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Acute Parenchymal Lung Disease in Immunocompetent Patients

Diagnostic Accuracy of High-Resolution CT

¹ Department of Radiology, Vancouver General Hospital and University of British Columbia, 855 W. 12th Ave., Vancouver, B. C., V5Z 1M9, Canada.
² Department of Radiology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
³ Department of Radiology, National Kinki Chuo Hospital for Chest Disease, 1180 Nagasone-cho, Sakai, Osaka, 591-8025, Japan.
⁴ First Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, 860-0811, Japan.

Received October 7, 1999; accepted after revision November 22, 1999.

 
Address correspondence to N. L. Müller.

Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
OBJECTIVE. The purpose of this study was to determine whether acute parenchymal lung diseases can be differentiated on the basis of the pattern and distribution of abnormalities revealed on high-resolution CT.

MATERIALS AND METHODS. High-resolution CT scans of 90 patients with acute parenchymal lung diseases (19 with bacterial pneumonia, 13 with mycoplasmal pneumonia, 21 with acute interstitial pneumonia, 18 with hypersensitivity pneumonitis, 10 with acute eosinophilic pneumonia, and nine with pulmonary hemorrhage) were independently assessed by two observes who had no knowledge of clinical or pathologic data. The observers recorded abnormalities, their first-choice diagnosis, and their degree of confidence in their first-choice diagnosis.

RESULTS. The two observers made a correct first-choice diagnosis in an average of 55 (61%) of 90 cases. Correct first-choice diagnosis was made in 50% of cases of bacterial pneumonia, 62% of mycoplasmal pneumonia, 90% of acute interstitial pneumonia, 72% of hypersensitivity pneumonitis, 30% of acute eosinophilic pneumonia, and 28% of pulmonary hemorrhage. CT findings allowed distinction between infectious and noninfectious causes in 81 (90%) of 90 cases.

CONCLUSION. High-resolution CT is helpful in the differential diagnosis of infectious from noninfectious acute parenchymal lung disease. However, high-resolution CT is of limited value in making a specific diagnosis.

Introduction

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A large number of acute infectious and noninfectious diseases may result in parenchymal lung disease in immunocompetent patients. The most common cause is community-acquired pneumonia. In most of these patients, a diagnosis is made on the basis of a combination of clinical, radiographic, and laboratory findings. High-resolution CT is performed only in patients with nonspecific clinical and radiologic findings and in patients with progression of disease despite therapy. High-resolution CT is also often performed in patients with noninfectious causes of acute parenchymal lung disease such as acute interstitial pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and pulmonary hemorrhage. These diseases often have clinical and functional features similar to one another but obviously requiring different treatment. Therefore, the differential diagnosis of these entities is important in daily clinical practice.

Several recent studies have suggested that the various acute parenchymal lung diseases in immunocompetent patients have characteristic high-resolution CT findings [1,2,3,4,5,6,7,8,9,10,11,12,13]. However, to our knowledge, no study has assessed the value of high-resolution CT in distinguishing these entities. The aim of our study was to determine whether the various acute parenchymal lung diseases in immuno-competent patients could be differentiated on the basis of the pattern and distribution of abnormalities on high-resolution CT.

Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
We examined the high-resolution CT images of 90 immunocompetent patients in whom a definitive diagnosis had been established and who had undergone imaging for acute parenchymal lung disease at one of our four institutions. The patients were 47 males and 43 females. The mean age was 50 years (range, 12-78 years). The study group included 19 patients with bacterial pneumonia, 13 with mycoplasmal pneumonia, 21 with acute interstitial pneumonia, 18 with hypersensitivity pneumonitis, 10 with acute eosinophilic pneumonia, and nine with pulmonary hemorrhage (idiopathic in six, caused by Wegener's granulomatosis in two, and caused by systemic lupus erythematosus in one).

All patients fulfilled the diagnostic criteria for the specific diagnosis of each of the diseases [8, 14,15,16,17,18,19,20]. The pathologic diagnosis was made on the basis of specimens obtained at open lung biopsy in four patients with acute interstitial pneumonitis and in eight patients with pulmonary hemorrhage; at autopsy in 17 patients with acute interstitial pneumonia; and at transbronchial biopsy in 18 patients with hypersensitivity pneumonitis, nine with acute eosinophilic pneumonia, and one with pulmonary hemorrhage. The diagnosis of bacterial pneumonia was based on the presence of positive sputum cultures and response to appropriate antibiotic therapy. The diagnosis of mycoplasmal pneumonia was based on the presence of a four-fold increase in antibody titers and on negative bacterial culture of sputum. Patients with collagen vascular disease, immunocompromised patients, and patients with pulmonary edema were excluded from the study. Acute parenchymal lung disease was defined by the presence of symptoms for less than 1 month and the presence of interstitial or air-space parenchymal abnormalities on CT.

All patients underwent high-resolution CT of the chest as part of the patient evaluation. CT scans consisted of 1- to 3-mm collimation sections reconstructed using a high-spatial-frequency algorithm. The protocols consisted of thin sections obtained at 1-cm intervals (31 patients), 1.5-cm intervals (25 patients), or 2-cm intervals (29 patients), and three to five thin sections that complemented a complete conventional CT scan of the chest (five patients). All CT scanning was performed at end-inspiration with the patient in the supine position. CT scans were obtained on a variety of scanners. No IV contrast material was used.

The CT scans were randomized and then reviewed separately by two independent chest radiologists. The observers were unaware of any clinical or pathologic findings other than the age and sex of patients.

The high-resolution CT scans were assessed for the presence, extent, and anatomic distribution of air-space consolidation, areas of ground-glass attenuation, centrilobular branching structures, centrilobular nodules, interlobular septal thickening, thickening of bronchovascular bundles, intralobular reticular opacities, traction bronchiectasis, honeycombing, and pleural effusion. The cross-sectional distribution was classified as central if a predilection of abnormalities was seen in the inner third of the lung, peripheral if a predominance of abnormalities was seen in the outer third of the lung, and random if no predominance was seen. The anatomic distribution was noted to be segmental if there was a predilection of the abnormalities to have a wedge-shaped configuration along the bronchial tree and nonsegmental if there was no predominance. Zonal predominance was assessed as being upper, lower, or random. Upper lung zone predominance was considered present when most of the abnormalities were above the level of the tracheal carina, and lower zone predominance, when most of the abnormalities were below this level.

The CT findings were interpreted on the basis of previously published data on the CT appearance of these six diseases [1,2,3,4,5,6,7,8,9,10,11,12,13]. Subsequently, each observer recorded first-choice diagnosis for each patient and graded the degree of confidence of their diagnosis as high (level 1) or low (level 2). Furthermore, these six diseases were divided into two categories: infectious diseases (bacterial pneumonia and mycoplasmal pneumonia) and noninfectious diseases (acute interstitial pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and pulmonary hemorrhage). Each observer recorded the cause as being either due to an infectious or non-infectious origin for each patient and graded the degree of confidence of their diagnosis as high (level 1) or low (level 2). Agreement between the two observers was assessed using the kappa statistic [21]. Kappa values larger than zero were considered to indicate a positive correlation; values up to 0.20 were considered positive but showing poor agreement; values of 0.21-0.40, showing fair agreement; values of 0.41-0.60, showing moderate agreement; values of 0.61-0.80, showing good agreement; and values greater than 0.81, showing excellent agreement.

Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
On average, the two observers made a correct first-choice diagnosis in 55 (61%) of 90 cases. These included 9.5 (50%) (average of two observers) of 19 cases of bacterial pneumonia, eight (62%) of 13 cases of mycoplasmal pneumonia, 19 (90%) of 21 cases of acute interstitial pneumonia, 13 (72%) of 18 cases of hypersensitivity pneumonitis, three (30%) of 10 cases of acute eosinophilic pneumonia, and 2.5 (28%) of nine cases of pulmonary hemorrhage (Table 1).

The two observers made a correct first-choice diagnosis with a high degree of confidence in 40.5 (79%) of 51 cases. The confident diagnosis was correct in 81% cases of bacterial pneumonia, 64% of cases of mycoplasmal pneumonia, 92% of cases of acute interstitial pneumonia, 81% of cases of hypersensitivity pneumonitis, 50% of cases of acute eosinophilic pneumonia, and 33% of cases of pulmonary hemorrhage. Fair agreement existed between the observers for the correct diagnosis (=0.39), and moderate agreement for the correct diagnosis with a high degree of confidence (=0.54).

When the various infectious and noninfectious causes were grouped together, the interpretation of the two observers was correct in distinguishing between infectious and noninfectious origins in 81 (90%) of 90 cases (Table 2). On the average, the two observers made a correct distinction between infectious and noninfectious causes with a high degree of confidence in 73.5 (96%) of 76.5 cases (Table 2).

Areas of ground-glass attenuation were found in almost all patients (Figs. 1,2,3,4,5,6), and air-space consolidation was found in most patients except for those with hypersensitivity pneumonitis (Table 3). Centrilobular branching structures were identified in 69% of patients with mycoplasmal pneumonia (Fig. 2) and 34% of patients with bacterial pneumonia, and were less commonly seen in the other diseases. Centrilobular nodules were found in most patients with mycoplasmal pneumonia (96% of interpretations) (Fig. 2), hypersensitivity pneumonitis (81% of interpretations) (Fig. 4), and bacterial pneumonia (61% of interpretations) (Fig. 1), and were found less commonly in the other entities. In the patients with mycoplasmal pneumonia and bacterial pneumonia, the centrilobular nodules were patchy in distribution, whereas in patients with hypersensitivity pneumonitis they were diffusely and profusely distributed (Fig. 4). Traction bronchiectasis was common in acute interstitial pneumonia (81% of interpretations) (Fig. 3) and less common in the other entities.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1. —Bacterial pneumonia in 78-year-old woman. High-resolution CT scan (1-mm collimation) at level of truncus basalis of left lower lobe shows areas of air-space consolidation (arrow), ground-glass attenuation in segmental distribution, and centrilobular nodules (arrowhead).

View larger version (146K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2. —Mycoplasmal pneumonia in 44-year-old man. High-resolution CT scan (1-mm collimation) at level of tracheal carina reveals area of ground-glass attenuation (white arrow) and centrilobular nodules (black arrow). Note heterogeneous involvement of secondary pulmonary lobules.

View larger version (155K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3. —Acute interstitial pneumonia in 58-year-old woman. High-resolution CT scan (2-mm collimation) through superior segment of left lower lobe shows extensive area of ground-glass attenuation and traction bronchiectasis (solid arrow). Note intralobular reticular opacities (arrowhead) and traction bronchiectasis. Also noted is small pneumothorax (open arrow) on right side.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4. —Hypersensitivity pneumonitis in 48-year-old woman. High-resolution CT scan (1.5-mm collimation) at level of tracheal carina reveals centrilobular nodules (arrow) and areas of ground-glass attenuation.

View larger version (151K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5. —Acute eosinophilic pneumonia in 48-year-old man. High-resolution CT scan (2-mm collimation) through left basal segment shows area of ground-glass attenuation (long arrow) and interlobular septal thickening (short arrow). Also noted are thickening of bronchial walls and interlobar fissures. Small bilateral pleural effusions are present but are difficult to see on lung windows.

View larger version (161K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6. —Pulmonary hemorrhage in 39-year-old woman. High-resolution CT scan (1-mm collimation) targeted to right lung base reveals heterogeneous involvement of lung parenchyma by pulmonary hemorrhage resulting in areas of ground-glass attenuation (large arrow), air-space consolidation (small arrow), and sparing of adjacent lobules. Note mild interlobular septal thickening.

Lower lung zone predominance was found in 65% of patients with mycoplasmal pneumonia, 47% of patients with bacterial pneumonia, and 33% of those with pulmonary hemorrhage (Table 4). Segmental distribution was found in all patients with mycoplasmal pneumonia (Fig. 2) and in 76% of patients with bacterial pneumonia (Fig. 1). A predominantly peripheral distribution was seen in 24% of patients with bacterial pneumonia, 20% of patients with acute eosinophilic pneumonia, and 15% of those with mycoplasmal pneumonia.

A combination of air-space consolidation, centrilobular nodules, and segmental distribution was found in 85% of patients with mycoplasmal pneumonia, 45% of those with bacterial pneumonia (Fig. 1), 10% of those with acute eosinophilic pneumonia, 6% of those with pulmonary hemorrhage, but in no patient with acute interstitial pneumonia or hypersensitivity pneumonitis. A combination of air-space consolidation, traction bronchiectasis, and random distribution in both cephalocaudal and cross-sectional planes was found in 57% cases of acute interstitial pneumonia, 10% of acute eosinophilic pneumonia, 6% of hypersensitivity pneumonitis, but in no patient with bacterial pneumonia, mycoplasmal pneumonia, or pulmonary hemorrhage. A combination of ground-glass attenuation, centrilobular nodules, and non-segmental distribution was found in 78% of patients with hypersensitivity pneumonitis (Fig. 4), 39% with pulmonary hemorrhage, 25% with acute eosinophilic pneumonia, 8% with bacterial pneumonia, but in none of the patients with either mycoplasmal pneumonia or acute interstitial pneumonia.

Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Acute parenchymal lung diseases are a heterogeneous group of diseases with acute onset and presence of interstitial or air-space abnormalities. Our study includes six diseases (bacterial pneumonia, mycoplasmal pneumonia, acute interstitial pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and pulmonary hemorrhage) in which high-resolution CT scanning was performed as part of the patient evaluation. Although CT findings observed in many acute lung diseases have been reported, to our knowledge no study to date has attempted to compare high-resolution CT findings in patients with these diseases. The clinical benefits would be obvious if it were possible to differentiate many of these diseases, because invasive procedures such as bronchoscopy, bronchoalveolar lavage, and open lung biopsy may be more complicated in patients with acute respiratory illnesses, particularly if the patient requires mechanical ventilation.

Bacterial pneumonia is one of the most frequent acute lung diseases. The most common high-resolution CT finding consists of areas of air-space consolidation that may be segmental or nonsegmental in distribution [1]. Other findings seen in the current study included ground-glass attenuation, centrilobular nodules, and centrilobular branching structures present in 97%, 61%, and 34% of patients with bacterial pneumonia, respectively.

Mycoplasmal pneumonia is characterized by an infiltration of inflammatory cells predominantly in the bronchiolar and peribronchiolar regions [15, 22, 23]. The characteristic high-resolution CT findings consist of centrilobular branching structures and nodules, bronchial wall thickening, air-space consolidation, and ground-glass attenuation with lobular distribution [1]. These findings can resemble those of bacterial pneumonia.

Acute interstitial pneumonia is characterized histologically by diffuse alveolar damage. The predominant high-resolution CT findings of acute interstitial pneumonia consist of extensive bilateral air-space consolidation and patchy or diffuse bilateral areas of ground-glass attenuation [3, 4]. Traction bronchiectasis is also often seen in the areas of air-space consolidation or ground-glass attenuation [5].

The characteristic high-resolution CT findings of hypersensitivity pneumonitis consist of areas of ground-glass attenuation, centrilobular nodules, and patchy air-space opacification with micronodules [6,7,8]. In the acute stage, air-space consolidation may also be seen [7].

Acute eosinophilic pneumonia is characterized by infiltration of eosinophils, mononuclear cells, and edema in alveoli, bronchial walls, and, to a lesser degree, the interstitial space and pleura. The high-resolution CT findings of acute eosinophilic pneumonia consist of bilateral areas of air-space consolidation, ground-glass attenuation, interlobar septal thickening with no zonal predominance, and pleural effusion [9,10,11]. In the present study, thickening of bronchovascular bundles was also common, seen in 55% of cases.

The high-resolution CT findings of pulmonary hemorrhage consist of areas of ground-glass attenuation and air-space consolidation [12, 13]. Another common finding seen in the current study was interlobular septal thickening, present in 67% of patients with pulmonary hemorrhage.

Even though overlap exists, each of the acute lung diseases had a combination of findings that was characteristic. For example, the pleural effusion, traction bronchiectasis, and lungs with honeycombing were seen much more commonly in acute interstitial pneumonia than in the other acute processes. Upper or lower distribution and segmental distribution were seen predominantly in bacterial pneumonia or mycoplasmal pneumonia.

In our study, higher accuracy in both diagnosis and diagnosis with high degree of confidence was observed in cases of acute interstitial pneumonia and hypersensitivity pneumonitis. Both diseases often have a characteristic appearance on CT [3,4,5,6,7,8], which, combined with the radiologists' familiarity with the CT findings, allowed a correct diagnosis in most cases.

Lower accuracy in diagnosis was observed in cases of acute eosinophilic pneumonia and pulmonary hemorrhage. The CT findings of pulmonary hemorrhage are nonspecific, consisting of areas of air-space consolidation and ground-glass attenuation that may be diffuse or patchy in distribution. These findings can resemble those of acute eosinophilic pneumonia, which accounts for the low accuracy in the diagnosis of pulmonary hemorrhage in this study. As a consequence, pulmonary hemorrhage was most frequently misdiagnosed as acute eosinophilic pneumonia, and acute eosinophilic pneumonia was most frequently misdiagnosed as pulmonary hemorrhage. Acute eosinophilic pneumonia had the highest incidence of pleural effusion. Therefore, with attention to pleural effusion, acute eosinophilic pneumonia could be diagnosed correctly.

The most helpful finding in distinguishing infectious from noninfectious causes was the presence of centrilobular nodules. Centrilobular nodules in a patchy distribution are most suggestive of infectious disease. Centrilobular nodules distributed diffusely and profusely throughout the lungs are characteristic of hypersensitivity pneumonitis. Centrilobular nodules were uncommon in the other noninfectious causes of acute diffuse infiltrative lung disease.

Our study has several limitations. Because no clinical information was given, the observers were at an unrealistic disadvantage. In clinical practice, an infectious cause is usually readily identified by a combination of clinical and laboratory findings. The study is also biased because in clinical practice the differential diagnosis includes a large number of disorders rather than only the six diseases included in our study. Furthermore, the study has a selection bias, with an underrepresentation of infectious causes of acute lung disease. However, the main goal of the study was to determine whether the various acute parenchymal lung disease findings are characteristic enough to allow their distinction on high-resolution CT. This goal was achieved, we believe, by having the observers review the findings without awareness of the clinical data and by committing to a diagnosis based on previous data in the literature. The previous data were often based on review of findings in patients with known diagnoses and, therefore, biased to recognition of expected pattern and distribution of abnormalities. On the basis of the results of this study, we consider that the most helpful finding in distinguishing acute diffuse infiltrative lung disease is the presence of a combination of air-space consolidation, centrilobular nodules, and segmental distribution to diagnose mycoplasmal pneumonia and bacterial pneumonia; a combination of air-space consolidation, traction bronchiectasis, and random distribution to diagnose acute interstitial pneumonia; and a combination of ground-glass attenuation, centrilobular nodules, and nonsegmental distribution to diagnose hypersensitivity pneumonitis. However, the study shows considerable overlap between the CT findings of the various diseases that precludes a confident diagnosis in most cases.

In conclusion, high-resolution CT is helpful in the differential diagnosis of infectious from noninfectious acute parenchymal lung disease in immunocompetent patients. However, the CT findings overlap considerably. Therefore, CT is of limited value in making a specific diagnosis.

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