High resolution computed tomography of the lungs

INTRODUCTION — The initial imaging tool for the lung parenchyma remains the chest radiograph. It is unsurpassed in the amount of information it yields in relation to its cost, radiation dose, availability, and ease of performance. However, the chest radiograph has its limitations. It is normal in 10 to 15 percent of symptomatic patients with proven infiltrative lung disease, in up to 30 percent of those with bronchiectasis, and in close to 60 percent of patients with emphysema [1]. In several studies, the chest radiograph has been shown to have an overall sensitivity of 80 percent and a specificity of 82 percent for detection of diffuse lung disease [2]. Chest radiography could provide a confident diagnosis in only 23 percent of cases, and those confident diagnoses proved correct only in 77 percent of cases.

For these reasons, high resolution computed tomography (HRCT, also called thin-section CT scanning), is frequently used to help clarify specific problems. Typical features of the lung parenchyma and of the small airways correlate with obstructive or restrictive pulmonary function tests [3].The clinical applications of HRCT will be reviewed here. The principles of CT imaging are discussed separately. (See "Principles of computed tomography of the chest".)

CLINICAL APPLICATION OF HRCT — HRCT, which has a sensitivity of 95 percent and a specificity approaching 100 percent [2,4-7], can often provide more information than either chest radiography or conventional CT scanning. A confident diagnosis is possible in roughly one-half of cases, and these are proven correct an estimated 93 percent of the time.

HRCT may be particularly useful in the following settings:

●It can detect lung disease in symptomatic patients with a normal chest radiograph.

●It can provide an accurate assessment of the pattern, distribution, and to a lesser degree, assess the activity and potential reversibility of diffuse lung disease.

●It demonstrates a high correlation between radiographic and histopathologic appearances.

●In patients with nondiagnostic findings on chest radiography, it can provide a more specific diagnosis or exclude certain diseases.

●It can be used to determine the type and site of lung biopsy. (See "Role of lung biopsy in the diagnosis of interstitial lung disease".)

●It can be used to detect or evaluate specific problems or diagnoses, such as metastatic lesions, solitary pulmonary nodules, emphysema, bullous lung disease, bronchiectasis, and diffuse parenchymal disease.

Conventional helical CT scanning is the preferred method for the detection and evaluation of mediastinal disease, rather than HRCT (see "Approach to the adult patient with a mediastinal mass"). Multislice, multidetector-row CT scanning employs routinely thin sections of 1 to 1.25 mm and high spatial frequency algorithm which provides "high resolution" in the vast majority of thoracic CT scans. HRCT should be performed without intravenous contrast material injection in order to avoid pseudo-ground-glass opacities or so-called hurricane artifacts.

Resolution — The technical features of HRCT include a thin collimation of 1 to 1.25 mm and the use of a high spatial frequency (bone) algorithm. The in–plane spatial resolution of modern CT scanners can reach 0.25 mm. Thus, interlobar fissures, which are 0.15 mm in thickness, can frequently be imaged (image 1). The pattern of scanning varies with the suspected diagnosis. Scanning should occur at 1 cm intervals for diffuse lung disease but should be limited to the involved area for focal lung processes and solitary pulmonary nodules. In posterobasal lung disease, prone scanning can eliminate gravitational changes or dependent atelectasis that can mimic lung disease (image 2). Prone scans are useful in patients with subtle abnormalities or with normal chest radiographs. With current multislice, multidetector row helical CT scanners, a complete volumetric, helical data set without gaps is commonly obtained with 1 to 1.25 mm reconstructed section thickness.

Normal anatomy — The basic lung unit that is regularly visible on HRCT is the secondary pulmonary lobule, which is surrounded by interlobular septa. The diameter of the secondary pulmonary lobule varies from 1 to 2.5 cm. It is formed by a congregation of three to five acini and has a polyhedral shape. It contains core structures formed by pulmonary arteriole, bronchiole and peribronchiolar lymphatics, adjacent lung parenchyma, and septal structures which can contain lymphatic structures as well. An acinus encompasses the lung unit distal to a terminal bronchiole and contains an average of 400 alveoli. It has a diameter of 5 to 10 mm and can occasionally be seen on thin sections. Centrilobular arterial branches are important for localization of pathological processes and are located 5 to 10 mm from the pleura.

HRCT PATTERNS — The diagnostic approach for HRCT relies upon the predominant pattern of abnormalities, on the zonal distribution of disease, on associated findings such as pleural plaques, calcifications, thickening, effusions, lymph node enlargement, and the clinical history. Criteria of importance include the chronicity of the disease process and the patient's immune status.

The basic HRCT patterns are a reflection of altered normal anatomy, including terminal and respiratory bronchioles, alveolar ducts, alveolar sacs, pulmonary arterioles, lymphatics, and the loose interstitial connective tissue network. The patterns include reticular and nodular structures, increased opacity (ground-glass and air space filling or consolidation), and decreased opacity, including cystic lesions, mosaic attenuation, and gas trapping. Accompanying lesions include linear opacities, parenchymal bands and architectural distortion.

Reticular pattern — The interstitial pulmonary network is responsible for the reticular pattern. It is composed of the axial (ie, bronchovascular) interstitium, the interlobular (including subpleural and sub-fissural) interstitium, and the alveolar-septal (ie, intralobular) interstitium. The pulmonary lymphatics follow the interstitial network.

A reticular pattern can be classified as large (coarse), intermediate, or fine. The large (coarse) reticular pattern (1 cm) is due to thickening of interlobular septa; intermediate reticular changes can be seen with honeycombing, which form stacked subpleural, small cystic spaces; fine reticular changes are seen with alveolar-septal, intralobular thickening. Irregular intersecting lines can produce a "steel wool" pattern.

Perilobular pattern — The perilobular region includes the bordering structures of the secondary pulmonary lobules like pleura, interlobular septa, pulmonary veins, paraseptal interstitium, paraseptal alveoli, and subpleural interstitium. Thickening of these structures can produce a coarse reticular pattern with polygonal and arcade-like opacities. The pattern has been described in up to half of patients with organizing pneumonia [8].

Nodular pattern — Nodular patterns include airspace lesions with fuzzy borders, and interstitial nodules with sharp, unsharp, or stellate margination.

Sharp interstitial nodules can be seen with [9]:

●Langerhans cell histiocytosis (LCH)

●Silicosis

●Metastatic disease

●Miliary tuberculosis

●Disseminated fungal disease

Unsharp interstitial nodules are found in [9]:

●Sarcoidosis

●Subacute phase of hypersensitivity pneumonia

Stellate interstitial nodules have been described in [10]:

●LCH (so-called starfish nodules)

Nodules can be further classified according to their distribution as:

●Perilymphatic

●Random, hematogenous (capillary pattern), or perivascular

●Centrilobular

●Airspace

Perilymphatic nodules — Perilymphatic nodules are subpleural in location, and are also found along interlobular septa, interlobar fissures, and along bronchovascular bundles. These nodules tend to be nonuniform and patchy in distribution, and have a tendency to cluster. They are most frequently found in sarcoidosis, lymphangitic carcinomatosis, and silicosis. When the clustering occurs in a subpleural location, pseudo-plaques can form. Perilymphatic nodules can be seen with sarcoid-like reactions in the lungs after cancer therapy with check point inhibitors like pembrolizumab.

Random, hematogenous, or perivascular nodules (capillary pattern) — Random or perivascular nodules have a similar subpleural distribution but show a uniform and diffuse distribution. They do not cluster. They are the result of hematogenous dissemination and are characteristically found in miliary tuberculosis, miliary fungal disease, septic embolization, and metastatic spread of tumor (image 3A-B). They may have a basal predominance with centrilobular and subpleural location, as well as proximity to their feeding vessels. If small hematogenous metastatic nodules cavitate they can form a so-called "cheerio" pattern. This pattern has also been described in minute pulmonary meningothelial-like nodules, likely related to chemodectomas [11].

Centrilobular nodules — Centrilobular nodules spare the subpleural region and the lung underlying the interlobar fissures; they are found 5 to 10 mm removed from the pleural surfaces. They have a diffuse or patchy distribution, and tend to surround small vessels. They are found in hypersensitivity pneumonitis, sarcoidosis, LCH, and respiratory, follicular, and cellular bronchiolitis (image 4 and image 5). Centrilobular nodules are described in rare cases of diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH). Centrilobular nodules with subtle cavitation can be identified in LCH and are another source of a "cheerio" pattern.

An accompanying tree-in–bud pattern is indicative of infectious bronchiolitis or aspiration. Rare causes of centrilobular nodules with tree-in-bud appearance are diffuse panbronchiolitis, follicular bronchiolitis, vascular tumor spread (tumor embolization), and so-called cellulose or talc granulomatosis in intravenous drug abusers.

Centrilobular ground-glass nodules can be seen in respiratory bronchiolitis of smokers, follicular bronchiolitis, and hypersensitivity pneumonitis (usually in non-smokers).

In rare instances, centrilobular nodules can be found in patients with plexogenic changes of pulmonary arterial hypertension, pulmonary veno-occlusive disease, and the related pulmonary capillary hemangiomatosis [12].

Airspace nodules — Airspace nodules, previously also called "acinar" nodules, are centrilobular and can also form the "tree-in-bud" pattern, but they are slightly larger than typical centrilobular nodules. They are seen in bronchogenic (endobronchial) spread of tuberculosis, aspiration, infectious bronchiolitis, and diffuse panbronchiolitis. The pathologic correlate is an accumulation of pus, mucus, caseous material, or inflammatory infiltration of bronchiolar walls.

General approach — An algorithmic approach to small nodules on HRCT can be attempted by asking, "Do the nodules touch the parietal pleura or the interlobar fissures?"

●If yes, then the nodules are likely to be perilymphatic or hematogenous. Clustering of the nodules suggests sarcoidosis, silicosis or lymphangitic carcinomatosis, the latter frequently with thickening of interlobular septa. Nonclustered, diffuse nodules that abut the pleural or the interlobar fissures are likely random, hematogenous nodules (eg, miliary tuberculosis, fungal dissemination, hematogenous metastatic disease, or septic embolization).

●If no, then the presence or absence of a tree-in-bud pattern has to be determined: centrilobular nodules without tree-in-bud pattern are found in respiratory bronchiolitis, hypersensitivity pneumonitis, and LCH. Centrilobular nodules with tree-in-bud pattern are primarily found with infectious bronchiolitis and aspiration.

Increased attenuation — Increased attenuation of lung parenchyma on HRCT is generally due to infectious or inflammatory processes.

Ground-glass opacification — Ground-glass opacification refers to focal or diffuse veil-like opacification of the lung, which does not obscure the vascular structures or the rest of the anatomic details and does not yield air-bronchograms (image 6 and image 7 and image 8 and image 9 and image 10). Ground-glass opacification was initially described on chest radiographs. The term was later adopted in CT reporting. It indicates sub-threshold parenchymal abnormalities below the spatial resolution of HRCT. It has an attenuation between minus 300 and minus 600 HU. Ground-glass opacification occurs in early interstitial lung disease (image 11), with incomplete, early alveolar filling, with increased pulmonary capillary blood volume, and with partial collapse of alveoli, particularly on expiratory scans performed close to functional residual capacity of the lungs [13-16]. Claims that it solely represents early "alveolitis" have proven inaccurate. In approximately one-third of patients with interstitial lung disease, ground-glass opacity correlates with established fibrosis. In such cases, accompanying traction bronchiectases can usually be detected [17].

In rare instances, increased lung attenuation may be difficult to detect if it is diffuse, homogeneous, and subtle. A very conspicuous display of bronchi (ie, the "black bronchus" sign) is a helpful finding that suggests diffuse, subtle increased lung attenuation.

Subtle radiographic abnormalities may be accompanied by a marked decrease in the diffusion capacity for carbon monoxide (DLCO) of up to 50 percent, facilitating their recognition [16]. Examples of diseases that may present with subtle increased lung attenuation include early hypersensitivity pneumonitis, Pneumocystis jirovecii (formerly called Pneumocystis carinii) pneumonia, cellular nonspecific interstitial pneumonia, desquamative interstitial pneumonia, and subacute diffuse alveolar damage. In contrast, most diffuse lung diseases that present with ground-glass opacification are patchy, with multifocal variability in attenuation that is readily detected on an expiratory scan.

Multifocal, large, rounded, subpleural ground-glass opacities are characteristic for the early, exudative form of SARS-CoV-2-pneumonia (COVID-19 pneumonia) [18,19].

Acute diseases that manifest with diffuse ground-glass opacities include pulmonary edema, pulmonary hemorrhage (image 12), Pneumocystis jirovecii pneumonia, mycoplasma and viral pneumonia, acute interstitial pneumonia (AIP), acute eosinophilic lung disease, and early hypersensitivity pneumonitis [15]. Among HIV-positive patients, ground-glass attenuation is present in 90 percent of patients with Pneumocystic jirovecii pneumonia and absent in 95 percent of patients who do not have Pneumocystic jirovecii pneumonia. Among immunocompromised patients without AIDS, ground-glass opacities may indicate Pneumocystic jirovecii pneumonia, drug reactions, pulmonary hemorrhage, or lymphoma.

Chronic pulmonary disorders that induce diffuse ground-glass opacification either as the only finding or in conjunction with fibrosis, interlobular and intralobular septal thickening, or nodules include hypersensitivity pneumonitis, desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), nonspecific interstitial pneumonia (NSIP), pulmonary alveolar proteinosis (PAP), bronchioloalveolar carcinoma also called adenocarcinoma-in-situ, organizing pneumonia, and sarcoidosis [15].

"Crazy paving" refers to ground-glass opacities with interspersed thickened interlobular and intralobular septa. Initially described in PAP, it can also be found in atypical pneumonia, including the early organizing phase of SARS-CoV-2 pneumonia, pulmonary hemorrhage, diffuse alveolar damage, and pseudoalveolar sarcoidosis [20,21]. (See "Treatment and prognosis of pulmonary alveolar proteinosis in adults" and "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults".)

Ground-glass opacities may be focal. Such opacities typically represent focal atelectasis, focal fibrosis, focal inflammation, atypical alveolar hyperplasia, or bronchioloalveolar carcinoma (ie, adenocarcinoma-in-situ) [16]. Follow-up scans after three months may show clearing if the focal ground-glass opacity is inflammatory in origin. However, if the focal ground-glass opacity persists and exceeds 10 mm in diameter, bronchioloalveolar carcinoma (adenocarcinoma-in-situ) should be suspected [16]. Smaller, circumscribed, persistent ground-glass opacities usually represent atypical alveolar hyperplasia. They grow in only 10 percent of cases and only 1 percent can yield a solid component and convert to a minimally invasive adenocarcinoma. This conversion takes at least 3.5 years [22].

Consolidation or airspace filling — Consolidation or airspace filling causes opacification but, in contrast to ground-glass attenuation, it results in obscuration of vascular structures accompanied by air bronchograms (image 13A-B). These changes are due to replacement of alveolar gas by pus, edema, blood, surfactant, or cells. In acute cases, pneumonia, pulmonary edema, diffuse alveolar damage [23], and pulmonary hemorrhage should be considered. In chronic cases, cryptogenic organizing pneumonia, chronic eosinophilic pneumonia, and bronchioloalveolar carcinoma (mucinous adenocarcinoma) are likely possibilities.

In rare cases, an interstitial process such as sarcoidosis can widen the alveolar septa and compress the alveoli but spare the bronchi, thus mimicking airspace filling disease (ie, pseudoalveolar sarcoidosis).

Decreased attenuation — Decreased attenuation can result from emphysema, cystic lung disease, asthma, bronchiolitis obliterans with hypoxic vasoconstriction and gas-trapping, bronchial obstruction with gas-trapping due to a check valve obstruction, or pulmonary hypoperfusion from severe pulmonary hypertension, particularly if it is due to chronic thromboembolic disease (CTEPH). A generalized decrease in attenuation is unusual, but may be seen with increasing age due to an increase in the size of alveoli from 250 micrometers to 500 micrometers in diameter. It may also be seen in individuals with pulmonary arterial hypertension or a systemic sclerosis-related pulmonary vasculopathy, likely reflecting reduced compliance of the pulmonary arterial tree [16]. Emphysematous decrease in lung attenuation can measure minus 950 Hounsfield Units (HU) or lower on CT scans obtained during sustained inspiration whereas expiratory gas trapping due to small airways disease can register an attenuation of minus 856 HU [24].

Mosaic attenuation — Redistribution of blood flow towards normal parts of the lung may lead to increased attenuation of uninvolved parenchyma. This pattern of variable regional attenuation of lung parenchyma due to regional differences in perfusion is known as mosaic perfusion or mosaic attenuation and leads to sharply defined heterogeneity of lung attenuation. In a majority of cases, it can result from regional variations in perfusion due to airway abnormalities with hypoxic vasoconstriction, less likely due to obstructive vascular disease [25], or areas of infiltrative lung disease with ground-glass attenuation interspersed between islands of normal lung [26]. It can be seen in up to 20 percent of abnormal HRCT studies performed for diffuse infiltrative lung disease.

Differentiation of increased attenuation due to focal increase in blood flow from true ground-glass attenuation can be made by evaluating the vessel size: vessel size and number will be equal in areas of increased and decreased attenuation when caused by infiltrative lung disease. Vessel size and number will be decreased in regions of hypoattenuation, when dealing with airways or vascular disease. Expiratory scans will amplify the areas of hypoxic vasoconstriction and gas-trapping in airways disease but will not affect regions of hypoperfusion resulting from vascular obstruction. In addition, bronchiolitis obliterans is frequently associated with bronchial wall thickening, bronchiectasis, bronchiolectasis, and lobular lucencies, whereas chronic thromboembolic disease and idiopathic pulmonary arterial hypertension are accompanied by dilation of the central pulmonary arteries and larger, better defined areas of hypoattenuation. Mosaic attenuation will accurately depict 95 percent of diffuse infiltrative diseases and 85 percent of small airways obstruction but only 40 percent of patients with chronic obstruction of pulmonary arterial branches.

Lobular gas-or air-trapping has been described in 40 to 60 percent of asymptomatic, nonsmoking individuals. It can be regarded as a normal variant, particularly on expiratory scans [16]. Lung affected by gas or air trapping usually shows a decrease in attenuation below minus 856 HU [24,27].

Cystic lung disease — Cysts are defined as focal regions of low attenuation with perceptible, well delineated walls, 2 mm or less in thickness. Emphysematous spaces and bullae usually have an imperceptible wall and occasionally central vessels. Bronchiectatic cysts display the signet ring or Cabochon ring sign due to an accompanying artery in their wall. Cysts can be seen in end-stage lung disease with honeycombing in IPF, collagen-vascular diseases with fibrosing alveolitis, Langerhans cell histiocytosis (LCH), lymphangioleiomyomatosis (LAM), lymphocytic interstitial pneumonia (LIP) with follicular bronchiolitis, and, rarely, in desquamative interstitial pneumonia (DIP).

The cysts in IPF characteristically are subpleural in location and multilayered, stacked or multi-tiered. In LCH, they are typically associated with nodules, have irregular, bizarre shapes, are diffusely or randomly distributed throughout the lung parenchyma, predominant in the upper and middle lung regions, and tend to spare the lung bases. In LAM, the cysts are round and are diffusely distributed throughout the entire lung. Tuberous sclerosis shows similar cysts but they can be accompanied by peripheral ground-glass or solid pulmonary nodules, three to eight mm in diameter due to micronodular pneumocyte hyperplasia (MNPH), resulting from proliferation of Type 2 pneumocytes. In immunocompromised patients, Pneumocystis jirovecii pneumonia can be associated with cysts that are upper lung predominant in up to 30 percent of cases. This is particularly common after aerosolized therapy or prophylaxis with Pentamidine which cannot reach the apices, rendering them more susceptible to Pneumocystis jirovecii pneumonia than the rest of the lungs.

Lung cysts are a characteristic finding in Birt-Hogg-Dubé syndrome which is the most common cause of familial spontaneous pneumothorax [28-30]. These basal, multiseptate, perivenous, "floppy," or paramediastinal cysts are associated with skin tags formed by fibrofolliculomas in hair follicles and renal tumors (eg, renal cell carcinoma). (See "Hereditary kidney cancer syndromes", section on 'Birt-Hogg-Dubé syndrome' and "Pneumothorax in adults: Epidemiology and etiology".)

Pneumatoceles are associated with blunt or penetrating trauma, barotrauma in ventilated patients with ARDS, with Staphylococcal pneumonia, or after kerosene inhalation. Pneumatoceles have a tendency to enlarge with mechanical ventilation, but can regress with resolution of the underlying disease. Occasionally, cavitating metastatic nodules can resolve after chemotherapy or immunotherapy, eg, tumor necrosis factor inhibitors, leaving behind residual thin-walled cysts. Scattered, thin-walled cysts can be seen in up to 25 percent of healthy, nonsmoking older individuals in the absence of classic emphysema [16,31].

HRCT DISEASE DISTRIBUTION — The zonal distribution of different lung diseases can be of help in arriving at a specific diagnosis.

●The upper (cranial) parts of the lung are typically involved in granulomatous diseases (eg, sarcoidosis and hypersensitivity pneumonitis), Langerhans cell histiocytosis, idiopathic pleuroparenchymal fibroelastosis and pneumoconioses, such as silicosis and coal workers' pneumoconiosis, but not asbestosis.

●The lower (basal) parts of the lung tend to be affected in fibrosing lung diseases, such as idiopathic pulmonary fibrosis, collagen-vascular diseases, nonspecific interstitial pneumonia (NSIP), asbestosis, fibrosing drug reactions, and benign age-related or smoking-related [32] pulmonary fibrosis.

●Preferential involvement of the central, axial lung parenchyma occurs in sarcoidosis, lung parenchymal lymphoma, Kaposi's sarcoma, and with centrifugal extension of lymphangitic tumor from hilar lymph nodes into the lung periphery. Hydrostatic pulmonary edema can display a perihilar, so-called butterfly or batwing configuration. Acute pulmonary hemorrhage can also have a central, perihilar distribution with typical subpleural sparing. E-cigarette or vaping use-associated lung injury shows central and midlung involvement with sparing of the outer periphery of the lung [33]. Postengraftment pulmonary consolidation in patients with hematopoietic stem cell transplantation has a central distribution. Radiation pneumonitis has a central perihilar distribution after mediastinal tumor radiation therapy [34].

●The periphery of the lung is more frequently affected in idiopathic pulmonary fibrosis, collagen-vascular diseases, asbestosis, drug reactions, eosinophilic lung disease, organizing pneumonia, desquamative interstitial pneumonia, rare cases of pseudoalveolar sarcoid, graft-versus-host disease, and unusual cases of mucinous adenocarcinoma (bronchioloalveolar cell carcinoma). In its early stages, COVID-19 pneumonia shows a predilection for the pulmonary periphery.

●The anterior (ventral) or posterior (dorsal) parts of the lungs can be involved in pulmonary edema. In most diseases, the anterior lung clears earlier than the dependent, basal lung due to the "bucket handle motion" of the anterior ribs during ventilation with larger excursions of the anterior lung. In diffuse alveolar damage, the dependent dorsal lung is initially consolidated and noncompliant, and the middle region of the lung shows primarily ground-glass changes that can revert with mechanical ventilation. The anterior or ventral aspects of the lung are least involved acutely and tend to be hyperventilated during mechanical ventilation. This ventral, disease-free lung has been called "baby lung" and is susceptible to barotrauma, volutrauma of mechanical ventilation and oxygen toxicity with subsequent delayed fibrosis of the anterior or ventral aspects of the lung in the recovery phase of diffuse alveolar damage [35].

●A predisposition for involvement of the posterosuperior regions of the lung is found in reactivation mycobacterial or fungal infections, as well as silicosis. A predilection for involvement of the posteroinferior parts of the lung is observed in aspiration pneumonia, hydrostatic pulmonary edema, and asbestosis.

●Diffuse involvement of the lung can be seen in lymphangioleiomyomatosis and in advanced stages of all of the above mentioned infiltrative lung diseases.

PULMONARY DISEASES — Many diseases can be well characterized by HRCT, as discussed in this section.

Emphysema — Emphysema formation follows a marked reduction in terminal and respiratory bronchioles with subsequent destruction of alveoli by neutrophils and macrophages. Four types of emphysema can be differentiated by HRCT with a high degree of sensitivity and specificity [32,36,37]:

●Centrilobular emphysema occurs preferentially in the upper lobes and produces holes in the center of the secondary pulmonary lobules (image 14 and image 15), frequently with a visible vessel in the center of the lucency. The secondary pulmonary lobules are not destroyed. Centrilobular emphysema can become confluent and eventually lead to advanced destructive emphysema which can mimic panlobular emphysema [38,39].

●Panlobular emphysema more commonly involves the lung bases, resulting in a generalized paucity of vascular structures; it also affects the entire secondary pulmonary lobule (image 16). Classic panlobular emphysema is infrequent and is the result of alpha-1 antitrypsin deficiency [40].

●Paraseptal (distal acinar) emphysema produces small, subpleural, and sub-fissural collections of gas located in the periphery of the secondary pulmonary lobule (image 17). It is considered a panlobular form of subpleural or subseptal destruction and represents a precursor of bullae (image 18 and image 19).

●Paracicatricial or pericicatricial (irregular) emphysema is found in the vicinity of scars and is frequently accompanied by lung parenchymal distortion.

●Combined pulmonary fibrosis and emphysema consists of apical-predominant emphysema accompanied by basal pulmonary fibrosis with concurrent pulmonary arterial hypertension and a more dismal long-term prognosis. This combination of findings has been identified in 8 percent of patients with emphysema [41,42].

The attenuation coefficient of emphysematous lung usually decreases to a value below minus 950 HU [27,41].

Bullous disease — HRCT is useful in the evaluation and treatment of patients with bullous disease (image 20). The number, location, and extent of bullae, the state of the remaining lung, and the effect of the dominant bulla on other thoracic structures can be assessed. Large bullae do not compress adjacent structures since they display the property of increased compliance. Rather, the normal lung retracts away from the large bullae as a result of the normal, preserved elastic recoil of the lung parenchyma. Solitary giant bullae that produce marked relaxation atelectasis in the neighboring parenchyma and are not associated with generalized emphysema respond best to surgical therapy. Bullous disease is a manifestation of paraseptal emphysema in most cases [43].

Airways diseases — HRCT is useful in assessing the caliber of the airways, as well as in detecting diseases of both large and small airways (eg, bronchiectasis and bronchiolitis) [32,44].

Airway caliber — The caliber of a bronchus is assessed by comparing it to the diameter of the adjacent pulmonary artery branch. The normal arterial to bronchial ratio is close to 1 in the midlung, decreases to 0.8 to 0.9 in the upper lobes, and increases to about 1.2 in the lower lobes. At high altitude, these ratios are lower due to a reduced diameter of the pulmonary artery branches caused by hypoxic vasoconstriction. In older individuals, these ratios are similarly lower due to mild dilation of the bronchi [16]. Small airways are defined as bronchioles devoid of cartilage and with a luminal diameter of 2 mm or less. Bronchial wall thickening is a manifestation of chronic obstructive pulmonary disease (COPD) in smokers and of asthma in non-smokers; it is diagnostic when the thickness of a main, lobar or segmental bronchial wall exceeds 1.2 to 1.4 mm or the bronchial wall thickness exceeds 20 percent of the internal bronchial luminal diameter [38,45].

Bronchiectasis — HRCT has replaced bronchography as the method of choice for diagnosing bronchiectasis (image 21A-G and image 22); it has a sensitivity of 97 percent when using bronchography as the gold standard [46]. HRCT is also useful in the evaluation of hemoptysis, which is frequently due to subclinical bronchiectasis and endobronchial tumors; HRCT can detect the bleeding source in nearly 50 percent of cases [47,48]. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

Minimum intensity projection is another effective way of postprocessing axial thin section and evaluating bronchiectases. The etiology of bronchiectases can be deduced from the cranio-caudal or axial-to-periphery distribution of involved airways:

●Bronchiectases with upper or mid-lung predominance are found in patients with cystic fibrosis, sarcoidosis, tuberculosis, allergic bronchopulmonary aspergillosis.

●Bronchiectases with anterior or ventral predominance are seen with atypical mycobacterial infection, as a sequela of acute respiratory distress syndrome.

●Bronchiectases with lower lung predominance are expected in chronic aspiration, pulmonary fibrosis, primary ciliary dyskinesia, common variable immunodeficiency (CVID), and alpha-1 antitrypsin deficiency.

●Bronchiectases with central predominance (in the fourth to sixth generation of bronchi) are found in tracheobronchomegaly Mounier-Kuhn syndrome, Williams-Campbell syndrome [49], and allergic bronchopulmonary aspergillosis.

●Focal bronchiectases are visible with endobronchial or peribronchial tumors and in Swyer-James-McLeod syndrome.

●Diffuse bronchiectases can be seen accompanying diffuse bronchiolitis obliterans [50]. Diffuse bronchiectases can be seen in CVID in tandem with granulomatous-lymphocytic interstitial lung disease, a necrotizing and lymphoproliferative disease process. It presents with widespread solid or ground-glass micronodules, smooth interlobular septal thickening with lower-lobe predominance, and accompanying enlarged hilar lymph nodes [51].

Bronchiectatic airways are easily seen as tubular structures that do not taper and can be seen within 1 cm of the pleura [52]. The dilated bronchi are usually 1.5 times wider in diameter than the accompanying pulmonary artery branch. This cross-sectional configuration resembles a signet ring and is therefore called the signet ring or Cabochon ring sign; it can help to differentiate a bronchiectatic cyst from other kinds of cysts. Larger cysts can mimic bullae, but their location in the central rather than the subpleural region and their segmental clustering are suggestive of bronchiectatic cysts (image 23 and image 24 and image 25 and image 26).

Airways remodeling also leads to thickening of the bronchial walls with luminal irregularities due to corrugation of cartilage and hypertrophy of mucus glands. Bronchial diverticulosis arises from focal depression, fusion, and dilation of bronchial gland ducts with herniation through muscle fibers. It can be seen in 12 percent of heavy smokers [32].

Bronchiolitis — HRCT contributes to the diagnosis of small airways disease (bronchiolitis) [25] (see "Overview of bronchiolar disorders in adults"). Several types of bronchiolitis can be identified [53,54]:

●Respiratory bronchiolitis affects most smokers but is seen only in 20 percent of smokers on HRCT. It results from inertial impaction of particles at the bifurcation of small airways. It affects preferentially the upper lobes and yields centrilobular ground-glass nodules. It is frequently associated with respiratory bronchiolitis interstitial lung disease. (See "Respiratory bronchiolitis-associated interstitial lung disease".)

●Bronchiolitis obliterans, also called constrictive bronchiolitis, is characterized by a pattern of mosaic attenuation with alternating oligemia and pseudo-ground glass. Normal parts of the lung are hyper-perfused and have increased attenuation, while abnormal lung regions are hypoperfused due to hypoxic vasoconstriction. Paired inspiratory and expiratory CT scans can define regions of lung involved with bronchiolitis by demonstrating unequal ventilation with gas trapping, leading to formation of a mosaic pattern. Some patients with constrictive bronchiolitis have mild associated bronchial dilation and bronchiectasis. Patients with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may display findings similar to constrictive bronchiolitis, associated with centrilobular nodules [55]. Patients with severe refractory asthma may also show gas trapping on expiratory CT scans similar to bronchiolitis obliterans [56,57].

●Cellular bronchiolitis with nodules and branching lines, or "tree-in-bud" pattern. The pathologic basis for "tree-in-bud" pattern is an active bronchiolitis with inflammatory cells in the walls of distal airways together with inflammatory exudates and mucus impacting the lumen of bronchioles. The "tree-in-bud" pattern corresponds to dilated and impacted bronchioles imaged parallel or perpendicular to the imaging plane of CT. In rare instances, "tree-in-bud" pattern can be seen due to vascular abnormalities like tumor embolization or intravascular talc and methylcellulose particles deposited in pulmonary arterioles of intravenous drug abusers. Tree-in-bud opacities have been described in unusual cases of plexogenic pulmonary arterial hypertension and pulmonary capillary hemangiomatosis.

Cellular bronchiolitis is a feature of infections, including bronchogenic/endobronchial spread of tuberculosis, respiratory syncytial virus, adenovirus, mycoplasma, and bronchiolo-invasive aspergillosis in immune compromised hosts. Aspiration, diffuse panbronchiolitis in Asian patients, asthma, postinflammatory bronchiectasis, and cystic fibrosis can also display this pattern. A similar pattern can be found in patients with hypersensitivity pneumonia leading to intense bronchiolar and peribronchiolar inflammation.

●Follicular bronchiolitis is defined as lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT). It is characterized by the presence of hyperplastic germinal centers along the bronchioles. It may represent a variant of lymphocytic interstitial pneumonia (LIP). This type of bronchiolitis is seen in tandem with immunodeficiencies, collagen-vascular disease, and hypersensitivity reaction. The CT manifestations include centrilobular nodules, larger peribronchial nodules, and associated ground-glass opacities [58]. In conjunction with LIP, follicular bronchiolitis can lead to the formation of random cysts.

Lymphangitic carcinomatosis — Pulmonary lymphangitic carcinomatosis is part of the spectrum of metastatic disease. Most cases result from dissemination of adenocarcinomas. Microhematogenous spread to the periphery of the lung, with subsequent retrograde, centripetal lymphatic extension toward the hilar region, is the responsible mechanism in approximately 75 percent of patients. The remaining cases are due to centrifugal extension from a hilar tumor or from an ipsilateral lung or breast carcinoma. In the latter settings, the lymphangitic spread is unilateral; in comparison, microhematogenous seeding is frequently bilateral.

HRCT can detect lymphangitic tumor in up to 50 percent of patients who are symptomatic but have normal appearing lungs on chest radiography. The imaging features of lymphangitic tumor are determined by the pattern of bronchovascular and lymphatic spread (image 27A-B and image 28 and image 29) [59]. The characteristic findings are thickening of the interlobular septa, with beading caused by perilymphatic nodules, polygon or polygonal arcade formation, and thickening of the central bronchovascular structures (so-called central dots). In spite of the extensive involvement, the lung parenchyma is not distorted. The absent distortion distinguishes lymphangitic spread from sarcoidosis, which can otherwise produce similar findings but usually with less conspicuous thickening of interlobular septa.

Sarcoidosis — Sarcoidosis affects both the lung parenchyma and lymphatic tissue with noncaseating granulomata. The classic presentation consists of enlargement of hilar and mediastinal lymph nodes with or without lung parenchymal involvement. In some patients, however, parenchymal disease occurs in the absence of obvious lymph node enlargement. Marked parenchymal distortion can occur in the late stages. HRCT can also detect pulmonary involvement in a subset of symptomatic patients who have a normal chest radiograph, thereby expediting or facilitating biopsy and diagnosis. Sarcoid-like granulomatosis with lymph node enlargement has been described as a complication of targeted cancer therapy with programmed death PD-1/PD-L1 inhibitors (checkpoint inhibitors) like nivolumab and pembrolizumab [60-62].

Characteristic features of sarcoidosis on HRCT include bilateral, symmetric hilar and mediastinal lymph node enlargement, thickening of bronchovascular bundles, bronchial wall thickening, bronchial narrowing, thickening and beading of interlobular septa, peribronchiolar and perilymphatic small unsharp nodules, ground-glass opacification; larger, parenchymal masses which consist of merged, confluent small nodules with individual separate nodules at the periphery of this conglomerate mass: this constellation of findings has been dubbed the galaxy sign [63]; consolidation (pseudoalveolar pattern), parenchymal bands, distortion of lung architecture, cysts, and traction bronchiectasis (image 30A-C and image 31 and image 32 and image 33) [64,65] are other frequently described findings in patients with sarcoidosis. Preferential patchy subpleural, upper lobe, and peribronchovascular involvement is present. (See "Clinical manifestations and diagnosis of sarcoidosis".)

Amyloidosis can present with a nodular pattern or with an alveolar septal form. The nodular form of pulmonary amyloidosis manifests with solitary amyloidomas or multiple macronodules that mimic granulomatous disease with punctate or coarse calcifications or mimic malignant pulmonary metastatic disease. Alveolar septal amyloidosis is less common than the nodular form. It is characterized by well-defined micronodules, 2 to 4 mm in diameter in tandem with reticular opacities, interlobular septal thickening, confluent consolidations with a basal and peripheral predominance. The nodular form can be asymptomatic or only mildly symptomatic and has a good prognosis whereas the alveolar septal form is symptomatic and progressive, likely leading to pulmonary hypertension and respiratory failure [66].

Idiopathic interstitial pneumonias — The idiopathic interstitial pneumonias (IIPs) are a subset of diffuse interstitial lung diseases of unknown cause, characterized by expansion of the interstitial compartment (ie, that portion of the lung parenchyma sandwiched between the epithelial and endothelial basement membranes) by an infiltrate of inflammatory cells. The inflammatory infiltrate is sometimes accompanied by fibrosis, either in the form of abnormal collagen deposition, collapse of alveoli, or proliferation of fibroblasts capable of collagen synthesis [67].

Seven types of idiopathic interstitial pneumonias have been described. They include usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF), nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis interstitial lung disease (RBILD), acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), and LIP. (See "Idiopathic interstitial pneumonias: Classification and pathology".)

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) has been added to the group of idiopathic interstitial pneumonias.

Radiologic evaluation of the IIPs may obviate the need for tissue diagnosis (particularly in some cases of UIP/IPF). More often, it narrows the differential diagnosis.

●Idiopathic pulmonary fibrosis – IPF (pathologically defined by the presence of UIP pattern) [68] is associated with characteristic radiographic changes [69-73]. The UIP pattern on HRCT is characterized by the presence of bibasal and peripheral, subpleural reticular opacities, often associated with traction bronchiectasis which is a marker for fibrosis. Membranes of collapsed alveoli as a result of scarring contribute to the linear and reticular opacities. Honeycombing is common and is critical for making a definitive diagnosis of IPF [74]. Honeycombing on HRCT is usually defined as subpleural, clustered, multilayered, stacked, or multi-tiered cystic air spaces with well-defined walls. The cystic spaces are typically 3 to 10 mm in diameter, but occasionally may be as large as 2.5 cm and may represent collapsed secondary pulmonary lobules around respiratory bronchioles (image 34A-B and image 35 and image 36) [75,76]. Honeycombing may represent simplification of the lung architecture with collapsed secondary pulmonary lobules and bronchiolectasis. Temporal and spatial heterogeneity with concurrent injury and repair, are pathologic characteristics of IPF. Diffuse pulmonary ossifications manifesting as dendriform or nodular calcific opacities have been detected in up to 28 percent of patients with UIP/IPF and in 8 percent of patients with other IIPs. These ossifications were characterized by at least 10 small calcific opacities, particularly in regions of fibrotic lung disease with areas of reticulations [77]. They have to be differentiated from small calcified granulomata seen primarily in fungal diseases like histoplasmosis or remote mycobacterial disease. Diffuse or focal calcifications can also be seen with metastatic calcifications in patients with renal failure and a high calcium phosphate product or with dystrophic calcifications after healed diffuse alveolar damage.

The presence of coexisting pleural abnormalities, micronodules, gas trapping, non-honeycomb cysts, extensive ground-glass opacities, consolidation, or a peribronchovascular-predominant distribution should lead to consideration of an alternative diagnosis [75]. End-stage hypersensitivity pneumonitis [78], nonspecific interstitial pneumonia, rheumatoid arthritis-interstitial lung disease (RA-ILD), Sjögren's disease [79], drug reactions and, rarely, sarcoidosis can also cause radiological findings similar to IPF [80]. Chronic cryptogenic organizing pneumonia can occasionally be mistaken for IPF; however, its radiologic features (peripheral abnormal regions of consolidation with air bronchograms or ground-glass opacities) and shorter time course are differentiating features [81].

The most recent consensus conference classifies the HRCT findings into (1) a UIP pattern with, peripheral, subpleural, basal-predominant reticular opacities, traction bronchiectases, and honeycombing; typical UIP pattern correlates with UIP pathology in 90 percent of cases, (2) probable UIP pattern where the above mentioned findings are present except for honeycombing; corresponds with UIP pathology in 80 percent of cases, (3) indeterminate for UIP where the basal, peripheral predominance of opacities is absent and ground-glass or peribronchovascular opacities are present, and (4) alternate diagnosis. The indeterminate and alternative categories can still correlate with UIP pathology in 50 percent of cases.

Fibrosis in connective tissue disease-associated interstitial lung disease can have the features of basal UIP with exuberant honeycomb cysts and a straight-edge sign, ie, horizontal demarcation of fibrosis from the upper lung, which can be normal or show anterior upper-lobe subpleural reticular changes and honeycombing [82].

Variant patterns of interstitial pulmonary fibrosis are described in systemic lupus erythematosus, like island-like fibrosis with sharp margins, anterior upper-lobe sign, exuberant fibrosis, straight-edge sign, heterogeneous lung destruction with geographic areas of cicatricial emphysema, and architectural distortion with cystic changes distinct from classic subpleural honeycombing [83,84].

In about 10 percent of patients with IPF, accelerated UIP occurs with sudden deterioration, diffuse alveolar damage, peripheral consolidation, and/or ground-glass opacification superimposed on the chronic UIP pattern with poor prognosis. These findings can be similar to de novo AIP, which is described below.

●Combined pulmonary fibrosis and emphysema – The combination of emphysema in the upper lobes and fibrosis in the lower lobes is increasingly recognized as a distinct clinical phenotype in smokers, particularly in men in their sixth and seventh decade, and is compatible with two simultaneous conditions [85]. Honeycombing, reticular opacities, and traction bronchiectases are the most common findings in the lower lungs, while the upper lungs exhibit paraseptal and centrilobular emphysema [86]. The pattern of fibrosis reflects either IPF or NSIP. The emphysematous foci may have thicker walls than typically expected in bullae [31]. The total lung volume is preserved without the typical hyperexpansion of severe emphysema. Patients typically exhibit marked reduction in the diffusing capacity for carbon monoxide (DLCO) with otherwise near-normal pulmonary function tests [3]. Pulmonary arterial hypertension and lung cancer are more common in this cohort of patients [85].

●Nonspecific interstitial pneumonia – NSIP can occur in either a cellular or a fibrotic form. HRCT features include ground-glass attenuation in a diffuse or patchy distribution, preferentially along bronchovascular bundles, with reticular opacities and traction bronchiectasis [87,88]. Honeycombing is only rarely noted. NSIP also displays pathologically temporal and spatial homogeneity, which distinguishes this entity from UIP [89]. Relative sparing of the lung immediately adjacent to the pleura in the dorsal regions of the lower lobes is characteristic and can be seen in up to 30 percent of affected patients [90]. The radiographic appearance of NSIP is discussed in greater detail separately [91]. (See "Causes, clinical manifestations, evaluation, and diagnosis of nonspecific interstitial pneumonia", section on 'Chest imaging studies'.)

●Respiratory bronchiolitis interstitial pneumonia – RB-ILD is a smoking-related disease characterized by small peribronchiolar nodules and ground-glass opacification related to the accumulation of dusky pigmented macrophages in the bronchioles and adjacent alveoli. It represents the most common form of bronchiolitis and has an upper lobe predominance. Paired inspiratory and expiratory CT scans can define regions of lung involved with bronchiolitis by demonstrating unequal ventilation with gas trapping. (See "Idiopathic interstitial pneumonias: Classification and pathology".)

●Desquamative interstitial pneumonia – DIP is diagnosed almost exclusively in smokers. It is likely that DIP and RBILD are highly related if not identical lesions, differing only in the severity, location, and extent of the abnormality (ie, RBILD = mild/early DIP) [92]. RBILD has upper lobe predilection and is less likely at the bases, whereas desquamative interstitial pneumonia has a basal predominance. HRCT shows homogeneous ground-glass opacities without the peripheral reticular opacities and honeycombing that are typical of UIP. Rather, DIP is characterized by more confluent ground-glass and consolidative opacification of the basal lung periphery.

●Acute interstitial pneumonia – AIP (previously called Hamman–Rich syndrome) is clinically unique among the IIPs because of its rapid progression. It is also described as idiopathic acute respiratory distress syndrome (ARDS). HRCT shows bilateral symmetric areas of ground-glass opacification and consolidation with traction bronchiectasis [93]. These findings are due to diffuse alveolar damage (DAD) with increased permeability edema and hyaline membrane formation. (See "Acute interstitial pneumonia (Hamman-Rich syndrome)".)

●Lymphocytic interstitial pneumonia – LIP is characterized by homogeneous infiltration of the interstitium with a monoclonal or polyclonal population of T lymphocytes and represents diffuse lymphoid hyperplasia of bronchial-associated lymphatic tissue. It can be seen in patients with Sjögren's disease but has become an AIDS-defining disease, particularly in children. It can progress to lymphoma of the lung parenchyma. On HRCT, pulmonary cysts, measuring up to 30 mm in diameter, occur in up to 70 percent of affected patients. The cysts are thin walled and predominantly located in the middle and lower lung zones with perivascular and subpleural distribution. These cysts are most likely associated with follicular bronchiolitis and are the result of gas-trapping and focal destruction of alveolar walls. Associated findings include bilateral ground-glass opacities, small centrilobular and subpleural nodules, thickening of the bronchovascular bundles, thickening of the interlobular septa, and mediastinal lymph node enlargement [94]. (See "Lymphoid interstitial pneumonia".)

●Organizing pneumonia – Organizing pneumonia, characterized pathologically by plugs of organizing fibroblastic tissue that originates in the alveolar ducts and extends into the bronchioles; it typically shows peribronchial and peripheral, subpleural areas of consolidation, ground-glass opacities, band-like opacities, interlobular septal thickening on HRCT, occasionally with traction bronchiectases and interspersed fibrotic, reticular changes with a perilobular pattern that forms poorly defined arcade-like or polygonal structures in subpleural location (image 37 and image 38 and image 39 and image 40 and image 41 and image 42 and image 43) [95]. Another suggestive finding is the presence of rings or crescents of consolidation surrounding ground-glass opacities, which have been called the reversed halo sign and the atoll sign [8,96]. (See "Cryptogenic organizing pneumonia".)

●Interstitial pneumonia with autoimmune features (IPAF) – These patients have an NSIP pattern, an organizing pneumonia pattern, a combined NSIP and organizing pneumonia pattern, or a LIP pattern in tandem with clinical, morphologic and laboratory, serologic findings suspicious for an underlying autoimmune disease but without overt findings of a classic connective tissue disease. Additional radiologic findings include pleural effusions and pleural thickening, pericardial effusions and pericardial thickening, bronchiolitis and bronchiectasis, pulmonary arterial hypertension, pulmonary veno-occlusive disease and pulmonary hypertension related to hypoxic vasoconstriction [97].

●Idiopathic pleuro-parenchymal fibroelastosis (IPPFE) – IPPFE results in apical-predominant fibrosis with extensive fibrosis of the visceral pleura and apical parenchymal loss of volume. It is observed in older men and occasionally after solid organ transplants. It can have a poor prognosis with a case-fatality rate of up to 50 percent in four months to two years.

Asbestosis — Asbestosis leads to predominantly basal and dorsal lung parenchymal fibrosis (image 44). Other characteristic findings include: peribronchiolar fibrosis that forms centrilobular nodules, intralobular and interlobular septal fibrosis that forms subpleural short lines, coarse parenchymal bands, and subpleural curvilinear bands that parallel the pleura and represent fibrotic bridging from one centrilobular region to the next [98]. Coarse honeycombing can be seen in advanced stages. Coexistent pleural plaques are frequently identified, particularly in patients with curvilinear subpleural lines. Some radiologists favor prone HRCT in patients with asbestosis to better display the fixed, nongravitational changes at the lung bases. (See "Asbestos-related pleuropulmonary disease".)

In larger studies, up to 30 percent of asbestos-exposed individuals demonstrate an abnormal HRCT in spite of a normal chest radiograph. Asbestosis is associated with more parenchymal bands or long scars than UIP/IPF [98].

Langerhans cell histiocytosis — Langerhans cell histiocytosis (LCH; eosinophilic granuloma, histiocytosis X) accounts for approximately 3 percent of all chronic infiltrative lung diseases. It presents in three forms:

●Pulmonary involvement only in 60 percent of patients. This isolated pulmonary form (PLCH) is seen primarily in adult smokers, who account for 90 percent of such cases.

●Pulmonary and skeletal structures are affected in 20 percent.

●Other systemic, visceral manifestations are seen in 20 percent.

On conventional radiographs, PLCH shows upper-lobe predominance, particularly in the initial stages. The first visible change includes small nodular opacities 2 to 5 mm in diameter with scattered rounded opacities or diffuse, miliary nodules. An intermediate reticular pattern becomes visible on chest radiograph in advanced disease.

HRCT has changed our understanding of the true imaging findings in this disorder [99]. Sharply defined or stellate centrilobular nodules are the initial finding on HRCT. In early stages, the nodules composed of Langerhans cells (antigen presenting cells) and eosinophils are centered on respiratory bronchioles and the adjacent interstitium. These nodules can cavitate and form a "cheerio pattern." Multiple thin-walled cysts of varying size and bizarre shape, are typically present diffusely throughout the upper and middle lung zones with relative sparing of the bases (image 45A-B). Some of these cysts can resemble emphysematous bullae; the differentiating features are the slightly thicker wall and their diffuse location, permeating the entire cross-section of the lung parenchyma rather than the peripheral, subpleural region of the lung. The cysts have bizarre, irregular shapes, which can appear in combination with nodules, some of them cavitating, in the intermediate stages of the disease. Their etiology is not clear, but they seem to result from cavitation of nodules or represent dilated airways, imaged in cross-section. They result from inflammation that destroys bronchiolar walls and dilates airways. In addition pericicatricial emphysema can contribute to cyst formation [100].

Patients with PLCH preserve their lung volumes throughout the course of the disease. This contrasts with most other advanced interstitial lung diseases, in which shrinking lung volumes are the rule. (See "Pulmonary Langerhans cell histiocytosis".)

Lymphangioleiomyomatosis — Pulmonary lymphangioleiomyomatosis (LAM) affects women of reproductive age. It results from a hamartomatous proliferation and agglomeration of smooth muscle cells in the lung, likely related to excessive production of vascular endothelial growth factor. (See "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis".)

The chest radiograph shows coarse reticular opacities, with or without pleural effusion and pneumothorax, as well as large lung volumes. HRCT demonstrates multiple cysts distributed diffusely throughout the lung (image 46A-B and image 47 and image 48) [101]. The cysts in LAM are rounded and can be similar to those seen in LCH, though bizarre cyst shapes are unlikely in LAM. The distribution of cysts is different in these disorders. The cysts involve all compartments of the lung in LAM, but show an upper lobe predominance in LCH.

Pulmonary alveolar proteinosis — Pulmonary alveolar proteinosis (PAP), also called pulmonary alveolar lipoproteinosis, is a rare disorder that is marked by alveolar filling with lipid-rich proteinaceous material accompanied by large, foamy macrophages and relatively few inflammatory cells. The median age at diagnosis is 39 years; most patients are male and around 70 percent have a history of smoking [102]. PAP has been described in severe combined immunodeficiency [103]. It is the result of disturbed clearance of surfactant from alveoli most likely due to lack of granulocyte-macrophage colony stimulating factor (GM-CSF). Auto-antibodies that target GM-CSF cause PAP in the majority of cases with subsequent dysfunction in alveolar macrophages and subsequent impaired catabolism and accumulation of surfactant lipids and proteins.

The predominant CT feature of PAP is ground-glass opacification with smoothly thickened interlobular septal and intralobular alveolar septal lines. This pattern is called "crazy paving" [21]. Lobular or geographic sparing are accompanying features. The differential diagnostic considerations include pulmonary edema, pneumonia, alveolar hemorrhage, and ARDS with diffuse alveolar damage [104]. (See "Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults".)

Severe acute respiratory syndrome coronavirus 2019 (SARS-COVID-19) — The pandemic of COVID-19 began in December 2019 in Wuhan, China and spread around the globe. The virus affects multiple organ systems, but the most prevalent and life-threatening manifestation is the atypical pneumonia it induces.

Four stages in the evolution of CT findings were described:

●In the early stage (zero to four days after symptom onset) ground-glass opacities were found, though some patients had initially normal findings [105]. This acute, exudative stage of pneumonia presents in the first three to four days with multifocal, subpleural, and basal-predominant rounded and large ground-glass opacities (image 49 and image 50).

●In stage two, typically five to eight days after symptom onset, findings transition to an early organizing pneumonia with crazy paving pattern (image 51).

●Stage three (the peak stage), which is typically 9 to 13 days after symptom onset, is characterized by multifocal or diffuse consolidation, which can evolve into acute fibrinous organizing pneumonia and diffuse alveolar damage (image 52).

●After 14 days, in the late stage, a gradual resolution of consolidation and ground-glass opacification occurs while parenchymal bands, architectural distortion, and traction bronchiectases ensue [105,106]. More than 50 percent of hospitalized patients will show residual ground-glass opacities, parenchymal bands, perilobular thickening, reticular opacities, traction bronchiectases, or mosaic attenuation. These findings may persist for months and may only slowly resolve over 6 to 12 months [107].

Pneumocystis pneumonia — Pneumocystis jirovecii pneumonia is one of the most common pulmonary infections in patients with AIDS. The chest radiograph is deceptively normal in about 10 percent of symptomatic patients, but subtle abnormalities can be seen on HRCT. The primary change is diffuse or patchy ground-glass opacification, occasionally forming a "crazy paving" pattern (image 53A-B) [21,108]. Consolidative changes, nodules, and thickening of interlobular septa are rarely seen. Patients treated with aerosolized pentamidine may have preferential Pneumocystis involvement of the upper lobes and often display cystic changes, due to lack of pentamidine penetration in the pulmonary apices (image 54). (See "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV".)

Hypersensitivity pneumonitis — Hypersensitivity pneumonitis (ie, extrinsic allergic alveolitis) represents a type 3 allergic reaction or immune complex disease. The disease can be classified into cluster one and cluster two hypersensitivity pneumonia: Cluster one displays a mixture of diffuse or patchy ground-glass opacification with lobular sparing, lobular gas-trapping (so-called head-cheese pattern or three-attenuations pattern) similar to a mosaic pattern, and may resemble nonspecific interstitial pneumonia or may display centrilobular poorly defined airspace nodules in 50 percent of cases similar to respiratory bronchiolitis. The airways component is likely due to an allergic, cellular bronchiolitis incited by a variety of allergens and haptens [54].

Cluster two hypersensitivity pneumonitis is characterized by linear and reticular opacities with relative basal sparing (image 55A-C and image 56 and image 57) [109,110]. Untreated patients can eventually develop frank honeycombing and coarse fibrosis with scarring, traction bronchiectases, and loss of volume primarily in the upper lobes. Patients with fibrotic hypersensitivity pneumonitis can develop a UIP pattern [54,78]. (See "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Clinical manifestations and diagnosis".)

HRCT OF INTERLOBULAR SEPTAL THICKENING — Normally, only scattered interlobular septa are visible on HRCT, particularly in the upper lobes, since their thickness is at the limit of spatial resolution and only rarely exceeds 0.1 mm. Thickening of interlobular septa may result from accumulation of interstitial liquid, cells, or collagen and can be simulated by alveolar, paraseptal, perilobular pathological changes. Interlobular septal thickening can be smooth, nodular, or irregular in contour [111].

Smooth interlobular septal thickening is seen in hydrostatic interstitial pulmonary edema, allergic pulmonary edema, eg, transfusion-associated lung injury [62], central lymphatic obstruction due to bronchogenic carcinoma, fibrosing mediastinitis or pulmonary veno-occlusive disease (in conjunction with ground-glass opacities, mosaic attenuation pleural effusions, and dilated main pulmonary artery with normal-sized or small pulmonary veins), and lymphangitic carcinomatosis. Rarely, it can be seen in pulmonary alveolar proteinosis and when combined with ground-glass opacities, it yields the "crazy paving" pattern [21].

Nodular interlobular septal thickening can be observed in patients with lymphangitic carcinomatosis, sarcoidosis, silicosis, lymphoma, diffuse alveolar septal amyloidosis, and Kaposi's sarcoma. Occasionally, nodular thickening has been described in miliary tuberculosis and histoplasmosis, where random, perivascular nodules predominate.

Irregular interlobular thickening is seen in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis, collagen vascular diseases, and asbestosis.

Calcific interlobular septal thickening can be a rare feature of alveolar microlithiasis [112]. This disease actually only simulates interlobular septal thickening due to the high concentration of calcospherites in close apposition to the perilobular region of secondary pulmonary lobules rather than actual calcification of the interstitium [113].

HRCT IN FOCAL LUNG DISEASE — HRCT can be helpful in focal lung diseases, such as granulomatosis with polyangiitis, conglomerate masses in sarcoidosis and pneumoconiosis with the so-called galaxy sign (a large mass or nodule formed by confluence of several nodules and surrounded by several smaller nodules), focal organizing pneumonia with the reversed halo sign and atoll sign [114], amiodarone-induced pneumonitis characterized by iodine deposition, rounded atelectasis, and cavitating malignancies (image 58A-E and image 59) [63]. It can facilitate morphologic characterization of lesions, since bronchiectasis, air bronchograms, cavitation, clustered nodules, and spiculation of edges can be detected with a high degree of certainty.

The relationship of a nodule to fissures, as well as precise localization to a segment or lobe, can be achieved. If a bronchus feeds into a focal abnormality, the yield of bronchoscopic biopsy will be higher: HRCT can guide the procedure and predict its success rate (image 60 and image 61).

EFFECTS OF NORMAL AGING — Progressive decrease in attenuation of the lungs is seen in healthy nonsmoking adults due to a progressive increase in alveolar diameter from 250 microns to 500 microns. A decrease of minus 50 HU has been registered between the ages of 20 and 70 years of age [16]. A physiologic increase in collagen with age may lead to subtle fibrosis with basal subpleural reticular opacities, identified in 60 percent of individuals beyond 75 years of age. This senile, age-related pulmonary fibrosis has been called by different designations, including presbyteric lung, geriatric interstitial lung disease, and mature interstitial lung disease (MATILD). It is related to a mild degree of interstitial fibrosis with traction bronchiectases and bronchiolectasis. Scattered thin-walled cysts in individuals older than 75 years of age with a random distribution have been described as well [31]. Gas or air trapping on expiratory scans becomes more common and can be seen in more than 60 percent of examined individuals. Mild senile bronchial dilation with a concurrent decrease in the arterial to bronchial ratio should not lead to the diagnosis of bronchiectases [16]. (See 'Airway caliber' above.)

EFFECTS OF SMOKING — Smoking plays an important role in the development of several interstitial and small airways diseases including respiratory bronchiolitis, desquamative interstitial pneumonia, pulmonary Langerhans cell histiocytosis, and probably in idiopathic interstitial fibrosis, since about 70 percent of patients with interstitial pulmonary fibrosis (IPF) are current or former smokers. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) occurs three times more frequently in smokers than in nonsmokers with rheumatoid arthritis. A centrilobular pattern is associated with respiratory bronchiolitis, which is characterized by accumulation of pigmented macrophages in the alveoli and alveolar ducts. These centrilobular nodules are precursors of smoker’s emphysema and can progress to centrilobular emphysema (ie, the nodules are replaced by centrilobular lucencies). Acute eosinophilic pneumonia in binge smokers and acute pulmonary hemorrhage with anti-glomerular basement membrane antibodies can be precipitated by smoking.

Asymptomatic smokers with normal lung function can display parenchymal nodules with low attenuation, ground-glass opacities, subpleural micronodules, subpleural reticular opacities, occasional honeycombing and traction bronchiectases, and nonemphysematous cysts. These findings occur in up to eight percent of the population of smokers [41,85]. The subpleural reticular opacities are similar to those seen in older individuals, but at an earlier age in smokers. Interstitial changes may mask the functional effect of concurrent emphysema with less overall hyperexpansion of the lungs. These interstitial findings in smokers may represent a mild form of nonspecific interstitial pneumonia, fibrosis subtype, and may indicate premature aging of the lungs [16,85,115]. Of note, smoking can be protective of hypersensitivity pneumonitis and sarcoidosis with an odds ratio for these diseases of 0.62. This protection may be the result of mild immunosuppression triggered by smoking.

Interstitial lung abnormalities (ILA) are detected as an incidental finding in more than 4 to 9 percent of smokers and 2 to 7 percent of nonsmokers on routine, non-contrast enhanced CT scans performed in older individuals without suspected interstitial lung disease. These findings have been identified in the COPDGene study and in the National Lung Cancer Screening Trial. ILAs have been defined as nondependent ground-glass opacities or diffuse centrilobular nodularity, reticular abnormalities, nonemphysematous cysts, honeycombing, and traction bronchiectasis. They are not regularly reported by radiologists when interpreting supine CT scans under the assumption that they are gravitational, dependent findings. Prone CT scans can determine the fixed nature of these abnormalities. ILAs are an emerging concept but are age-related or smoking-related and seen in patients with COPD. They can progress in more than 50 percent of identified individuals [116]. ILAs are associated with a decreased diffusion capacity for carbon monoxide and a decrease in total lung capacity likely associated with a greater risk of all-cause mortality, particularly due to respiratory diseases like pulmonary fibrosis and a higher likelihood of developing acute respiratory distress syndrome and diffuse alveolar damage [116,117].

Electronic cigarette or vaping product use — Electronic cigarettes can lead to complications. After vaping of tetrahydrocannabinol, nicotine, and possibly vitamin E acetate additives, patients can present with nondiagnostic respiratory (E-cigarette or vaping use associated lung injury [EVALI]), gastrointestinal, and constitutional symptoms.

Imaging patterns described in EVALI have a basal predominance, including consolidation and ground-glass opacification of the lung parenchyma with regions of subpleural and lobular sparing (image 62).

Chest CT findings in EVALI most commonly show a pattern of organizing pneumonia.

Characteristic findings show consolidation and ground-glass opacification, sparing the peripheral and central subpleural regions, sparing of the peribronchovascular interstitium, and intermixed lobular sparing. Subtle interlobular septal thickening, centrilobular ground-glass nodules, and occasional bulla formation with subsequent spontaneous pneumothorax can be identified.

Overall, most pulmonary findings associated with vaping usually improve with therapy [33].

Diagnosis, pathology, and treatment of EVALI are discussed separately. (See "E-cigarette or vaping product use-associated lung injury (EVALI)" and "Vaping and e-cigarettes".)

SUMMARY AND RECOMMENDATIONS

●High resolution CT (HRCT, also called thin-section CT scanning) provides more detail than either chest radiography or conventional CT scanning, with an overall sensitivity of 95 percent and a specificity approaching 100 percent. Compared with chest radiography, HRCT can more accurately assess the pattern and distribution of diffuse lung disease, which may be beneficial when trying to narrow the differential diagnosis or define a target for lung biopsy. (See 'Clinical application of HRCT' above.)

•HRCT patterns include linear and reticular opacities, nodular opacities, large confluent opacities (eg, ground-glass opacities, consolidation), and decreased parenchymal opacity (eg, emphysema, cystic lesions, mosaic attenuation, gas trapping). These patterns may be accompanied by parenchymal bands and architectural distortion. (See 'HRCT patterns' above.)

•Distributions of disease include apical versus basal, central versus peripheral, anterior versus posterior, and diffuse. (See 'HRCT disease distribution' above.)

●Major diseases that can be optimally characterized by HRCT include emphysema, bullous disease, airways diseases (eg, bronchiectasis, bronchiolitis), lymphangitic carcinomatosis, sarcoidosis, the idiopathic interstitial pneumonias, asbestosis, Langerhans cell histiocytosis, lymphangioleiomyomatosis, Pneumocystis pneumonia (PCP, now called Pneumocystis jirovecii pneumonia), hypersensitivity pneumonia, severe acute respiratory syndrome from COVID-19, and asymptomatic interstitial lung abnormalities. (See 'Pulmonary diseases' above.)