1

What is a respiratory tract infection?

A respiratory tract infection (RTI) represents a disease process of the lung and the airways caused by a pathogenic micro-organism, which can be classified according to:

a)

pathogen – bacteria, mycobacteria, viruses and fungi;

b)

anatomic pattern – upper airways (URTI) or lower airways (LRTI, pneumonia);

c)

clinical course – acute or chronic.

2

What is the relationship between thoracic surgery and respiratory infections?

Infection represents an important cause of pathology in thoracic surgery and a major source of complications following thoracic surgery.

Surgeons are involved in the treatment of primary pulmonary infection by:

a)

providing access to specimens and tissue for diagnosis by bronchoscopy, endoscopic ultrasound-guided fine needle aspiration (FNA), transthoracic FNA, core biopsy or wedge biopsy;

b)

managing the complications of an infection when medical treatment fails;

c)

management of complex infection.

General anaesthesia and thoracic surgery result in reduced cough, atelectasis and reduced mucociliary clearance, which may cause sputum retention and secondary infection.

The risk of postoperative pneumonia can be reduced by optimal patient selection, pre-operative rehabilitation, smoking cessation, prompt mobilisation, good pain control and physiotherapy after surgery.

3

What is a lower respiratory tract infection?

LRTI or pneumonia can be defined as an infection of the respiratory bronchioles, alveolar ducts and alveoli.

It commonly occurs as the result of bronchogenic spread of infection, where micro-organisms reach the terminal airways.

Smoking, malnutrition, impaired clearing mechanisms, large pathogenic load and virulent strains of pathogens increase the risk of developing pneumonia.

As well as by pathogen, pneumonia can be classified according to:

a)

origin:

i)

community-acquired pneumonia (CAP);

ii)

hospital-acquired pneumonia (HAP) – a subset of which is ventilator-associated pneumonia (VAP);

iii)

healthcare-associated pneumonia (HCAP);

b)

extent:

i)

bronchial pneumonia;

ii)

lobar pneumonia;

iii)

interstitial pneumonia;

c)

subtype:

i)

aspiration pneumonia/chemical pneumonitis;

ii)

opportunistic pneumonia;

iii)

eosinophilic pneumonia;

iv)

bronchiolitis obliterans organising pneumonia (BOOP);

v)

necrotising pneumonia.

4

What is community-acquired pneumonia?

CAP is defined as a LRTI in someone who has not been hospitalised in the last 14 days.

It is the most common type of pneumonia and can be subclassified according to the pathogen into typical and atypical pneumonia.

Although a causative organism is not always isolated, Streptococcus pneumoniae (commonest), Haemophilus influenzae and Moraxella catarrhalis are responsible for 85% of cases of typical CAP (Table 1).

Risk factors for typical pneumonia include advanced age, alcoholism, cigarette smoking, dementia, malnutrition, infection with HIV and the presence of chronic illness.

Risk factors for atypical pneumonia include young age, severe comorbidities, exposure to birds, ticks, deer or sheep, travel, air conditioning and frequent use of hot tubs and spas.

Viral CAP (see below) can be caused by the influenza virus, respiratory syncytial virus (RSV) and Cytomegalovirus (in immunosuppressed patients).

5

What is hospital-acquired pneumonia (HAP)?

Hospital-acquired pneumonia (HAP) is defined as the onset of a LRTI occurring at least 48-72 hours after admission to hospital.

It is the second most common hospital-acquired infection (after urinary tract infections) and is also known as nosocomial pneumonia.

The causative aetiology, pathogens, treatment and prognosis is different to community-acquired pneumonia.

The presence of a HAP increases the average hospital length of stay by 7-9 days and the risk of in-hospital mortality.

Risk factors for the development of HAP include increasing age, underlying respiratory disease, mechanical ventilation (see ventilator-associated pneumonia), neurological disorders and impaired mucociliary clearance of secretions (pain, impaired cough or recent smoking).

Ventilator-associated pneumonia (VAP) is a subtype of HAP, which arises in patients >48-72 hours after endotracheal intubation.

Mechanical ventilation increases the risk of a hospital-acquired pneumonia by 6-20-fold.

Both HAP and VAP can be subclassified according to the timing of onset, which are associated with different risk factors, pathogens, treatment and prognosis:

a)

early – which occurs within 4 days of hospital admission, is usually associated with a better prognosis and is more likely to be caused by antibiotic-sensitive organisms;

b)

late – which occurs 5 or more days after hospital admission, is usually associated with a worse prognosis and is more likely to be caused by multidrug-resistant (MDR) organisms.

Bacteria account for the majority of HAP and VAP, with viral and fungal infections uncommon in immunocompetent patients.

With hospitalisation, the oropharyngeal flora shifts towards Gram-negative organisms, including Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter species, which are the most prevalent type of pathogen identified in HAP and VAP (Table 2).

6

What is healthcare-associated pneumonia?

Healthcare-associated pneumonia (HCAP) represents a subset of patients who are not hospitalised but whose aetiology, pathogens, prognosis and treatment are more similar to HAP than community-acquired pneumonia.

HCAP patients include those who have:

a)

resided in a nursing home or long-term care facility;

b)

received recent intravenous antibiotic therapy, chemotherapy or wound care within 30 days of the current infection;

c)

been hospitalised for 2 or more days within 90 days of the infection;

d)

received haemodialysis.

As the pathogens responsible for HCAP (Table 2) are similar to HAP and VAP, treatment guidelines are similar to HAP and, hence, are more aggressive than CAP.

7

What is aspiration pneumonia?

Aspiration pneumonia occurs following inhalation of foreign material from the oropharynx or gastrointestinal tract into the bronchial tree and may be implicated in approximately 10% of all pneumonias.

It most commonly affects the right lung due to the more vertical angle of the right main bronchus.

Patients with a reduced conscious level, neurological problems associated with impaired swallowing, or oesophageal dysfunction (such as achalasia) are most at risk.

The presence of gastric acid and other intestinal contents in the respiratory tree results in a chemical pneumonitis, which serves as the background for the growth of enteric micro-organisms.

The most common organisms identified include Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas, Enterobacteriaceae and Haemophilus influenzae. Anaerobic organisms, including Bacteroides, Fusobacterium and Peptostreptococcus, have also been implicated.

Mortality following aspiration pneumonia is approximately 20%.

8

What is opportunistic pneumonia?

Opportunistic pneumonia represents a LRTI in an immunocompromised patient, including those with:

a)

human immunodeficiency virus (HIV) infection;

b)

haematologic malignancy;

c)

chemotherapy;

d)

immunosuppressive agents.

A search for causal organisms and judicious administration of appropriate therapy under the guidance of an infectious diseases specialist is advised.

Common agents implicated in opportunistic pneumonia include Mycobacterium avium-intracellulare, Pneumocystis jiroveci, Cytomegalovirus, and fungal infection with Aspergillus or Candida.

9

What are the radiological features of pneumonia?

Consolidation and interstitial opacification – which is caused by the presence of an inflammatory suppurative exudate (Figure 1).

Air bronchogram – which represents air remaining in the larger bronchi.

Aspiration pneumonia is more commonly identified in the basal segments of the lower lobes (especially right) in upright patients and posterior segments of the upper lobes in supine patients (Figure 2).

Secondary complications of pneumonia, including abscess formation, bronchiectasis, parapneumonic effusion and empyema, may also be present.

10

What are the principles of management in a patient with pneumonia (Tables 3 and 4)?

Patients with CAP should be risk stratified using the CURB-65 score, where the presence of each of the following features scores 1 point:

a)

confusion;

b)

uraemia (urea >7mmol/L);

c)

tachypnoea (respiratory rate >30);

d)

hypotension (systolic <90mmHg, diastolic <60mmHg);

e)

age >65.

Such scoring systems are only a guide and clinical judgement must be exercised in determining what level of care is required.

Supportive treatment with oxygen, nutrition and hydration is important.

Microbiological confirmation should be sought for patients with severe pneumonia to achieve appropriate antimicrobial coverage (Table 4).

If pneumonia is suspected, the administration of antibiotics should not be delayed.

Patients who fail to respond to first-line treatment should be carefully re-evaluated for complications, such as empyema or abscess.

Resolution of radiological consolidation should be assessed 4-6 weeks after infective symptoms have improved and antibiotics have been completed. Failure of complete resolution of consolidation may indicate underlying malignancy, allergic bronchopulmonary aspergillosis (ABPA) or bronchiectasis.

For hospital-acquired pneumonia in the postoperative patient, treatment regimes include:

a)

doxycycline;

b)

ciprofloxacin;

c)

piperacillin/tazobactam.

Treatment regimes for ventilator-associated pneumonia include:

a)

combination therapy – aminoglycoside or third-generation cephalosporin with a carbapenem (imipenem or meropenem);

b)

monotherapy – ciprofloxacin, third-generation cephalosporin or a carbapenem.

In the setting of the intensive care unit, anti-pseudomonal coverage must be considered and double coverage is usually prudent.

Treatment regimes for aspiration pneumonia include:

a)

ceftriaxone plus levofloxacin;

b)

piperacillin/tazobactam or imipenem plus vancomycin.

As antibiotic resistance is a major and increasing problem, it is important for surgeons to familiarise themselves with local policies and seek the involvement of infectious diseases or microbiology specialists.

Specialist advice is also required for the treatment of multidrug-resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter species and Klebsiella pneumoniae.

11

What is the aetiology of viral pneumonia?

The commonest causes of viral pneumonia in children and immunocompetent adults are:

a)

influenza virus (subtypes A, B and C);

b)

respiratory syncitial virus (RSV);

c)

parainfluenza viruses (subtypes 1, 2, 3 and 4);

d)

adenovirus.

Other causes of viral pneumonia include:

a)

rhinovirus;

b)

enterovirus;

c)

hantavirus;

d)

parechovirus;

e)

Epstein-Barr virus;

f)

human Herpes virus 6 and 7;

g)

Herpes simplex virus;

h)

mimivirus;

i)

Cytomegalovirus (mostly in developing countries);

j)

measles virus (mostly in developing countries) .

Viruses causing severe pneumonias include:

a)

severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV);

b)

avian influenza virus;

c)

swine influenza virus;

d)

Varicella zoster virus.

Viruses of recent identification include:

a)

human metapneumovirus;

b)

human bocavirus (mainly in children).

12

What are the characteristic features of viral pneumonia?

Viral respiratory infections are most common in childhood and the incidence increases again in the elderly.

Immunosuppression, chronic cardiac or respiratory disease, and pregnancy increase the risk of viral infection.

Some reports suggest that respiratory viruses may be implicated in up to 50% of all pneumonias.

Respiratory viruses cause a spectrum of infection from mild illness to severe life-threatening pneumonia.

Viral infection may damage the respiratory epithelium, allowing secondary bacterial infection

Although viral polymerase chain reaction (PCR) analysis may be used to facilitate the diagnosis, distinguishing viral pneumonia from bacterial pneumonia may be difficult.

13

What are the principles of treatment of viral pneumonia?

In mild respiratory viral infections – no antiviral therapy is necessary and treatment is aimed at the control of symptoms.

In severe cases, patients may develop acute hypoxia and parenchymal consolidation, consistent with adult respiratory distress syndrome (ARDS), and treatment may require:

a)

supplemental oxygen and ventilation;

b)

judicious fluid balance – to replenish depleted intravascular volume but to avoid fluid overload in the context of acute lung injury;

c)

systemic antiviral agents (which are effective within 48 hours of the onset of symptoms) including:

i)

ribavirin – for adenovirus, parainfluenza virus and measles virus;

ii)

oseltamivir or zanamivir – for influenza virus A and B;

d)

Type 1 interferons;

e)

intravenous immunoglobulins;

f)

steroids;

g)

antibiotics for treatment and prevention of secondary bacterial infection (including S. pneumoniae, S. aureus);

h)

extracorporeal membrane oxygenation (ECMO).

14

What is the role of surgery in the management of respiratory infections?

Surgical intervention may be required following:

a)

failure of medical treatment for bronchiectasis, lung abscess, parapneumonic effusion or empyema;

b)

management of haemorrhagic complications.

15

What is bronchiectasis?

Bronchiectasis is an obstructive lung disease characterised by persistently dilated, inflamed and easily collapsible bronchi, resulting in airway obstruction and impaired clearance of secretions.

It may present as a focal disease, affecting a lobe or a segment, but often is more widespread suggesting a systemic cause.

16

What is the epidemiology of bronchiectasis?

The estimated incidence is approximately 1 in 1000 adults but a prevalence of up to 9% has been found in screening computed tomography (CT) programmes.

The incidence is greater in women than men and rises with age.

An overlap with chronic obstructive pulmonary disease (COPD) has also been described, with some studies demonstrating 30-50% of COPD patients also showing signs of bronchiectasis.

17

What is the pathophysiology of bronchiectasis?

Persistent airway infection is probably due to a combination of an environmental insult and a genetic susceptibility to poor mucociliary clearance.

Inhaled pathogens set up a ‘vicious cycle’ of chronic airway inflammation resulting in further impairment of mucociliary clearance.

The ensuing abnormal airway dilation is secondary to loss of elastin and subsequent destruction of the muscle and cartilage, with the small airways being the most vulnerable.

Damage to the lung parenchyma, a secondary feature, results from persistent and recurrent infection and release of inflammatory mediators.

If the diagnosis is delayed, bronchiectasis may progress to become a severe life-threatening illness.

Most patients have experienced symptoms attributable to bronchiectasis for 10 years before the diagnosis is made.

18

What is the aetiology of bronchiectasis?

Congenital causes include:

a)

congenital biochemical defects:

i)

cystic fibrosis (see below);.

ii)

α1-antitrypsin deficiency;

b)

cilia disorders:

i)

1° ciliary dyskinesia;

ii)

Young’s syndrome – which represents a triad of bronchiectasis, rhinosinusitis and reduced fertility;

c)

bronchial structural defects:

i)

tracheobronchomalacia;

ii)

bronchial atresia;

iii)

bronchopulmonary sequestration;

iv)

Williams-Campbell syndrome – which represents deficiency of distal bronchial cartilage;

v)

Mounier-Kuhn syndrome – which represents tracheo-bronchomegaly;

vi)

Marfan syndrome;

vii)

Ehlers-Danlos syndrome;

d)

primary immunodeficiency;

e)

yellow nail syndrome.

Acquired causes include:

a)

acquired immune deficiency:

i)

human immunodeficiency virus (HIV);

ii)

post-chemotherapy;

iii)

post-transplant;

iv)

chronic lymphocytic leukaemia (CLL);

b)

infection (particularly childhood infection):

i)

tuberculosis;

ii)

non-tuberculous mycobacteria;

iii)

viral;

iv)

bacterial, including pertussis;

v)

fungal;

c)

excessive immune response:

i)

allergic bronchopulmonary aspergillosis (ABPA) – classically proximal bronchiectasis;

ii)

inflammatory bowel disease;

iii)

coeliac disease;

iv)

ankylosing spondylitis;

d)

obstructive lung disease:

i)

chronic obstructive pulmonary disease (COPD);

ii)

asthma;

iii)

obliterative bronchiolitis, including Swyer-James syndrome;

e)

autoimmune:

i)

rheumatoid arthritis;

ii)

vasculitis;

iii)

systemic lupus erythematosus (SLE);

iv)

Sjögren’s syndrome;

f)

focal mechanical airway obstruction:

i)

post-surgical;

ii)

inhaled foreign body;

iii)

slow-growing tumour;

iv)

chemical pneumonitis and aspiration pneumonia;

v)

thermal injury;

g)

miscellaneous:

i)

pulmonary endometriosis;

ii)

amyloidosis;

iii)

post-radiation;

iv)

traction bronchiectasis due to interstitial lung disease.

19

What are the clinical features of bronchiectasis?

The clinical presentation is often insidious and often misdiagnosed as asthma or COPD.

Bronchiectasis typically presents with a chronic cough and daily production of often copious amounts of purulent sputum.

The severity is variable but the usual pattern is of a baseline daily burden of symptoms interrupted by symptoms of infective exacerbation.

Associated symptoms include malaise, fatigue, weakness, weight loss, haemoptysis and pleuritic chest pain.

Signs on clinical examination include wheeze, crackles and clubbing, although chest examination may be unremarkable.

20

What are the radiological findings of bronchiectasis?

A chest radiograph (CXR) (Figure 3A) and a high-resolution computed tomography (HRCT) scan (Figure 3B) may demonstrate: