extent
(usually a change in FEV1 of lt 15), and the
distinction between asthma and COPD can be
difficult. Lung volumes may be normal or
increased, and the gas transfer coefficient of
carbon monoxide is low when significant emphysema
is present. Chest X-ray is often normal, even
when the disease is advanced. The classic
features are the presence of bullae, severe
overinflation of the lungs with low, flattened
diaphragms, and a large retrosternal air space on
the lateral film. There may also be a deficiency
of blood vessels in the periphery of the lung
fields compared with relatively easily visible
proximal vessels.
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Haemoglobin level and PCV can be elevated as a
result of persistent hypoxaemia (secondary
polycythaemia). Blood gases are often normal. In
the advanced case there is evidence of hypoxaemia
and hypercapnia. Sputum examination is
unnecessary in the ordinary case as Strep.
pneumoniae or H. influenzae are the only common
organisms to produce acute exacerbations.
Occasionally Moraxella catarrhalis may cause
infective exacerbations. Electrocardiogram. In
advanced cor pulmonale the P wave is taller (P
pulmonale) and there may be right bundle branch
block (rSR' complex) and the changes of right
ventricular hypertrophy Echocardiogram -
performed to assess cardiac function.
a1-Antitrypsin levels. The normal range is 2-4
g/L.
Global Initiative in Obstructive Lung Disease
(GOLD) criteria
Symptoms FEV () Stage of COPD
None 80 At risk 0
variable 80 mild 1
mild to moderate 50-79 moderate 11
limited exertion 30-49 sever 111
limited daily activities lt30 Very sever 1V
Management

• Smoking cessation
• Enforcing the patient to stop smoking is vital.
  Even at a late stage of the disease this may slow
  down the rate of deterioration and prolong the
  time before disability and death occur.
• Drug therapy
• This is used both for the short-term management
  of exacerbations and for the long-term relief of
  symptoms. In many cases the drugs used are
  similar to those used in asthma .
• -Bronchodilators Many patients feel less
  breathless following the inhalation of a
  ß-adrenergic agonist such as salbutamol (200 µg
  every 4-6 hours).
• -More prolonged and greater bronchodilatation is
  achieved with antimuscarinic agents ipratropium
  (40 µg four times daily) or oxitropium (200µg
  twice daily).

Objective evidence of improvement in the peak
flow or FEV1 may be small and decisions to
continue or stop therapy should be based on the
patient's reported symptoms. Long-acting
preparations of theophylline are of little
benefit. In symptomatic patients with COPD, a
trial of corticosteroids is always indicated,
since a proportion of patients have a large,
unsuspected, reversible element to their disease
and airway function may improve considerably.
Prednisolone 30 mg daily should be given for 2
weeks, with measurements of lung function before
and after the treatment period. If there is
objective evidence of a substantial degree of
improvement in airflow limitation (FEV1 increase
gt 15), prednisolone should be discontinued and
replaced by inhaled corticosteroids
(beclometasone 400µg twice daily in the first
instance, adjusted according to response). The
long-term value of regular inhaled
corticosteroids in all patients with COPD has not
been proven.
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• Antibiotics Prompt antibiotic treatment
  shortens exacerbations and should always be given
  in acute episodes as it may prevent hospital
  admission and further lung damage. Long-term
  treatment with antibiotics remains controversial
• Diuretic therapy This is necessary for all
  oedematous patients. Daily weights should be
  recorded during acute inpatient episodes.
• a1-Antitrypsin replacement Weekly or monthly
  infusions of a1-antitrypsin have been recommended
  for patients with serum levels of this compound
  below 310 mg/L and abnormal lung function.
  Whether this modifies the long-term progression
  of the disease has still to be determined.
• Vaccines Patients with COPD should receive
  yearly influenza vaccine. These patients should
  also receive one dose of the polyvalent
  pneumococcal polysaccharide vaccine (a single
  dose usually provides lifelong immunity).

Secondary polycythaemia - venesection is
recommended if the PCV is gt 55.