Category 1

Question 1

TRAUMATIC CONDITIONS

Chest wall trauma

Question 2

TRAUMATIC CONDITIONS

Traumatic aortic injury

Answer 2

• most common type of traumatic aortic injury
• Pathology
  May result in:
  1) minimal aortic injury
  2) aortic laceration: a tear in the intima which may extend through the vessel wall; the tear is typically transverse
  aortic transection: laceration of all three layers of the vessel wall, also known as traumatic aortic rupture
  3) aortic pseudoaneurysm: aortic rupture contained by adventitia or periaortic tissue
  4) aortic intramural haematoma: haematoma within the wall of the aorta

An aortic dissection is a longitudinal tear in the aortic wall and is rarely a sequela of trauma.

Blunt thoracic aortic injury is uncommonly an isolated injury. A large autopsy study found that 97% of victims of aortic injury had other traumatic injuries outside the chest.

Grading
grade 1: intimal tear
grade 2: intramural haematoma
grade 3: pseudoaneurysm formation
grade 4: free rupture

Aetiology
1) blunt trauma (more common)
rapid deceleration (eg. motor vehicle accident, fall from great height)
crush injury
2) penetrating trauma

Location
aortic isthmus: 90% (portion of the proximal descending thoracic aorta between the left subclavian artery origin and the ligamentum arteriosum.)

X-ray:
- widened mediastinum
- indistinct or abnormal aortic contour
- deviation of trachea, ETT or NGT to the right
- depression of left main bronchus
- loss of the aortopulmonary window
- widened paraspinal stripe
- widened paratracheal stripe
- left apical pleural cap
- large left haemothorax

CTA chest
Investigation of choice (sensitivity and specificity of 100% at showing direct signs of aortic injury as well as indirect signs.)

Signs of mediastinal haematoma:
- abnormal soft tissue density around mediastinal structures
- location is important – periaortic haematoma much more suggestive of aortic injury than isolated mediastinal haematoma remote from the aorta.

Signs of aortic injury:
- intraluminal filling defect (intimal flap or clot)
- abnormal aortic contour (mural haematoma)
- sudden change in and/or decreased diameter
- pseudoaneurysm
- extravasation of contrast

Treatment is with an aortic stent graft or open repair. Mortality is very high:
>95% if untreated
~80% die immediately
>30% if in hospital and treated

Complications
- death from aortic rupture and haemorrhage
- chronic traumatic pseudoaneurysm
- embolisation from pseudoaneurysm

Question 3

TRAUMATIC CONDITIONS

Rib fractures including flail chest

Answer 3

three (3) or more contiguous ribs are fractured in two (2) or more places.

non-ventilated patient as a paradoxical movement of the flail segment.

defined as ≥3 adjacent ribs with segmental fractures and/or >5 adjacent rib fractures
traumatic 1st rib fracture: a marker of severe chest trauma, as the rib is protected by the clavicle and scapula

Question 4

TRAUMATIC CONDITIONS

Pneumothorax including nontraumatic

Answer 4

• primary spontaneous pneumothoraces occur in younger patients (typically less than 35 years of age) whereas secondary spontaneous pneumothoraces occur in older patients (typically over 45 years of age)

1) Primary spontaneous
A primary spontaneous pneumothorax occurs in a patient with no known underlying lung disease. Tall and thin habitus are more likely to develop a primary spontaneous pneumothorax. Associations :
- Marfan syndrome
- Ehlers-Danlos syndrome
- alpha-1-antitrypsin deficiency
- homocystinuria

2) Secondary spontaneous
When the underlying lung is abnormal, a pneumothorax is referred to as secondary spontaneous.
- cystic lung disease
- parenchymal necrosis
- others (endometriosis)

3) Iatrogenic/traumatic

Question 5

TRAUMATIC CONDITIONS

Pneumomediastinum

Answer 5

Aetiology
- blunt or penetrating chest trauma
- secondary to neck, thoracic, or retroperitoneal surgery
- oesophageal perforation (Boerhaave syndrome, endoscopic intervention,
oesophageal carcinoma)
- tracheobronchial perforation
- vigorous exercise
- asthma
- barotrauma (diving, ventilator)
- infection
- interstitial lung disease 12
- idiopathic

Question 6

TRAUMATIC CONDITIONS

Pneumopericardium

Answer 6

Aetiology
- positive pressure ventilation
- thoracic surgery/pericardial fluid drainage
- penetrating trauma
blunt trauma (rare)
- infectious pericarditis with gas-producing organisms
- fistula

Continuous diaphragm sign may be present.

Complications
- cardiac tamponade

Differential diagnosis
A pneumopericardium can usually be distinguished from pneumomediastinum since gas in the pericardial sac should not rise above the anatomic limits of the pericardial reflection on the proximal great vascular pedicle. Also on radiographs obtained with the patient in the decubitus position, gas in the pericardial sac will shift immediately, while gas in the mediastinum will not shift in a short interval between films.

Question 7

TRAUMATIC CONDITIONS

Pulmonary contusion/laceration

Answer 7

CONTUSION
- interstitial and/or alveolar lung injury without any frank laceration. It usually occurs secondary to non-penetrating trauma.

Pathology
Contusions follow blunt or penetrating chest trauma, and are almost always seen with other chest (and abdominal) injuries. It is usually caused by disruption of the capillaries of the alveolar walls and septa, and leakage of blood into the alveolar spaces and interstitium

CT
Typically seen as focal, non-segmental (typically crescentic) areas of parenchymal opacification, usually peripheral. It can have subpleural sparing with smaller contusions which can be a distinguishing feature. More common posteriorly and in lower lobes.

Treatment and prognosis
Manifest at the time of the initial examination and show little tendency to increase in severity with subsequent examinations. Signs of contusion have often resolved within 48 hours. By day 10-14 they should have resolved completely. If increases, think infection

LACERATION: frank laceration of lung parenchyma secondary to trauma. There is almost always concurrent contusion.

Pathology
Due to the elastic recoil of the lung, spheres of torn lung parenchyma form and can fill with blood (termed a haematocele), air (pneumatoceles) or both blood and air. If gas-filled, they tend to fill with blood or fluid over time (days to weeks) and can take months to resolve.

CT
Regions of pulmonary contusion with added blebs (pneumatoceles) with gas-fluid levels.

Question 8

TRAUMATIC CONDITIONS

Haemothorax including nontraumatic

Answer 8

Pathology
A haemothorax is sometimes defined as pleural fluid with a haematocrit ≥50% of the peripheral blood haematocrit.

Complications
- infection
- empyema formation
- pneumonia
- chronic fibrothorax

Aetiology
It usually occurs from penetrating or blunt trauma. OTHERS:
- intrathoracic malignancy
- spontaneous pneumothorax - spontaneous haemopneumothorax
- anticoagulant medication
- vascular rupture
- aortic dissection
- rupture of coronary arteries such as RCA during an angioplasty
- thoracic arteriovenous malformations
- pulmonary arteriovenous malformation
- thoracic endometriosis
- pulmonary infarction
- pleural adhesions with pneumothorax
- haematologic abnormalities: coagulopathy, haemophilia
- connective tissue disease:
Ehlers-Danlos syndrome (EDS) type IV:
- congenital bony exostoses

Question 9

TRAUMATIC CONDITIONS

Haemopericardium including nontraumatic

Answer 9

Aetiology
- ruptured myocardial infarction
- ruptured left ventricular aneurysm
- aortic dissection
- pericarditis
- trauma
- blunt/penetrating/deceleration
- iatrogenic, e.g. pacemaker wire insertion
- cardiac malignancies
- ruptured coronary artery aneurysm
- post-thrombolysis

Plain radiograph
- enlargement of the cardiac silhouette
- “straight left heart border”
- Oreo cookie sign on lateral CXR

Question 10

TRAUMATIC CONDITIONS

Diaphragmatic rupture

Answer 10

• from blunt abdominal trauma. The mechanism of injury is typically a motor-vehicle collision.

Pathology
- The left hemidiaphragm is involved three times more frequently than the right
- The most common site of rupture is the posterolateral aspect of the hemidiaphragm between the lumbar and intercostal muscle slips.
- Ruptures occur radially and most are >10 cm in length.
- The most commonly herniated viscera are the stomach and colon.

Question 11

TRAUMATIC CONDITIONS

Oesophageal rupture/ Boerhaave syndrome

Answer 11

Aetiology
- iatrogenic: post-instrumentation or post-thoracic surgery (most common: ~80% of cases)
- complication of acute radiation-induced oesophagitis
- trauma: both blunt (crush-type injury) and penetrating
- foreign body ingestion
- corrosive material ingestion
- oesophageal cancer
- spontaneous rupture post-vomiting (Boerhaave syndrome)
- acute oesophageal necrosis

High mortality rate, estimated between 25 to 50% in some series

Complications: acute mediastinitis, oesophagopleural fistula, pneumonia, empyema, sepsis

BOERHAAVE SYNDROME: secondary to forceful vomiting and retching.

Epidemiology
It tends to be more prevalent in males, with alcoholism a risk factor.

Mackler’s triad: vomiting, chest pain and subcutaneous emphysema.

Pathology
Due to a forceful ejection of gastric contents in an unrelaxed oesophagus against a closed upper oesophageal sphincter/cricopharyngeus. The tears are vertically orientated, 1-4 cm in length. Approximately 90% occur along the left posterolateral wall of the distal oesophagus, 3-6 cm above the oesophageal hiatus of the diaphragm

The classic chest radiographic findings include pneumomediastinum, left pleural effusion and left pneumothorax.
Naclerio V sign,: focal, sharply marginated region of paraspinal radiolucency on the left side immediately above the diaphragm

Question 12

TRAUMATIC CONDITIONS

Non-accidental injury

Answer 12

Patient’s age: skeletal survey should always be performed in suspected abuse if the patient is under two years of age(2-4)
. Between the ages of two and five years, the need for a
skeletal survey is dictated by the clinical assessment and it may not be required
. Above five years
the skeletal survey is of little use.

Consent
Consent for a child to undergo a skeletal survey needs to be obtained from the child’s legal guardian.
The referrer usually obtains consent and the legal guardian needs to be informed that the purpose of
the examination is the assessment for possible non-accidental injury. If consent cannot be obtained
from the legal guardian, the Child Protection Team will need to liaise with the local Statutory Child
Protection Agency to obtain consent by Court Order, however this is infrequently required.

Radiation Dose
Approximately a month of background radiation

Initial Skeletal Survey
Head, chest, spine and pelvis:
1) Anterior-posterior (AP) and lateral skull 2) AP and lateral chest, both obliques
3) AP abdomen and pelvis
4) Lateral views of the whole spine.

Upper limbs:
1) AP of the whole arm (centred at the elbow if possible)
2) Coned lateral elbow
3) Coned lateral wrist
4) Posterior-anterior (PA) hand and wrist

Lower limbs:
1) Whole AP lower limb, hip to ankle
2) Coned lateral knee
3) Coned lateral ankle
4) Coned AP ankle (mortise view)
5) Coned AP knees
6) DP foot

Fractures of the hands and feet are strongly associated with abuse; sternal fractures are highly associated with NAI

A bone scan is higher than a skeletal survey and approximates one year of background radiation

Traumatic abdominal injuries are the second most common cause of death from abuse after brain injury

CT and/or MRI brain should be performed in all children under one year of age with suspected NAI.

Question 13

TRAUMATIC CONDITIONS

Inhaled and swallowed foreign bodies

Answer 13

Radiographic features
Lung volume that does not change during the respiratory cycle.

Plain radiograph
- the patient should be radiographed on expiration: this will exaggerate the differences between the lungs

• the normal lung should appear smaller and denser than the affected lung
• check valve mechanism: the affected lung will usually appear overinflated and hyperlucent, with concomitant rib flaring and a depressed ipsilateral hemidiaphragm
• in uncooperative patients, bilateral decubitus views can be performed, which will demonstrate air trapping on the affected side
• interrupted bronchus sign
• unilateral emphysema or atelectasis are the most common findings; only uncommonly will a radiopaque foreign body be demonstrated

Complications
- pneumonia or atelectasis
- bronchitis
- bronchospasm
- pneumothorax
- broncho-oesophageal fistula
- bronchiectasis

Question 14

CONDUCTIVE AIRWAY CONDITIONS

Bronchiolitis including infectious

Answer 14

CT
- centrilobular micronodules (often seen as tree-in-bud opacities),
- bronchial wall thickening
- bronchiolar dilatation (often referred to as bronchiolectasis)
- mosaic attenuation (and/or air trapping if expiratory imaging is used)

Aetiology
- viruses: respiratory syncytial virus (RSV): particularly in children (RSV bronchiolitis)
- bacterial species
- mycobacterial species
- Mycobacterium tuberculosis:
- atypical mycobacterial species
- fungal species, e.g. Aspergillus fumigatus, particularly in immunocompromised patients

Question 15

CONDUCTIVE AIRWAY CONDITIONS

Chronic obstructive pulmonary disease including asthma, chronic bronchitis and emphysema (centrilobular, paraseptal, pan lobular)

Answer 15

Epidemiology
- ***cigarette smoking.
- industrial exposure (e.g. mining)
- cystic fibrosis
- alpha-1 antitrypsin deficiency
- intravenous drug use (IVDU)
- immune deficiency syndromes
- vasculitides and connective tissue disorders

Pathology
Histologic changes of COPD are irreversible and gradually progress over time.

In chronic bronchitis, there is diffuse hyperplasia of mucous glands with associated hypersecretion and bronchial wall inflammation.

Emphysema involves the destruction of alveolar septa and pulmonary capillaries, leading to decreased elastic recoil and resultant air trapping. The morphological subtypes of emphysema include:
- centrilobular (centriacinar): associated with smoking and spreads peripherally from bronchioles
- panacinar: homozygous AAT1 deficiency and uniformly destroys alveoli
- paraseptal (distal acinar): involves the distal airways

Centrilobular emphysema is the most frequently encountered type and affects the proximal respiratory bronchioles, particularly of the upper zones. It has a strong dose-dependent association with smoking 3. Rarely, severe centrilobular emphysema can be seen in the bases in patients with Salla disease.

Panlobular emphysema (also known as panacinar emphysema), in contrast, affects the entire secondary pulmonary lobule and is more pronounced in the lower zones, matching areas of maximal blood flow. It is seen particularly in alpha-1-antitrypsin deficiency (exacerbated by smoking), intravenous injection of methylphenidate (Ritalin lung) or Swyer-James syndrome.

Paraseptal emphysema affects the peripheral parts of the secondary pulmonary lobule and is usually located adjacent to the pleural surfaces (including pleural fissures). It is also associated with smoking and can lead to the formation of subpleural bullae and spontaneous pneumothorax

Question 16

CONDUCTIVE AIRWAY CONDITIONS

Congenital Pulmonary Airway Malformation (CPAM)

Answer 16

Multicystic masses of segmental lung tissue with abnormal bronchial proliferation.

Associations
- hybrid lesion: i.e. CPAM and pulmonary sequestration
- renal agenesis 7
- polyhydramnios
- hydrops fetalis
- lung malignancy:
~10% of paediatric lung cancers have a history of CPAM
mucinous adenocarcinoma associated with type 1 CPAM
pleuropulmonary blastoma associated with type 4 CPAM

Pathology
Results from failure of normal bronchoalveolar development with a hamartomatous proliferation of terminal respiratory units in a gland-like pattern (adenomatoid) without proper alveolar formation.

Histologically, they are characterised by adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands.

These lesions have intracystic communications and, unlike bronchogenic cysts, can also have a connection to the tracheobronchial tree.

Subtypes
Five subtypes are currently classified, mainly according to cyst size:

type I: most common: 70% of cases, large cysts, one or more dominant cysts: 2-10 cm in size, may be surrounded by smaller cysts

type II: 15-20% of cases, cysts are <2 cm in diameter, associated with other abnormalities (renal agenesis or dysgenesis, pulmonary sequestration, congenital cardiac anomalies)

type III: ~10% of cases, microcysts: <5 mm in diameter, typically involves an entire lobe, has a poorer prognosis

type IV: unlined cyst, typically affects a single lobe, indistinguishable from type I on imaging

type 0: very rare, lethal postnatally, acinar dysgenesis or dysplasia, represents global arrest of lung development

Question 17

CONDUCTIVE AIRWAY CONDITIONS

Broncopulmonary sequestration

Answer 17

Aberrant formation of segmental lung tissue that has no connection with the bronchial tree or pulmonary arteries. It is a bronchopulmonary foregut malformation (BPFM).

Clinical presentation:
Extralobar sequestration (ELS) more commonly presents in newborns as respiratory distress, cyanosis, or infection, whereas intralobar sequestration (ILS) presents in late childhood or adolescence with recurrent pulmonary infections.

Pathology:
- Intralobar sequestration (ILS): accounts for the majority (75-85% of all sequestrations), present later in childhood with recurrent infections.
- Extralobar sequestration (ELS) less common (15-25% of all sequestrations):
usually present in the neonatal period with respiratory distress, cyanosis, or infection
recognised male predilection M: F ratio ~4:1; can be infradiaphragmatic in ~10% of cases

The two types of sequestration are similar in their relationship to the bronchial tree and arterial supply/venous drainage but differ in their relationship to the pleura.

By definition, there is no communication with the tracheobronchial tree. In the vast majority of cases, the abnormal lung tissue has a systemic arterial supply which is usually a branch of the aorta:

Intralobar sequestrations: venous drainage commonly occurs via the pulmonary veins

Extralobar sequestrations: venous drainage most commonly through the systemic veins into the right atrium
(but is variable); separated from any surrounding lung by its own pleura

Location: preferentially affects the lower lobes. 60% of intralobar sequestrations affect the left lower lobe, and 40% the right lower lobe. Extralobar sequestrations almost always affect the left lower lobe, however, ~10% of extralobar sequestrations can be subdiaphragmatic

Associations
Associated disease is common with the extralobar type (50-60%):
- CPAM
- congenital heart disease
- congenital diaphragmatic hernia
- Scimitar syndrome

Question 18

CONDUCTIVE AIRWAY CONDITIONS

Allergic Broncho-Pulmonary Aspergillosis (ABPA)

Answer 18

Mild end of the spectrum of disease caused by pulmonary aspergillosis and can be classified as an eosinophilic lung disease.

Patients with longstanding asthma, and only occasionally in patients with cystic fibrosis.

In general, patients are young and are diagnosed before the age of 40 years.

It is considered the most common cause of eosinophilic lung disease in developed countries.

major criteria:
- clinical asthma
- radiographic features: pulmonary opacities (transient or chronic), central bronchiectasis.
- immune system, blood eosinophilia, immediate skin reactivity to Aspergillus antigen (elevated IgG and/or IgE against A. fumigatus), increased serum IgE

Pathology
Result of hypersensitivity towards Aspergillus spp. which grows within the lumen of the bronchi, without invasion. The hypersensitivity initially causes bronchospasm and bronchial wall oedema, which is IgE-mediated. Ultimately, there is bronchial wall damage with loss of muscle and bronchial wall cartilage resulting in bronchiectasis (typically central bronchiectasis)

Question 19

CONDUCTIVE AIRWAY CONDITIONS

Bronchiectasis including knowing of Williams-Campbell syndrome

Answer 19

Two groups make up the majority of cases: post-infectious and cystic fibrosis.

Pathology
Aetiology
Bronchiectasis is the common response of bronchi to a combination of inflammation and obstruction/impaired clearance. Causes include:
- idiopathic (most common)
- impaired host defences: cystic fibrosis (most common cause in children), primary ciliary dyskinesia, e.g. Kartagener yndrome, Young syndrome, primary immunodeficiency disorder, e.g. common variable immunodeficiency, hypogammaglobulinaemia, chronic granulomatous disease, HIV/AIDS
- postinfective (most common known non-cystic fibrosis cause in adults): bacterial pneumonia and bronchitis, e.g S. aureus, H. influenzae, B. pertussis; mycobacterial infection, e.g. tuberculosis; Mycobacterium avium-intracellulare complex
- allergic and autoimmune: allergic bronchopulmonary aspergillosis (ABPA),
connective tissue disease, e.g. rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus (SLE), inflammatory bowel disease
- obstruction: severe obstructive lung disease: asthma or chronic obstructive pulmonary disease (COPD); neoplasm, e.g. bronchial carcinoid, bronchogenic carcinoma; inhaled foreign bodies
- congenital: bronchial tree malformations, e.g. Mounier-Kuhn syndrome, Williams-Campbell syndrome, pulmonary sequestration, bronchial atresia, alpha-1-antitrypsin deficiency
- others: chronic aspiration, traction bronchiectasis due to diffuse lung disease, e.g. pulmonary fibrosis; radiation-induced lung disease; post-transplantation

Subtypes:
cylindrical: ~ 47%
varicose: ~ 9.9%
cystic: ~ 45.1%
multiple types: ~ 24.3%

Williams-Campbell syndrome (WCS) is a rare form of congenital cystic bronchiectasis, in which distal bronchial cartilage is defective.

Clinical presentation
Recurrent pneumonia, wheezing, barrel-chest deformity, and Harrison sulcus.

Pathology
It is thought to develop from a deficiency of cartilage formation in the 4th to 6th order sub-segmental bronchi, resulting in distal airways collapse and bronchiectasis.

Radiographic features
CT
Cystic central bronchiectasis changes, usually symmetric and bilateral, typically involving 4th to 6th order bronchi with preservation of the trachea and main bronchi 2. On expiratory aquisitions, there is characteristic collapse of affected bronchi.

Question 20

CONDUCTIVE AIRWAY CONDITIONS

Atelectasis including lobar collapse

Answer 20

1) resorptive (obstructive) atelectasis occurs as a result of complete obstruction of an airway
- no new air can enter the portion of the lung distal to the obstruction and any air that is already there is eventually absorbed into the pulmonary capillary system, leaving a collapsed section of the affected lung
- because the visceral and parietal pleura do not separate in resorptive atelectasis, traction is created, and if the loss of volume is considerable, mobile thoracic structures may be pulled toward the side of volume loss (“mediastinal shift”)
- potential causes of resorptive atelectasis include obstructing neoplasms, mucus plugging in asthmatics or critically ill patients and foreign body aspiration
- resorptive atelectasis of an entire lung (“collapsed lung”) can result from complete obstruction of the right or left main bronchus

2) passive (relaxation) atelectasis occurs when contact between the parietal and visceral pleura is disrupted
- the three most common specific aetiologies of passive atelectasis are pleural effusion, pneumothorax and diaphragmatic abnormality

3) compressive atelectasis occurs as a result of any thoracic space-occupying lesion compressing the lung and forcing air out of the alveoli

4) cicatrisation atelectasis occurs as a result of scarring or fibrosis that reduces lung expansion
- common aetiologies include granulomatous disease, necrotising pneumonia and radiation fibrosis

5) adhesive atelectasis ​occurs from surfactant deficiency
- depending on aetiology, this deficiency may either be diffuse throughout the lungs or localised

6) gravity dependant atelectasis (dependent atelectasis) in the most dependent portions of the lungs due to the weight of the lungs

7) osteophyte-induced adjacent pulmonary atelectasis and fibrosis

Question 21

CONDUCTIVE AIRWAY CONDITIONS

Transient tachypnoea of the newborn

Answer 21

Epidemiology
The most common causes of neonatal respiratory distress, particularly in term or near term newborns. It is estimated to affect 1-2% of all neonates with an equal gender predilection. Risk factors include caesarean section delivery, maternal diabetes and maternal asthma.

Pathology
Amniotic fluid is normally expressed from the lungs during vaginal delivery and then absorbed after birth. Also, prostaglandins dilate pulmonary lymphatics to absorb excess fluid. In transient tachypnoea of the newborn there is build-up of fluid in the lungs thought due to the reduced mechanical squeeze and reduced capillary and lymphatic removal of amniotic fluid. This reduced clearance of fluid from the lungs is why some have proposed that it is more commonly seen in caesarean section deliveries since the thoracic compression that would occur in a normal vaginal delivery does not take place. This prostaglandin imbalance is also worsened in other situations like maternal diabetes or asthma, and in male newborns.

Plain radiograph
interstitial oedema - predominantly perihilar
often seen as perihilar streakiness
pleural effusions that are usually small
mild to moderate cardiomegaly has been described rarely
severe cases may have perihilar alveolar opacities
normal chest radiograph by 48-72 hours postpartum

Question 22

CONDUCTIVE AIRWAY CONDITIONS

Tracheobronchiomalacia

Answer 22

Pathology
The underlying aetiology is one of reduced or abnormal connective tissues in the trachea, particularly the cartilaginous rings which results in increased flaccidity of the membranous portion of the central airways.

Aetiology
- ageing
- COPD: sometimes considered as the most common acquired cause
- prolonged intubation, especially in those with tracheostomy
- chronic or recurrent infection
- asthma

Congenital tracheomalacia refers to a diverse group of conditions which result in a dilated trachea with increased compliance. Causes include:

• cystic fibrosis: seen in up to 69% of patients 4
• Mounier-Kuhn syndrome: idiopathic or associated with Ehlers-Danlos syndrome (in adults)
• cutis laxa (in children)
• Marfan syndrome
• Kenny-Caffey syndrome
• Cornelia de Lange syndrome
• Bruton-type agammaglobulinemia
  Although all of these conditions are congenital, tracheomalacia may not become apparent until later in life, e.g. Mounier-Kuhn syndrome.

Question 23

CONDUCTIVE AIRWAY CONDITIONS

Tracheo-oesophageal fistula

Answer 23

Associations
In just over half of cases, there are other associated congenital abnormalities, including:

cardiac anomalies (15-19%)
VATER/VACTERL
gastrointestinal anomalies (22%): imperforate anus, malrotation, intestinal atresia
aneuploidic chromosomal abnormalities: trisomy 21, 18, 13
non-aneuploidic syndromic associations

Pathology
The trachea is an out-budding from the ventral foregut, and tracheo-oesophageal fistulae represent incomplete/abnormal division. They are very closely related to oesophageal atresia, and represent a spectrum of disease. As such, the types of oesophageal atresia / tracheo-oesophageal fistula can be divided into 1,2:

type A: isolated oesophageal atresia (8%)
type B: proximal fistula with distal atresia (1%)
type C: proximal atresia with distal fistula (85% - most common)
type D: double fistula with intervening atresia (1%)
type E: isolated fistula (H-type) (4%)

Acquired tracheo-oesophageal fistula

Pathology
Acquired causes of tracheo-oesophageal fistulae can be divided into those that are related to malignancy (common) and those from other causes (uncommon).

Malignancy-related causes:
- malignancy
- Radiotherapy

Non-malignancy related causes: infrequent
- trauma (blunt, penetrating, or iatrogenic) e.g. gunshot wounds 3
- chronic inflammation: chronic infections - tracheal wall necrosis or necrotising inflammation is usually the cause for fistulization

tuberculosis

histoplasmosis

post-tracheostomy 2

corrosive substances ingestion

(e.g. battery ingestion, acid)

Question 24

INFECTION / INFLAMMATORY CONDITIONS

Pneumonia (lobar/bronchopneumonia) including community acquired, institutional, aspiration, neonatal and nosocomial

Answer 24

The gross and histologic appearance of the infected lung can be broken down into four stages of inflammation 2:

congestion: hyperaemia, with alveolar oedema and bacterial proliferation
red hepatisation: haemorrhagic inflammatory alveolar exudate
grey hepatisation: fibrinopurulent inflammatory alveolar exudate
resolution: final stage of processing the residual exudate
Red and grey hepatisation refers to the gross morphological appearance of a lung with inflammatory exudate in the alveolar spaces.

Question 25

INFECTION / INFLAMMATORY CONDITIONS

Bacterial infections including pneumococcal, staphylococcal, klebsiella, MRSA, legionella, nocardia & actinomycosis

Question 26

INFECTION / INFLAMMATORY CONDITIONS

Viral pneumonia including influenza, varicella, Cytomegalovirus (CMV),

Question 27

INFECTION / INFLAMMATORY CONDITIONS

Severe Acute Respiratory Syndrome associated Corona Virus (SARS-CoV-2)

Answer 27

Pathophysiology
The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, effects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE2) receptor. This receptor is commonly found on alveolar cells of the lung epithelium.

According to a Fleischner Society:
- imaging is not indicated in patients with suspected COVID-19 and mild clinical features unless they are at risk for disease progression
- imaging is indicated in a patient with COVID-19 and worsening respiratory status
- in a resource-constrained environment, imaging is indicated for medical triage of patients with suspected COVID-19 who present with moderate-severe clinical features and a high pretest probability of disease

CT protocol
Patients requiring CT should receive a non-contrast chest CT (unless iodinated contrast medium is indicated), with reconstructions of the volume at 0.625 mm to 1.5 mm slice thickness (gapless). If iodinated contrast medium is indicated, for example, a CT pulmonary angiogram (CTPA), a non-contrast scan should be considered prior to contrast administration, as contrast may impact the interpretation of ground-glass opacification (GGO) patterns.

Currently, there is no diagnostic benefit to performing a CTPA examination on initial presentation. Although the risk of pulmonary thrombosis is higher in severe cases of COVID-19, it is recommended that D-dimer values are used to guide clinical pathways to justify a CTPA.

Radiographic features
The primary findings of COVID-19 on chest radiograph and CT are those of atypical pneumonia or organising pneumonia. Bilateral and/or multilobar involvement is common.

Xray:
The most frequent findings are airspace opacities, whether described as consolidation or, less commonly, GGO. The distribution is most often bilateral, peripheral, and lower zone predominant. In contrast to parenchymal abnormalities, pleural effusion is rare (3%).

The British Society of Thoracic Imaging (BSTI) has published a reporting proforma for the plain chest radiographic appearances of potential COVID-19 cases:
- classic/probable COVID-19: lower lobe and peripheral predominant multiple opacities that are bilateral (» unilateral)

• indeterminate for COVID-19: does not fit classic or non-COVID-19 descriptors
• non-COVID-19: pneumothorax / lobar pneumonia / pleural effusion(s) / pulmonary oedema / other
• normal: COVID-19 not excluded

CT:
- ground-glass opacities (GGO): bilateral, subpleural, peripheral, basal
- crazy paving appearance (GGOs and inter-/intra-lobular septal thickening)
- air space consolidation
- bronchovascular thickening in the lesion
- traction bronchiectasis

1) typical appearance: peripheral, bilateral, GGO +/- consolidation or visible intralobular lines (“crazy paving” pattern), multifocal GGO of rounded morphology +/- consolidation or visible intralobular lines (“crazy paving” pattern), reverse halo sign or other findings of organising pneumonia

2) indeterminate appearance: absence of typical CT findings and the presence of multifocal, diffuse, perihilar, or unilateral GGO +/- consolidation lacking a specific distribution and are non-rounded or non-peripheral; few very small GGO with a non-rounded and non-peripheral distribution

3) atypical appearance: absence of typical or indeterminate features and the presence of isolated lobar or segmental consolidation without GGO, discrete small nodules (e.g. centrilobular, tree-in-bud), lung cavitation, smoother interlobular septal thickening with pleural effusion

4) negative for pneumonia: no CT features to suggest pneumonia, in particular, absent GGO and consolidation

Question 28

INFECTION / INFLAMMATORY CONDITIONS

Mycobacterium pneumonia including tuberculosis and nontuberculous infections

Answer 28

Risk factors
- immunocompromised including HIV infection, diabetes, long-term immunosuppressants
- close contact with others with active TB
- malnourishment, alcoholism and intravenous drug use
- patient from endemic countries
- workers and residents in long-term residential facilities including jails, nursing homes, care homes

Location
- primary infection can be anywhere in the lung in children whereas there is a predilection for the upper or lower zone in adults
- post-primary infections have a strong predilection for the upper zones
- miliary tuberculosis is evenly distributed throughout both lungs

Primary pulmonary tuberculosis:
The initial focus of infection can be located anywhere within the lung and has non-specific appearances ranging from too small to be detectable, to patchy areas of consolidation or even lobar consolidation.

1. Cavitation is uncommon in primary TB
2. In most cases, the infection becomes localised and a caseating granuloma forms (tuberculoma) which usually eventually calcifies and is then known as a Ghon lesion.

The more striking finding, especially in children, is that of ipsilateral hilar and contiguous mediastinal (paratracheal) lymphadenopathy, usually right-sided. This pattern is seen in over 90% of cases of childhood primary TB, but only 10-30% of adults. These nodes typically have low-density centres with rim enhancement on CT. Occasionally these nodes may be large enough to compress adjacent airways resulting in distal atelectasis 1.

Pleural effusions are more frequent in adults, seen in 30-40% of cases, whereas they are only present in 5-10% of paediatric cases.

As the host mounts an appropriate immune response both the pulmonary and nodal disease resolve. Calcification of nodes is seen in 35% of cases 2. When a calcified node and a Ghon lesion are present, the combination is known as a Ranke complex.

Post-primary pulmonary tuberculosis
Occurs years later, frequently in the setting of a decreased immune status. In the majority of cases, post-primary TB within the lungs develops in either:

• posterior segments of the upper lobes
• superior segments of the lower lobes

The typical appearance of post-primary tuberculosis is that of patchy consolidation or poorly defined linear and nodular opacities.

Post-primary infections are far more likely to cavitate than primary infections and are seen in 20-45% of cases. In the vast majority of cases, they develop in the posterior segments of the upper lobes (85%). The development of an air-fluid level implies communication with the airway, and thus the possibility of contagion. Endobronchial spread along nearby airways is a relatively common finding, resulting in relatively well-defined 2-4 mm nodules or branching lesions (tree-in-bud sign) on CT.

Hilar nodal enlargement is seen in only approximately a third of cases. Lobar consolidation, tuberculoma formation, and miliary TB are also recognised patterns of post-primary TB but are less common.

Tuberculomas account for only 5% of cases of post-primary TB and appear as a well defined rounded mass typically located in the upper lobes. They are usually single (80%) and can measure up to 4 cm in size. Small satellite lesions are seen in most cases. In 20-30% of cases, superimposed cavitation may develop.

Miliary pulmonary tuberculosis
Uncommon but carries a poor prognosis. It represents haematogenous dissemination of an uncontrolled tuberculous infection. It is seen both in primary and post-primary tuberculosis. Although implants are seen throughout the body, the lungs are usually the easiest location to image.

Miliary deposits appear as 1-3 mm diameter nodules, which are uniform in size and uniformly distributed 1-2. If the treatment is successful, no residual abnormality remains.

Complications
- the colonisation of cavities by fungus, e.g. aspergilloma
- bronchiectasis
- arterial pseudoaneurysms
- bronchial artery pseudoaneurysm
- pulmonary artery pseudoaneurysm/Rasmussen aneurysm
- empyema - tuberculous empyema
- fibrothorax
- bronchopleural fistula

Question 29

INFECTION / INFLAMMATORY CONDITIONS

Fungal infections including aspergillus, candida, cryptococcosis, pneumocystis jiroveci, histoplasmosis and coccidioidomycosis

Answer 29

Pulmonary aspergillosis

1) Aspergillomas
Occur in patients with normal immunity but structurally abnormal lungs, with pre-existing cavities. Demographics will, therefore, match those of the underlying condition, such as:
- pulmonary tuberculosis: most common, accounting for 25-80% of cases depending on the prevalence of tuberculosis in the population
- pulmonary sarcoidosis
- bronchiectasis from any cause
- other pulmonary cavities: bronchogenic cyst, pulmonary sequestration, Pneumocystis pneumonia associated pneumatocoeles

Pathology
An aspergilloma is a mass-like collection of fungal hyphae, mixed with mucous and cellular debris, within a cavity, the walls of which demonstrate vascular granulation tissue

Allergic bronchopulmonary aspergillosis
Most commonly encountered in patients with longstanding asthma, and only occasionally in patients with cystic fibrosis

Pathology
Allergic bronchopulmonary aspergillosis is the result of hypersensitivity towards Aspergillus spp. which grows within the lumen of the bronchi, without invasion. The hypersensitivity initially causes bronchospasm and bronchial wall oedema, which is IgE-mediated. Ultimately, there is bronchial wall damage with loss of muscle and bronchial wall cartilage resulting in bronchiectasis (typically central bronchiectasis). Both types I and III allergic reactions have been implicated

Invasive pulmonary aspergillosis
Form of pulmonary aspergillosis seen in patients with decreased immunity. It comprises a number of entities:
1) subacute invasive pulmonary aspergillosis (previously known as chronic necrotising aspergillosis (CNA) or semi-invasive aspergillosis)
2) airway invasive aspergillosis (bronchopneumonic aspergillosis)
3) angioinvasive aspergillosis

Pathology (angioinvasive aspergillosis)
Spores of a variety of Aspergillus spp. are inhaled and begin to proliferate in the alveoli. The hyphae are able to invade pulmonary arteries resulting in pulmonary necrosis and haemorrhage. They may also gain access to the systemic circulation and are haematologically-disseminated to the kidneys, gastrointestinal tract, and the central nervous system. Systemic dissemination occurs in 25-50% of cases.

If the neutrophil count recovers (in patients where neutropenia is the cause of the immunosuppression), the central necrotic area of lung demarcates, shrinks and separates from the adjacent viable tissue. It is this separation that creates the air crescent sign.

Pulmonary Pneumocystis jiroveci infection
Most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS).

Plain radiograph
Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include 5:
- small pneumatoceles
- subpleural blebs
- fine reticular interstitial changes
- predominantly perihilar in distribution
- Pleural effusions are normally not a feature, seen in less than 5% of cases

CT:
- ground-glass pattern: considered a principal finding
- predominantly involving perihilar or mid zones
- there may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolised medication
if they are, then the poorly ventilated upper zones are prone to infection, whereas, in those who are not, the lower zones are more frequently involved
- there may be relative preservation of previously irradiated areas
- show some peripheral sparing in a considerable number of patients
- reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present
- pneumatoceles
- pleural effusions are rare
- lymphadenopathy is uncommon (10%)

Question 30

INFECTION / INFLAMMATORY CONDITIONS

Mycoplasma pneumonia

Answer 30

type of community-acquired pneumonia caused by the organism Mycoplasma pneumoniae. It is usually grouped under atypical pneumonia.

Epidemiology
It is relatively common in the paediatric population where it is considered the most common community-acquired pneumonia in 5 to 20-year-olds (may account for 40% of such cases 7). It may account for 10-15% of community-acquired pneumonia in adults. In adults, mycoplasma can rarely result in bronchiolitis without giving pneumonia.

Question 31

INFECTION / INFLAMMATORY CONDITIONS

Lung abscess

Answer 31

Epidemiology
The elderly, immunocompromised, malnourished, debilitated are particularly susceptible and have the worst prognosis. The rate is on the rise, though, particularly due to an increased number of immunocompromised patients (secondary to HIV/AIDS and iatrogenic immunosuppression).

Pathology
Usually, occurs from liquefactive necrosis of tissue.

A primary abscess is one that develops as a result of a primary infection of the lung. These most commonly arise from aspiration, necrotising pneumonia or chronic pneumonia, e.g. in the setting of pulmonary tuberculosis or immunodeficiency.

In patients who develop abscesses as a result of aspiration, mixed infections are most common, including anaerobes.

Some organisms are particularly prone to causing significant necrotising pneumonia resulting in cavitation and abscess formation. These include: Staphylococcus aureus; Klebsiella sp: Klebsiella pneumonia, Pseudomonas sp, Proteus sp

In immunocompromised patients, additional organisms may also be implicated, including: pulmonary candidiasis, Legionella pneumonia, Pneumocystis jirovecii (uncommon).

A secondary abscess is one that develops as a result of another condition. Examples include:
- bronchial obstruction: bronchogenic carcinoma, inhaled foreign body
- haematogenous spread: bacterial endocarditis, intravenous drug use
- direct extension from adjacent infection: mediastinum, subphrenic, chest wall

Treatment and prognosis
- Prolonged antibiotics and physiotherapy with postural drainage.
- Bronchoscopy
- surgical resection
-.Percutaneous drainage under CT guidance has also been advocated in selected cases (e.g. patients refractory to conventional therapy).

Conservative treatment is less likely to be successful in the case of larger abscesses (>4 cm in diameter). These have a higher mortality rate, irrespective of treatment

Complications
Complications of surgery or percutaneous drainage include : empyema, bronchopleural fistula, haemorrhage (from chest wall or the lung), pneumothorax

Question 32

INFECTION / INFLAMMATORY CONDITIONS

Meconium aspiration

Answer 32

Pathology
Aspirated meconium can cause small airways obstruction and a chemical pneumonitis.

Plain radiograph
- increased lung volumes
- obstruction and gas trapping
- asymmetric patchy pulmonary opacities
due to subsegmental atelectasis; may be ‘rope like’
- pleural effusions can be seen
- pneumothorax or pneumomediastinum in 20-40% of cases; due to increased alveolar tension from obstructed airways
- multifocal consolidation due to chemical pneumonitis

Question 33

DIFFUSE LUNG DISEASE

Acute Respiratory Distress Syndrome (ARDS)

Answer 33

Acute lung injury and occurs as a result of a severe pulmonary injury that causes alveolar damage heterogeneously throughout the lung. It can either result from a direct pulmonary source or as a response to systemic injury.

Pathology
Lung damage results in leakage of fluid into alveoli, leading to non-cardiogenic pulmonary oedema and decreased arterial oxygenation.

Pulmonary causes
fat embolism
drowning
infection: viral pneumonia, bacterial pneumonia
pulmonary irritants: chlorine, chloramines, ammonia, phosgene,oxides of nitrogen
oxygen toxicity: smoke inhalation, polymer fume fever
disseminated intravascular coagulopathy
aspiration: gastric contents, barium contrast
thoracic trauma: lung contusion

Extra-pulmonary causes
systemic inflammation
pancreatitis
burns
trauma
sepsis
neurogenic pulmonary oedema
transfusion-related lung injury (TRALI)
post-cardiopulmonary bypass
abdominal compartment syndrome
systemic toxicologic exposures

Question 34

DIFFUSE LUNG DISEASE

Smoking-related lung disease including Respiratory Bronchiolitis Interstitial Lung Disease (RB-ILD), Desquamative Interstitial Pneumonia (DIP), Combined Pulmonary Fibrosis and Emphysema (CPFE)

Answer 34

Respiratory bronchiolitis-interstitial lung disease
- Epidemiology: heavy tobacco smoking in young middle-aged patients (30-40 years of age).
- Pathology: pigment-laden macrophages are found within alveoli, and peribronchial inflammation noted. Unlike simple respiratory bronchiolitis, fibrosis extends beyond the tissues immediately adjacent to respiratory bronchioles and extends into alveolar septae.
- CT
. ground glass opacities: may have a slight upper zone predilection 9
. poorly defined centrilobular nodules
. no particular distribution with both upper and lower zones potentially affected
. if advanced, fibrosis may be evident typically affecting the subpleural regions and more so in the lower lung zones
. patchy areas of hypoattenuation (~40%) with a lower lung predominance 10
. bronchial wall thickening: can be central +/- peripheral
. centrilobular emphysema

Desquamative interstitial pneumonia (DIP) is an interstitial pneumonia closely related to and thought to represent the end stage of respiratory bronchiolitis interstitial lung disease (RB-ILD). It is associated with heavy smoking.

• Predisposing factors include:
  . autoimmune/systemic disorders, e.g. rheumatoid arthritis, scleroderma 7
  . infection, e.g. HIV 4
  . toxin, occupational or environmental exposure, e.g. asbestos 6,7
  . drugs

CT
DIP is usually characterised by diffuse ground-glass opacities (sometimes has a granular or nodular texture), which correlate histologically with the spatially homogeneous intra-alveolar accumulation of macrophages and thickening of alveolar septa

Combined pulmonary fibrosis and emphysema is a smoking-related lung diseases characterised by the coexistence of usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) with emphysema in tobacco smokers.

• centrilobular and/or paraseptal emphysema
• often upper zone predominant 5
• the emphysema component may have a tendency to be more paraseptal 9
• pulmonary fibrosis of the lower lobes: can be of UIP or NSIP pattern

Question 35

DIFFUSE LUNG DISEASE

Usual interstitial pneumonia pattern of lung disease including primary and secondary

Answer 35

On imaging, usual interstitial pneumonia usually presents with a lung volume loss and an apicobasal gradient of peripheral septal thickening, bronchiectasis, and honeycombing.

Pathology
The histological diagnosis of UIP is based on temporal and spatial heterogeneity, which is the identification of fibrotic lesions at different stages (fibroblastic infiltrates, mature fibrosis, and honeycombing) within the same biopsy specimen and architectural distortion. Honeycombing, particularly if it involves more than 5% of the lung volume, is an almost 100% specific finding.

Aetiology
* connective tissue disorders (CTD associated UIP): falls under the broader spectrum of connective tissue disorder interstitial lung disease (CTD-ILD)
* rheumatoid arthritis: UIP is considered to be the dominant pattern in those with rheumatoid arthritis who have concurrent interstitial lung disease 3
* systemic sclerosis (scleroderma): either a UIP or NSIP (more common) pattern 4
* polymyositis/dermatomyositis: a UIP, NSIP, or cryptogenic organising pneumonia pattern 4
* mixed connective tissue disease: either a UIP or NSIP pattern 4
* asbestos-related interstitial lung disease: asbestosis 1
* chronic hypersensitivity pneumonitis
* radiation
* medications/drug toxicity: amiodarone lung
* ANCA associated vasculitides
Hermansky-Pudlak syndrome (very rare)

Differential diagnosis
* non-specific interstitial pneumonia pattern (especially fibrotic non-specific interstitial pneumonia)
* chronic hypersensitivity pneumonitis (HP)
* hypersensitivity pneumonitis usually involves the mid and upper zones of the lung, and also the presence of centrilobular nodules and areas of air trapping are very useful hints to differentiate it from UIP
* UIP cases are also thought to have honeycombing and peripheral or lower lung zone predominance of disease, and less likely to have micronodules
* amiodarone lung fibrosis: helpful clues are the presence of hyperdense pulmonary nodules or hyperdense liver on a non-contrast CT
* systemic sclerosis: presence of patulous oesophagus and correlation with hand radiographs if available can be helpful
* asbestosis: bilateral pleural plaques with or without calcification or peritoneal calcification are helpful in diagnosis
* combined pulmonary fibrosis and emphysema (CPFE): especially if there is added upper lobe-predominant emphysema

Question 36

DIFFUSE LUNG DISEASE

Idiopathic Pulmonary Fibrosis (IPF)

Answer 36

Idiopathic pulmonary fibrosis (IPF) is a clinical syndrome and considered the most common and the most lethal form of pulmonary fibrosis corresponding to the histologic and imaging pattern of usual interstitial pneumonia. It is more common in elderly men and diagnosed by:

• histological or imaging pattern of usual interstitial pneumonia (UIP) and
• absence of alternative causes such as drug toxicity, environmental exposure (e.g. asbestos) or collagen vascular disease (e.g. scleroderma, rheumatoid arthritis)

Pathology
IPF, as the name states, is idiopathic, however, there is an association with concurrent or previous history of smoking in 60% of patients and genetic factors. Up to 5–20% of patients with IPF have a family history of interstitial lung disease (ILD) or pulmonary fibrosis.

Histopathology
Histology shows a UIP pattern which is characterised by spatial and temporal heterogeneity. One of the hallmarks is the absence of inflammation. Spatial heterogeneity denotes biopsy sample showing patchy lung involvement with normal lung interspace between diseased lung. Temporal heterogeneity denotes different stages of disease seen on a single specimen, including normal lung, interstitial fibrosis and fibroblastic foci 4.

Question 37

DIFFUSE LUNG DISEASE

Non-Specific Interstitial Pneumonia (NSIP)

Answer 37

Non-specific interstitial pneumonia (NSIP) is the second most common morphological and pathological pattern of interstitial lung diseases. NSIP has two main subtypes:

• fibrotic type: most common, having a more dismal outcome
• cellular type: less common, but carries a much better prognosis due to a very good response to treatment
• On imaging, the most common features are relatively symmetric and bilateral ground-glass opacities with associated fine reticulations and pulmonary volume loss, resulting in traction bronchiectasis. Immediate subpleural sparing, when present, is considered very specific for NSIP.

Epidemiology
Middle-aged adults, 40-50 years of age 1. It may be common in Caucasian-European populations 9. Overall prevalence is higher in women due to a high association with collagen vascular disease but the prevalence of idiopathic NSIP is similar in both genders.
Smoking is neither protective nor a risk factor for NSIP.

Associations
Primarily idiopathic but the morphological pattern can be seen in association with a number of conditions:

• connective tissue disorders: systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, polymyositis, dermatomyositis 5
• other autoimmune diseases: rheumatoid arthritis, primary biliary cirrhosis, Hashimoto thyroiditis, antisynthetase syndrome
• drug-induced lung disease: especially chemotherapy agents, thalidomide 16
• hypersensitivity lung disease
• slowly healing diffuse alveolar damage (DAD)
• relapsing organising pneumonia
• occupational exposure
• immunodeficiency (mainly HIV infection) 13
• graft versus host disease (GVHD) 13
• immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlapping features with Rosai-Dorfman disease 13
• multicentric Castleman disease 13
• myelodysplastic syndrome 13

Pathology
Temporal and spatial homogeneity in a specimen is an essential feature:

• fibrotic non-specific interstitial pneumonia
  1. more common
  2. interstitial thickening is due to uniform dense or loose fibrosis and mild chronic inflammation
  3. despite fibrotic changes, lung structures are still preserved
• cellular non-specific interstitial pneumonia
  1. less common
  2. interstitial thickening is mainly due to infiltration of inflammatory cells and type II pneumocyte hyperplasia
  3. lung architecture is preserved 8
• Important negative histological findings are the absence of acute lung injury, including hyaline membranes, granulomas, organisms or viral inclusions, dominant airways disease or organising pneumonia, eosinophils and coarse fibrosis.

Question 38

DIFFUSE LUNG DISEASE

Acute Interstitial Pneumonia (AIP) (diffuse alveolar damage)

Answer 38

Acute interstitial pneumonitis (AIP), also known as Hamman-Rich syndrome, is a rapidly progressive non-infectious interstitial lung disease of unknown aetiology. It is considered the only acute process among the idiopathic interstitial pneumonias.

AIP has a similar clinical presentation and histological features to those seen in acute respiratory distress syndrome (ARDS), showing extensive diffuse alveolar damage (DAD). Both conditions likely represent the same pathology, with AIP probably accounting for some of the idiopathic cases of ARDS.

Epidemiology
Truly idiopathic AIP tends to occur in those without pre-existing lung disease and typically affects middle-aged adults (mean ~50 years 5). However, in certain conditions such as leflunomide-induced acute interstitial pneumonia, patients have pre-existing lung disease.

Pathology
AIP is characterised histologically by diffuse alveolar damage (DAD) and is indistinguishable from acute respiratory distress syndrome (ARDS). The alveolar damage comprises three phases:
* an acute exudative phase
* a subsequent organising phase
* a final fibrotic phase

CT
During the initial stages, AIP can have features similar to acute respiratory distress syndrome (ARDS), which include:

• areas with ground-glass attenuation: generally tend to be bilateral and symmetrical 10
• traction bronchiectasis: can be seen in ~80% of cases during the course of the disease 4 and correlates with disease duration 2
• parenchymal architectural distortion of the lung
• air space consolidation: may have a slight predilection towards the dependent portions

Diffuse alveolar damage (DAD) is a common manifestation of drug-induced lung injury that results from necrosis of type II pneumocytes and alveolar endothelial cells.

Drugs that most commonly cause diffuse alveolar damage are bleomycin, busulfan, carmustine (BCNU), cyclophosphamide, melphalan, mitomycin, and gold salts.

Question 39

DIFFUSE LUNG DISEASE

Organising pneumonia including primary and secondary

Answer 39

Cryptogenic organising pneumonia (COP) is a disease of unknown aetiology characterised on imaging by multifocal ground glass opacifications and/or consolidation. A wide variety of infectious as well as noninfectious causes may result in a similar histologic pattern.

• patchy consolidation with a predominantly subpleural and/or peribronchial distribution
• small, ill-defined peribronchial or peribronchiolar nodules
• large nodules or masses
• bronchial wall thickening or dilatation in the abnormal lung regions
• a perilobular pattern with ill-defined linear opacities that are thicker than the thickened interlobular septa and have an arcade or polygonal appearance
• arcade-like sign of perilobular fibrosis describes an arch pattern in more than half of the patient with COP 13
• ground glass opacity or crazy paving
• The reverse halo sign (atoll sign) is considered to be highly specific, although only seen in ~20% of patients with COP 5.

Secondary organising pneumonia (SOP) refers to organising pneumonia that can be attributed to a specific cause, in contrast to cryptogenic organising pneumonia (COP) in which no cause is present.

Pathology
Aetiology
Secondary organising pneumonia can be attributed to the following causes 1:

Prior infection
bacteria
atypical pneumonia (e.g. Legionella, Mycoplasma, etc.)
Streptococcus pneumoniae
Staphylococcus aureus
Pseudomonas aeruginosa
fungi
Cryptococcus neoformans
Pneumocystis jiroveci
Penicillium janthinellum
viruses
adenoviruses
herpesviruses
cytomegalovirus (CMV)
influenza
HIV
respiratory syncytial virus (RSV)
COVID-19
parasites
Plasmodium vivax
Dirofilaria immitis
Drugs
antimicrobials
amphotericin B, cephalosporins, nitrofurantoin, minocycline
chemotherapeutics
bleomycin, busulfan, chlorambucil, doxorubicin, trastuzumab
interferons
methotrexate
amiodarone
phenytoin
Miscellaneous
inflammatory bowel disease
leukaemias, Hodgkin disease
lung transplantation
radiotherapy - radiation-induced organising pneumonia
rheumatological disorders e.g. rheumatoid arthritis, SLE, Sjogren, etc.

Question 40

DIFFUSE LUNG DISEASE

Pulmonary surfactant deficiency and complications

Answer 40

Risk factors include maternal diabetes, greater prematurity, perinatal asphyxia, and multiple gestations.

Associated conditions are those that can occur in prematurity: germinal matrix haemorrhage, necrotising enterocolitis, patent ductus arteriosus, delayed developmental milestones, hypothermia, and hypoglycaemia.

Pathology
Immature type II pneumocytes cannot produce surfactant. The lack of surfactant increases the surface tension in alveoli causing them to collapse. Patients have a decreased lecithin to sphingomyelin ratio. Damaged cells, necrotic cells, and mucus line the alveoli.

Although most cases are related to prematurity alone, rarely patients may have genetic disorders of surfactant production and can present in a similar clinical and radiological manner 6.

As the alveoli are collapsed (microscopically), the lungs are collapsed macroscopically as well. It is a diffuse type of adhesive atelectasis.

Plain radiograph
- low lung volumes
- diffuse, bilateral and symmetrical granular opacities
- bell-shaped thorax
- air bronchograms may be evident

Hyperinflation makes the diagnosis less likely, unless the patient is intubated.
If treated with surfactant therapy, there may be an asymmetric improvement as more surfactant may reach certain parts of the lungs than others.

Complications
Acute
* persistent patent ductus arteriosus (PDA) due to reduced oxygen stimulus
* pulmonary interstitial emphysema or air leak (secondary to requirement for mechanical ventilation)
* oxygen toxicity (from treatment)
* pulmonary haemorrhage

Chronic
* bronchopulmonary dysplasia
* recurrent pulmonary infection
* subglottic stenosis (secondary to intubation)

Question 41

DIFFUSE LUNG DISEASE

Bronchiolitis Obliterans (BO)

Answer 41

Refers to bronchiolar inflammation with submucosal peribronchial fibrosis associated with luminal stenosis and occlusions.

Associations
* inflammatory bowel disease
* rheumatoid arthritis: considered the commonest connective tissue disease to be associated with obliterative bronchiolitis 11,12
* medications, e.g. penicillamine
* as a complication following lung transplantation: post lung transplant bronchiolitis obliterans 2; can occur in up to 10% of patients, usually within 6-12 months following bone marrow transplantation 10
* Swyer-James syndrome 13

Pathology
The condition is characterised by concentric luminal narrowing of the membranous and respiratory bronchioles as a result of submucosal and peribronchiolar inflammation and fibrosis without any intraluminal granulation tissue or polyps/polyposis. There is an absence of diffuse parenchymal inflammation.

Aetiology:
* idiopathic/cryptogenic
* post-infectious
* post-viral (e.g. adenovirus)
* post-atypical infection (e.g. Mycoplasma pneumonia)
* noxious fume inhalation
* “popcorn lung”: workers of a microwave popcorn plant who had inhaled diacetyl, a chemical used for flavouring, developed obliterative bronchiolitis; the term has since become a colloquial synonym for obliterative bronchiolitis
* neuroendocrine hyperplasia (pulmonary tumourlets) 4
* post-transplant patients: heart/lung transplants, representing the obstructive form of chronic lung allograft dysfunction (CLAD); haematopoietic stem cell transplants 7

CRITTS
C: cryptogenic organising pneumonia (COP), cystic fibrosis
R: rheumatoid arthritis
I: infectious: post-viral/post-atypical infection (e.g. Mycoplasma pneumonia)
T: transplant: heart/lung/haematopoietic stem cell transplants
T: toxins: noxious gas inhalation
S: sarcoidosis, Swyer-James syndrome

Radiographic features

• hyperinflation
• attenuation of vascular markings
• occasionally reticular/reticulonodular markings
• bronchiectasis
• bronchial wall thickening 6
• ground glass opacities 6

Question 42

TOXIC CONDITIONS

Pulmonary fibrosis associated with smoking

Respiratory bronchiolitis interstitial lung disease (RB-ILD)

Answer 42

Epidemiology
In almost all cases, respiratory bronchiolitis-interstitial lung disease is associated with heavy tobacco smoking (usually 30 pack-years or more) and is often seen in 30-40 years age group.

Clinical presentation
Chronic cough and progressive dyspnoea 4 differentiate RB-ILD from RB. Inspiratory crackles are heard in up to half of patients. Clubbing is rare 1. RB-ILD is a clinical diagnosis.

Pathology
Pigment-laden macrophages are found within alveoli, and peribronchial inflammation noted.
Fibrosis extends beyond the tissues immediately adjacent to respiratory bronchioles and extends into alveolar septae.

Very similar to desquamative interstitial pneumonia (DIP) and many authors feel that the two conditions are closely related, or even variants of the same condition. Thought of as end-stage/severe RB-ILD 5.

Radiographic features
CT
ground glass opacities: may have a slight upper zone predilection 9

poorly defined centrilobular nodules

no particular distribution with both upper and lower zones potentially affected

if advanced, fibrosis may be evident typically affecting the subpleural regions and more so in the lower lung zones

patchy areas of hypoattenuation (~40%) with a lower lung predominance 10

other changes related to smoking

bronchial wall thickening: can be central +/- peripheral

centrilobular emphysema

Treatment and prognosis
Giving up smoking.

Differential diagnosis
With typical HRCT chest appearances consider:

non-specific interstitial pneumonitis (NSIP)

changes of fibrosis: lung volume loss, reticular opacities, and traction bronchiectasis

ground glass opacities have a random distribution

non-fibrotic or fibrotic hypersensitivity pneumonitis (HP)

Question 43

DIFFUSE LUNG DISEASE

Pulmonary fibrosis associated with smoking
Desquamative interstitial pneumonia (DIP)

Answer 43

End stage of respiratory bronchiolitis interstitial lung disease (RB-ILD). It is associated with heavy smoking.

Epidemiology
DIP is considered one of the rarest of idiopathic interstitial pneumonias 11. There is a recognised male predilection (M:F = 2:1).

Clinical presentation
Presentation tends to be in middle age (30-60 years of age) with progressive shortness of breath and chronic cough 4.

The vast majority of patients are heavy smokers (90%) with an average smoking history of 18 pack-years. However, other predisposing factors include:

autoimmune/systemic disorders, e.g. rheumatoid arthritis, scleroderma 7

infection, e.g. HIV 4

toxin, occupational or environmental exposure, e.g. asbestos 6,7

drugs

Diagnosis
Despite differences in the CT appearance of RB-ILD and DIP, imaging findings may overlap and may be indistinguishable from each other. To improve diagnostic accuracy, lung biopsy is required in all cases of suspected RB-ILD or DIP ref.

Pathology
No desquamation of alveolar epithelium is present, but rather the cells that fill the alveoli are pigment-laden macrophages. This is more pronounced than in RB-ILD.

Radiographic features
Plain radiograph
non-specific

may show bilateral interstitial opacities 8: they may have a greater predilection for the lower-lung zones and, sometimes, peripheral predominance 9

has been classically described as one of triangular-shaped regions of increased density radiating from the hilar regions to the periphery; although, this is seen in only a minority of cases 10

CT
DIP is usually characterised by diffuse ground-glass opacities (sometimes has a granular or nodular texture), which correlate histologically with the spatially homogeneous intra-alveolar accumulation of macrophages and thickening of alveolar septa:

bilateral and symmetric (86%) 7

basal and peripheral (60%)

patchy (20%)

diffuse (20%) 4

Other frequent CT findings include spatially limited, irregular linear opacities and small cystic spaces, which are indicative of fibrotic change (50% of patients 7).

Other changes related to background smoking-related lung disease are often seen, e.g. bronchial wall thickening and centrilobular emphysema.

Honeycombing may be seen in less than one-third of cases, and if present tends to be usually peripheral and limited in extent 9.

Treatment and prognosis
With smoking cessation and corticosteroid therapy, the prognosis is good. The overall prognosis of has been described as being significantly better than that of fibrotic non-specific interstitial pneumonia 11. Nevertheless, progressive disease with eventual death can occur, notably in patients with continued cigarette smoking.

Question 44

TOXIC CONDITIONS

Pulmonary fibrosis associated with smoking
Pulmonary Langerhans cell histiocytosis (PLCH)

Answer 44

Epidemiology
Pulmonary Langerhans cell histiocytosis is usually identified in young adults (20-40 years of age). A history of current or previous cigarette smoking is identified in up to 95% of cases 1,4. It is a rare disorder with no well-established gender predilection, which appears to be more common in White populations 4.

Associations
Haematopoietic neoplasms:

acute lymphoblastic leukaemia (ALL) 11,12
acute myeloid leukaemia (AML) 10

Clinical presentation
Dyspnoea or non-productive cough. Other symptoms include constitutional symptoms (fatigue and weight loss), pleuritic chest pain, or spontaneous pneumothorax 1,4. Up to a quarter of patients are asymptomatic.

Pathology
Langerhans cells proliferate in the bronchiolar and bronchial epithelium, forming granulomas. It is postulated that as these cellular granulomas evolve, peripheral fibrosis forms resulting in traction on the central bronchiole which becomes cyst-like 3. This explains the presumed evolution from a nodule, through cavitating nodule and thick-walled cysts, to the “stable” thin-walled cysts 3,4. An immune-mediated mechanism has been postulated, although an inciting agent has not been isolated 4. This proliferation is accompanied by inflammation and granuloma formation. Electron microscopy may reveal characteristic Birbeck granules 1,2.

More recent evidence suggests that pulmonary Langerhans cell histiocytosis represents a myeloid neoplasm with inflammatory properties 9.

Radiographic features
Pulmonary Langerhans cell histiocytosis has variable appearance depending on the stage of the disease, ranging from small peribronchiolar nodular opacities to multiple irregularly-shaped cysts. There is a mid and upper zone predilection 1,3,4.

Plain radiograph
The earliest change is a diffuse bilateral symmetrical reticulonodular pattern with a predilection for the mid and upper zones. The ill-defined nodules range from 1-10 mm in size. Later, cyst formation may be seen or may mimic a honeycomb appearance due to a summation of air-filled cysts. Cysts can be identified in only 1-15% of cases 1, and range from 1-3 cm in diameter. There is a preservation of lung volumes or even hyperinflation .

CT
As is usually the case, CT and especially HRCT is superior to plain chest radiography in identifying both the reticulonodular opacities and cysts 1,3,4. Distribution is the key in differentiating pulmonary Langerhans cell histiocytosis from other cystic lung diseases with a predilection for the mid and upper zones and regional sparing of the costophrenic recesses, anterior right middle lobe and lingula of the left upper lobe 1,3,4.

nodules
more pronounced early in the disease
may range in number from a few to innumerable
1-10 mm in diameter (typically 1-5 mm 4)
centrilobular distribution: may also be peribronchial or peribronchiolar
usually have irregular margins
may be cavitary nodules with thick walls, later becoming cysts
surrounding lung parenchyma appears normal
cysts
more pronounced later in the disease
usually less than 10 mm in diameter
may measure up to 2-3 cm in size
the extreme bases may be preserved
usually thin-walled, but on occasion may be up to a few millimetres thick
confluence of 2 or more cysts results in bizarre shapes
bilobed
cloverleaf
branching
internal septations
Other common findings include 1,3:

ground-glass and/or reticular opacities
DIP-like change 1
mosaic attenuation
interlobular septal thickening
emphysema
In late disease, other findings include:

coalescent cysts
fibrosis
honeycombing
The appearance of new nodules later in the disease (when cystic change is established) indicates disease progression but is a rare finding 3.

Treatment and prognosis
Overall prognosis is generally good with over 50% of patients demonstrating spontaneous resolution or stabilisation even without treatment 3. This is especially the case in patients who stop smoking.

In a minority of patients (~20%) and more frequently in those who continue to smoke, the disease is progressive with deterioration in respiratory function and eventual end-stage pulmonary fibrosis 3.

Treatment may not be required once smoking has ceased. Corticosteroids are frequently used and appear beneficial. In patients with rapidly progressive disease, no proven therapy has been found. In some selected patients lung transplantation may be an option, provided smoking has ceased. Recurrence in the transplanted lung has been described 4.

Complications
cyst rupture
spontaneous pneumothorax: may be the first presentation
pneumomediastinum
interstitial fibrosis
pulmonary arterial hypertension and cor pulmonale
end-stage pulmonary fibrosis and respiratory failure

Differential diagnosis
Differential depends on whether the nodular or cystic change is the dominant feature.

Early in the disease, when nodules are the dominant feature, consider:

granulomatous disease
granulomatosis with polyangiitis
sarcoidosis
metastases
miliary tuberculosis

Later in the disease, when cysts are prominent, consider:

lymphangioleiomyomatosis (LAM)
diffuse distribution
regular shaped and sized cysts
cystic bronchiectasis from ABPA
central distribution
mucous plugging
centrilobular emphysema
lack of visible cyst wall 1-3
Pneumocystis jiroveci pneumonia
idiopathic pulmonary fibrosis
basal and subpleural distribution
reduced lung volumes
lymphocytic interstitial pneumonitis (LIP)
smooth-walled simple cysts
associated with autoimmune disease

Question 45

TOXIC CONDITIONS

Pulmonary fibrosis associated with smoking
Acute eosinophilic pneumonia

Answer 45

Combination of clinical and radiographic findings occur 5,7:

febrile illness of less than five days’ duration
hypoxaemia
diffuse alveolar or mixed alveolar-interstitial opacities on chest radiography
bronchoalveolar lavage (BAL) fluid consisting of >25% eosinophils
absence of parasitic, fungal, or other infection
prompt and complete response to corticosteroids
no relapse after discontinuation of corticosteroids

Pathology
Most cases are idiopathic, however, a link to new or binge smoking in a subset of patients has been suggested 8. Peripheral blood eosinophil counts are usually normal, although they can become elevated during the subsequent clinical course. A very high eosinophil count in bronchoalveolar lavage is characteristic of the condition.

Radiographic features
Imaging features should be interpreted in the correct clinical context.

CT
Described features include 4,6,9:

bilateral ground-glass areas: common
interlobular septal thickening: common
pleural effusions: can be present in ~80% (range 60-100%) of cases
thickening of bronchovascular bundles: present in around two-thirds of cases
air-space consolidation: present in around half of the cases
ill-defined centrilobular nodules: present in around one-third of cases
Zonal distribution:

central-to-peripheral zonal distribution 6
random ~60%
peripheral ~30%
central ~10%
apicobasal overall zonal distribution 6
random ~65%
lower lobes ~30%
upper lobes ~15%