Upper lung refers to the upper one third of the lung, which includes the majority of the upper lobes and the uppermost portion of the superior segments of the lower lobes. In the normal upright lung, blood flow and ventilation predominate in the lung base; in many lung disorders, however, the greatest degree of abnormality occurs in the upper lung. Alterations in
ventilation–perfusion, lymphatic flow, metabolism, and mechanics are proposed as pathogenic factors in upper lung localization of lung disease (1). Two mnemonics, "SHRIMP" and "CASSET," can be used to recall common and uncommon disorders occurring in the upper lungs (Table 10-1). Because it may be difficult to appreciate a predominantly upper lung distribution of disease on chest radiography, it is useful to consider the differential diagnoses given in Table 10-1, even if the disease appears diffuse, any time the upper lungs are as affected as much or more than the middle and lower lungs.

Sarcoidosis is a common systemic disease of unknown etiology characterized by widespread development of noncaseating granulomas. These granulomas are nonspecific and resemble those in many other granulomatous processes, except for tuberculosis, a disease in which caseous necrosis of granulomas is usually seen. Sarcoidosis is ten times more common in African-Americans than in Caucasians (2). Most patients who present with sarcoidosis are between the ages of 20 and 40, but the disease occurs as early as 1 year and as late as 80 years of age (3). The disease is two to three times more common in African-American women than in African-American men (3). The lung is the most commonly involved organ in patients with sarcoidosis and accounts for most of the morbidity and mortality, with an overall mortality rate between 2.2% and 7.6% (3).

Sarcoidosis can be classified according to its appearance on the chest radiograph (Table 10-2) (4). Patients commonly, but not necessarily, progress through each class, and the class at presentation can, but does not always, correlate with prognosis (5). Forty-five percent to 65% of patients are class I at the time of presentation. Lymphadenopathy is the most common intrathoracic manifestation of sarcoidosis and occurs in 75% to 80% of patients at some point in their illness (6). The classic pattern of lymphadenopathy is bilateral hilar and right paratracheal nodal enlargement, the so-called Garland triad or 1-2-3 sign (Figs. 10-1 and 10-2), although any mediastinal nodes can be and frequently are involved. The hilar lymph nodes are usually symmetric in appearance and can be massively enlarged ("potato nodes") but are usually clear of the cardiac borders, a feature that helps distinguish sarcoidosis from lymphomatous lymphadenopathy, as the latter usually abuts the cardiac margins. Of patients with class I disease at initial examination, about 60% go on to complete resolution (7), with parenchymal disease occurring in the remaining patients. Nodal calcification is seen in up to 20% of cases (8), and in some of these cases (approximately 5%), the calcification is of a peripheral "eggshell" pattern (Figs. 10-3 and 10-4). Eggshell calcification is largely limited to sarcoidosis and silicosis, but it can be seen in other disorders (Table 10-3) (9).

Parenchymal disease is seen on chest radiography at the time of presentation in approximately half of patients with sarcoidosis. Radiographic patterns of parenchymal disease include reticulonodular opacities, ill-defined opacities that have an appearance of alveolar filling, large nodules, and lung fibrosis. Reticulonodular opacities are the most common pattern, seen in 75% to 90% of patients with parenchymal disease; the opacities are usually bilaterally symmetric with a distribution predominantly in the middle and upper lungs (10) (Fig. 10-5). In 10% to 20% of patients, opacities with airspace features develop, which can be ill defined or focal, nodular, and well defined. The term alveolar sarcoid refers to this pattern, although the "airspace" disease represents an interstitial process that compresses and obliterates alveoli. Alveolar sarcoid generally consists of bilateral, multifocal, poorly defined opacities showing a predilection for the peripheral lungs (11) (Fig. 10-6). The peripheral distribution is particularly well seen with computed tomography (CT).

Sarcoid granulomas may resolve completely or heal by fibrosis. Pulmonary fibrosis occurs in approximately 20% of patients with sarcoidosis, and the radiologic features are considered by some authors to be almost pathognomonic. The findings consist of permanent, coarse, linear opacities radiating laterally from the hilum into adjacent upper and middle lungs. Bullae can form in the upper lungs. The hila are pulled upward and outward, and vessels and fissures are distorted. The fibrosis is occasionally so severe that massive parahilar opacities in the middle and upper lungs, resembling those of progressive massive fibrosis of silicosis, are seen.

CT can define the anatomic location of parenchymal sarcoid granulomas much more accurately (12,13,14). The most common finding of sarcoidosis on CT is multiple, 1- to 5-mm nodules, usually with irregular margins, in a lymphatic distribution (bronchovascular margins, along interlobular septa, subpleurally, and in the center of secondary pulmonary lobules) (Fig. 10-7). Septal thickening from sarcoidosis has a beaded appearance, a feature that helps distinguish it from pulmonary edema, in which the septal thickening is typically smooth. Patchy ground-glass opacities are seen in about 50% of

patients with sarcoidosis and rarely may be the only CT abnormality (Fig. 10-8). Fibrosis is better characterized on CT than on chest radiography. CT can show findings of sarcoidosis when the chest radiograph is normal, and patients can have a normal CT study yet have sarcoidosis proved by lung biopsy (13).

Fungus balls (mycetomas) can develop in cystic areas that develop from sarcoidosis, and sarcoidosis is the second most common predisposing condition (after tuberculosis) leading to the development of mycetoma (15). Hemoptysis resulting from mycetoma formation can be life threatening. Mycetomas occur in the upper lobes and should be suspected when new opacities are seen in an area of chronic cystic or bullous disease, especially when they are accompanied by new apical pleural or extrapleural opacity on chest radiography. There are myriad other atypical features of sarcoidosis, including pleural effusions, pleural thickening, cavitary nodules, bronchostenosis, pulmonary artery hypertension from periarterial granulomatosis (Fig. 10-9), cor pulmonale, and pneumothorax from chronic fibrosis.

Silicosis is a disease of the lungs caused by inhalation of dust containing silicon dioxide, or silica, the predominant constituent of the earth's crust. Silica dust is prevalent in mining, quarrying, and tunneling operations. Occupations associated with the development of silicosis include mining of heavy metals, the pottery industry, sandblasting, foundry work, and stonemasonry. When silica particles are inhaled, they are deposited in the alveoli and engulfed by alveolar macrophages,
where they are acted on by lysosomal enzymes. The affected macrophage dies and liberates mediators (leading to stimulation of collagen production) and the silica particles. The silica particles are then free to be taken up by other macrophages, and the cycle continues, leading to progressive lung disease even without continued occupational exposure to silica. Silicosis can be classified as simple silicosis, complicated silicosis, acute silicosis, or Caplan syndrome. Coal worker's pneumoconiosis, caused by inhalation of coal dust, is different pathologically from silicosis, but it produces chest radiographic findings similar to and often indistinguishable from those of silicosis.

Patients with simple silicosis are usually asymptomatic. Between 10 and 20 years' exposure is usually necessary before the chest radiograph becomes abnormal (16). The chest radiograph shows multiple nodules, 1 to 10 mm in diameter, with a diffuse but upper lung–predominant distribution (Fig. 10-10). Occasionally, the nodules may calcify. Enlargement of mediastinal and hilar nodes is common and is occasionally associated with eggshell calcification similar to that seen with sarcoidosis.

Complicated silicosis refers to progression of simple silicosis, where the nodules become confluent and larger than 1 cm. On chest radiography, these opacities are seen predominantly in the periphery of the upper lungs, which, over time, tend to migrate toward the hilum as the fibrotic process progresses. These conglomerate masses, which can reach several centimeters in size and contain obliterated blood vessels and bronchi, are referred to as progressive massive fibrosis (Fig. 10-11). The conglomerate masses are often surrounded by paracicatricial emphysema, which is best appreciated on chest CT. As conglomeration of the nodules occurs, the lungs gradually lose volume, and cavitation of the masses can occur. Patients who have advanced to this stage are at increased risk of active tuberculosis, and this diagnosis should be suspected when a new area of cavitation is seen on chest radiography.

Acute silicosis is a rare condition related to heavy acute exposure to silica in enclosed spaces with minimal or no protection. Histologically, the appearance is identical to that of pulmonary alveolar proteinosis; hence the term silicoproteinosis is used. The disease is rapidly progressive, often leading to death as a result of respiratory failure. The chest radiographic pattern is that of nonspecific diffuse airspace disease or ground-glass opacities, with a perihilar distribution and air bronchograms identical to the radiographic findings of pulmonary edema.

Caplan syndrome consists of the presence of large necrobiotic rheumatoid nodules superimposed on a background of simple silicosis. The syndrome is a manifestation of rheumatoid lung disease and is seen in both coal worker's pneumoconiosis and silicosis.

Langerhans cell histiocytosis (LCH), also referred to as histiocytosis X or eosinophilic granuloma, is a granulomatous disorder of unknown cause characterized by the presence within the granulomas of a histiocyte, the Langerhans cell. The disease is equally prevalent in male and female patients, it is unusual in African-Americans (17), and 95% of adult patients are cigarette smokers (17). In most patients, symptoms appear in the third or fourth decades, but the disease can occur in teenagers and those over age 60. The diagnosis can be made in asymptomatic patients with abnormal chest radiographs. Pneumothorax is a classic manifestation of LCH, and the frequency of pneumothorax as the initial manifestation is as high as 14% (18). The pneumothoraces are commonly recurrent and may be bilateral. Approximately one third of patients with LCH improve, one third remain stable, and one third deteriorate (18).

The chest radiograph of patients with LCH shows a diffuse, symmetric, reticulonodular pattern or, less commonly, a solely nodular pattern. Both patterns have a predominantly middle and upper lung distribution. The nodules are usually ill defined, vary in size from 1 to 15 mm, and are often innumerable but can be few in number. Large nodules can mimic metastases. With time, small cystic airspaces develop, and larger airspaces up to 5 cm in diameter will form only rarely. Because of the development of these abnormal airspaces, lung volume does not decrease with time but often increases. Pleural effusion and hilar or mediastinal nodal enlargement are uncommon.

CT of the lungs shows cysts and nodules, often in combination (19,20) (Fig. 10-12). Cysts range in diameter from 1 to 30 mm or more and, unlike centrilobular emphysema, usually have very thin discrete walls and no centrilobular core structure. Some cysts have bizarre shapes, which can help to distinguish them from the uniformly round cysts that are typical of lymphangioleiomyomatosis. Nodules are typically 1 to 5 mm in diameter, have irregular margins, and may be cavitary. The disease is thought to progress from solid nodules to cavitary nodules to cysts, although this is controversial. End-stage disease can resemble that of generalized centrilobular pulmonary emphysema.

Radiation injury to the lung is most commonly seen after radiation therapy for breast cancer, lung cancer, and Hodgkin disease. On the chest radiograph, the changes of radiation
pneumonitis are almost always confined to the field of irradiation. The first change is a diffuse haze in the irradiated region, with obscuration of the normal vascular markings. Patchy opacities appear, which may coalesce into a nonanatomic but geometric area of pulmonary opacification. These radiographic changes usually appear about 8 weeks after treatment, depending on the radiation dose and dosing interval (21); peak reaction occurs at 3 to 4 months. With time, the opacities become more linear or reticular, and fibrous contraction and distortion of lung architecture occurs. The fibrosis and contraction continue over a 12- to 18-month period. When only the apices of the lung are affected by radiation, such as with treatment for head and neck neoplasms, the radiographic changes do not appear geometric but ill defined and patchy (Fig. 10-13). When bilateral apical airspace opacities are seen on chest radiography, radiation pneumonitis should be considered in the appropriate patient population. Radiation of the axilla, an adjuvant treatment for patients with breast cancer who have undergone lumpectomy or mastectomy, can result in ipsilateral peripheral upper lung patchy airspace opacities (Fig. 10-14).

Once a disease of childhood, more than half of cases of initial infection with Mycobacterium tuberculosis, or primary tuberculosis (TB), are now seen in the adult population (22). In primary tuberculous infections, the pulmonary focus and lymphadenopathy may resolve without a trace, or they may leave a focus of caseous necrosis, scarring, or calcification. Several terms are used to describe the form of tuberculosis that develops after a primary infection under the influence of established hypersensitivity including reactivation TB, postprimary TB, and secondary TB.

The predominant radiographic feature of primary TB is the presence of hilar lymphadenopathy (usually unilateral) and mediastinal lymphadenopathy contiguous to the affected hilum. Lymphadenopathy is less common and milder in adults than in children, with the exception of immunocompromised adults, especially those with AIDS. On CT, the enlarged nodes typically have a low-density center with rim enhancement (Fig. 10-15) (23). The pulmonary foci of primary TB are randomly distributed throughout the lungs, and they range from small, occasionally imperceptible, ill-defined parenchymal opacities to segmental or lobar consolidation, often with an appearance similar to that of other bacterial pneumonias (Figs. 10-16 and 10-17). The incidence of cavitation varies between 10% and 30% (22). Hilar or mediastinal lymph node calcification is observed in 35% of cases (24). Pleural effusions are not uncommon, are generally unilateral, and are usually, but not always, associated with some identifiable pulmonary parenchymal disease (Fig. 10-18). Bronchial stenosis, bronchial occlusions, and polypoid endobronchial tuberculous lesions may be seen on CT.

The earliest chest radiographic findings of reactivation TB consist of one or more ill-defined patchy opacities, with or without small satellite foci in the adjacent lung, occurring in the posterior segments of the upper lobes in the majority of patients and in the superior segment of the lower lobes in most of the remainder of patients. This distribution of disease is very helpful in suggesting the diagnosis of reactivation TB. Cavitation with or without the presence of air–fluid levels is a distinct feature of reactivation TB and indicates a high likelihood of active infection (Figs. 10-19, 10-20, 10-21). The presence of cavitation implies that the disease is highly contagious, and patients with cavitary disease should be placed under immediate infective precautions (respiratory isolation) on the basis of radiographic findings alone. With healing, the chest radiograph shows gradually increasing definition of the lung opacities, development of fibrosis in the surrounding lung, contraction and volume loss of the affected segment or lobe with fissural displacement or distortion of the vascular structures in the hilum, bronchiectasis, and calcification (Fig. 10-22). Fluid levels in cavities disappear, and the cavities either disappear or persist with a smooth inner wall.

Other patterns of reactivation TB include lobar pneumonia, diffuse bronchopneumonia, endobronchial TB, tuberculoma formation, miliary TB, and tuberculous pleuritis. A
calcified lymph node may erode into an adjacent airway, becoming a broncholith, and be associated with hemoptysis or postobstructive atelectasis or pneumonia. Broncholiths can be suggested when a previously documented nodal calcification on chest radiography has disappeared or changed position. On rare occasion, a patient can cough up pieces of a calcified broncholith, a phenomenon referred to as lithoptysis. Tuberculomas are discrete tumorlike foci of TB in which there is a fine balance between inflammation and healing. The margins of a tuberculoma are usually well circumscribed. Tuberculomas may be single or multiple, are occasionally as large as 5 cm in diameter, and may grow slowly over an extended period of time. Calcification develops in the central caseous core with time and may be seen radiographically, but it is better characterized with CT. When the calcification is dense and assumes the majority of the volume of the tuberculoma as seen on chest radiography, the diagnosis of a benign inactive granuloma can be assumed. Such a parenchymal tuberculoma, known as a Ghon lesion, in combination with calcified nodes, is referred to as a Ranke complex. Miliary TB, which results from hematogenous dissemination
of disease, is an uncommon but serious complication of both primary and reactivation TB. The chest radiograph shows innumerable 2- to 3-mm nodules likened to millet seeds in size and appearance. The nodules are uniformly distributed and equal in size. Because there is a threshold below which the nodules are imperceptible, miliary TB can be present in patients with a "normal" chest radiograph. Miliary TB does not leave residual calcifications.

A number of mycobacteria other than M. tuberculosis can cause pulmonary infection. These atypical mycobacteria are common in the natural environment, and numerous species exist, including M. kansasii and M. avium-intracellulare; the latter is a very important pathogen in human immunodeficiency virus (HIV)–infected individuals. The classic features of atypical mycobacterial infections of the lung are those of a chronic indolent fibrocavitary process, usually involving one or both apical regions of the lungs in a middle-aged or older individual with underlying chronic obstructive pulmonary disease (25), or in chronic lower lung bronchiectasis. In many cases, the radiographic features are indistinguishable from those of reactivation TB. The lesions have the same predilection for the posterior aspects of the upper lobes or the superior segments of the lower lobes as reactivation TB. Cavitation occurs in up to 96% of patients with atypical mycobacterial infection (26).

Fungi of the genus Aspergillus are ubiquitous saprophytes that are commonly laboratory contaminants but on occasion can become human pathogens. Infection is acquired primarily through the respiratory tract. Exposure to Aspergillus is almost universal, yet the nonimmunocompromised patient usually does not develop Aspergillus infection (27).

Aspergillosis represents a spectrum of diseases based on the degree of immune impairment at one end of the spectrum and hypersensitivity at the other end of the spectrum (28). Four basic types of pulmonary aspergillosis are (i) noninvasive (saprophytic), (ii) semi-invasive, (iii) invasive, and (iv) allergic.

Noninvasive pulmonary aspergillosis refers to colonization of a pre-existing cavity or cystic area in the lung with Aspergillus organisms, creating a "fungus ball" or mycetoma. Prior tuberculous infection, emphysematous bullae, sarcoidosis (Fig. 10-23), or other processes, such as ankylosing spondylitis, that result in cavities, cysts, or cystic bronchiectasis, can lead to mycetoma formation (29,30). In noninvasive aspergillosis, the fungus causes the development of vascular granulation tissue within the cavity wall, which can lead to hemoptysis. With peripheral cavities, there is also a pleural response to the
presence of the organism, leading to marked pleural thickening and extrapleural fatty hypertrophy as clues to the chronic inflammation. Chest radiography and CT typically show a mobile, intracavitary mass, usually in an upper lobe (Figs. 10-24 and 10-25). Specific therapy is not required for patients with an asymptomatic aspergilloma; however, this type of aspergillosis can cause massive hemoptysis that can sometimes lead to death. Bronchial artery embolization, surgery, or instillation of amphotericin B into the aspergilloma cavity can be used to treat patients with an aspergilloma and hemoptysis.

Semi-invasive pulmonary aspergillosis refers to a chronic, indolent form of Aspergillus infection that leads to cavity formation and then a classic aspergilloma. This form of aspergillosis tends to occur in patients with depressed immune systems (e.g., those with a neoplasm, those who have undergone radiation, those who are of advanced age or debilitated, those with diabetes or chronic obstructive lung disease, or those on chronic corticosteroid therapy) (31). The disease typically begins as an upper lung opacity on chest radiography, which, over a period of weeks to months, gradually develops cavitation with formation of an "air crescent sign." As the disease progresses, extensive apical pleural thickening develops. As cavitation progresses, a thick-walled cavity often becomes thin walled, containing a mycetoma (Fig. 10-26). Therapy is the same as for noninvasive aspergillosis.

Invasive pulmonary aspergillosis is the most pathologically aggressive form of aspergillosis and occurs in severely immunocompromised patients (Fig. 10-27). Chest radiographs show a solitary pulmonary nodule or mass, or multifocal opacities. In some cases, multiple poorly defined nodules (likely representing infarcts) are seen and extend to the periphery of the lungs. In patients with leukemia, cavitation of the nodules develops as the neutrophil count recovers from the chemotherapy-induced nadir (32). Cavitation leads to the air crescent sign, which is seen as a crescent-shaped collection of air between the cavity wall and the intracavitary contents. In contrast to noninvasive and semi-invasive forms of aspergillosis, in which a fungus ball occupies the cavity, in invasive aspergillosis the central mass within the cavity is almost always necrotic lung and not an aspergilloma. Early in the course of infection during bone
marrow aplasia, before air crescent formation or cavitation, CT often shows the CT "halo sign," a zone of ground-glass opacification surrounding the pulmonary nodule or mass. In patients with acute leukemia, the presence of the CT halo sign (representing a zone of hemorrhage) strongly suggests the diagnosis of invasive aspergillosis (Fig. 10-28) (33). Intravenous amphotericin B remains the frontline therapy for invasive aspergillosis. Patients who do not respond to therapy usually die of the disease.

Allergic bronchopulmonary aspergillosis(ABPA) is a form of hypersensitivity reaction to inhaled Aspergillus organisms. It is seen most commonly in patients with underlying asthma, it is seen in approximately 10% of patients with cystic fibrosis, and it is seen occasionally in patients with no known underlying pulmonary disease (34). The fungus grows noninvasively within the bronchi, releasing an antigen that causes host sensitization and a subsequent immunologic reaction. Mucus traps the organisms in the bronchi. Bronchiectasis either results from or is a predisposing factor to development of ABPA. Patients with ABPA typically present with symptoms of asthma. Typical radiographic findings consist of central bronchiectasis with mucoid material filling the bronchi. The appearance of mucus-filled bronchi on chest radiography has been variously described as finger in glove, rabbit ears, Mickey Mouse, toothpaste-shaped, and Y- or V-shaped opacities. The diagnosis of ABPA is based on major and minor criteria (35). Major criteria include asthma, blood eosinophilia, immediate skin reactivity to Aspergillus antigen, increased serum immunoglobulin E, transient or fixed pulmonary opacities on chest radiography, and central bronchiectasis. Minor criteria include fungal organisms in the sputum, history of expectoration of brown plugs or flecks, and delayed skin reactivity to fungal antigens. Because ABPA is an allergic disease, the primary treatment consists of corticosteroids.

Bronchocentric granulomatosis, characterized histologically by necrotizing granulomas that may obstruct and destroy bronchioles, is a histopathologic pattern that is generally believed to represent a nonspecific response to a variety of forms of airway injury. Approximately half of all cases are associated with asthma and ABPA, and among these patients,
bronchocentric granulomatosis may represent a histopathologic manifestation of fungal hypersensitivity. Aspergillus hyphae can be identified within the granulomas in up to 50% of patients. Although the imaging features may be similar to those of conventional ABPA, the lung involvement in bronchocentric granulomatosis is more commonly focal and peripheral (36).

Cystic fibrosis is an autosomal recessive disease involving chromosome 7 and characterized by dysfunction of exocrine glands, which form a thick, tenacious material. The incidence is 1 in 1,600 live births, with Caucasians affected most frequently. Organs involved include the lung, upper respiratory tract, pancreas, liver, gallbladder, and reproductive tract. The earliest chest radiographic findings include peribronchial inflammatory changes (peribronchial cuffing) and both atelectasis and hyperinflation. With progression of the disease, ring shadows and tram tracking are seen as signs of bronchiectasis, usually with an upper lobe predominance (Fig. 10-29). Not uncommonly, air–fluid levels can be seen in areas of cystic bronchiectasis. Small, ill-defined or tubular opacities occur as a result of mucus plugging in dilated airways (Figs. 10-30 and 10-31). Larger opacities usually represent pneumonia, most commonly caused by Staphylococcus aureus or Pseudomonas species. Bilateral hilar lymphadenopathy is common. Severe disease can lead to pulmonary arterial hypertension and cor pulmonale, which may be suggested when enlargement of the central pulmonary arteries and enlargement of the right heart, respectively, are seen on the chest radiograph. ABPA occurs in 10% of patients with cystic fibrosis, as discussed earlier in this chapter. Hypertrophic pulmonary osteoarthropathy, a disorder involving the long bones and joints, occurs in approximately 15% of patients with cystic fibrosis.

Infection is the leading cause of chest radiographic abnormalities in immunocompromised patients and is a direct result of a deficiency in immune defenses (e.g., immunoglobulin abnormalities, cell-mediated dysfunction, and phagocytic defense disorders) or a nonspecific reduction in host resistance
(e.g., advanced age, alcoholism, diabetes, starvation or malnutrition, and cancer). In addition to infection, radiographic abnormalities in immunocompromised patients can result from many other causes, as listed in Table 10-4.

Pulmonary infections occur in at least half of all patients after bone marrow transplantation and are the most significant cause of death in this patient population (63) (Fig. 10-50). Infections occurring in immunocompromised patients were discussed earlier in this chapter. [AU: Are BMT patients, AIDS patients, and lung transplant patients, then, not considered "immunocompromised"?]

Graft-versus-host disease (GVHD) results from the transplantation of immunocompetent donor lymphocytes that attack the recipient's tissues, especially the skin, liver, and gastrointestinal tract. Acute GVHD occurs 20 to 100 days after transplantation and involves primarily extrapulmonary organs. Chronic GVHD occurs at least 100 days after transplantation in approximately one third of patients surviving this long (64), and it results in lymphocytic infiltration of the airways and obliterative bronchiolitis. Chest radiograph and CT findings include diffuse patchy perihilar opacities, reflecting the airway distribution of disease. In severe cases, a diffuse interstitial pattern is seen. CT may be normal on inhalational images but may show air trapping on exhalational images, reflecting obliterative bronchiolitis.

Pulmonary veno-occlusive disease rarely occurs in patients after bone marrow transplantation but can lead to patient death. The pulmonary veins thrombose and develop intimal fibrosis, possibly as a result of pulmonary infection. Occlusion of the pulmonary veins leads to pulmonary venous and capillary congestion, pulmonary edema, alveolar hemosiderin deposits, pulmonary arterial hypertension, and right heart failure. Chest radiographs, when abnormal, show signs of pulmonary arterial hypertension (enlarged central pulmonary arteries) and, in some cases, interstitial and alveolar pulmonary edema (65). The left atrium is not enlarged, differentiating this entity from mitral valve disease and left atrial myxoma.

Pulmonary hemorrhage can occur in the absence of any evidence of a coagulopathy and in the absence of hemoptysis. It usually develops within 20 days of transplantation and is a fulminant condition with a 75% mortality rate. Chest radiographs most commonly show diffuse alveolar lung disease, although in some cases a pattern of reticular interstitial disease predominates (66).

The first successful lung transplantation was performed in 1983. As of June 2004, 3,154 heart–lung and 19,296 lung transplantations had been performed [AU: Worldwide?] according to data from an international registry (67). Single lung transplantation is the preferred procedure for lung replacement because fewer donor organs are required compared with heart–lung or bilateral lung transplantation. Cystic fibrosis is the most common indication for bilateral lung transplantation because of the incidence of recurrent infections in the native lung after single lung transplantation and institution of immunosuppression.

In single lung transplantation, the chest is entered through the bed of the fifth rib. This avoids complications of a sternotomy, which is performed for heart–lung and double lung transplantation. The surgery involves pulmonary artery,

bronchial, and donor–recipient left atrial cuff anastomoses (68). Bilateral lung transplantation involves sequential single lung transplants and is commonly performed via a "clamshell" approach through a lower sternotomy.

Infection is the leading cause of death in the lung transplant population, accounting for 48% of early postoperative mortality (69). Factors that increase the susceptibility to infection include immunosuppression, reduced mucociliary clearance, interruption of lymphatic drainage, and direct and constant contact of the transplant with the outside environment via the airways (70). Bacterial agents predominate in the first month after transplantation (Figs. 10-51 and 10-52), CMV infections occur mainly in the second and third months (Fig. 10-53), and fungal infections (Fig. 10-54) occur both early and later after transplantation (70,71,72,73). PCP is uncommon secondary to antibiotic prophylaxis. If CMV pneumonia develops, a fulminant course proceeding to respiratory failure and death within a few days can develop (74).

Acute rejection may be observed at any point after transplantation, with the first episode occurring as early as 48 hours and most occurring in the first 100 days after surgery. Most recipients experience at least one episode (75). CT of the chest shows ground-glass opacification as the only significant finding (76). Chest radiograph and CT findings overlap with those of infection (77).

Reperfusion edema is seen within 24 hours after transplantation and resolves over a period of days to months, usually within 1 to 2 weeks. The radiographic appearance ranges from mild perihilar haze to dense consolidation, and it results from surgical trauma, ischemia, organ preservation, denervation,
and lymphatic interruption (70). The diagnosis is one of exclusion and is characterized by all radiographic changes beginning soon after surgery that are not the result of left ventricular failure, rejection, fluid overload, infection, or atelectasis (75).

Pleural effusions are common after lung transplantation, secondary to impaired fluid clearance through the lymphatics of the visceral pleura. Most effusions develop immediately following surgery and continue for up to 9 days, with output declining steadily during the first week (78). Pneumothoraces are evident on postoperative radiographs in 60% of patients; they are generally small and apical in location (79).

Chronic rejection is a major problem in patients surviving longer than 3 months, and it occurs in more than 50% of patients. Obliterative bronchiolitis represents the pathologic finding in chronic rejection. CT findings of bronchiectasis/bronchiolectasis, decreased vascular markings, and air trapping on exhalational scans are findings associated with obliterative bronchiolitis (71,72,80).

Posttransplantation lymphoproliferative disease, thought to be induced by the Epstein-Barr virus, manifests as a spectrum of lymphoproliferation that ranges from a mild, polyclonal lymphoid hyperplasia to frank lymphoma. Of all transplantation procedures, this disorder occurs most often after lung transplantation, with a prevalence of 5% to 20%, occurring most often within the first year after surgery (81). Intrathoracic involvement is most commonly characterized by the presence of discrete nodules, either solitary or multiple, with or without mediastinal lymphadenopathy (Fig. 10-55)
(61,81,82). Bronchogenic carcinoma occurs after lung transplantation, most commonly in the native lung in patients with single lung transplantation for emphysema (Fig. 10-56) or idiopathic pulmonary fibrosis (83).

Recurrence of disease has occurred in patients transplanted for sarcoidosis (most common), LCH, lymphangiomyomatosis, bronchioloalveolar carcinoma, desquamative interstitial pneumonitis, pulmonary alveolar proteinosis, giant cell interstitial pneumonitis, diffuse panbronchiolitis, talc granulomatosis, and bronchiectasis from aspiration (84). It is important to consider recurrence of native disease when new abnormalities are seen on chest radiography or CT in the appropriate clinical situation.