Chap

ter

66Wallace T. Miller, Jr., MD, and

Drew A. Torigian, MD

InterstItIal lung DIsease

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1. What radiographic features distinguish interstitial diseases from air space diseases?Two primary characteristics radiographically distinguish interstitial from air space diseases. First, interstitial diseases displace little of the air within the lung, whereas air space diseases displace large amounts of air. Interstitial diseases change the overall opacity of the lung very little, whereas air space diseases in most cases dramatically increase the opacity (whiteness) of the lung on chest radiography. Second, interstitial diseases appear as increases in small nodules (generally <5 mm in diameter) or thin lines (<5 mm in width) (or both) within the lung, whereas air space diseases appear as indistinctly marginated patches of opacity. See Fig. 66-1 for the normal appearance of the lungs on frontal chest radiography.

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Figure 66-1. Normal frontal chest radiograph of the lungs. Note normal sharp delineation of branching vessels from the bilateral hila outward.

2. What factors influence the likelihood of one interstitial disease over another interstitial disease?

Three primary factors affect the likelihood of a given interstitial disease.

• The relative incidence of a given disease in the general population. Typical presentations of common diseases are most likely, followed by atypical presentations of common diseases, typical presentations of uncommon diseases, and atypical presentations of uncommon diseases.

• The clinical history of the patient.• The radiographic pattern of the interstitial disease.

3. What is the most common interstitial abnormality identified on chest radiography?

Interstitial pulmonary edema, usually caused by congestive heart failure, is the most common interstitial abnormality encountered in daily practice. A diagnosis of interstitial pulmonary edema should be considered in all cases of interstitial abnormality detected on a chest radiograph. In many cases, it might be advisable to diurese the patient and repeat the chest radiograph as the first diagnostic test.

4. Name the most common interstitial abnormalities other than interstitial pulmonary edema.Idiopathic pulmonary fibrosis and sarcoidosis are the most common chronic interstitial disorders in the United States and should be among the first diagnoses considered when encountering a chest radiograph with an interstitial abnormality.

5. What radiographic characteristics help determine the diagnosis of interstitial disorders?Interstitial abnormalities may be roughly subdivided into abnormalities that produce small round opacities (nodular interstitial diseases) and abnormalities that produce small networks of holes (reticular interstitial diseases). In this chapter, we describe one nodular pattern of interstitial disease and the three following reticular patterns of interstitial disease: the peripheral reticular pattern, the linear pattern, and the cystic pattern.

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Figure 66-2. Nodular pattern of interstitial lung disease.

6. What is the appearance of a nodular interstitial pattern on chest radiography?A normal chest radiograph typically shows many small nodular opacities that represent normal blood vessels end on. In most cases, these small nodules can be recognized as blood vessels because they overlap with a small line of similar diameter, which represents an adjacent branch of the pulmonary vascular tree. The nodular pattern of interstitial lung disease appears as increased numbers of small nodular opacities (<10 mm in diameter) that are randomly distributed throughout the lung parenchyma. These small nodules do not overlap with the normal vascular lines of the lung (Figs. 66-2 and 66-3).

7. What disorders cause nodular interstitial diseases?

Three broad groups of disorders cause nodular interstitial diseases:

• Granulomatous lung diseases• Nodular pneumoconioses• Small metastases

A B

Figure 66-3. A, Nodular pattern of interstitial lung disease caused by cryptococcal infection on frontal chest radiograph. Note the subtle, tiny nodular densities throughout lung fields bilaterally. B, Magnified view of chest radiograph. Note the subtle, tiny nodular densities throughout lung.

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8. Discuss granulomatous lung diseases that cause nodular interstitial disease.Sarcoidosis is the most common granulomatous interstitial lung disease to cause a micronodular pattern. This idiopathic disorder typically manifests in middle-aged individuals, especially African Americans. Miliary infections also cause a small nodular pattern and are typified by miliary tuberculosis, but also include miliary spread of histoplasmosis, cryptococcosis, coccidioidomycosis, and blastomycosis. These infections typically affect immunocompromised individuals, such as patients with human immunodeficiency virus (HIV) infection, patients who have undergone organ transplantation, or patients with a history of long-term steroid use. Many physicians are unaware that extrinsic allergic alveolitis or hypersensitivity pneumonitis not only causes a granulomatous interstitial fibrosis, but may also produce an interstitial nodular pattern of lung disease. Langerhans cell histiocytosis, also known as eosinophilic granuloma of the lung, may also produce a nodular pattern of interstitial lung disease. In most cases, pulmonary Langerhans cell histiocytosis is associated with a history of smoking, and typically manifests as persistent cough or dyspnea or both in young and middle-aged adults. In the early stages of disease, the patient develops small nodular areas of interstitial fibrosis. As the disorder progresses, cystic lesions may develop in association with an obstructive lung disease.

9. Discuss pneumoconioses and tumors that lead to nodular interstitial lung disease.Pneumoconioses that may produce a micronodular interstitial pattern are silicosis, coal workers’ pneumoconiosis, talcosis, and berylliosis. Pneumoconioses are diffuse interstitial lung diseases caused by inorganic dusts, most often related to occupational exposures. Mining, sandblasting, gravestone engraving, and pottery are some occupations in which workers may be exposed to silica dust with resultant silicosis; as identified in the name, coal workers’ pneumoconiosis is seen in coal miners. Berylliosis is an uncommon chronic pneumoconiosis that may be encountered in individuals who mine beryllium, who manufacture beryllium ceramics, or who previously manufactured beryllium lighting (these types of lights are no longer manufactured because of the high risk of acute and chronic berylliosis). Talcosis may occur as a result of the mining of talc or excessive inhalation of talcum powder and in intravenous drug abusers. Thyroid carcinoma is the prototypic tumor that produces thousands of tiny micronodular metastases and may appear as a nodular interstitial lung disease. Breast cancer may also produce this pattern of metastasis; other primary tumors rarely produce a micronodular pattern of lung metastasis.

10. What is the chest radiographic staging system for sarcoidosis, and what is the clinical significance?Table 66-1 summarizes the staging system for sarcoidosis. The higher the stage of sarcoidosis, the greater the likelihood that the patient will experience chronic respiratory deficits.

Table 66-1. Chest Radiographic Staging System for Sarcoidosis

STAGE RADIOGRAPHIC APPEARANCE

0 Chest radiograph appears normal

I Chest radiographic evidence of hilar or mediastinal lymphadenopathy without evidence of interstitial disease

II Chest radiographic evidence of hilar or mediastinal lymphadenopathy and evidence of interstitial lung disease

III Chest radiographic evidence of interstitial disease without evidence of hilar or mediastinal lymphadenopathy

IVChest radiographic evidence of interstitial fibrosis with distortion of

pulmonary structures, such as blood vessels, without evidence of hilar or mediastinal lymphadenopathy

11. Give some examples of hypersensitivity pneumonitis (extrinsic allergic alveolitis).Farmer’s lung is the prototypic example of a hypersensitivity pneumonitis. There are a wide variety of other hypersensitivity pneumonitides; some of the many other causes are listed in Table 66-2. These disorders represent an allergic lung reaction to various organic dusts that can initially manifest as capillary leak pulmonary edema, but chronically result in granulomatous interstitial fibrosis. In most cases, the offending antigens are microorganisms that grow within decaying vegetable matter. Antigens from these organisms are delivered to the lung via inhalation of dust or aerosolized contaminated water. Notable exceptions to this general concept are bird-related hypersensitivity pneumonitides. In bird fancier’s lung, hypersensitivity occurs against bird-related antigens, such as those found in bird feathers.

12. Why do intravenous drug abusers get talcosis?Not all intravenous drug abusers get talcosis. The process that can result in talcosis is the intravenous injection of oral medications. These medications are ground into a fine powder, suspended in fluid, and injected intravenously. Pills contain fillers, including talc and methylcellulose, which are inorganic substances that embolize to the lung

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Table 66-2. Causes of Hypersensitivity Pneumonitis

EXPOSURES CAUSES

Occupational Organic dust

Farmer’s lung Hay

Baker’s lung Flour

Sugar cane worker’s lung Sugar cane dust

Cotton worker’s lung Cotton dust

Mushroom worker’s lung Mushrooms

Hobbies

Bird fancier’s lung Bird feathers

Other exposures

Down pillows and comforters Bird feathers

Hot tubs Aerosolized water

Humidifiers Aerosolized water

microvasculature and result in a foreign body giant cell granulomatous reaction, which may appear as small nodules on chest radiography.

13. What radiographic feature of nodular pneumoconioses is most strongly associated with respiratory deficits?Progressive massive fibrosis (PMF), also know as conglomerate masses, is the radiographic feature most strongly associated with respiratory deficits. In PMF, the small nodular areas of fibrosis associated with nodular pneumoconioses progressively coalesce into large (>3 cm) fibrotic masses. These masses are typically found in the upper lung zones and result in fibrotic distortion of the surrounding lung parenchyma. All of the nodular pneumoconioses can cause PMF, but it is most strongly associated with silicosis. Many patients with simple silicosis (nodular interstitial disease without PMF) are clinically asymptomatic. Nearly all patients with complicated silicosis (nodular interstitial disease with PMF) have dyspnea, however. The causes of the nodular interstitial pattern are reviewed in Table 66-3.

Table 66-3. Causes of Nodular Interstitial Lung Disease Pattern

CATEGORY DISEASES

Granulomatous diseases Sarcoidosis

Miliary infections

Tuberculosis

Histoplasmosis

Coccidioidomycosis

Cryptococcosis

Blastomycosis

Hypersensitivity pneumonitis

LCH (eosinophilic granuloma)

Nodular pneumoconiosis Silicosis

Coal workers’ pneumoconiosis

Berylliosis

Talcosis

Metastasis Thyroid carcinoma

Other malignancies

LCH, Langerhans cell histiocytosis.

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Figure 66-4. Peripheral reticular pattern of interstitial lung disease.

A

Figure 66-5. A, Peripheral reticular pattern of interstitial lung disease radiograph. Note peripheral and basilar distribution. B, Magnified view ofopacities in peripheral and basilar distribution of the lungs forming small

14. What are the radiographic characteristics of the peripheral reticular pattern?

The peripheral reticular pattern has two distinguishing features:

• Small size of the holes (typically <5 mm) seen within a network of fine crisscrossing linear opacities

• Peripheral and basilar distribution of the network

The network typically is seen filling the costophrenic angles on frontal and lateral chest radiographs (Figs. 66-4 and 66-5).

15. Which diseases cause the peripheral reticular pattern?

Although various disorders may occasionally result in the peripheral reticular pattern, most cases are caused by idiopathic pulmonary fibrosis (IPF), a connective tissue disorder, or asbestosis.

16. What demographic features can help distinguish the cause of the peripheral reticular pattern?Asbestosis and IPF are disorders of elderly patients, usually individuals older than 50, whereas connective tissue disorders tend to affect younger individuals, often in their 30s and 40s. Patients must have had an extensive exposure to asbestos dust to acquire asbestosis. Nearly all patients with asbestosis have an occupational exposure to asbestos, such as from mining, roofing, car brake shoe repair, shipyard work, or boiler making. Asbestosis is almost exclusively seen in men because few women have sufficient asbestos dust exposure to acquire the disease. Connective tissue disorders are more commonly encountered in women, and more patients with connective tissue–related interstitial disease are women.

B

secondary to idiopathic pulmonary fibrosis on frontal chest chest radiograph. Note the network of fine crisscrossing linear holes between opacities.

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17. Which connective tissue disorders can result in interstitial disease?Scleroderma, or progressive systemic sclerosis, has the highest incidence of interstitial fibrosis among all connective tissue disorders. Rheumatoid arthritis has the highest prevalence of interstitial disease because it is one of the most common connective tissue disorders and may occasionally cause interstitial fibrosis. Dermatomyositis/polymyositis may also result in interstitial fibrosis. By virtue of its potential to overlap with progressive systemic sclerosis, rheumatoid arthritis, or dermatomyositis/polymyositis, mixed connective tissue disorder may also cause interstitial fibrosis. Systemic lupus erythematosus is one of the most prevalent connective tissue disorders, but only rarely produces clinically significant interstitial fibrosis. Although pathologic and radiologic studies may show mild abnormalities, it is quite rare for patients with systemic lupus erythematosus to have respiratory symptoms related to interstitial fibrosis. When these disorders cause interstitial fibrosis, they produce a peripheral reticular interstitial pattern on chest radiography.

18. Are there any imaging features that can help distinguish the cause of the peripheral reticular pattern?In most cases, there are no imaging features that help distinguish the different causes of the peripheral reticular pattern. Occasionally, extrapulmonary findings help, however, in the differential diagnosis of the peripheral reticular pattern. Approximately two thirds of patients with asbestosis also have asbestos-related pleural plaques. Patients with progressive systemic sclerosis may have a radiographically identifiable dilated esophagus as a result of CREST syndrome; CREST stands for calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Patients with rheumatoid arthritis may have erosions of the distal clavicles as a result of acromioclavicular arthritis. Causes of the peripheral reticular pattern of interstitial lung disease are reviewed in Table 66-4.

Table 66-4. Causes of Peripheral Reticular Interstitial Lung Disease Pattern

Idiopathic pulmonary fibrosis

Connective tissue disorders

Scleroderma, or progressive systemic sclerosis

Rheumatoid arthritis

Polymyositis/dermatomyositis

Mixed connective tissue disorder

Systemic lupus erythematosus

Asbestosis

Figure 66-6. Linear pattern of interstitial lung disease.

19. Describe the imaging characteristics of the linear pattern on chest radiography.The lines visible on a normal chest radiograph represent the branching pulmonary arteries and veins. These begin centrally and radiate from the hilum toward the periphery of the lung. The linear pattern appears as increased numbers of lines radiating from the central hila bilaterally. In addition, the linear pattern may produce Kerley B lines. These are thin horizontal lines 1 to 2 cm long, extending from the lateral chest wall toward the central lung (Figs. 66-6 and 66-7). The most common cause of the linear pattern is congestive heart failure, and to the degree that an interstitial abnormality resembles congestive heart failure, it is more likely to represent the linear pattern of interstitial disease. Novice radiologists should take care not to overdiagnose the linear interstitial pattern. There is a wide variation in the normal

appearance of chest radiographs. If one is unsure of whether there is an interstitial abnormality present on a chest radiograph, it is usually best to assume that the examination is normal.

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A B

Figure 66-7. A, Linear pattern of interstitial lung disease caused by congestive heart failure on frontal chest radiograph. Note symmetrically increased number of lines radiating from the bilateral hila. B, Central linear pattern of interstitial lung disease caused by congestive heart failure on magnified view of chest radiograph. Note the symmetrically increased number of lines radiating from the bilateral hila.

20. What disorders cause the linear pattern of interstitial disease?Causes of the linear interstitial pattern include:

• Interstitial pulmonary edema• Lymphangitic carcinomatosis• Sarcoidosis• Diffuse pneumonia

Congestive heart failure and other causes of interstitial pulmonary edema are the most common causes of the linear pattern. In nearly all cases, the presence of a linear interstitial pattern should be assumed to represent interstitial pulmonary edema. Lymphangitic carcinomatosis is the most common chronic cause for the linear pattern. This is a form of hematogenous metastasis that grows along the interstitial framework of the lung, rather than growing concentrically as nodules. Breast and lung cancers are the malignancies most likely to cause a pattern of lymphangitic metastasis. Gastric, pancreatic, and ovarian carcinomas are other causes of lymphangitic carcinomatosis. Sarcoidosis typically causes peribronchial granulomas, which may also result in interstitial lung disease with a pattern of lines radiating from the hilum of the lung, producing a linear pattern. Very rarely, some diffuse pneumonias such as Mycoplasma pneumoniae, Pneumocystis carinii (jiroveci) pneumonia, and viral pneumonia appear as a linear interstitial pattern.

21. Are there any imaging clues that may help to distinguish the cause of the linear interstitial pattern?In most cases, no imaging clues help to distinguish the cause of the linear pattern of interstitial disease. One notable exception is the recognition of a markedly asymmetric linear pattern, in which one lung is considerably more affected than the other. This imaging finding is virtually always associated with lymphangitic carcinomatosis.

22. What are the imaging characteristics of the cystic pattern of interstitial lung disease?This pattern is characterized by a group of curved lines that produce a network of fine ring shadows in the more central lung. Although a reticular pattern, the cystic pattern is quite distinct from the peripheral reticular pattern. In the cystic pattern, the holes are, on average, approximately 10 mm in diameter, which are much larger than the holes seen in the peripheral reticular pattern. The rings of the cystic pattern are distributed in the more central lung, whereas the peripheral reticular pattern characteristically affects the subpleural and basilar lung (Figs. 66-8 and 66-9).

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Figure 66-8. Cystic pattern of interstitial lung disease.

23. What disorders produce the cystic interstitial pattern?The cystic interstitial pattern is the least common of the interstitial patterns on chest radiography, and the most common cause of the cystic pattern is not interstitial lung disease, but emphysema. Emphysema usually appears as a decrease in the number and conspicuity of the normal lines seen on chest radiography. It has been recognized for many years, however, that emphysema occasionally appears as an increase in the number and conspicuity of interstitial lines. When emphysema does this, it appears in the cystic interstitial pattern. Diffuse bronchiectasis may also appear as many ring shadows distributed throughout the lung parenchyma. Two rare disorders that may also cause this pattern are Langerhans cell histiocytosis (which was previously discussed along with the nodular pattern) and lymphangioleiomyomatosis. Lymphangioleiomyomatosis is a rare hormonally

mediated disorder of young and middle-aged women. Proliferation of interstitial smooth muscle results in air trapping and production of small uniform cystic spaces in the lung. Table 66-5 lists the causes of the cystic interstitial lung disease pattern.

A B C

Figure 66-9. A, Cystic pattern of interstitial lung disease caused by eosinophilic granuloma on frontal chest radiograph. Note the network of fine ring shadows in the more central lung and the larger holes between opacities (compared with the smaller holes in peripheral reticular pattern). B, Magnified view of chest radiograph. Note the network of fine ring shadows in the more central lung and the larger holes between opacities (compared with the smaller holes in peripheral reticular pattern). C, Cystic pattern of interstitial lung disease caused by eosinophilic granuloma on CT. Note the multiple cysts of variable size throughout the lungs.

Table 66-5. Causes of Cystic Interstitial Lung Disease Pattern

Emphysema

Langerhans cell histiocytosis (eosinophilic granuloma)

Lymphangioleiomyomatosis

Diffuse bronchiectasis

Cystic fibrosis

Dysmotile cilia syndrome

Allergic bronchopulmonary aspergillosis

Immunodeficiency states

Common variable immunodeficiency

Hyper-IgE syndrome

Other

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Key Points: Interstitial Lung Disease

1. Interstitial pulmonary edema, usually caused by congestive heart failure, is the most common interstitial abnormality encountered in daily practice.

2. The nodular pattern of interstitial lung disease appears as increased numbers of nodular opacities (<10 mm) that are randomly distributed throughout the lung parenchyma. The three broad groups of disorders that cause nodular interstitial disease are granulomatous lung diseases, nodular pneumoconioses, and small metastases.

3. The two distinguishing features of the peripheral reticular pattern of interstitial lung disease are the small size of the holes (typically <5 mm) seen within a network of fine crisscrossing linear opacities and a peripheral and basilar distribution of this network. Most cases are caused by IPF, a connective tissue disorder, or asbestosis.

4. The linear pattern of interstitial lung disease appears as increased numbers of lines radiating from the hila centrally. This pattern also may produce peripheral Kerley B lines. The most common cause of this pattern is congestive heart failure, although lymphangitic carcinomatosis is the most common chronic cause of this pattern.

5. The cystic pattern is characterized by a group of curved lines that produce a network of fine ring shadows in the more central lung with larger holes than are seen in the peripheral reticular pattern. The most common cause of this pattern is emphysema.

24. What disorders cause diffuse bronchiectasis?Although various disorders may result in bronchiectasis, only a few diseases cause widespread bronchiectasis that involves most of the lung parenchyma. The most common of these is cystic fibrosis. Other diseases include dysmotile cilia syndrome; allergic bronchopulmonary aspergillosis; and various immunodeficiency states, such as common variable immunodeficiency syndrome, natural killer cell deficiency, and hyper-IgE syndrome.

25. Are there any imaging features that help to distinguish the cause of the cystic pattern?In many cases, the disorders that cause the cystic pattern produce radiographically indistinguishable disease. One notable exception is diffuse bronchiectasis. The cystic spaces caused by bronchiectasis typically produce thick-walled, distinct ring shadows, whereas the other disorders often cause very faint rings (see Table 66-5 for causes of the cystic interstitial pattern).

26. When is computed tomography (CT) scanning indicated for the evaluation of interstitial lung disease?CT is more sensitive and more specific than chest radiography for interstitial abnormalities. In many advanced cases with obvious chest radiographic findings, no further imaging is necessary. Patients with apparently normal or minimally abnormal chest radiographs in whom there is a clinical suspicion of interstitial lung disease should receive a thin-section chest CT scan to evaluate better for the presence of interstitial lung disease. Patients with chest radiographs that are nonspecific may benefit from a CT study, which in many cases allows the clinician to narrow the differential diagnosis. Lastly, CT provides improved characterization of the extent of disease. In cases in which therapeutic decisions are based on imaging evidence of progression, stability, or regression of disease, CT scanning is indicated.

27. What type of CT scan is indicated for the evaluation of interstitial lung disease?CT scanning has inherently less spatial resolution than standard chest radiography. Because interstitial diseases are typified by very fine spatial abnormalities, it is necessary to maximize the spatial resolution of CT images. The spatial resolution is done by minimizing the collimation of the CT scanner. Collimation, at most, should be 1.5 mm. Many multislice spiral scanners obtain images at this resolution in nearly all studies, although older single-slice spiral and nonspiral scanners require special imaging protocols to minimize the slice collimation. These imaging protocols are often called high-resolution scans because of the improved spatial resolution that is characteristic of the studies.

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324–338.[3] N. Muller, R. Fraser, N. Colman, P.D. Pare, Radiologic Diagnosis of Diseases of the Chest, Saunders, Philadelphia, 2001.[4] W.R. Webb, N.L. Muller, D. Naidich, High-Resolution CT of the Lung, third ed., Lippincott-Raven, New York, 2001.