INTRODUCTIONAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major pulmonary causes of morbidity and mortality. Acute pulmonary injury often results in acute hypoxemic respiratory failure. Patients with acute pulmonary injury typically present clinically with ARDS. ARDS was formally defined in 1994 by the American–European Consensus Conference on ARDS as acute hypoxemia with a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (i.e., PaO2:FIO2) of 200 mm Hg or less, bilateral infiltrates with a radiographic appearance that is consistent with pulmonary edema, and no evidence of cardiac failure clinically. ALI is less severe than ARDS and has similar diagnostic criteria with the exception of PaO2:FIO2 of 300 mm Hg.

When examined pathologically, most patients with clinical ARDS and ALI will show histologic evidence of diffuse alveolar damage (DAD). However, it should be emphasized that these terms are not synonymous. Other histologic patterns have been described in association with ALI/ARDS. These include acute eosinophilic pneumonia (AEP), acute fibrinous and organizing pneumonia (AFOP), and diffuse alveolar hemorrhage (DAH). Organizing pneumonia (OP) is also included in the differential diagnosis of ALI. This exhibit will illustrate the HRCT findings in the spectrum of acute lung injury with histopathologic correlation.

DIFFUSE ALVEOLAR DAMAGEDiffuse alveolar damage (DAD) is the most common histologic manifestation of ARDS and ALI. Patients present with severe hypoxemia and almost always require mechanical ventilation. While the precise mechanism of injury is unclear, capillary endothelial and alveolar epithelial damage result in exudation of fluid and products of cellular breakdown. With time, pneumocyte hyperplasia and fibroblast proliferation ensue.

The histologic appearance of DAD is divided into three phases: the acute or exudative phase, the organizing or proliferative phase, and the chronic or fibrotic phase. The acute phase occurs during the first week after the initial insult, and findings may include intra–alveolar edema, interstitial widening, and hyaline membranes (composed of cellular and proteinaceous debris). Thrombi may also be seen as a result of localized alterations in the coagulation pathway. The organizing phase follows with features of interstitial fibrosis and type 2 pneumocyte hyperplasia. Squamous metaplasia, residual hyaline membranes, and organizing fibroblastic tissue within air spaces may also be present. The fibrotic phase is characterized by features of interstitial lung fibrosis.

Initially, HRCT usually shows heterogeneous foci of consolidation and ground–glass opacity with a posterior and basal predominance. In the healing phase, findings of fibrosis such as reticulation, architectural distortion and traction bronchiectasis may be present.

A recent study evaluating the predictive value of CT for survival in patients with ARDS demonstrated higher mortality in those

patients with greater than 80% lung involvement, RA/LA ratio greater than 1, and varicoid traction bronchiectasis.

CONCLUSIONThe patterns of acute lung injury and acute respiratory distress syndrome have different HRCT and histopathologic features. Knowledge of the characteristics and features of the different patterns in the spectrum of ALI and ARDS is important and helpful for guiding appropriate diagnosis and treatment of affected patients.

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIAAcute fibrinous and organizing pneumonia (AFOP) is a recently described histologic pattern associated with ALI. Most patients present with severe respiratory failure similar to ARDS. However, a small subset of patients may have a subacute clinical course not requiring ventilatory support. AFOP can be idiopathic or related to insults such as drug reaction.

The dominant histopathologic finding in AFOP is fresh intra–alveolar fibrin or so–called “fibrin balls.” Hyaline membranes should not be present, in contrast to DAD. Other histologic findings that can be seen with AFOP include mild interstitial widening, lymphocytic infiltrates, and organizing fibroblastic tissue.

HRCT findings of AFOP are not well described but include peripheral and peribronchial foci of consolidation and ground–glass opacity, similar to organizing pneumonia, but greater in extent with superimposed features more typical of DAD.

DIFFUSE ALVEOLAR HEMORRHAGE Diffuse alveolar hemorrhage (DAH) is characterized by hemorrhage into the alveolar spaces, and is due to injury to the alveolar microcirculation. Patients with DAH typically present with hypoxemia and occasionally present with fulminant respiratory failure. When there is significant alveolar hemorrhage, patients will often present clinically with hemoptysis. Although DAH can occur with or without capillaritis, it is the cases of DAH with capillaritis that may present with clinical findings of ALI. Causes of DAH include immune–mediated disorders such as collagen vascular diseases, microscopic polyangiitis, Goodpasture syndrome, Wegener granulomatosis, drug reactions, and infections.

Histopathologic findings seen in DAH include diffuse intra–alveolar blood admixed with hemosiderin–laden macrophages. Organizing fibroblastic tissue may also be present. In capillaritis, neutrophils are seen within alveolar septa with resultant vascular necrosis. Hyaline membranes may also be present.

HRCT findings of DAH consist of extensive bilateral ground–glass opacities, which may be diffuse or patchy, often in an “acinar” distribution. Subpleural sparing is often a useful diagnostic feature. With subacute DAH, small poorly defined centrilobular nodules and interlobular septal thickening can develop, presumably related to lymphatic resorption of the blood.

ORGANIZING PNEUMONIAOrganizing pneumonia (OP) most often presents with a subacute clinical course without fulminant respiratory failure. Although it is not associated with clinical ALI or ARDS, OP is discussed in this exhibit because it is frequently included in the pathologic differential diagnosis of ALI. The underlying causes of OP include infection, collagen vascular disease and drug reaction. It can also be idiopathic, which is clinically referred to as cryptogenic organizing pneumonia (COP).

Histopathologic findings seen in OP include patchy accumulation of loose plugs of granulation tissue (Masson bodies) in the alveoli and respiratory bronchioles. Mild alveolar septal chronic inflammation is often present.

HRCT findings of OP are airspace consolidation in a subpleural or peribronchial distribution. Ground–glass opacities may also be present, often with a bilateral asymmetric distribution. The reverse halo sign may be present in almost 20% of cases.

ACUTE EOSINOPHILIC PNEUMONIAAEP is characterized by fever, hypoxemia, peripheral eosinophilia and fulminant respiratory failure. AEP may be idiopathic or result from infection (especially parasites), toxic inhalation, drug reaction, and recent onset of heavy smoking. At BAL, eosinophils are generally greater than 25%. In contrast to other forms of ALI, patients with AEP usually have a dramatic response to corticosteroids.

Histopathologic findings of AEP include intra–alveolar fibrin, macrophages, hyaline membranes (similar to the acute phase of DAD), and numerous eosinophils. Eosinophils may be present in the interstitium, may infiltrate blood vessel walls, and may form eosinophilic microabscesses.

HRCT findings of acute eosinophilic pneumonia are nonspecific, and include consolidation and ground–glass opacities in a random (2/3) or peripheral (1/3) distribution. Smooth interlobular septal thickening and small pleural effusions are frequently present and, in the absence of cardiomegaly, are helpful clues to the diagnosis.

Acute Lung Injury: HRCT and Histopathologic SpectrumObadina ET1, Kanne JP1, Torrealba JR2, Meyer CA1

1. University of Wisconsin Department of Radiology, Madison, WI; 2. University of Wisconsin Department of Pathology, Madison, WI

Corresponding Author:Eniola Obadina, MD

University of Wisconsin Department of RadiologyE3/312 CSC

Madison, WI 53792–3252eobadina@uwhealth.org

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Figure 9 Organizing PneumoniaHRCT image of a patient with cryptogenic organizing pneumonia demonstrates ground–glass attenuation nodules with faint peripheral consolidation (“reverse halo”) in addition to nodular foci of lung consolidation.

Figure 5

Acute Eosinophilic PneumoniaHRCT image of a young female patient with recent onset of smoking shows diffuse septal thickening and multiple peripheral foci of lung consolidation.

Figure 6

Eosinophilic Pneumonia (200X)This section of lung shows

interstitial widening accompanied by mixed

infiltrates of lymphocytes, macrophages and

eosinophils. Focal alveolar fibroblastic proliferation is

also present (arrow).

Figure 7

Diffuse Alveolar HemorrhageHRCT image shows bilateral ground–glass acinar nodules, predominantly affecting the right lung, with relative sparing of the peripheral lung parenchyma.

Figure 8

Diffuse Alveolar Hemorrhage

8a. 100XLung tissue shows alveolar parenchyma with patchy, intra–alveolar cell infiltrates predominantly consisting of hemosiderin–laden macrophages.

8b. 400XIn this lung section, the alveolar spaces are filled with pigmented macrophages. The cytoplasms of these macrophages show coarse, thick granules, corresponding to hemosiderin. Rare interstitial polymorphonuclear cells and plasma cells are also seen in this case.

Figure 10

Organizing Pneumonia

10a. 40XLung section shows diffuse filling of the alveolar spaces with fibroblastic plugs (Masson bodies), involving the respiratory bronchioles, alveolar sacs and alveoli.

10b. 200XAlveolar spaces are diffusely occupied by proliferation of fibroblasts and myxoid connective tissue (Masson bodies) plugging the terminal bronchioles, alveolar sacs and alveoli. There is associated vascular congestion and minimal focal lymphocytic infiltrate.

Figure 2

Diffuse Alveolar Damage

2b. Organizing Phase, 200XAfter the acute phase, hyaline membranes become incorporated in alveolar septa with fibroblast proliferation and septal widening. Interstitial inflammatory infiltrates may persist at this stage.

2a. Acute Phase, 400XLung section shows alveolar lung parenchyma with hyaline membranes (arrows), intra–alveolar red cells and interstitial mononuclear inflammatory infiltrates.

1a. Acute PhaseHRCT image of a patient with acute DAD shows patchy consolidation and ground–glass opacities.

Figure 1

Diffuse Alveolar Damage

1b. Fibrotic PhaseHRCT of the same patient (from Figure 1a), obtained three months later, demonstrates interstitial fibrosis characterized by reticulation, traction bronchiectasis, and ground–glass opacity with a basal predominance.

Figure 4

AFOP, 200XLung tissue demonstrates alveolar parenchyma

with predominantly intra–alveolar fibrin aggregates (“fibrin balls”) within airspaces.

Associated mild interstitial mononuclear infiltrate is also noted.

Figure 3

AFOP HRCT image of a patient with drug–induced AFOP demonstrating extensive peribronchial, subpleural, and perilobular consolidation and ground–glass opacity, similar to but more extensive than organizing pneumonia.