1

What is chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) represents a collection of diseases, including chronic bronchitis and emphysema, which are characterised by irreversible chronic obstruction of airflow.

COPD replaces previous nomenclature, including chronic obstructive airways disease (COAD) and chronic airflow limitation (CAL).

2

How is COPD classified?

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the severity of COPD is classified based on spirometric airflow limitation and expressed as % predicted FEV₁ (Table 1).

The GOLD classification correlates both with the incidence of infective exacerbations and mortality.

It is widely used in international guidelines, including the 2010 National Institute for Health and Care Excellence (NICE) COPD guidelines.

3

What is the aetiology of COPD?

Smoking (including passive exposure) is the primary cause of COPD, with over 80% of sufferers being current or ex-smokers.

Long-term exposure to cigarette smoke leads to chronic airways inflammation, release of proteases, increased oxidative stress and eventual destruction of the lung parenchyma and damage to the airways.

Other aetiological factors include:

a)

industrial exposures, such as coal dust, isocyanate fumes (used in the production of polyurethane) and cadmium;

b)

genetic predisposition, such as alpha-1 antitrypsin deficiency. Antitrypsin normally counteracts endogenous neutrophil elastase and its deficiency leads to early-onset homogeneous emphysema, classically involving all lobes uniformly (panacinar). It represents an autosomal codominant inherited disease, caused by defects in the SERPINA1 gene.

4

What is the pathophysiology of COPD (Figure 1)?

COPD is caused by the inhalation of harmful chemicals and the resulting inflammatory response, which results in its principal clinical manifestations.

Chronic bronchitis, which is characterised by increased mucus production, ciliary dysfunction, oxidative stress and chronic inflammation with protease release (Figure 2).

Emphysema, which is mediated by the action of CD8 T-lymphocytes, results in:

a)

destruction of alveolar walls;

b)

enlargement of alveolar air spaces;

c)

reduction of radial support for small airways.

Small airways obstruction, where the expiratory collapse of these airways produces the physiological manifestations of the condition, namely airway obstruction and air-trapping.

Histologically, COPD produces airways inflammation and parenchymal emphysema. Within the airways, submucosal bronchial gland enlargement and cellular infiltrates with increased macrophage numbers are seen. Squamous metaplasia may also be seen.

Emphysema (Figure 3) is characterised by the loss of parenchyma rather than fibrous scarring and is usually classified into two principal subtypes:

a)

centriacinar emphysema (Figure 3B) – which mainly affects the proximal part of the acinus (beyond the respiratory bronchiole). This subtype is most closely related to smoke inhalation and is more prevalent in the better ventilated upper lobes;

b)

panacinar empysema (Figure 3C) – which involves alveolar wall damage and loss throughout the acinus. It is most closely related to alpha-1 antitrypsin deficiency.

In advanced cases, chronic hypoxia leads to pulmonary hypertension and its attendant vascular changes, including smooth muscle hypertrophy.

5

What are the symptoms of a patient with COPD?

Dyspnoea on exertion is the central symptom. The onset is usually insidious but the disease is slowly progressive once symptomatic. Presentation is unusual before the age of 40.

A chronic productive cough and wheeze are often reported.

Generalised muscle wasting occurs in some patients.

In addition to chronic symptoms, acute infective exacerbations characterise COPD. These involve increased sputum production, cough, fever and worsening dyspnoea.

Later in the disease, symptoms of right heart failure may develop, with peripheral oedema or ascites.

6

What are the clinical signs of a patient with COPD?

COPD leads to increased lung volumes. This is manifested clinically as hyperexpansion, with an increased anteroposterior diameter of the thorax (‘barrel’ chest) and relatively horizontal ribs.

Small airways collapse on expiration leads to a prolonged expiratory phase.

Some patients compensate by pursed-lip expiration, which generates increased positive end-expiratory pressure, thereby holding the collapsible small airways open for longer.

Secondary signs include finger clubbing and central cyanosis in those with hypoxia.

Secondary right-sided heart failure (cor pulmonale) can lead to a raised JVP, pulsatile hepatomegaly, ascites and peripheral oedema.

Generalised muscle wasting is sometimes present.

On auscultation, there are quiet respiratory sounds. An expiratory wheeze is common, especially during exacerbations.

Heart sounds are also quiet, muffled by large-volume lungs.

In cor pulmonale, the 2nd heart sound is split and in advanced cases, a pan-systolic murmur of tricuspid regurgitation or a 3rd heart sound can be heard.

7

What is the prognosis of a patient with COPD?

The clinical course is usually one of progressive gradual decline, punctuated by acute infective exacerbations. A higher frequency of infective exacerbations is associated with more rapid decline and a poorer prognosis.

COPD is currently responsible for around 1 in 8 emergency hospital admissions in the UK.

Definitive estimates of prognosis are difficult. The in-patient mortality from infective exacerbations is 3-4%.

COPD accounts for 5% of all UK deaths.

Age, disease severity, continued smoking and socioeconomic deprivation are associated with a poorer prognosis.

The BODE index (from BMI, airflow obstruction, dyspnoea and exercise capacity) is recommended by NICE as a more accurate assessment of prognosis than spirometry alone.

8

What are the radiological features of a patient with COPD?

Chest radiograph (CXR) (Figure 4):

a)

hyperexpansion of the lungs with a flattened and low diaphragm, and relatively horizontal ribs. Hyperexpansion can give the mediastinum a thin, elongated appearance;

b)

relative reduction in lung markings due to loss of parenchyma;

c)

signs of secondary pulmonary hypertension or right heart dilation may be present in advanced cases.

Computed tomography (CT) scan (Figure 5):

a)

hyperexpanded lungs that often ‘meet’ anterior to the mediastinum, separated only by the pleural membranes;

b)

emphysematous changes:

i)

smoking-related (often centriacinar) changes are generally more pronounced in the upper zones;

ii)

alpha-1 antitrypsin deficiency usually produces homogeneous change throughout the lung parenchyma;

c)

low attenuation areas are often seen, which represent areas of localised parenchymal destruction;

d)

bullae are common, ranging from small subpleural bullae to giant bullae, which may occupy over 30% of the hemithorax. A giant subpleural bulla can be mistaken for a pneumothorax. The lack of a defined concave surface and the presence of residual septae (visible as white lines) within a bulla can help to differentiate between the two (Figure 6).

CT scanning is also used as part of the work-up for lung volume reduction surgery (to detect heterogeneous disease) and giant bullectomy. It may also detect lung cancer or fibrotic lung disease, both of which are associated with COPD.

Ventilation perfusion (VQ) scans are not routinely used in the management of COPD but can demonstrate a matched ventilation and perfusion defect in the upper lobes (Figure 7).

9

What are the findings on lung function testing of a patient with COPD (Table 2)?

Spirometry typically shows airway obstruction with increased static lung volumes. The FEV₁ therefore falls, while the FVC can fall to a lesser extent, remain the same or rise. Values are expressed as a percentage of predicted values.

The reduction in FEV₁ in patients with COPD is defined by the GOLD criteria (see earlier) and can vary from >80% predicted (mild) to <30% predicted (very severe).

Forced vital capacity (FVC) is the volume of air expired forcefully between maximal inspiration and expiration. Calculation of the FEV₁/FVC ratio gives a useful index of airways obstruction, with results <70% defining airway obstruction.

Vital capacity (VC) is the volume of air that can be expired slowly between maximal inspiration and maximal expiration. It can be a more reliable measure of lung volume in COPD than the FVC. Increased lung volume in COPD usually leads to a rise in the VC.

The diffusing capacity of the lungs for carbon monoxide (DLCO) is a useful index of the overall gas transfer efficiency and is reduced in COPD. The subject inspires air containing a small fraction of carbon monoxide (CO) in a closed system. The difference in the partial pressure of CO in inspired and expired air is measured. It can be affected by other factors including smoking status, anaemia or pulmonary fibrosis, and is often used to assess fitness for surgery.

10

What are the principles of managing a patient with COPD?

Medical management:

a)

inhaled long-acting beta agonists, long-acting anti-muscarinics and corticosteroids are used for maintenance therapy;

b)

smoking cessation (with pharmacological therapy) and reduced exposure to environmental smoke;

c)

winter flu vaccination and pneumococcal vaccine are recommended;

d)

antibiotics and oral steroids for acute exacerbations;

e)

pulmonary rehabilitation has been shown to reduce disability in selected patients;

f)

long-term oxygen therapy (LTOT) for patients with chronic hypoxic respiratory failure or cor pulmonale.

Endobronchial therapies:

a)

endobronchial valves;

b)

endobronchial injection of heated water vapour;

c)

endobronchial bronchial occlusion;

d)

extra-anatomic bypass between bronchi and large bullae, followed by stent placement.

Surgery is reserved for a small minority of patients (see below), including:

a)

bullectomy;

b)

lung volume reduction surgery (LVRS);

c)

pulmonary transplantation;

d)

treatment of complications, such as pneumothorax.

11

What are the surgical options for the treatment of giant bullae?

Bullectomy.

Laser coagulation of bullae (although air leak is relatively common).

Monaldi procedure – where the giant bullae are first fixed to the parietal pleura by earlier pleurodesis or suture. The bulla is then opened and a drain placed within. Over time the bulla deflates and fibroses around the drain, which is removed.

Modified Monaldi procedure – where talc is introduced at the time of drain placement.

The alternative techniques to bullectomy evolved to avoid thoracotomy in unfit patients. With the increasing use of video-assisted thoracic surgery (VATS), their role is less clear.

12

What are the indications for surgery on bullae?

Although high-quality evidence is limited, three criteria are commonly cited, including:

a)

presence of a giant bulla (defined as a bulla that occupies greater than one-third of the hemithorax);

b)

otherwise normal lung parenchyma around the bulla;

c)

symptomatic dyspnoea.

Pulmonary hypertension and hypercapnoea are contraindications.

Very low FEV₁ or DLCO and major comorbidities increase the operative risk.

13

What are the surgical approaches for bullectomy?

Thoracotomy.

VATS.

Median sternotomy.

Although all chest incisions decrease peri-operative functional residual capacity (FRC) to some extent (secondary to pain), VATS is less painful than thoracotomy and is increasingly the approach of choice for bullectomy.

14

What are the principles of surgery for a VATS giant bullectomy?

Once the thoracoscope is placed, the remaining ports can be inserted under direct vision. Traditionally, three ports are used. The camera port is placed laterally in approximately the 7th intercostal space, with two further ports in approximately the 5th intercostal space, one posterior to the scapula and another in the anterior axillary line.

Other configurations including double-port (generally a working port anterior to the border of latissimus in the 4th or 5th intercostal space and a separate, inferior camera port) or single-port approaches are also possible.

As the thorax is often hyperexpanded and pleural adhesions are often present, it is important to avoid lung injury during port placement, especially as air leak from emphysematous lung is difficult to resolve.

Once the ports are placed, the lung is inspected and any adhesions identified are divided by diathermy, as they are often vascular.

The bullae are usually clearly seen as thin-walled air sacs (Figure 8).