Terminology and Classification1

Interstitial lung disease (ILD) is a heterogeneous group of disorders affecting the pulmonary interstitium comprising of interalveolar connective tissue, peribronchovascular and perilymphatic tissues including the alveolar epithelium, capillary endothelium and basement membranes.

The term ILD is often used interchangeably with diffuse lung diseases (DLDs), however neither all DLD (e.g. diffuse alveolar hemorrhage) involve the interstitium nor all ILDs are diffuse [e.g. idiopathic pulmonary fibrosis (IPF)].

In this book we will cover in subsequent chapters, the various conditions included under ILD as well as DLD which can mimic ILD.

Interstitial lung diseases (ILDs) can be broadly classified into idiopathic and those secondary to a known factor like connective tissue diseases, infections, drug or irritant exposure related.

The American Thoracic Society–European Respiratory Society classification of 2002 had described individual diseases in the idiopathic interstitial pneumonias (IIPs) and their diagnostic approach. This joint statement underwent a revision in 2013, with the multidisciplinary approach taking cognizance of the clinical, imaging and histopathological findings.^1,2

In the 2013 classification, the major entities in IIPs have been classified as:

The organization of structures in the subsegmental level consists of bronchovascular bundles and secondary pulmonary lobule.

Bronchovascular bundle consists of bronchi, arteries and associated connective tissue (central interstitium) (Fig. 1.1).

On CT, vessels are seen as solid linear or circular structures whereas bronchi are seen as parallel linear or ring shaped structures.5

Secondary pulmonary lobule is a polyhedral structure (around 2 cm) with bronchovascular structures in the center and perilobular veins (peripheral interstitium) in the periphery.

Lymphatics are seen in central as well as in the periphery of the lobule

Each secondary pulmonary lobule is supplies by a terminal bronchiole and a centrilobular pulmonary artery.

Centrilobular arteries can be seen on CT images whereas the bronchiole is not usually seen as it is too thin for the current resolution of scanners.

The terminal bronchiole is thin, does not have cilia and has muscular walls which makes them a favored location for bronchospasm leading to air-trapping.

Terminal bronchioles give rise to multiple respiratory bronchioles which lead to alveolar ducts.

There are fine septations seen with in the secondary pulmonary lobule which forms the framework of acini, alveolar ducts, alveolar sac, etc.

These intralobular interstitial structures are not seen routinely on CT scans

Pleuropulmonary interface forms the boundary for the lungs and it is usually smooth and devoid of irregularities.

This is one of the commonly seen abnormalities in ILDs.

It manifests as linear opacities on high-resolution computed tomography (HRCT) which is usually as a result of thickening of the peripheral interstitium especially interlobular septum.6

However, there can be associated central interstitial thickening as well.

There are various causes which can result in reticular pattern such as fibrosis, volume overload and malignant infiltration.⁴

The reticular pattern can be smooth, nodular or irregular.

Smooth reticular opacities are seen as smooth linear opacities without any irregularity or nodularity (Fig. 1.2).

It can be seen in edema or by infiltration of the interlobular septum

Nodular reticular opacities are usually because of interstitial thickening with associated micronodules making the interface nodular (Fig. 1.3).

It can be seen in sarcoidosis, pneumoconiosis, lymphangitis carcinomatosis etc.

Irregular reticular pattern is as a result of extensive interstitial fibrosis leading to irregular thickening of septae and distortion of the pulmonary lobule framework (Fig. 1.4).

Abnormality of the centrilobular interstitium can also be seen in the form of irregular thickening and tortuosity.

This pattern can be seen in a variety of fibrosing ILDs such as UIP, NSIP, sarcoidosis, etc.

This pattern consists of discrete nodules of varying sizes (micronodules <3 mm, macronodules 3 mm to 1 cm) distributed in the pulmonary lobule.

There are various causes such as granulomatous diseases, pneumoconiosis, metastases, etc.

There are three types of nodules based on the distribution in relation to the structures in secondary pulmonary lobule.

They can be centrilobular, perilymphatic and random.

The centrilobular nodules are seen in relation to the centrilobular interstitium and they are separated from the peripheral interstitium by a distance (Fig. 1.5).

On HRCT, they are usually seen roughly in the centre of the secondary pulmonary lobule and not along the pleura or fissures.8

The diseases primarily affecting the terminal part of the bronchioles such as hypersensitivity pneumonitis and RB-ILD produce this pattern.

They can be sometimes associated by surrounding ground glass opacity

Perilymphatic nodules are seen in along the peripheral interstitium which means the nodules are seen along the pleura and fissures on HRCT (Fig. 1.6).

Diseases which involve the lymphatics such as sarcoidosis and other granulomatous processes can manifest with this pattern.

Random nodules will not follow any particular pattern and in general the distribution is uniform in the secondary pulmonary lobule (Fig. 1.7).

They can be seen in relation to the central interstitium or the peripheral interstitium.

Diseases with hematogenous spread such as miliary TB and metastases can follow this pattern.

Both are abnormal increase in lung density with (consolidation) or without (ground glass) effacement of pulmonary vessels on CT (Figs 1.8 and 1.9).

This pattern results from the opacification of alveolar spaces and/or interstitium.

The type of manifestation will depend on the extent of involvement.

Sometimes ground glass opacity can be associated with reticular pattern in which case it is called as crazy paving pattern (Fig. 1.10).

Alveolar pattern can be seen in a variety of acute, subacute or chronic disease processes such as AIP, ARDS, alveolar hemorrhage, pneumocystis pneumonia, bronchoalveolar carcinoma, etc.10

Mosaic attenuation is another pattern which is commonly encountered presenting as patchy areas of increased or decreased lucencies leading to heterogeneous appearance of lung parenchyma (Fig. 1.11).

This pattern can be as a result of abnormality in small airway, peripheral pulmonary vasculature or interstitium.⁵

When there is abnormality in the small airway (terminal or respiratory bronchioles) the air gets trapped in distally and there will not be a normal outflow of air during expiration.

This leads to patchy areas of hyperlucency and it is a challenge to recognise the abnormal area (hyper or hypolucent area). There can be associated pulmonary oligemia in the affected areas because of hypoxia due to air trapping.

By performing expiratory scans the abnormal areas showing air trapping can be readily identified. There will be normal outflow of air in the normal lung during expiration whereas there will be air trapping in the affected areas which leads to accentuation of differential lucency.11

Whenever the heterogeneity is more pronounced in expiratory scans air trapping due to small airway disease.

Mosaic attenuation can also occur as a result of mosaic perfusion which occurs in patients with pulmonary hypertension of any cause such as chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension.⁶

In these patients there will be focal pulmonary oligemia in the affected areas however there will not be air trapping in expiratory scans.

Sometimes mosaic attenuation can be due to patchy ground glass infiltration wherein there will not be air trapping or pulmonary oligemia.

Tree in bud pattern is a manifestation of endobronchial spread of infection such as TB or aspiration (Fig. 1.12).

It is characterized by linear branching structures (opacified distal bronchioles) with nodular opacities (acinar opacification) at the tip.

It is characterized by the presence of complete lucency which may or may not have walls.

Cystic lesions in lung are usually formed by the abnormal dilatation of the bronchus/bronchioles or due to abnormal distention of air spaces.

There are various patterns of cystic lesions of lung such as cluster of grapes, string of pearls, honeycombing and random cysts.

Cluster of grapes pattern is usually due to the abnormal dilatation of airway involving a lobe of segment which is seen in cystic bronchiectasis (Fig. 1.13).

They usually have thick walls and may contain mucus, pus, debris or even fungal ball.

Air fluid level in these cystic lesions often denote secondary infection.12

String of pearls pattern is characterized by the presence of multiple cysts arranged in a single row along the pleura (subpleural blebs).

They may have a thin wall and when they are more than 1 cm in size they are called as bullae.

Paraseptal emphysema is a typical example for this type of pattern.

Honeycombing as the name suggests consists of relatively smaller thick walled cysts arranges in multiple layers (Fig. 1.14).

They are usually seen in fibrosing ILDs in which case there can be associated irregular reticular pattern, lung volume loss and tractional bronchiectasis.

The architecture of the secondary pulmonary lobules gets distorted due to extensive fibrosis.

Some disease processes such as centriacinar emphysema, pulmonary LCH and lymphangioleiomyomatosis can present with randomly distributed cysts (Fig. 1.15).13

Wall of the cysts, their craniocaudal distribution and other associated findings will dictate the differential diagnosis.