Evaluation of diffuse lung disease by conventional chest radiography

INTRODUCTION — The pulmonologist and radiologist commonly recognize a variety of abnormal patterns of diffuse parenchymal lung disease on the conventional chest radiograph. Identification of these patterns, along with recognition of other associated findings, can be extremely useful in guiding the development of a differential diagnosis [1]. The diagnostic approach to diffuse lung disease based on interpretation of the conventional chest radiograph will be discussed here, using examples to illustrate many of the radiographic features.

CRITIQUE OF PATTERN USE — The traditional approach to radiographic assessment of diffuse lung disease first involves determining whether the pulmonary parenchymal process is located within the interstitium or the alveolar spaces. However, although radiographic criteria for both types of processes have been established over the years, the correlation is relatively poor between the accuracy of the radiologic localization (to either the airspaces or the interstitium) and the actual pathologic findings. Specific issues include the following:

●Nodular patterns can be produced by either interstitial or alveolar disease.

●Interstitial pneumonias usually also involve the alveolar compartment.

●So-called alveolar disease regularly involves the interstitium as well. The paradigm of pure alveolar disease is pulmonary alveolar lipoproteinosis, yet high resolution computed tomographic (HRCT) scanning has shown that, even in this entity, the interlobular and intralobular septa are thickened, forming the “crazy paving” pattern on thin-section CT.

●Air bronchograms, the ultimate radiographic sign of air space disease, can be detected in a small percentage of cases of histologically pure or predominant interstitial lung disease, such as sarcoidosis, pulmonary lymphoma, and pulmonary calcinosis.

●Ground glass opacities are formed by either alveolar or interstitial disease.

Because of these limitations, a more descriptive approach has been promulgated by radiologists. This approach takes into account an analysis of predominant opacities, an analysis of lung volumes, distribution of disease, and the presence of associated findings as well as the acuity or chronicity of the disease process [2-4] (table 1).

CLASSIFICATION — An attempt to avoid the usage of histologic terminology was made by the International Labor Office (ILO) in graphically describing the radiographic findings of pneumoconioses. The ILO classification system uses standard chest radiographs, graphic rather than anatomic descriptors, and a semiquantitative scheme for profusion of opacities (based on a 12-point scale) [5]. This scheme has an acceptable interobserver variability.

●Small opacities are classified based upon shape (round, irregular, or a combination thereof) and size

●Round (ie, nodular) opacities are characterized as p (up to 1.5 mm) (image 1), q (1.5 to 3 mm) (image 2), and r (3 to 10 mm) (image 3)

●Irregular (ie, linear, reticular) opacities are labeled as s (up to 1.5 mm) (image 4), t (1.5 to 3 mm) (image 5), and u (3 to 10 mm)

●The profusion of these opacities is assessed, as well as their distribution in the upper, middle, or lower lung zones

In practical terms, the predominant small opacity is best identified on the frontal chest radiograph in areas of low profusion and on the lateral chest radiograph in the retrosternal clear space and over the cardiac silhouette.

This classification, or at least basic elements of it, can also be utilized for description of diffuse lung diseases outside the realm of the pneumoconioses.

Large opacities — The ILO classification also makes provision for describing large opacities (image 6 and image 7). The application of this principle to pulmonary consolidation avoids pseudo-histologic nomenclature that does not correspond to the actual findings or is misleading, eg, airspace disease, alveolar disease, or “infiltrate.” The terms parenchymal consolidation, parenchymal disease, or parenchymal opacification are more graphic and descriptive, allowing for creation of a differential diagnosis without implying a particular histology.

Large opacities can be described as:

●Diffuse homogeneous

●Multifocal patchy (image 8)

●Lobar without atelectasis

●Lobar with atelectasis

●Perihilar

●Peripheral (image 9 and image 10)

These six patterns cover the majority of consolidative lung parenchymal abnormalities. These terms should be used rather than the word "infiltrate," which often has an associated diagnostic connotation, ie, suggesting pneumonia [3].

BASIC PATTERNS — The main radiological patterns often used to describe diffuse lung disease are as follows [1,2]:

●Nodular (including micronodular and miliary)

●Reticular (fine or ground glass, medium or irregular, coarse or honeycomb) (image 11)

●Linear (interlobular septal or Kerley lines and intralobular septal lines)

●Combined reticular and nodular

●Destructive

●Alveolar

●Bronchial

●Vascular

Micronodular — Micronodules correspond to the p opacities of the International Labor Office (ILO) classification and have a diameter of less than 1.5 mm. They are seen only infrequently and are caused by a small number of diseases:

●Alveolar microlithiasis, a rare disorder characterized by the intraalveolar accumulation of lamellated calcospherites in the absence of abnormal systemic calcium homeostasis (image 12 and image 13)

●Intravenous talc injection (in drug abusers), with subsequent talc granulomatosis also called excipient lung disease.

●Embolization of Ethiodol (after bipedal lymphangiography)

●Early stages of pneumoconioses such as silicosis, coal worker's pneumoconiosis, inhalational talcosis (not to be confused with hematogenous talc granulomatosis), and beryllium disease

●Subacinar foci in air space disease, eg, early stages of pulmonary alveolar lipoproteinosis or Pneumocystis jirovecii pneumonia (see "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV")

●Rare cases of granulomatous disease like disseminated mycobacterial infection, disseminated fungal disease, or sarcoidosis

Nodular — The nodular pattern includes nodules up to 1 cm in diameter (image 14). Causes include:

●Infectious or inflammatory granulomata (eg, miliary tuberculosis, sarcoidosis, fungal diseases, hypersensitivity pneumonitis [extrinsic allergic alveolitis], Langerhans cell histiocytosis [previously eosinophilic granuloma], cytomegalovirus pneumonia, and, occasionally, influenza, parainfluenza, human metapneumovirus, measles, varicella, or respiratory syncytial virus pneumonia) (image 15) [6]

●Pneumoconioses (eg, silicosis, coal worker's pneumoconiosis, talcosis, and beryllium-induced disease) (image 16 and image 17 and image 18)

●Neoplasia (eg, disseminated primary adenocarcinoma of the lung, metastatic carcinoma, and lymphoma) (image 19)

●Pulmonary hemosiderosis

Nodular disease becomes visible through a summation effect unless the nodules are larger than 5 mm, their profusion is very low, or the nodules are displayed free of superimposition on HRCT (thin-section CT). Nodular disease can also appear as a combined reticular and nodular pattern on the chest radiograph, a variant of the so called moire effect.

Linear — Linear opacities are mostly due to thickened interlobular septa. Kerley, a British radiologist, first described these lines in coal worker's pneumoconiosis.

●Kerley A lines radiate from the hilum into the lung periphery preferentially towards the upper lobes. They represent thickening of the axial pulmonary interstitium. They appear frequently in acute left ventricular failure or in pulmonary edema due to altered capillary permeability (image 20 and image 21). These lines have a length of 2 to 4 cm.

●Kerley B lines result from thickening of the subpleural interstitium. They are about 1 cm in length, 1 mm in thickness, and have a predilection for the lower lung zones abutting a pleural surface. These lines are particularly well seen in chronic left ventricular failure, mitral valve disease, lymphangitic carcinomatosis, and asbestosis. Kerley B lines can be observed in viral pneumonia, particularly with Hantavirus, coronavirus, and measles pneumonia [6].

●Kerley C lines are due to thickening of the lung parenchymal interstitium and can yield a reticular rather than a linear pattern on chest radiography.

●Occasionally, the wall of subpleural emphysematous spaces due to paraseptal emphysema can form linear opacities that resemble Kerley B lines, but are longer and extend more cephalad. Infectious or respiratory bronchiolitis with associated interstitial lung disease (RBILD) can produce linear shadows that do not quite abut the pleura.

●Thickening of bronchial walls or bronchiectases can result in a linear pattern on chest radiographs, but with a more central, perihilar distribution also dubbed tram lines or tram tracks.

Reticular — A reticular pattern corresponds to the small irregular opacities in the ILO classification (image 4 and image 5). The differential diagnosis is based upon the acuteness or the chronicity of the process.

Acute diseases — Acute diseases which produce a reticular pattern include:

●Interstitial pulmonary edema due to left ventricular failure (so-called Kerley C lines)

●Acute viral, chlamydia, or mycoplasma pneumonia

●Acute pneumonia in collagen vascular disease, particularly systemic lupus erythematosus (image 22) (see "Pulmonary manifestations of systemic lupus erythematosus in adults")

●Acute allergic reactions, eg, transfusion reactions (image 20)

Chronic diseases — Chronic reticular changes are generally due to:

●Chronic interstitial pneumonias (primarily idiopathic pulmonary fibrosis [IPF]/usual interstitial pneumonia [UIP], but also nonspecific interstitial pneumonia in its fibrosing variant [fibrosing NSIP], desquamative interstitial pneumonia [DIP], lymphocytic interstitial pneumonia [LIP], and, occasionally, cryptogenic organizing pneumonia [COP]/bronchiolitis obliterans with organizing pneumonia [BOOP]) [7] (image 23 and image 24)

●Collagen vascular diseases (eg, scleroderma, rheumatoid lung) with UIP or NSIP histology (image 25 and image 26)

●Asbestosis

●Radiation pneumonitis

●End-stage hypersensitivity pneumonitis (ie, extrinsic allergic alveolitis)

●Drug reactions

●Lymphangitic spread of tumor (image 27 and image 28)

●End-stage granulomatous infections

●End-stage Langerhans cell histiocytosis (previously eosinophilic granuloma)

●Lymphangioleiomyomatosis

●Sarcoidosis (image 29)

●LIP

●Lymphoma – bronchovascular form

●Kaposi's sarcoma – bronchovascular form

The distribution of chronic reticular changes can also provide clues to the underlying diagnosis. These patterns include:

●Chronic interstitial pneumonias, asbestosis, drug reactions, and collagen vascular disease have a predilection for the periphery of the lung and are basal predominant. Sarcoid, lymphoma, and Kaposi's sarcoma tend to progress from the perihilar lung regions to the periphery. Early stages of Langerhans cell histiocytosis occur preferentially in the upper lung regions.

●Lymphangioleiomyomatosis, advanced Langerhans cell histiocytosis (previously eosinophilic granuloma), granulomatous infections, and lymphangitic spread of tumor have a diffuse distribution.

Reticular and linear changes can mimic combined reticulonodular pathology at the point of intersection of lines. This is called the moiré effect, defined as a visual perception that results from superimposition of a repetitive design and yields a pattern distinctive from its original components.

Honeycombing is a feature of endstage interstitial lung disease. It represents restructuring of the lung parenchyma, with simplification of the lung architecture and subsequent small cyst formation surrounded by fibrotic tissue. Accompanying bronchiolectasis is regularly present. The small subpleural spaces, which usually measure between 3 and 10 mm in diameter may connect with small airway and some collapse on expiratory imaging. Honeycombs are usually stacked and are not separated by intervening normal lung. Bronchiolectases which can mimic honeycombing are usually separated by interposed lung parenchyma. The expiratory collapse of some of these spaces distinguishes them from the subpleural spaces formed by paraseptal emphysema, which do not decrease in size with expiration. In addition, honeycombs have slightly thicker walls than emphysematous spaces. Honeycombing forms an array of multilayered, stacked spaces, while paraseptal emphysematous spaces are single-layered (ie, single-tiered) [8]. The differentiation of honeycombing, bronchiolectasis and paraseptal emphysema is best achieved with high resolution computed tomography.

Honeycombing is regularly seen in patients with:

●IPF/UIP

●Fibrotic non-specific interstitial pneumonia (NSIP)

●Langerhans cell histiocytosis (previously eosinophilic granuloma)

●Collagen vascular diseases, eg, rheumatoid ILD or scleroderma lung disease

●Healed necrotizing infections

●Endstage pneumoconiosis

●Endstage hypersensitivity pneumonitis (ie, extrinsic allergic alveolitis)

Destructive — Small lungs, diffuse consolidation, bronchiolectasis and honeycombing, bullae, cysts, coarse linear scarring, retraction of hilar structures cranially, and pulmonary hypertension with cor pulmonale are all part of the spectrum of destructive lung disease. This type of endstage lung disease can be found as a consequence of diffuse alveolar damage or as the final endpoint in interstitial pneumonias and granulomatous processes.

Alveolar — Radiologic features of alveolar or air space disease include:

●Airspace (ie, acinar) nodules, 0.6 to 1 cm in diameter (image 30 and image 31). These nodules do not represent an acinus in the strict anatomic sense, since they are encompassing peribronchiolar lung tissue.

●Ground-glass opacification in the early stages of the process (image 32).

●Coalescent opacities (image 33 and image 34 and image 35 and image 36).

●Consolidation that tends to follow lobar or segmental boundaries (image 37 and image 38 and image 39 and image 40).

●Consolidation with a bronchocentric distribution.

●Air bronchograms (image 37).

●Air alveolograms.

As noted above, these radiographic features do not guarantee the exclusive histologic presence of alveolar filling, but they are helpful in attempting to place a disease into a particular radiological category.

Bronchial — Diffuse bronchiectasis represents the classic example of a bronchial pattern. On conventional chest radiographs, linear opacities and lucencies are visible, conforming to the course of bronchi (image 41 and image 42 and image 43). In asthmatics and patients with chronic bronchitis, the wall of thickened bronchi can be seen en face as ring shadows with a wall thickness exceeding 1 mm or in tangent, forming so called tram lines. Mucoid impaction, seen in asthmatics or in patients with allergic bronchopulmonary aspergillosis, produces variable appearances, including abnormalities that are described as V-shaped, Y-shaped, toothpaste shadows, "cluster of grapes" opacities, or "finger in glove" opacities (image 44).

Cystic spaces are prevalent in saccular or cystic bronchiectasis, with occasional gas-liquid levels. The "dirty lungs" pattern seen in smokers with chronic bronchitis is likely due to peribronchial fibrosis and bronchial wall thickening, with accompanying mild cylindrical bronchiectasis and pulmonary hypertension. Bronchiectases have a central, perihilar predilection as they extend into the more peripheral lung [9].

Vascular — Several patterns of pulmonary blood flow can be distinguished on conventional chest radiographs [10]:

●Caudalisation is the normal flow pattern, with basal vessels being two to three times wider than apical vessels.

●Cephalization occurs with left ventricular failure (image 45), mitral valve stenosis (image 46), basal emphysema (image 47), or in recumbent patients. The upper lobe vessels are more dilated than the basal vessels.

●Equalization or balanced flow with hyperemia is seen in hyperkinetic circulation due to left-to-right shunts, hyperthyroidism (image 48), pregnancy, anemia, or after exercise. Equalization implies that the upper and lower lobe pulmonary vessels are similar in size with recruitment of the peripheral pulmonary vessels.

●Equalization or balanced flow with oligemia occurs in hypovolemia or right-to-left shunts (eg, tetralogy of Fallot).

●Centralization, which reflects dilation of central pulmonary arteries with a concurrently normal or diminished peripheral circulation, is seen in pulmonary hypertension (image 49 and image 50).

●Lateralization of flow to one lung over the other, ie, asymmetric perfusion, is seen with unilateral emphysema or unilateral obstruction of the pulmonary artery. Unilateral dilation of one central pulmonary artery with subtending oligemia, so called Fleischner sign, can indicate massive acute pulmonary embolism. If the right interlobar artery is abruptly cut off due to acute massive pulmonary embolism, it can form the “sausage sign” or Palla sign [11].

●Localization of flow or a mosaic pattern of perfusion is seen with patchy emphysema, chronic thromboembolic pulmonary arterial hypertension (CTEPH), bronchiolitis obliterans, or arteriovenous malformations (image 51A-B).

●Collateralization is seen with bronchial or other systemic arterial supply to the lungs, resulting in a lattice-like pattern of vessels. It is seen with severe tetralogy of Fallot or in proximal interruption of the pulmonary artery (image 52 and image 53).

LUNG VOLUMES — A frequent feature of chronic diffuse infiltrative lung disease is loss of lung volume. Occasionally, low lung volumes can represent the first manifestation of such a process.

However, some of the chronic diffuse infiltrative lung diseases are associated with normal or large lung volumes, often as a result of airflow obstruction or cystic changes that accompany the disease. Examples of chronic diffuse infiltrative lung disease that can be associated with normal or large lung volumes include:

●Langerhans cell histiocytosis (previously eosinophilic granuloma).

●Sarcoidosis (preserved lung volumes) (image 29).

●Lymphangioleiomyomatosis (hyperexpanded lungs).

●Cystic fibrosis (hyperexpanded lungs). It should be noted that cystic fibrosis is primarily a form of airways disease rather than infiltrative lung disease.

●Combined pulmonary fibrosis and emphysema (CPFE).

DISEASE DISTRIBUTION — The anatomic distribution of lung disease can greatly facilitate the approach to differential diagnosis.

Upper zone lung disease is found preferentially in:

●Tuberculosis

●Fungal disease

●Sarcoidosis (image 54)

●Pneumoconiosis (with the notable exception of asbestosis) (image 18)

●Langerhans cell histiocytosis (previously eosinophilic granuloma)

●Ankylosing spondylitis

●Cystic fibrosis (image 41)

●Cystic Pneumocystis jirovecii pneumonia

●Radiation fibrosis

●Endstage hypersensitivity pneumonitis (ie, extrinsic allergic alveolitis)

Basal lung disease is found in a different group of diseases:

●Bronchiectasis

●Aspiration pneumonia

●Desquamative interstitial pneumonia (DIP)

●Nonspecific interstitial pneumonia and fibrosis

●Idiopathic interstitial pneumonia (IPF)/usual interstitial pneumonia (UIP)

●Drug reactions

●Asbestosis

●Scleroderma

●Rheumatoid arthritis

●Vaping-induced lung disease (EVALI) (image 55) [12]

●COVID-19 pneumonia (image 56)

Central, perihilar lung disease occurs in chronic diseases including:

●Sarcoidosis

●Lymphoma

●Kaposi's sarcoma

●Bronchiectases

Central, perihilar lung disease also occurs acutely. As examples:

●Pulmonary edema (appears as perihilar, batwing, or butterfly pattern)

●Pulmonary hemorrhage

●Bacterial pneumonia

Peripheral lung disease is found in the following:

●Cryptogenic organizing pneumonia (COP; previously also called bronchiolitis obliterans organizing pneumonia [BOOP] as well as IPF/UIP and DIP)

●Asbestosis

●Coronavirus disease 2019 (COVID-19) pneumonia (image 56). Multifocal bilateral peripheral opacities with rounded morphology [13,14].

●Eosinophilic lung disease with the photographic negative of pulmonary edema pattern [15]

●Graft-versus-host disease

●Rare cases of pseudoalveolar sarcoidosis

●Rare cases of mucinous adenocarcinoma (bronchioloalveolar carcinoma)

These patterns of distribution are often quite useful, but any infiltrative lung process in advanced stages can involve both lungs diffusely [16].

ASSOCIATED FINDINGS — Associated radiographic findings related to the pleura, hilar regions, mediastinum, bronchi, cardiac structures, and pulmonary vasculature can provide diagnostic clues in the setting of diffuse parenchymal lung disease.

Pleural disease — Pleural disease occasionally accompanies diffuse lung disease and can help narrow the differential diagnosis.

●Pneumothorax is classically described in Langerhans cell histiocytosis (previously eosinophilic granuloma) of the lung, but it is also a relatively common complication of advanced interstitial lung disease of any etiology. The highest frequency of pneumothoraces is described in lymphangioleiomyomatosis. (See "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis".)

●Pleural effusions are seen in patients with metastatic malignancy (including lymphangitic carcinomatosis), collagen vascular diseases (especially systemic lupus erythematosus and rheumatoid arthritis), lymphangioleiomyomatosis with chylothorax (image 57), and, occasionally, as a complication of asbestos exposure. The entity of benign asbestos pleural effusion has no relationship to pleural plaques and occurs much earlier following exposure to the asbestos fibers.

●Pleural plaques are characteristically seen in longstanding asbestos exposure. They accompany the lung fibrosis of asbestosis in 30 to 50 percent of cases.

●Focal pleural thickening is, on occasion, seen as a sequela of amyloidosis involving the lungs.

Lymph node enlargement — Diffuse lung disease can be accompanied by enlarged intrathoracic lymph nodes, visible either on chest radiographs or on CT scans. The following diseases can be associated with diffuse pulmonary involvement and enlarged intrathoracic lymph nodes:

●Sarcoidosis (image 58)

●Lymphoma

●Tuberculosis

●Fungal diseases

●Pneumoconioses (especially silicosis, coal-worker’s pneumoconiosis, and beryllium disease)

●Bronchogenic carcinoma

●Metastatic tumors other than bronchogenic carcinoma

Cor pulmonale — Right ventricular hypertrophy and dilation subsequent to pulmonary hypertension is found in a high percentage of patients with end-stage diffuse lung disease. Obliteration of small peripheral pulmonary artery branches in combination with hypoxic vasoconstriction leads to pulmonary hypertension. This is classified as pulmonary hypertension, group 3 in the WHO classification of pulmonary hypertension [17]. (See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults".)

NORMAL RADIOGRAPHS IN SYMPTOMATIC PATIENTS — In about 10 percent of patients with biopsy-proven diffuse interstitial lung disease, the chest radiograph is initially normal, even though the patient is dyspneic, may have decreased exercise tolerance, or has a decreased diffusion capacity of carbon monoxide (DLCO). The best examples are:

●Desquamative interstitial pneumonia

●Sarcoidosis

●Hypersensitivity pneumonitis (ie, extrinsic allergic alveolitis)

●Pneumocystis pneumonia in HIV-infected patients

In such situations, high resolution CT scanning (thin-section CT) can add information and detect subtle ground-glass opacities not suspected on conventional radiographs. (See "High resolution computed tomography of the lungs" and "Approach to the adult with interstitial lung disease: Diagnostic testing".)

SUMMARY

●Pattern recognition - Pattern recognition on a conventional chest radiograph is an important first step in the evaluation of patients with diffuse lung disease, although a multitude of diseases can produce the same pattern. (See 'Critique of pattern use' above.)

●Classification - A graphic description is preferable to use of histologic terminology. (See 'Classification' above.)

●Basic patterns - The main radiological patterns used to describe diffuse lung disease are as follows: Nodular (including micronodular and miliary), reticular (fine or ground glass, medium or irregular, and coarse with or without honeycombing), linear (interlobular septal or Kerley lines), combined reticular and nodular, destructive, alveolar, bronchial, and vascular. (See 'Basic patterns' above.)

●Volume, distribution other findings - Additional aspects of lung disease that may be characterized by conventional chest radiography are the lung volumes, disease distribution, and associated findings. (See 'Lung volumes' above and 'Disease distribution' above and 'Associated findings' above.)

●Computed tomography - HRCT (thin-section CT) is a very helpful tool to supplement the information from conventional chest radiography. It can refine the differential diagnostic considerations and has improved sensitivity and specificity over conventional chest radiography, particularly in complex cases. In some situations, such as in idiopathic pulmonary fibrosis, HRCT can be definitive and obviate the need for a biopsy. However, in selected cases, biopsy may be needed for a definitive diagnosis, particularly if treatment depends on a specific diagnosis. (See "High resolution computed tomography of the lungs".)