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Respiratory system
Table28.3 Clinical features to help differentiate chronic
obstructive pulmonary disease and asthma
Features COPD Asthma
Smoker or
ex-smoker
Chronic
productive
cough
Symptoms at
age <35years
Dyspnoea Persistent and
Nocturnal
waking with
cough or
breathlessness
Significant
diurnal or day-today variability of
symptoms
COPD, Chronic obstructive pulmonary disease.
Nearly all Possibly
Common Uncommon
Rare Often
Variable
progressive
Uncommon Common
Uncommon Common
of disability and ensuring optimal medical therapies are in
place (National Institute for Health and Care Excellence
(NICE) guideline on chronic obstructive pulmonary disease, June 2010). Assessment of severity is based on FEV1,
as measured by spirometry, which is compared with the
predicted value (based on age, sex, height) and expressed
as a percentage (FEV1 % predicted). Stage 1 (mild) disease
is defined as 80% or over, stage 2 (moderate) is defined
as 50%–79%, stage 3 (severe) is defined as 30%–49% and
stage 4 (very severe) is defined as less than 30%. Symptoms
must be present for diagnosis in patients with FEV1 greater
than 80%.
Care should be multidisciplinary and include:
• Smoking cessation.
• Patient education.
• Optimizing pharmacological therapies.
• Pulmonary rehabilitation (a multidisciplinary
programme of graded exercise, nutritional advice,
psychological support and patient education; this
relieves symptoms and reduces exacerbations and can
increase exercise ability).
• Treatment of acute exacerbations.
• Management of cor pulmonale (right-sided heart
failure secondary to pulmonary dysfunction), if
present.
• Home oxygen therapy and/or home noninvasive
ventilation in persistent hypercapnic respiratory failure
nonresponsive to medical treatment.
Short-term management
General principles of treatment of exacerbations of COPD
include:
• oxygen therapy (clinical notes: oxygen use in COPD in
the acute setting);
• high-dose β2-agonists and anticholinergics;
• antibiotics if infection is suspected;
• systemic steroids (if oral therapy is indicated, 30 mg
prednisolone for 7–14days);
• chest physiotherapy;
• theophylline if appropriate;
• assisted ventilation.
HINTS AND TIPS
In acidotic or hypercapnic patients, air, not oxygen,
should be used to drive nebulizers.
CLINICAL NOTES
OXYGEN USE IN CHRONIC COPD IN THE ACUTE
SETTING
• Target oxygen saturations is 88%–92%.
• Use venturi masks to deliver a set oxygen
concentration; start with the lowest percentage
possible.
• Arterial blood gases should be measured within
1 hour of commencing or changing oxygen
therapy.
• Oxygen therapy should be titrated to maintain
normal pH with, generally, Pao2 greater than
7.5 kPa.
Long-term management
Smoking cessation remains the single most important intervention by the healthcare team to modify the natural course
of the disease. It will not repair damaged lung tissue, but
the rate of decline in FEV1 with time will revert to that of
a nonsmoker. Help from smoking cessation specialists and
pharmacological assistance with nicotine replacement, varenicline or bupropion may increase effectiveness.
Bronchodilators are important in symptom relief from
COPD, and long-acting agents reduce the number of exacerbations. They can reduce dynamic hyperinflation not
measurable by changes in FEV1 and exertional dyspnoea.
They include:
• short-acting β2-agonists (e.g. salbutamol and
terbutaline);
• long-acting β2-agonists (e.g. salmeterol and
formoterol);
• anticholinergics (e.g. ipratropium bromide (short
acting) and tiotropium (long acting));
• phosphodiesterase inhibitors (e.g. theophyllines);
• corticosteroids (e.g. fluticasone and budesonide).
208
Pneumonia
2828
Drugs can be delivered through inhalers, spacer devices or
nebulizers.
Oral steroids are used in exacerbations of COPD,
and some patients take them long-term, but this is not
recommended.
Orally administered theophylline should only be used if
inhaled phosphodiesterase inhibitor therapy is unsuccessful
or contraindicated.
Oral mucolitics (e.g. carbocysteine) should be considered in patients with chronic productive cough.
When you are titrating therapy, symptomatic relief,
quality of life, patient preference, side-effect profile and cost
should be considered.
Long-term oxygen therapy is indicated in:
• stable nonsmokers with Pa2 below 7.3 kPa;
• stable nonsmokers with Pa2 between 7.3 and 8.0 kPa
and one of the following: pulmonary hypertension,
peripheral oedema, nocturnal hypoxaemia or
secondary polycythaemia.
Prophylactic antibiotic use is not recommended.
Vaccination against influenza virus and pneumococcus
should be offered. Regular assessment of nutritional and
psychological status is recommended.
Some patients may be suitable for bullectomy or lung
volume reduction surgery to relieve symptoms. In end-stage
disease, lung transplantation is an option for some, often
younger, patients.
clearance such as cystic fibrosis, α1-antitrypsin deficiency
or Kartagener syndrome (primary ciliary dyskinesia). Most
commonly, it occurs as a result of infection. Adenovirus and
influenza virus are the main viral causes; infections with
necrotizing organisms (e.g. Mycobacterium tuberculosis or
anaerobes) remain important. Localized bronchial obstruction can also lead to bronchiectasis.
Clinical features
Patients typically present with persistent or recurrent cough
and purulent sputum production. Intermittent haemoptysis occurs in more than half of cases and can cause massive
bleeding. Physical examination of the chest may reveal any
combination of coarse crepitations and wheeze, reflecting
the damaged airways containing significant secretions.
Clubbing may be present.
Investigations
Chest radiography may show ‘tramline shadows’ due to
bronchial wall thickening. High-resolution CT (HRCT)
is the gold standard investigation and confirms the diagnosis. Lung function and reversibility should be assessed by spirometry, and sputum culture should guide
antibiotic therapy. Immunodeficiency testing should be
considered.
COMMUNICATION
Discussing the patient's wishes with regard to
the level of treatment and resuscitation status in
severe chronic obstructive pulmonary disease
(COPD) is difficult. It is, however, an important part
of the management plan and should be done at an
appropriate time with use of sensitive language.
In patients with end-stage COPD, the focus
of treatment should be comfort care aimed at
symptom relief and best possible quality of life.
BRONCHIECTASIS
General overview
Bronchiectasis is abnormal and permanent dilatation and
thickening of the bronchioles secondary to chronic inflammation. It is associated with bacterial colonization. It
can be focal, involving airways supplying a region of the
lung, or diffuse, involving airways in a more widespread
manner.
Bronchiectasis can be congenital. For example, it is
associated with conditions causing poor mucociliary
Management
Sustained lung damage is irreversible. Therapy is aimed
at halting or slowing down the progression of the disease.
The underlying cause should be managed with appropriate
treatment (e.g. antituberculous drugs for TB or steroids for
ABPA). Regular airway clearance physiotherapy is recommended. Antibiotics should be used according to organism
sensitivities. Lung resection surgery is occasionally effective
for localized bronchiectasis.
PNEUMONIA
General overview
Pneumonia is an infection of the pulmonary parenchyma
(i.e. the functional lung tissue) causing chest signs and
symptoms (cough, shortness of breath, wheeze, sputum,
fever, chest pain/discomfort). A CXR demonstrating air
space consolidation can confirm the diagnosis. It is a common condition with high mortality rates. Many bacterial
species, viruses, fungi and parasites can cause pneumonia.
Empirical antimicrobial treatment is often commenced before the causative microorganism is identified, after which
therapy is adjusted accordingly.
209
Respiratory system
COMMUNICATION
It is important to communicate to patients that their
symptoms should abate once treatment has been
started; however, it may take time for them to get
back to their baseline. The National Institute for
Health and Care Excellence recommends providing
the following information:
• 1week: fever should have resolved;
• 4weeks: chest pain and sputum production
should have substantially reduced;
• 6weeks: cough and breathlessness should have
substantially reduced;
• 3months: most symptoms should have resolved
but fatigue may still be present;
• 6months: most people will feel back to normal.
Aetiology
Community-acquired pneumonia
This is pneumonia that develops out of hospital or within 48
hours of admission. Causes include Streptococcus pneumo-
nia (pneumococcus; most common), Haemophilus influenzae and Staphylococcus aureus. Twenty percent of infections
in adults are thought to be of viral origin. In preexisting
lung disease (e.g. COPD/bronchiectasis), organisms such
as Pseudomonas aeruginosa and Moraxella catarrhalis are
more common.
Atypical pneumonia
This is caused by organisms such as Mycoplasma, Legionella
and Chlamydia species. They can be acquired in the community or in institutions. Detailed travel history and occupational and social history are important in identifying risk
factors.
Hospital-acquired pneumonia (nosocomial)
This is new-onset pneumonia that develops 48 hours or
more after admission to hospital. It can be caused by all of
the aforementioned agents, but Gram-negative organisms
such as Pseudomonas and Klebsiella are responsible for most
cases.
Aspiration pneumonia
Aspiration pneumonia occurs as a result of aspiration of
foreign material, usually oral or gastrointestinal contents,
into the airway. This is most commonly because of the inability to protect the airway such as after a cerebral vascular
event or with a decreased consciousness level. Anaerobic
organisms may be implicated.
HINTS AND TIPS
Speech and language therapists are particularly
helpful in assessing a patient’s risk of aspiration,
and can recommend useful techniques to
minimalize this risk. Patients especially at risk of
aspiration include stroke patients and dementia
patients.
Opportunistic pneumonia
Opportunistic pneumonia occurs in predisposed individuals. Patients with cystic fibrosis are at increased risk of
Pseudomonas pneumonia because of changes in the composition of airway surface mucus. Immunocompromised
patients (e.g. HIV positive, organ transplant patients) are
at increased risk of fungal (e.g. Aspergillus), Pneumocystis
jiroveci (formerly Pneumocystis carinii) or viral (e.g. CMV,
herpes simplex virus) pneumonia. Ventilated patients are
at increased risk of ventilator-associated pneumonia, commonly caused by Pseudomonas or Klebsiella.
Clinical features
Typical
Typical pneumonia is characterized by fever, chills, tachypnoea,
dyspnoea, cough productive of purulent sputum and, in some
cases, pleuritic chest pain. The causative pathogens are usually
S. pneumonia, S. aureus, M. catarrhalis and H. influenzae.
Atypical
It was traditionally stated that ‘atypical’ pneumonia has
a more gradual onset, a dry cough and extrapulmonary
symptoms (headache, muscle aching, fatigue, sore throat,
nausea, vomiting and diarrhoea). The symptoms are more
of a gradual onset. The term ‘atypical pneumonia’ remains
in use but it is the organisms that are ‘atypical’ and not the
symptoms. Causative pathogens include Mycoplasma pneu-
monia, Legionella pneumophila, Chlamydophila species and
Coxiella burnetii (causing Q fever). Viruses, fungi and pro-
tozoa can also be implicated.
Investigations
Bedside
• FBC: neutrophilia may be present.
• U&Es: raised urea level is indicative of dehydration and
is a part of the CURB65 score.
• CRP: level may be raised and can help in assessing
response to treatment.
• ABG: hypoxia and hypercapnia may be present.
• Blood cultures in pyrexic patients, before
commencement of antibiotic therapy may help in
determining the cause.
210
Pneumonia
2828
• Sputum sample for microbiology, culture and
sensitivities.
• If clinically indicated, pneumococcal and Legionella
urinary antigens; respiratory virus screen.
Imaging
• CXR: diffuse or lobar pulmonary infiltrates may
be seen. Air bronchograms are characteristic of
consolidation. Pleural effusions, pulmonary cavitation
or hilar lymphadenopathy may be present. Cavitating
lesions may be caused by TB, oral anaerobic bacteria,
enteric gram-negative bacilli, S. aureus, Pseudomonas,
Legionella, Aspergillus spp. and fungi.
• CT: not commonly used as a first-line imaging
modality. However, if the CXR is suggestive of a spaceoccupying lesion, a CT scan would be indicated.
Other tests
• Pleural tap: pleural effusion, if thought to be
parapneumonic, may be aspirated/drained. The fluid
should be sent for microscopy, culture and sensitivity
testing. If a sinister cause is suspected, a sample should
be sent for cytology.
• Bronchoscopy: in pneumonia this is mainly used
to collect samples that could aid in identifying the
causative pathogen. This can be achieved by either
bronchoalveolar lavage or transbronchial biopsy at the
site of the pulmonary consolidation.
CURB65 score
The management of community-acquired pneumonia is guided
by its severity. The CURB65 score is a validated tool to assess
the risk of death. Each the following components scores 1 point:
• confusion: new confusion, abbreviated mental test
score of 8 or less;
• urea level greater than 7 mmol/L;
• respiratory rate of 30 per minute or greater;
• systolic blood pressure less than 90 mmHg and/or
diastolic blood pressure of 60 mmHg or less;
• age 65years or older.
A score of 0 or 1 indicates a risk of death of less than 3%
and a possibility of home treatment, a score of 2 indicates a
risk of death of 3%–15% and hospital treatment should be
considered and a score of 3 or above indicates a risk death
of more than 15% and severe pneumonia requiring hospital
admission and aggressive treatment.
Management
The mainstay treatment for pneumonia is antibiotics.
Hypoxia is treated with oxygen, dehydration is treated with
fluids and pleuritic pain is treated with analgesia (clinical
notes: pleuritic chest pain). A guide to antimicrobial treatment of pneumonia is given in Table28.4. However, check
hospital- specific guidelines as pathogen prevalence and local
antibiotic sensitivities differ. Pneumonia is a leading cause of
sepsis (clinical notes: sepsis).
CLINICAL NOTES
PLEURITIC CHEST PAIN
Appropriate management of pleuritic chest pain is
extremely important. Pain will hinder recovery by
reducing mobility and cough effectiveness. This
will lead to inadequate sputum clearance and can
worsen the course of the disease. Mild pleuritic
chest pain can be treated with paracetamol and
nonsteroidal antiinflammatory drugs (unless
contraindicated). Moderate and severe pain
may require opiates. In addition to adequate
pain management, saline nebulizers and chest
physiotherapy are also of benefit.
CLINICAL NOTES
SEPSIS
Sepsis is a syndrome caused by the body’s
abnormal response to infection associated with
organ dysfunction. It is a life-threatening condition
with very high morbidity and mortality rates. As such,
early recognition is key. Sepsis used to be defined as
systemic inflammatory response syndrome (two from
heart rate greater than 90 bpm, temperature above
38°C or below 36°C, respiratory rate greater than
20 per minute and white cell count greater than
12 × 109 L or less than 4× 109 L) in the presence of
an infective cause; however, use of these criteria for
the diagnosis is no longer recommended.
CLINICAL NOTES
SEPSIS SIX
Sepsis Six is a care bundle used for early
management of sepsis that was developed to
improve patient outcomes. It consists of six steps:
• oxygen
• blood cultures
• serum lactate and full blood count measurement
• empirical intravenous antibiotics
• intravenous fluids
• urine output measurement
These steps should be delivered within 1 h of
diagnosis.
211
Respiratory system
Table28.4 Drug choice for pneumonia (this will differ between countries and hospitals and is intended as a guide only)
Community-acquired pneumonia Atypical pneumonia
Low severity
CURB65 score of 0–1
Moderate
CURB65 score of 2
Severe
CURB65 score ≥3
Broad-spectrum
penicillin (e.g.
amoxicillin)
Macrolide (e.g.
clarithromycin) if
allergic to penicillin or
if atypical organism
suspected
Flucloxacillin if
Staphylococcus aureus
suspected
5-day course
Consider dual therapy
with amoxicillin and a
macrolide
7–10-day course
Consider dual therapy
with a β-lactamase
stable β-lactam (such
as co-amoxiclav,
piperacillin-tazobactam,
cefuroxime, cefotaxime
or ceftriaxone) and a
macrolide for atypical
organisms
Flucloxacillin if
Staphylococcus aureus
suspected
Erythromycin or other
macrolide
Tetracycline for
Chlamydia or
Mycoplasma
10–14-day course
Hospital-acquired
pneumonia Aspiration pneumonia
Follow hospitalspecific guidelines.
Use extendedspectrum antibiotics
such as piperacillin–
tazobactam,
third-generation
cephalosporins,
aminoglycosides,
carbapenems
Treatment is usually
continued for 5–10days
Follow hospitalspecific guidelines.
Ensure anaerobic
organism cover with,
e.g. metronidazole
PULMONARY EMBOLISM
PE is a common, potentially fatal and frequently missed diagnosis. It results from obstruction of a pulmonary artery,
causing hypoxia and circulatory collapse. Venous thrombosis is the most common cause, whereas fat (after long
bone fracture/orthopaedic surgery), air (after, e.g. central
venous catheter insertion) or amniotic fluid emboli are less
frequent.
Risk factors include immobility, including ‘economy
class syndrome’ with air travel, surgery, malignancy, obesity,
pregnancy, contraceptive pill use and one of the thrombophilic conditions (e.g. factor V Leiden or the prothrombin
20210A gene mutation).
Clinical features
Dyspnoea is the most frequent symptom and tachypnoea is
the most frequent sign in PE. Dyspnoea, syncope, hypotension or cyanosis indicates a massive PE, whereas pleuritic
chest pain, cough or haemoptysis often suggests a small embolism located near the pleura. On examination, young or
previously healthy individuals may simply appear anxious
but otherwise well, even with a large PE.
212
NICE recommends assessment of the clinical probability
of PE by the use of the modified Well score (Table28.5).
Investigations
• ABG: levels often normal, but can show hypoxaemia,
low Pa2 (secondary to hyperventilation) or acidosis.
Table28.5 Well score to assess the probability of
pulmonary embolism
Score
Clinically suspected DVT 3.0
Alternative diagnosis is less likely than PE 3.0
Tachycardia 1.5
Immobilization/surgery in previous 4weeks 1.5
History of DVT or PE 1.5
Haemoptysis 1.0
Malignancy (either treated within 6months or
palliative care)
A score of 4 points or less means PE is unlikely; a score of more
than 4 points means PE is likely.
DVT, Deep vein thrombosis; PE, pulmonary embolism.
1.0
Lung cancer
2828
• D-dimer: its main value is as a negative result to
exclude thromboemboli in low-risk patients.
• ECG: often normal but tachycardia is the most
common finding; right bundle branch block and right
ventricular strain are indicative. The S1Q3T3 pattern
(deep S wave in I, Q waves in III and inverted T waves
in III) is ‘textbook’ but uncommon.
• CXR: usually normal but may show atelectasis or a
small wedge shadow (Hampton hump).
• CTPA: the gold standard for diagnosing PE. It allows
visualization of the pulmonary vasculature.
•
• Lower limb compression venous ultrasound scan: to
• Echocardiography may show evidence of acute
scanning (isotope lung scanning): looking for a
mismatch defect. This method requires a normal CXR.
confirm deep vein thrombosis (DVT).
right ventricular dysfunction, especially in large
haemodynamically significant PEs.
Management
Follow the ABCDE approach. NICE guidelines recommend
the following:
• Patients with confirmed proximal DVT or PE should
receive low-molecular-weight heparin (LMWH)
or fondaparinux, unless they have severe renal
impairment or established renal failure or are at
increased risk of bleeding, when unfractionated
heparin (UFH) or LMWH should be offered.
• Haemodynamically unstable patients with a PE
should be considered for thrombolytic therapy or
embolectomy.
• Patients at increased risk of bleeding should be treated
with UFH.
• Subcutaneous or intravenous anticoagulation should
be continued for a minimum of 5days or until the
international normalized ratio is 2.0 or more for 24
hours or more.
• Treatment with oral anticoagulants should be
commenced within 24 hours of diagnosis and
continued for 3months, when the risk–benefit ratio of
treatment should be reassessed.
• Different types of oral anticoagulants are available.
Warfarin is the classically used vitamin K antagonist.
Monitoring of efficacy of treatment is performed
regularly, aiming at keeping the international
normalized ratio in the range 2.0–3.0.
The non-vitamin K antagonist oral anticoagulants
rivaroxaban, dabigatran etexilate, apixaban and
edoxaban are options recommended by NICE. These
do not require monitoring; however, until recently there
were no specific reversibility agents for these drugs.
Idarucizumab is a specific reversal agent for dabigatran
etexilate, and is the first compound to be licensed in the
United Kingdom. Antidotes for other non-vitamin K
antagonist oral anticoagulants are being developed.
• Inferior vena cava filters are implantable
devices recommended for use in patients with
contraindications to anticoagulation or those with
recurrent thromboembolisms despite adequate drug
therapy.
HINTS AND TIPS
Many drugs interact with warfarin to enhance or
diminish its effect. Ask the patient to report any
changes in treatment. Certain dietary factors can
also lead to international normalized ratio changes.
Patients who have recurrent or a strong family
history of thromboembolic events should be
screened for recognized hypercoagulable states.
Lifelong anticoagulation may be necessary.
LUNG CANCER
General overview
The World Health Organization reports that lung cancer was
responsible for most cancer deaths worldwide in 2015. In the
United Kingdom, more than 46,000 new cases are diagnosed
every year. The 10-year survival rate is as low as 5%, and
the 5-year survival rate is 10% (Table28.6). The term ‘lung
cancer’ is usually reserved for primary tumours arising from
the respiratory epithelium (bronchi, bronchioles and alveoli)
rather than metastases from distant malignancies. Lung metastases are common. Sites of origin include the gastrointestinal tract, kidney, ovary, bone, breast and prostate.
Lung cancer types can be divided into two main groups:
small cell lung cancer (SCLC, 10%–15%) and non-small
cell lung cancer (NSCLC, 85%–90%). Four major cell types
make up 90% of all primary lung neoplasms:
• Adenocarcinoma (including bronchioloalveolar cell
carcinoma): usually located peripherally, more common
in nonsmokers. Arises from epithelial mucous cells.
• Squamous cell carcinoma: most common type of lung
cancer, from the large airways, usually located centrally,
it grows slowly and spreads late.
• Large cell (anaplastic) carcinoma: heterogeneous group
of undifferentiated tumours.
• Small cell (oat cell) carcinoma: from central airways, it
grows rapidly and spreads early.
The remainder include undifferentiated carcinomas, carcinoids and rarer tumour types (e.g. mesothelioma arising
from the pleura following asbestos exposure or bronchoalveolar cell lung cancer). All cell types have different natural
histories and responses to therapy, and therefore making
a correct histological diagnosis is essential to appropriate
management.
213
Respiratory system
Table28.6 Estimates of 5-year survival rates of treated
patients with lung cancer
Stage
Non-small cell
lung cancer
Small cell lung
cancer
0 (T1 N0 M0):
carcinoma in situ
1 (T1–T2 N0 M0):
no nodes or
metastases
II (T1–T2 N1 M0):
ipsilateral local
nodes only
IIIa (T1–T4 N0–
N2 M0): more than
T2 with ipsilateral
mediastinal nodes
IIIb, IIIc (any T, any
N, M0): invading
mediastinal
structures, or
nonresectable
nodes but no
extrathoracic
spread
IV (any T, any N,
M1): extrathoracic
distant metastases
Patients rarely
live for 5years
after diagnosis—
mean survival
with combined
chemotherapy
(e.g. with
cisplatin-containing
regimens) is
40–70weeks,
compared with
6–20weeks if
untreated
Five-year survival
rate (%)
70–80
66–82
47–52
36
15–19
6
Aetiology
Eighty-six percent of lung cancers are attributable to smoking. Active smoking accounts for 83% of cases, whereas the
remaining 3% are due to passive smoking in nonsmokers.
Cigarette smoke contains numerous well-documented carcinogens. The risk of developing lung cancer rises with the
number of smoking pack years (Table28.7). Smoking ces-
sation improves patient outcomes and reduces the risk of
developing lung cancer.
Other risks are much less common and include increasing age, radon exposure, asbestos exposure and previous or
current lung disease. Mutations in the epidermal growth
factor receptor tyrosine kinase (EGFR-TK) have been
linked to NSCLC.
Table28.7 The risk of death from lung cancer related to
the number of cigarettes smoked
Pattern of smoking
Never smoked 14 1
Ex-smoker 58 4
Current smoker
1–14 cigarettes/day
15–24 cigarettes/day
>25 cigarettes/day
Deaths per
100,000 people Relative risk
105
208
355
7.5
15
25
Pathology
Like other carcinomas, lung cancer is not caused by a single insult but follows the pattern of cellular dysplasia progressing to carcinoma and spread as the burden of genetic
damage accumulates and key oncogenes are mutated. For
example, the K-ras proto-oncogene is implicated in 10%–
30% of all adenocarcinomas.
Clinical features
Unexplained or persistent (duration of more than 3weeks)
cough, dyspnoea, chest signs, voice hoarseness, lymphadenopathy (cervical or supraclavicular) and stridor, as well as
unexplained haemoptysis in people aged 40years or older
and signs of superior vena cava obstruction (face or neck
swelling with raised jugular venous pressure) should raise
the suspicion of lung cancer and warrant urgent CXR referral. Clubbing and tar staining of the fingers may be present.
As with any type of malignancy, patients can exhibit systemic symptoms such as anorexia, cachexia, fatigue, malaise
and unintentional weight loss.
Local invasion of the tumour, depending on the struc-
tures involved, may lead to the following symptoms:
• Endobronchial growth: this may result in cough,
haemoptysis, wheeze, stridor, dyspnoea and
postobstructive pneumonitis (fever and productive cough).
• Invasion of the chest wall: this could cause pain (pleural
or chest wall involvement), cough, dyspnoea and
symptoms of lung abscess due to tumour cavitation.
• Transbronchial spread: transbronchial spread
(especially bronchioloalveolar carcinoma) produces
growth along multiple alveolar surfaces with resultant
impairment of oxygen transfer, dyspnoea, hypoxia and
the production of copious sputum.
• Invasion of other thoracic structures: this may lead
to airway obstruction, oesophageal compression with
dysphagia, recurrent laryngeal nerve paralysis with
hoarseness, phrenic nerve paralysis with elevation of
the hemidiaphragm and dyspnoea and sympathetic
nerve paralysis with Horner syndrome (ptosis, miosis,
enophthalmos and ipsilateral facial loss of sweating).
Pancoast tumour growing in the apex of the lung extends
locally with involvement of the eighth cervical and first
214
Lung cancer
2828
and second thoracic nerves of the brachial plexus. There is
shoulder pain, which characteristically radiates in the ulnar
distribution of the arm, often with destruction of the first
and second ribs seen on CXR.
Other problems of regional spread include superior vena
cava syndrome from vascular obstruction, pericardial and cardiac extension with resultant effusion or tamponade, lymphatic
obstruction with resultant pleural effusion and lymphangitic
spread through the lungs with hypoxaemia and dyspnoea.
Paraneoplastic syndrome
Lung cancer can also present as a paraneoplastic syndrome.
About 15%–20% of lung cancer patients will have signs
and symptoms that result from extrapulmonary organ dysfunction unrelated to space-occupying metastases. Most
commonly they are due to tumour secretory products.
Important paraneoplastic syndromes associated with lung
cancer are listed in Table28.8. Resection of the primary tu-
mour may result in resolution of symptoms.
Table28.8 Important paraneoplastic syndromes
associated with lung cancer
Organ/system Syndrome
Endocrine and
metabolic
Connective tissue
and bone
Neuromuscular Peripheral
Haematological Anaemia All
Cardiovascular Thrombophlebitis Adenocarcinoma
DIC, Disseminated intravascular coagulation; HPOA, hypertrophic
pulmonary osteoarthropathy; SIADH, syndrome of inappropriate
antidiuretic hormone secretion.
Cushing
syndrome
SIADH Small cell
Hypercalcaemia Squamous cell
Gynaecomastia Large cell
Clubbing and
HPOA
neuropathy
Subacute
cerebellar
degeneration
Eaton–Lambert
myasthenic
syndrome
(myasthenia)
Dermatomyositis All
DIC All
Eosinophilia All
Thrombocytosis All
Nonbacterial
thrombotic
endocarditis
Lung cancer
histological type
Small cell
Squamous cell,
adenocarcinoma
and large cell
Small cell
Small cell
Small cell
Adenocarcinoma
Investigations
• CXR: abnormal in most cases. Common findings
include hilar masses (squamous and small cell),
peripheral masses (adenocarcinoma), atelectasis,
infiltrates, cavitation (squamous cell) and pleural
effusions. Compare the CXR with old CXRs if
possible.
• CT: contrast-enhanced chest CT should include the
liver and adrenal glands (for staging purposes).
• Positron emission tomography–CT: all patients with
potential for curative treatment.
• MRI: not routinely recommended for staging purposes
unless superior sulcus tumour is present.
• Head imaging: consider head CT and MRI (if CT
findings are normal) in patients with suspected
intracranial disease.
• Options for diagnostic pathology include biopsy
of either the mass or the lymph nodes: fibre-optic
bronchoscopy, CT, positron emission tomography–CT,
non-ultrasound-, neck ultrasound-, or endobronchial
ultrasound-guided fine-needle aspiration. Surgical
staging is also possible.
• Sputum cytology: patients with centrally located lesions
in whom other tests are contraindicated.
• EGFT-TK genetic testing.
Tumour, Node, Metastasis (TNM) staging
Eighty percent of patients have inoperable disease at the
time of presentation. Small cell lung cancer is nearly always
disseminated at presentation. Diagnosis of this histological
type excludes surgical resection, except in very rare circumstances where there is a single, small, peripheral lesion. In all
other cell types, surgery is possible. The disease is staged on
the basis of the TNM classification as shown in Table28.9.
This allows estimation of the prognosis.
Management
Histological classification of the tumour will guide treatment (Table28.10). Smoking cessation is crucial but should
not delay treatment. In general, SCLCs have already spread
at the time of presentation, so curative surgery cannot be
performed, and they are managed primarily by chemotherapy, with or without radiotherapy.
In contrast, NSCLCs that are found to be localized at the
time of presentation should be considered for curative treatment with either surgery or radiotherapy with or without
adjuvant chemotherapy. Curative radiotherapy is offered
to those patients with poorer respiratory reserve. Hilar and
mediastinal lymph node sampling en bloc is always performed along with surgery with curative intent. Targeted
therapy with EGFR-TK inhibitors is recommended by
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Respiratory system
Table28.9 TNM classification of lung cancer
TNM Stage Characteristics
Primary tumour (T) TX No lesions seen but cytology positive for malignant cells
T0 No signs of primary tumour
T1 ≤3 cm diameter surrounded by lung or pleura
T2 >3 cm and ≤5 cm diameter and/or collapse or obstructive pneumonitis extending
T3 >5 cm and ≤7cm diameter or extending to chest wall, phrenic nerve, parietal
T4 >7 cm or invading mediastinum, diaphragm, carina and/or malignant pleural
Lymph nodes (N) NX Cannot be assessed
N0 No involvement
N1 Ipsilateral hilar and/or peribronchial nodes and intrapulmonary nodes
N2 Ipsilateral mediastinal and/or subcarinal nodes
N3 Contralateral mediastinal and/or hilar nodes; or any scalene or supraclavicular
Metastases (M) M0 None known
M1 Metastases present
to hilum, invading visceral pleura and/or main bronchus but not the carina
pericardium but not involving mediastinal structures
effusion
nodes
Table28.10 Treatment strategies for lung cancer
Histological type Extent of disease Treatment modality
Non-small cell lung cancer Stage 0–II Surgery and/or postoperative radiotherapy with or
Stage III–IV Radiotherapy and/or chemotherapy
Small cell lung cancer Proven single peripheral
lesion (rare)
Limited stage Combination chemotherapy and radiotherapy
Disseminated at
presentation (usual)
NICE as a possible option in locally advanced or metastatic
EGFR-TK mutation-positive NSCLC.
Surgical options include segmentectomy or wedge resection, which are parenchymal-sparring procedures; lobectomy; bilobectomy; bronchoangioplastic surgery; and
pneumonectomy. These can be either thoracoscopic or
open surgeries. Spirometry should be offered to all patients
with potential for curative therapy.
If the tumour is inoperable, palliative care is essential.
without adjuvant chemotherapy
Curative surgery attempted
Combination chemotherapy with or without
radiotherapy
COMMUNICATION
Patients are rarely surprised when the final
diagnosis of lung cancer is explained to them. Ask
open questions and seek their opinion as to what
might be wrong with them; this can enable cancer
to be discussed more easily as they have used the
word first.
Breathlessness responds to opiates. Radiotherapy may relieve endobronchial obstructive symptoms, bone pain secondary to metastases or superior vena cava obstruction.
Patients with endobronchial obstruction can undergo pal-
TUBERCULOSIS
liative debulking or stenting. Symptomatic malignant pleural effusions can be aspirated or drained. Talc pleurodesis
is a long-term symptom relief measure. Brain metastases
are managed with dexamethasone for symptomatic relieve.
Whole-brain radiotherapy can be considered for palliative
symptom control.
General overview
TB is a chronic granulomatous disease caused by a cellmediated immune response to bacteria belonging to the
Mycobacterium tuberculosis complex. It is an airborne
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Tuberculosis
2828
disease that usually affects the lungs, although extrapulmonary involvement occurs in up to one-third of cases. If
properly treated, TB caused by drug-susceptible strains is
curable in virtually all cases.
Of the pathogenic species belonging to the M. tuberculosis
complex, the most frequent and important agent of human
disease is M. tuberculosis. Closely related organisms that can
also infect humans include Mycobacterium bovis (the bovine
tubercle bacillus, once an important cause of TB transmitted
by unpasteurized milk) and Mycobacterium africanum.
M. tuberculosis is a rod-shaped, non-spore-forming,
aerobic bacterium measuring 0.5–3 μm. Although strictly
gram-positive, it may not stain readily, and is often neutral
on the Gram stain. However, once stained, the bacilli cannot be decolorized by acid alcohol, a characteristic justifying their classification as acid–alcohol-fast bacilli (AAFB).
In most developed countries the incidence of TB fell
until the 1980s. It then reached a plateau, and is now increasing again in the United Kingdom (Table28.11). This is
due to an increase in susceptible groups. These include the
elderly, immigrants, people from ethnic minorities, people
with alcoholism, the homeless and the immunocompromised (both iatrogenic and pathological; HIV is the most
important group of the latter, with estimated 60% of individuals with AIDS having TB). Worldwide, TB remains a
leading cause of death. Multidrug resistant and extensively
drug resistant strains of TB continue to be global problem.
Pathogenesis
TB is usually classified as pulmonary or extrapulmonary.
Before HIV infection, 80% of all cases of TB were limited to
the lungs; now two-thirds of HIV-infected patients with TB
have both pulmonary and extrapulmonary disease, or even
extrapulmonary disease on its own.
Table28.11 Notification of tuberculosis in the United
Kingdom, from the Health Protection Agency
Year Number of cases notified
1920 73,332
1930 67,401
1940 46,572
1950 49,358
1960 23,605
1970 11,901
1980 9142
1990 5204
1995 5606
2000 6572
2005 7628
2009 7240
2012 8751
Pulmonary tuberculosis
Pulmonary TB can be classified as primary or secondary.
Primary pulmonary TB results from an initial infection with tubercle bacilli. Alveolar macrophages take up
the inhaled pathogens for transit to hilar lymphoid tissue,
facilitating the host’s immune response and control of the
infection. Occasionally, dissemination occurs and bacteria
are spread to various parts of the body via blood or lymphatic fluid, where granulomas containing the organisms
are formed. In most cases, host immunity mechanisms lead
to spontaneous healing of these lesions and elimination of
the bacteria. In some cases, pathogens persist in a dormant
state. Ghon focus is a calcified caseating granuloma that indicates past primary infection.
Patients with impaired immunity who develop primary
pulmonary TB may progress rapidly to clinical illness. This
may result from spread of infection by:
• pleural effusion: may lead to tuberculous empyema;
• necrosis and acute cavitation of the primary lesion:
known as ‘progressive primary TB’;
• bloodstream dissemination: resulting in miliary TB
with a possible tuberculous meningitis.
Reactivation of dormant bacteria leads to secondary TB. This
is usually a result of debility or immunocompromise and
tends to localize to the apical and posterior segments of the
upper lobes. CXR changes can range from small infiltrates
to extensive cavitation. Widespread involvement of the lung
with coalescing lesions produces tuberculous pneumonia.
The pathogenicity of pathogenicity of Mycobacterium tuberculosis varies, with one-third of untreated patients dying
of severe pulmonary TB within weeks or months, whereas
the rest undergo spontaneous remission or proceed along a
chronic course often involving lung fibrosis.
Extrapulmonary tuberculosis
This most commonly involves lymph nodes, the pleura,
genitourinary tract, bones and joints, meninges, liver, gut
and peritoneum.
Clinical features
TB is a disease of insidious onset, with primary infection usually being asymptomatic. Clinical features of secondary TB
are nonspecific and differ depending on the organs affected.
Systemic
• B-symptoms: night sweats, fevers and weight loss.
• Fatigue.
• Anorexia.
• Clubbing.
Pulmonary
• Cough: chronic and productive.
• Chest pain.
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