High resolution computed tomography of the lungs: An over view

Introduction

Computed tomography (CT) of the chest can be extremely useful when chest radiographs provide insufficient information to answer important clinical questions about diagnosis, extent of disease, and prognosis. High resolution computed tomography (HRCT) is now widely recognized as more sensitive and specific than chest radiography for the assessment of patients with diffuse lung disease.

HRCT of the chest include detecting lung disease in the presence of normal or equivocal chest radiographic findings. More accurate and detailed assessment of pulmonary parenchymal abnormalities by HRCT allows refinement of differential diagnosis and a more confident diagnosis. Thus HRCT has become a valuable tool for the evaluation of patients with diffuse pulmonary diseases.

What is HRCT?

Conventional computed tomography of the chest examines 7- to 10-mm slices obtained at 10-mm intervals. High-resolution CT examines 1.0- to 1.5-mm slices at 10-mm intervals using a narrow collimation and  high-spatial-frequency reconstruction algorithm and illustrates lung parenchymal details better than conventional CT. This technique seeks to maximize spatial resolution and thereby approach a pathologic representation of a disease process. Maximizing spatial resolution allows HRCT findings frequently to correlate closely with pathologic findings.

Scans are done at full inspiration in the supine patient. Prone positioning may be helpful in distinguishing gravity-dependent atelectasis in the dorsal bases seen on supine images from early changes of idiopathic pulmonary fibrosis (IPF).

Expiration images may be helpful in evaluating the mosaic pattern (patchwork of lung regions of varied radiological attenuation) and patients with obstructive lung diseases to show air trapping. If the findings are sufficiently characteristic of a specific diagnosis, HRCT may obviate a lung biopsy.When a biopsy is needed, HRCT of the chest may guide the selection of the appropriate biopsy procedure and locate optimal sites for biopsy.

By use of a dedicated diagnostic algorithm  based on characteristic high-resolution CT scan features coupled with clinical findings can provide either a specific diagnosis or a markedly shortened list of differential diagnoses in a majority of patients presenting with diffuse lung  diseases.

Due to its ability to evaluate the lung parenchyma in cross-section, eliminating the superimposition of densities, CT scanning offers a unique opportunity to evaluate lung lesions in exquisite detail.

A detailed knowledge of normal pulmonary anatomy and an understanding of how normal anatomy is altered in disease states are required to appreciate fully HRCT findings in patients with pulmonary disease.

Gross airways anatomy   

Airways divide by dichotomous branching with approximately 23 generations of branches identifiable from the trachea to the alveoli. The trachea divides into main bronchi that divide into lobar bronchi. The lobar bronchi divide into segmental bronchi that in turn divide into subsegmental bronchi. These bronchi divide into several generations of smaller bronchi and finally the terminal bronchi are reached.

These terminal bronchi divide into respiratory bronchioles.

Bronchioles differ from the bronchi in that the bronchi contain cartilage and glands in their walls; whereas the bronchioles do not. The bronchioles include two categories: the membranous bronchioles (lobular and terminal) and the respiratory bronchioles.

The lobular bronchioles enter the core of the secondary pulmonary lobule and divide into a number of terminal bronchioles according to the size of the lobule.

These terminal bronchioles represent the most distal purely conducting portion of the tracheobronchial tree; that is they conduct air without being involved in gas exchange.

The terminal bronchioles give rise to the respiratory bronchioles, which are so designated because alveoli bud directly from their walls Hence, respiratory bronchioles not only are conducting but  are also involved in gas exchange.

The respiratory bronchioles give rise to alveolar ducts. In contrast to the respiratory bronchioles where alveoli only  rise occasionally from the wall, these alveolar ducts  have so many alveoli originating from their wall  that there is virtually no wall structure between  the alveolar orifices. The alveolar ducts finally lead into the alveolar sacs containing several alveoli.

Adjacent alveoli originating from different air sacs are known to communicate directly with one another through the pores of Kohn. The canals of Lambert communicate distal bronchioles, particularly preterminal bronchioles with alveoli. The secondary pulmonary lobule is a fundamental functional unit of lung structure, and an understanding of lobular anatomy is essential to the interpretation of thin-section high resolution computed tomographic  scans of the lung. Thinsection HRCT can show many features of the secondary pulmonary lobule in both normal and abnormal lungs, and many lung diseases produce characteristic abnormalities of lobular anatomy.

The primary pulmonary lobule is made of the alveolar ducts, alveolar sacs, and alveoli distal to the last respiratory bronchiole, along with their associated blood vessels, nerves, and connective tissues.

Secondary pulmonary lobule (SPL)-Microanatomy

Airways, pulmonary arteries and veins, lymphatics, and the various components of the pulmonary interstitium are all represented at the level of the secondary lobule.

Secondary lobules are marginated by the connective-tissue interlobular septa, which extend inward from the pleural surface. The interlobular septa are part of the peripheral interstitial fiber system which extends over the surface of the lung beneath the visceral pleura and envelopes the lung in a fibrous sac from which the connective-tissue septa penetrate the lung parenchyma. Pulmonary veins and lymphatics lie within this connective tissue.

Secondary pulmonary lobules measures between 1 and 2.5 cm across. They are polyhedral in shape bounded by fibrous septa (the interlobular septa) which are themselves continuous with the peribronchovascular interstitium (axial connective tissue) and pleura (peripheral connective tissue).The secondary pulmonary lobule refers to the smallest anatomic unit of lung structure.and contains a variable number of acini. Each lobule contains a up to a dozen acini and 30-50 primary pulmonary lobules. Each secondary pulmonary lobule is supplied by a terminal bronchiole and a pulmonary artery branch. They are drained by pulmonary veins which form in at the periphery of the lobule and pass though the interlobular septa. Within the secondary lobule, separating adjacent acini is a much less pronounced network of supporting connective tissue which forms the intralobular septa.

The secondary pulmonary lobule has three principal components (Fig. 1)

• The interlobular septa that marginate the lobule and that contain the pulmonary veins and lymphatics surrounded by connective tissue.
• The centrilobular region containing the bronchiolar branches that supply the lobule, their accompanying pulmonary arteries and adjacent to them supporting connective tissue and lymph vessels.
• The lobular lung parenchyma is the part of the secondary lobule surrounding the lobular core and contained within the interlobular septa. It consists of functioning lung grouped in 3–12 acini that contain alveoli (organised in alveolar ducts and sacs) and their associated pulmonary capillary bed together with their supplying small respiratory airways and arterioles and with draining veins. This parenchyma is supported by connective tissue stroma.

The pulmonary acinus is (Fig.2) smaller than the secondary lobule. It is defined as the portion of lung distal to a terminal bronchiole (the last purely conducting airway) and is supplied by a first-order respiratory bronchiole or bronchioles.Each secondary pulmonary lobule contains 3-12 acini, and adjacent acini are separated by incomplete intralobular septae. Acini are usually described as ranging from 6 to 10 mm in diameter.

The substance of the secondary lobule, which surrounds the centrilobular region and is contained within the interlobular septa, consists of functioning lung parenchyma—namely, alveoli and the associated pulmonary capillary bed supplied by small airways and branches of the pulmonary arteries, veins, and lymphatics. This parenchyma is supported by a connective-tissue stroma, a fine network of very thin fibers within the alveolar septa termed the “septal fibers”

Note; SPL-Borders of lobule are interlobular septa. At center of each lobule is a bronchiole (white ) and a branch of  pulmonary artery (blue). Pulmonary vein (red) run in interlobular septa. Lymphatics (green) are found in interlobular septa and in central  and  axial interstitium that surrounds bronchovascular bundles.

Specific important anatomic details

1. The interlobular septae

   The interlobular septae  are located between secondary pulmonary lobules and are continuous with both the subpleural interstitium (peripheral connective tissue) and the peribronchovascular interstitium (axial connective tissue) as well as the more delicate intralobular septa.

   These septae are composed of connective tissues within which run the pulmonary veins and lymphatics which drain towards the pleura. A second set of lymphatics runs along with arteries and drains centrally. The interlobular septa are incomplete allowing for communication between adjacent secondary pulmonary lobules (Canals of Lambert and pores of Kohn).

   The intralobular septae are delicate strands of connective tissue separating adjacent pulmonary acini and primary pulmonary lobules. They are continuous with the interlobular septae which surround and define the secondary pulmonary lobules.

2. Lung inerstitium

   The lung is supported by a network of connective tissue fibers referred to as the lung interstitium. The interstitium has three components that communicate freely: (1) the peripheral connective tissue, (2) the axial connective  tissue, and (3) the parenchymal connective tissue .

   The peripheral connective tissue includes the subpleural space and the lung septa. The septa are fibrous strands that penetrate deeply as incomplete partitions from the subpleural space into the lung not only between lung segments and subsegments but also between secondary pulmonary lobules and acini So the pleura is in anatomic  continuity with the different lung septa including the interlobular septa and the septa between the acini.

   The axial connective tissue is a system of fibres that originates at the hilum, surrounds the     bronchovascular structures and extends peripherally. It terminates at the centre of the acini in the form of a fibrous network that follows the wall of the alveolar ducts and sacs .The alveoli are formed in  the meshes of this fibrous network. The peribronchovascular interstitium refers to the connective-tissue sheath that encloses the bronchi, pulmonary arteries, and lymphatic vessels. It extends from the hilar regions through to the lung peripheries.

   There are many diseases that could affect peribronchovascular interstitium .eg Sarcoidosis, silicosis, pulmonary odema, etc.

3. Lymphatics

   There are two lymphatic systems: 

   1. a central network, that runs along the bronchovascular bundle towards the centre of the        lobule and

   2. a peripheral network, that is located within the interlobular septa and along the pleural          linings.

4. Central lobular area:

   Central lobular area is the central part of the secondary pulmonary lobule. The centrilobular region comprises the central portion of the secondary pulmonary lobule, consisting of the pulmonary artery, bronchiole and surrounding lung interstitium.It is usually the site of diseases, that enter the lung through the airways (i.e. hypersensitivity pneumonitis, respiratory bronchiolitis, centrilobular emphysema). Therefore, the bronchiolar disease that produces an enhancement of the centrilobular structure occurs when there is thickening of the bronchiolar wall or filling of the bronchiolar lumen . Centrilobular patterns include: (a) nodules; (b) tree-in-bud pattern; (c) thickening of the peribronchovascular peripheral interstitium; and (d) areas of low attenuation without visible walls (emphysema).

5. Perilymphatic area:

   Perilympatic area is the peripheral part of the secundary lobule.It contains  the interlobular septa that marginate the lobule and contain the pulmonary veins and lymphatics surrounded by connective tissue.It is usually the site of diseases, that are located in the lymphatics of in the interlobular septa ( i.e. sarcoid, lymphangitic carcinomatosis, pulmonary edema). These diseases are usually also located in the central network of lymphatics that surround the bronchovascular bundle.

   Note: A side-by-side diagrammatic representation of two normal secondary pulmonary lobules. The lobule is fed by a terminal bronchiole and artery, the periphery is partly septated. In between ,are the primary lobules-acinus- fed by respiratory bronchioles where gas exchange takes place.Veins run in the septa. The centrilobular structures, include pulmonary arterioles and their accompanying bronchioles, and peripheral structures, including the pulmonary veins and lymphatics within the interlobular septae.

   Secondary pulmonary lobules in the lung periphery are relatively large and are marginated by interlobular septa that are thicker and better defined than lobules in other parts of the lung . Peripheral lobules tend to be relatively uniform in appearance, often having a cuboidal or pyramidal shape. Secondary lobules in the central lung zone are smaller and more irregular in shape than those in the peripheral lung and are marginated by interlobular septa that are thinner and less well defined. It should be kept in mind, however, that the size, shape, and appearance of secondary lobules as seen on thin-section CT images are markedly affected by their orientation relative to the scan plane, slice thickness and respiratory phase.

   Interlobular septa are thickest and most numerous in the apical, anterior, and lateral aspects of the upper lobes, the anterior and lateral aspects of the middle lobe and lingula, the anterior and diaphragmatic surfaces of the lower lobes, and along the mediastinal pleural surfaces thus, secondary lobules are best defined in these regions. Septa measure about 100 μm (0.1 mm) in thickness in a subpleural location

   Interlobular septa in the peripheral lung are at the lower limit of thin-section CT resolution,  In healthy patients, a few septa are often visible in the lung periphery, normal septa are most often seen in the apices anteriorly and along the mediastinal pleural surfaces  Occasionally, when interlobular septa are not clearly visible, their locations can be inferred by identifying septal pulmonary vein branches.Veins can sometimes be seen as linear, arcuate, or right angled branching structures 1.0–1.5 cm from the pleural surface.

   On thin-section CT scans, a linear, branching, or dot-like opacity seen in the center of a lobule or within 1 cm of the pleural surface represents the intralobular artery branch or its divisions. The smallest arteries resolved extend to within 3–5 mm of the pleural surface or lobular margin and are as small as 0.2 mm in diameter.

   With thin-section CT, intralobular bronchioles are not normally visible, and bronchi or bronchioles are rarely seen within 1 cm of the pleural surface in most locations.

   Physiologic ground-glass attenuation can be seen in the dependent lung areas.It is also a normal finding on the expiratory CT In many healthy subjects, one or more areas of air-trapping can be seen on expiratory scans, particularly in the lower lobes.

   There is density gradient between the dependent and the nondependent lung, which is larger on expiratory scans than on inspiratory scans.

What are the HRCT patterns seen?

Generally the diagnosis of lung disease on a chest CT is based on three elements. Recognition of the appearance pattern of disease, i.e. classifying the abnormalities in a category that is based on their appearance. Determination of location and distribution of the abnormalities in the lung: the distribution pattern. Careful analysis of the patient data that are available at the time the CT scan is performed.

In chest x-ray the Pulmonary patterns may be classified as alveolar, interstitial, bronchial, and vascular. Interstitial patterns on chest radiography have been described as linear, reticular, nodular, and reticulonodular. The interstitial patterns on HRCT include linear and reticular pattern, nodular pattern, decreased lung density, and increased lung density.

Common HRCT patterns (Fig 3 & 4). 

Generally, HRCT findings can be classified into four large categories based on their appearance: (Table 1)

1. Abnormalities associated with an increase in lung opacity, i.e. increased lung attenuation (opacity). eg.ground glass pattern, consolidation.

2. Abnormalities associated with a decrease in lung opacity,  i.e. decreased lung attenuation (lucency), eg microcyst, emphysema, bronchiectasis.

3. Abnormalities presenting as nodular opacities.

4. Abnormalities presenting as reticular /linear opacities.

Patterns found on high-resolution CT

Showing normal secondary pulmonary lobule; linear marking-- Interlobular septal thickening, Intralobular septal thickening, centrilobularbronchovascular core- thickening; Nodules cysts, bronchiectasis–traction type, honeycombing,; consolidation, ground glass pattern.

White- increased attenuation –increased density

Black-decreased attenuation-decreased density

G-ground glass opacity

C-consoildation

White double arrow- parenchymal  bands \White single arrow-Mosaic perfusion

White single  arrow head-subpleural line

White double  arrow head-paraseptal emphysema

Double Small black arrow-centrilobular nodule

Single Small black arrow-tree-in-bud appearance

Single Black arrow head-perilymphatic, fissural, subpleural nodules

Double Black arrow head—peribronchovascular nodules, Asterix- lung cyst

Basic interpretation of HRCT scans 

1. Interpretation of interstitial lung diseases is based on the type of involvement of the various components of  a secondary lobule.
2. Identify the major or predominant pattern  as - opacity,lucency,nodular or reticular. Then find out the zonal distribution as- upper, lower, central, peripheral. Then locate the exact site of involvement in SPLie. centrilobular, perilymphatics or random.³ first the assess lesions by anatomic distribution and second by morphology.
3. Further Pathologic alternations in secondary lobular anatomy visible on thin-section CT scans may be described as

Table 1 showing common HRCT patterns

1.  Perilobular when interlobular septa are involved (eg.interlobular septal thickening),
2. Centrilobular when central bronchovascular part is involved, ( eg centrilobular nodules ) and
3. Panlobular (intralobular) when entire lobule is involved.random distribution (eg.panlobular empjysema).

Image Plate 2: Increased attenuation pattern

1. Depending on the degree of involvement, two types,

a. Ground-glass opacity or ground-glass attenuation when involvement is mild-the of                increased  lung attenuation (high density) can be described:hazy increase in lung opacity            with preservation of the bronchial and vascular markings.

     Ground-glass opacification /opacity (GGO)

is a descriptive term referring to a hazy area of increased attenuation in the lung with preserved bronchial and vascular markings. It is a non-specific sign with a wide aetiology including infection, chronic interstitial disease and acute alveolar disease. This image pattern is related to interstitial thickening, partial filling of air spaces partial collapse of  alveoli, increased capillary blood volume or a combination of all of these mechanisms.

b. Consolidation when involvement is more advanced, the increased pulmonary density obscures the vessels and the margins of the airways. Airspace consolidation or alveolar filling is character- ized by indistinct margins, the tendency to coalesce, and the presence of air bronchogram or silhouette sign (efface- ment of an anatomical soft-tissue border. Airspace consolidation may be caused by accumulated water, blood, pus, cells, and other material. Diffuse alveolar infiltrates may be acute or chronic (Table 2).

Image plate 3: Nodular pattern

Multinodular disease is defined as a disease in which there are too many nodules to easily count on routine CT scan studies, with most of these nodules measuring 1 cm in diameter. presence of innumerable small rounded opacities with soft tissue density that are discrete and range in diameter from 2 to 10 mm. It is a focal opacity that is rounded, or at least partially delineated, smaller than 3.0 cm in diameter and generally presenting soft tissue or calcified tissue density.

When the opacity is smaller than 10 mm, it is recommended that the term “small nodule” be used.

When the opacity is smaller than 3 mm, it is recommended that the term “micronodule” be used.When the opacity is between 10-30 mm the term solitary pulmonary nodule.

Nodules should be described according to the characteristics of their borders (well- or ill-defined), to their location or to their distribution (random, perilymphatic, centrilobular or pleural).

Nodules must be described as to whether they are

1. Diffuse or focal or clustered;
2. Central (peri- bronchovascular) or peripheral (subpleural or peri- fissural);3 upper or lower lung distribution. Most importantly, nodules also need to be characterized by their relation to secondary lobular anatomy.

For example, diseases such as sarcoidosis that localize within or adjacent to lymphatics predominate in those regions in which lymphatics are most extensive, specifically along the pleural and fissural surfaces, within the interlobular septae, and along the peribronchovascular axial interstitium. (Table-3).

Diseases that are primarily hematogenous in origin, such as miliary infections or hematogenous metastases, give rise to nodules that are randomly distributed throughout the secondary lobule, with the greatest profusion in the lung bases.

These patterns are clearly separate from nodules that result from inhalational disorders such as occur in patients with endobronchial spread of infection or hypersen- sitivity pneumonitis (HP), in which nodules are predominantly centrilobular in distribution, sparing the lobular periphery.

Further assessing a number of characteristics including whether nodules are as follows: uniform or variable in size; sharply or poorly marginated; solid or subsolid in density (so-called ground-glass opacities) ; or have a so-called tree-in-bud appearance. Additionally, nodules may ei-ther be calcified, as occurs in fungal disease, or cavitary, as is seen, for example, in patients with septic emboli, metastatic disease, or Langerhans cell histiocytosis (LCH).

Image Plate 4 : Linear /reticular pattern

Pulmonary disease occurring predominantly in relation to interlobular septa and the periphery of lobules is called “perilobulardistribution”. Septa easily seen on thin-section CT scans are abnormally thickened. In the peripheral lung, thickened septa 1.0–2.5 cm in length may outline part of or an entire lobule and are usually seen extending to the pleural surface .Lobules delineated by thickened septa commonly contain a visible dotlike or branching centrilobular pulmonary artery. Septal thickening can be seen in the presence of interstitial fluid, cellular infiltration, or fibrosis and can have a smooth, nodular, or irregular contour in different pathologic processes EG. smoothinterlobular septal thickening-pulmonary odema. Kerley B lines, nodular-interlobular septalthickening lymphangitic spread of neoplasm (Table-4 & 5 ).

Decreased attenuation (Low density)

Generally decreased lung attenuation can be found if there is any of the following are present. Hypoperfusion, Air-trapping, Cystic and cyst-like lesions,

Pulmonary emphysema

1.    Pulmonary emphysema Pulmonary emphysema is characterized by permanently enlarged airspaces distal to the terminal bronchiole with destruction of the alveolar walls. Emphysema is classified, using both histopathologic techniques and HRCT imaging,according to the acinar region affected: proximal (centriacinar or centrilobular emphysema), distal (paraseptal emphysema), or whole acinus (panacinar or panlobular emphysema). The tomographic findings are areas of low attenuation, typically without visible walls. ( Table 6 ) (Image Plate 5).

2.    Cyst A cyst is any rounded, well-circumscribed space surrounded by an epithelial or fibrous wall of variable thickness. On CT scans, a cyst is seen as a rounded area with low attenuation coefficient on the lung parenchyma, having a well-defined interface with the adjacent normal lung .The cyst wall is usually thin (< 2 mm), but it can vary in thickness. Cysts are usually filled with air but can also contain liquid (e.g., bronchogenic cyst) or even a solid material. Diseases accompanied by multiple pulmonary cysts include lymphangioleiomyomatosis (LAM ), Langerhans cell histiocytosis (LCH), lymphocytic interstitial pneumonia and Birt-Hogg-Dubé syndrome. (Table 7) (Image plate 6).

3.    Bronchiectasis Bronchiectasis is defined as localized, irreversibledilation of the bronchial tree. HRCT findings of bronchiectasis include increased bronchoarterial ratios, lack of appropriateairway tapering, bronchial wall thickening and irregularity, mucoid impaction, and mosaic perfusionwith air trapping. .Bronchial dilation (increased bronchoarterialratio). Bronchial dilation is the most specificfinding for bronchiectasis. In general, bronchiectasis is present when the bronchoarterial ratio (the ratio of the internal diameter of the bronchus to its adjacent pulmonary artery) exceeds 1. When an increased bronchoarterial ratio is seen in cross-section, it has been termed the ‘‘signet ring’’ sign. (Table 8).

Mixed attenuation pattern

     A) Crazy paving refers to the appearance of ground-glass opacity with superimposed i                     nterlobular septal thickening and intralobular reticular thickening. It is a nonspecific finding             that can be seen in a number of conditions. Common causes of crazy paving includeacute               respiratory distress syndrome, bacterial pneumonia. acute interstitial pneumonia: essentially             ARDS of unknown etiology, pulmonary alveolar proteinosis (PAP)

B) Honeycomb lung Honeycomb lung represents the presence of end-stage lung. Pathologically, honeycomb cysts consists of air-containing spaces with thick walls that are lined with bronchiolar epithelium and fibrous tissue. The HRCT demonstration of honeycomb cysts allows for a confident diagnosis of a fibrosing pulmonary process, and the specific distribution of the honey-comb cysts may be a clue to the etiology of the fibrotic lung disease. Honeycombing suggests extensive lung fibrosis with alveolar destruction and can result in a cystic appearance on gross pathology. HRCT shows thick-walled, air-filled cysts, usually between the size of 3mm to 1cm in diameter.

C) Tree-in-bud sign describes the CT appearance of multiple areas of centrilobular nodules with a linear branching pattern.. Tree-in-bud sign is not visible on plain film 2 and is best seen on HRCT. Typically they are composed of centrilobular nodules (which are usually 2-4 mm in diameter and peripheral, within 5 mm of pleural surface) connected by opacified or thickened branching structures extending proximally (representing the dilated and opacified bronchioles. Pathogenesis -bronchioles filled with pus or inflammatory exudates,e.g. pulmonary tuberculosis, aspiration bronchopneumonia ;bronchiolitis: thickening of bronchiolar walls and bronchovascular bundle,e.g. cytomegalovirus pneumonitis, obliterative with mucus plugging bronchiolitis; bronchiectasis

D) Mosaic attenuation is the description given to the appearance at CT where there is a patchwork of regions of differing attenuation. It is a non-specific finding, which may be seen in any of the following:

• Obstructive small airways disease: low attenuation regions are abnormal and reflect decreased perfusion of the poorly ventilated regions, e.g. bronchiectasis, cystic fibrosis, constrictive bronchiolitis
• Occlusive vascular disease (can be termed a mosaic perfusion pattern in this setting 7): low attenuation regions are abnormal and reflect relative oligaemia, e.g. chronic pulmonary embolism
• Parenchymal disease: high attenuation regions are abnormal and represent ground-glass opacity.

Anatomic nodule localization on HRCT.

ABPA, allergic bronchopulmonary aspergillosis; BAC, bronchio-loalveolar carcinoma; CF, cystic fibrosis; COP, cryptogenicorganizing pneumonia; EG, Langerhans’ cell histiocytosis; HP, hypersensitivity pneumonitis; infxn, infection (bacterial,fungal, or viral); LIP, lymphocytic interstitial pneumo-nia; MAC,Mycobacterium-avium–complex; PLC, pulmo-nary lymphangitic carcinomatosis; PNA, pneumonia (mostcommonly bacterial); RB-ILD, respiratory bronchiolitis–interstitial lung disease; TB, Mycobacterium tuberculosis; tib, tree-in-bud.