Centrilobular Emphysema Research Articles

HYPERSENSITIVITY PNEUMONITIS

Emphysema is most commonly associated with smoking but also occurs in hypersensitivity pneumonitis (HP). The aim of this study was to further explore this relationship.A retrospective, computer-assisted search was performed to identify patients with HP seen at Mayo Clinic in Rochester, Minnesota, from January 1997 through February 2014. Demographic, clinical, and imaging features were analyzed. Patients were excluded if they had a smoking history of 10 pack-years or more.Twelve patients (9 males) with HP and computed tomographic evidence of emphysema were identified. Ten were never smokers and 2 were ex-smokers. The median age at diagnosis was 47 (range, 29–77) years; median symptom duration was 2.2 (range, 0.2–13.4) years. The most common presenting symptoms were dyspnea (83%) and cough (67%). On pulmonary function testing, 6 patients (50%) had a restrictive defect, 2 (17%) had airflow obstruction, and 4 (33%) had an isolated reduction in diffusing capacity of lung for carbon monoxide. The severity of emphysema ranged from mild to severe to focal bullae. All patients had chronic hypersensitivity pneumonitis (CHP). Centrilobular emphysema was most commonly seen with coexistent paraseptal emphysema in 5 patients.Emphysema was most frequent in the upper lung but could be seen in any lobe.Emphysema can occur in patients with CHP independently of smoking history and exposure to specific types of antigens. Emphysematous changes seem to progress at a slower pace compare to reticulations/fibrosis.

High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity.

To determine the prevalence of "nonobstructive" (impairment of gas transfer) emphysema in a select population of smokers with dyspnea, a retrospective study of patients with emphysema evident at high-resolution computed tomography (HRCT) was undertaken. Four hundred seventy HRCT studies were reviewed. In 47 cases, centrilobular emphysema was the dominant or sole parenchymal abnormality. Concomitant chest radiographs were available in 41 of these cases; 16 of the 41 lacked radiographic findings of emphysema. Among these 16 patients, pulmonary function testing revealed 10 to have normal flow rates (ratio of forced expiratory volume in 1 second to forced vital capacity and forced expiratory volume in 1 second greater than 80% predicted) and impaired gas transfer (single-breath carbon monoxide diffusing capacity [DLCOSB] less than 80% predicted). With the exclusion of one patient with congestive heart failure from the group of 10, the severity of emphysema at HRCT correlated inversely with DLCOSB (r = -.643). These results indicate that HRCT allows detection of emphysema in symptomatic patients when chest radiographs and pulmonary function tests are nondiagnostic.

Histological features of the airways in asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions which make definitive morphological comparisons difficult. Broadly, the airways in asthma are occluded by tenacious plugs of exudate and mucus, there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina and bronchial vessel congestion and oedema. There is increased inflammatory infiltrate comprising 'activated' lymphocytes and eosinophils with release of granular content in the latter, and there is enlargement of bronchial smooth muscle particularly in medium sized bronchi. Three conditions contribute to COPD. In chronic bronchitis there is mucous hypersecretion with enlargement of tracheo-bronchial submucosal glands and a disproportionate increase of mucous acini. In small (peripheral) airways disease, there is inflammation of bronchioli, mucous metaplasia and hyperplasia, with increased intralumenal mucus, increased wall muscle, fibrosis and airway stenoses. Respiratory bronchiolitis is a critically important early lesion which may predispose to the development of centrilobular emphysema. The severity of destruction of alveolar wall in emphysema appears to be the most important determinant of chronic deterioration of airflow.

Centrilobular and Panlobular Emphysema in Smokers: Two Distinct Morphologic and Functional Entities

In order to investigate the hypothesis that different morphologic patterns of disease might correspond to different mechanical properties of the lung in emphysema, pulmonary function tests and lung mechanics were measured in 34 subjects undergoing lung resection for peripheral lung tumors. Using standard microscopic criteria, pure or predominant centrilobular (n = 18) or panlobular (n = 16) emphysema was diagnosed in lungs. The degree of emphysema measured by the mean linear intercept (Lm) was not significantly different between the two groups. However, the coefficient of variation of the interalveolar wall distance (CV) was significantly higher for the same Lm in CLE than in PLE. This indicates that CLE has an uneven pattern of destruction, whereas PLE is more homogeneous. CLE had a higher degree of abnormalities in the small airways (SAD) than did PLE (p less than 0.05) mainly because of significantly higher muscle score (p less than 0.001) and fibrosis. CLE also had a higher proportion of airways less than 400 microns in diameter than did PLE (p less than 0.05). Static compliance, specific compliance, and the exponential constant (K) were significantly lower (p less than 0.005, p less than 0.001, and p less than 0.05, respectively) in CLE than in PLE. FEV1/FVC was significantly correlated with SAD in CLE (r = -0.69, p less than 0.01) but not in PLE (r = 0.29 p greater than 0.05); conversely, FEV1/FVC was significantly correlated with elasticity (K) in PLE (r = -0.72, p less than 0.01) but not in CLE (r = 0.08, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Scanning Electron Microscopic Observations of Emphysema in Humans: A Descriptive Study

We have performed dissecting light and scanning electron microscopy (SEM) on 14 lungs with mild centrilobular emphysema, two of which also had mild panacinar emphysema. The lungs were surgically resected, mainly for cancer. The walls of centrilobular emphysema were either thick or thin. The former were less common and represented fibrosis of the walls. The latter were less fibrotic, but some fibrosis was seen. Adjacent alveoli were compressed and distorted, and overlapping walls of air spaces occurred. In panacinar emphysema alveolar ducts were enlarged and flattened with transverse linear bands interpreted as flattened walls of enlarged alveoli. The walls of air spaces were chiefly lined by type I and type II epithelial cells, but occasionally bronchiolar epithelium lined the proximal emphysematous spaces. Supplying bronchioles showed diminished numbers of ciliated cells with cilia of reduced height. SEM was much more sensitive than dissecting microscopy in recognizing emphysema. The apparent fibrosis suggests that the definition of emphysema may have to be reconsidered and that if fibrosis is apparent, the proteolysis-antiproteolysis hypothesis of the pathogenesis of emphysema may have to be modified.

Sequential Morphologic Changes of Elastase-Induced Pulmonary Emphysema in Pig Lungs

The authors evaluated the early morphologic changes of elastase-induced pulmonary emphysema in the pig and correlated the findings with high-resolution computed tomography (HRCT). Nine Yorkshire pigs were included in this investigation; in seven, pulmonary emphysema was induced by 2 mg/kg body weight of elastase instilled selectively into the left lower lobe bronchus. Animals were studied by CT at 0, 1, 2, 3, 7, 14, and 21 days. At the completion of the experiment, the lungs were removed, inflated, fixed and dried, and subsequently sliced corresponding to the CT sections. The gross appearance, histologic appearance, and HRCT were correlated. On HRCT, sequential changes from early edema to development of emphysema were noted. Panlobular, centrilobular and paraseptal emphysema were observed. Elastase-induced pulmonary emphysema in the pig is a useful and reproducible animal model, and high-resolution computed tomography depicts the morphologic changes observed both by gross pathologic observations and histologic observations.

Morphology of the Airway Wall in Asthma and in Chronic Obstructive Pulmonary Disease

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions, which make definitive morphologic comparisons difficult. Broadly, the airways in asthma are occluded by tenacious plugs of exudate and mucus, and there is fragility of airway surface epithelium, thickening of the reticular layer beneath the epithelial basal lamina, and bronchial vessel congestion and edema. There is increased inflammatory infiltrate comprising "activated" lymphocytes and eosinophils with release of granular content in the latter, and there is enlargement of bronchial smooth muscle, particularly in medium-sized bronchi. Three conditions contribute to COPD. In chronic bronchitis there is mucous hypersecretion with enlargement of tracheobronchial submucosal glands and a disproportionate increase of mucous acini. In small or peripheral airways disease, there is inflammation of bronchioli and mucous metaplasia and hyperplasia, with increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses. Respiratory bronchiolitis is a critically important early lesion that may predispose to the development of centrilobular emphysema. The severity of emphysema, rather than type, appears to be the most important determinant of chronic deterioration of airflow, and in this there may be significant loss of elastic recoil prior to the observed morphologic destruction of the acinus.

Computed Tomography in the Etiologic Assessment of Idiopathic Spontaneous Pneumothorax

In an attempt to elucidate the origin of the so-called idiopathic spontaneous pneumothorax (ISP), clinical examination, pulmonary function tests, and computed tomography (CT) with visual quantification and density analysis were performed in 20 young patients two months after an ISP episode. Twenty controls were recruited for CT. The chest roentgenograms were normal in the two groups. The results indicated the presence of various types of emphysematous lesions (EL) in the ISP group located predominantly in the apical fields with subpleural location in 16 patients. Interestingly, diffuse but moderate centrilobular emphysema was noted in 12 of 20 patients. The EL visual quantification was always less than 5 percent of the CT slices' total areas. The lung mean density shifted significantly toward the air density in the patient group (patients: -743 +/- 57.5 HU vs controls -713 +/- 59.5 HU, p less than 0.01). These findings suggest that CT may be useful for early assessment of EL in patients with ISP.

Toxicity of Intratracheally Instilled Cotton Dust, Cellulose, and Endotoxin

Cotton dust includes respirable particles containing endotoxin and elastase, agents associated with emphysema. To examine whether a respirable fraction of cotton dust could produce emphysema in an animal model, we intratracheally instilled hamsters with respirable cotton dust particles (0.75 mg/100-g animal), mass median aerodynamic diameter less than or equal to 4.8 microns, twice weekly for 6 wk. We also examined whether instilled endotoxin (255 micrograms/100-g animal) could produce emphysema in hamsters and whether cellulose (0.75 mg/100-g animal) is an appropriate inert comparison dust. A saline-instilled group was the control. Hamsters were killed 8 wk after the last instillation. Static pressure-volume deflation curves of air-filled excised lungs were analyzed to measure lung distensibility. Lungs were fixed in inflation using glutaraldehyde and were examined morphometrically to obtain surface area and numbers of granulomata. Endotoxin-treated animals had increased distensibility, reduced surface-to-volume (S/V) ratio, and morphologically apparent mild centrilobular emphysema. Cellulose-treated animals had decreased distensibility, normal S/V ratio, and significant numbers of granulomata with patchy areas of thickened interalveolar septa. Cotton-dust-instilled animals had normal distensibility, reduced S/V ratio, significant numbers of granulomata, and mild centrilobular emphysema. These data suggest that cotton dust produces a significant parenchymal lesion with elements similar to both the emphysematous response to endotoxin and the fibrotic nodular response to cellulose.

Neutrophil Elastase Activity and superoxide Production Are Diminished in Neutrophils of Alcoholics

Several lines of evidence indicate that neutrophil elastase and oxidants secreted by phagocytic inflammatory cells play key roles in the development of centrilobular emphysema. A recent report suggests that ethanol consumption may have a protective role against this disease in smokers. The aim of this study was to examine the effect of ethanol consumption on neutrophil elastase activity and superoxide production of peripheral blood neutrophils. These activities were measured in neutrophils from 52 male intoxicated patients and compared to activities in neutrophils from 20 male volunteers. Neutrophils from intoxicated patients contained 31% less elastase activity than that found in controls, 0.99 +/- 0.27 versus 1.44 +/- 0.23 micrograms/10(6) neutrophils (p less than 0.0001) and produced 25 to 27% less superoxide than controls in response to phorbol 12-myristate-13-acetate, 0.90 +/- 0.17 versus 1.2 +/- 0.21 nmol/min/10(6) PMN (p less than 0.0001) or N-formylmethionylleucylphenylalanine, 0.64 +/- 0.19 versus 0.88 +/- 0.24 (p less than 0.001). In follow-up studies of 10 patients admitted for acute alcoholism, elastase activity and superoxide production remained low for 2 to 4 days. After 6 to 10 days, elastase activity and superoxide production were significantly greater than they were at Day 0 and approached normal levels. Neutrophils isolated from blood samples of healthy abstaining donors, which had been exposed to ethanol or to plasma from inebriated patients for 16 to 20 h, showed no loss of elastase activity or superoxide production.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathology of Chronic Airflow Obstruction

Classification of chronic airflow obstruction may be based on the site of the obstructing lesions. It is seldom that only one type of lesion is present, but one may often dominate. In chronic bronchitis, the major disease of large airways, chronic mucus hypersecretion, is reflected by an increase in size of bronchial mucous glands. This may be a factor in airway narrowing, especially with coexisting edema of the airway wall. Excess intralumenal mucus compounds the obstruction. Increased airways reactivity is present in 15 to 70 percent of patients with chronic airflow obstruction. Increased airway muscle and cartilage atrophy are features of chronic bronchitis, but the association of increased muscle with increased airway reactivity is poor. Inflammation of the small airways (bronchiolitis) is a significant complication for cigarette smokers and is an important cause of mild chronic airflow obstruction. Goblet cell metaplasia is a reflection of chronic small airways inflammation and, together with intralumenal mucus, is an important feature. Permanent narrowing of the small airways presumably results from inflammation with consequent fibrosis, while functional narrowing results from release of mediators of inflammation. Increased muscle mass is present in some cases. Distortion and irregularity of small airways related to emphysema are major factors in severe obstruction. Lesser degrees of emphysema may be associated with a diminished number of alveolar attachments and mild chronic airflow obstruction. Emphysema, the dominant lesion in patients with severe chronic airflow obstruction, results from parenchymal lesions. Centrilobular emphysema, in which the respiratory bronchioles are selectively or dominantly involved, is the most common form.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between small airways disease and parenchymal destruction in surgical lung specimens.

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema.

The effect of cigarette smoking on neutrophil kinetics in human lungs.

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of radiolabeled neutrophils from the lung (0.08 +/- 0.04 of the total per minute, as compared with 0.13 +/- 0.06 in smokers who did not smoke during the experiment and 0.14 +/- 0.08 in non-smokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels.

Chronic obstructive pulmonary disease: a definition and implications of structural determinants of airflow obstruction for epidemiology.

Chronic obstructive pulmonary disease (COPD) may be defined as a process characterized by the presence of chronic bronchitis or emphysema that may lead to the development of airways obstruction; airways obstruction need not be present at all stage of the process and may be partially reversible. The pathologic changes in the lungs due to smoking affect three regions: the bronchi, bronchioles, and parenchyma. The bronchi show enlargement of the submucosal glands with dilation of their ducts; infiltration with neutrophils and lymphocytes is present but not prominent. Respiratory bronchiolitis is observed in persons smoking for only a few years; the membranous bronchioles show a mix of inflammation, luminal mucus, goblet cell metaplasia, and distortion due to fibrosis and loss of alveolar attachments. The lung parenchyma shows centrilobular emphysema. Bronchial changes are only weakly related to airflow obstruction but bronchiolar changes are also related. The relation between airflow limitation and bronchiolitis is progressively harder to show as the severity of emphysema increases because of the dominant role of emphysema in causing airflow obstruction. Emphysema is the predominant lesion in persons with severe airflow obstruction due to COPD. The diffusing capacity for carbon monoxide is related to the severity of emphysema but is nonspecific and is mildly abnormal in smokers without emphysema. The compliance of the lungs of smokers is decreased even when a emphysema and airflow limitation are mild. Standard epidemiologic tools do not differentiate emphysema from other causes of airflow obstruction. Most persons dying of COPD will have severe emphysema.

Pulmonary parenchymal disease: evaluation with high-resolution CT.

Usefulness of high-resolution computed tomography (HRCT) in locating pulmonary parenchymal disease in relation to the pulmonary lobule was evaluated in 71 patients, including 30 with normal pulmonary parenchyma and 41 with various pulmonary diseases. Both 10-mm-thick sections and 1.5- or 3.0-mm-thick HRCT scans were obtained. Distribution of pulmonary parenchymal disease was classified as centrilobular, panlobular, perilobular, bronchovascular, or nonlobular. Intralobular classification of disease distribution was more feasible in less severely diseased regions. HRCT revealed thickened intralobular bronchovascular bundles in patients with bronchiolitis obliterans, mycoplasma pneumonia, and pulmonary tuberculosis and thickening of both bronchovascular bundles and perilobular structures in patients with sarcoidosis, lymphangitis carcinomatosa, and malignant lymphoma. Centrilobular areas of increased attenuation were seen in patients with bronchopneumonia and pulmonary cryptococcosis. Centrilobular emphysema and bronchiolectasis were recognized only on HRCT images. The improved clarity and sharpness of parenchymal abnormalities on HRCT images, even in severely involved areas, provide additional information about disease distribution.

Chronic obstructive pulmonary disease: risk factors, pathophysiology and pathogenesis.

Chronic obstructive pulmonary disease (COPD) is defined in this chapter, and the relation between its two major components, (a) chronic bronchitis and emphysema and (b) nonremitting asthma, is discussed. Intensity of tobacco smoking and age are the major risk factors for the development of chronic airways obstruction. Environmental air pollution, childhood infections, and familial factors other than alpha-1 protease inhibitor deficiency appear to play only small roles. Emphysema is the major cause of severe airways obstruction; bronchiolitis is a contributing factor and likely is responsible for the minor reversible element of airways obstruction. The elastase-antielastase hypothesis, which is based mainly on indirect evidence, is the best explanation for the pathogenesis of emphysema. Extensive airspace enlargement with fibrosis is infrequently observed; this mechanism may play a role in the pathogenesis of the centrilobular emphysema of smokers.

Cadmium-chloride-induced air-space enlargement with interstitial pulmonary fibrosis is not associated with destruction of lung elastin. Implications for the pathogenesis of human emphysema.

To determine whether lung elastin is lost during the evolution of cadmium-induced air-space enlargement with pulmonary fibrosis, the lung elastin of 5- to 7-day-old golden Syrian hamster pups was radiolabeled by giving [3H]valine. At maturity, a single intratracheal instillation of 0.5 ml of 0.025% CdCl2 solution was given. Lung mechanics, histologic examination, and biochemistry were studied 5, 10, 21, 42, 105, and 180 days after the cadmium treatment. The animals developed fibrosis and air-space enlargement with decreased lung volumes, compliance, and forced expiratory flow; their functional residual capacity was increased. The total lung collagen and total lung elastin were increased, but there was no loss of radiolabel in lung elastin. We conclude that CdCl2-induced air-space enlargement with pulmonary fibrosis is not accompanied by loss of neonatally formed lung elastic fibers. We hypothesize that air-space enlargement with fibrosis represents a stereotyped response of the lung to fibrosing injuries, which we hypothesize is due to forces from more fibrotic and atelectatic areas causing overdistension of less abnormal air spaces. The air-space enlargement of fibrosing human diseases such as sarcoidosis and eosinophilic granuloma may have a similar basis. Evidence is reviewed that human centrilobular emphysema may be a form of focal air-space enlargement with interstitial fibrosis; there may be mechanisms in addition to elastase-antielastase imbalance that cause human emphysema.

Detection of Emphysema with Computed Tomography

We studied 60 male patients who had concurrent chest films (CXR), computed tomography scans (CT) and pulmonary function tests (PFT) to assess the sensitivity of CT and conventional films in detecting emphysema compared with PFT. We also sought to determine whether emphysema could be diagnosed by CT in patients with normal pulmonary function. Using a method similar to that proposed by Bergin, we scored the severity of emphysema depicted by CT, and using arterial deficiency and bullae as criteria, we estimated the degree of emphysema on CXR. There was a significant inverse correlation between CT scores for emphysema and percentage predicted values of DLco/VA (r = -0.650), FEV1 (r = -0.552), and FVC (r = -0.409), (P less than 0.001). A significant but smaller correlation also was noted with the CXR scores and percentage predicted: DLco/VA (r = -0.564), FEV1 (r = -0.454), and FVC (r = -0.355), (P less than 0.005). When decreased diffusion capacity and airway obstruction were used as functional criteria of emphysema, CT was as sensitive as PFT and more sensitive than CXR in detecting emphysema (96% vs. 68%). There was CT evidence of emphysema in 69% (24/35) of patients who did not have functional findings of emphysema. In 12 pathologic specimens available for review, 11 had emphysema by CT and pathologic examination; one patient had centrilobular emphysema undetected by CT. We conclude that CT is as sensitive as PFT in detecting emphysema and more sensitive than conventional radiography. CT may be more sensitive than PFT in detecting mild emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

High Resolution Computed Tomography of Inflation-fixed Lungs: Pathologic-Radiologic Correlation of Centrilobular Emphysema

Centrilobular emphysema (CLE) is a disease defined pathologically. Assessment of the accuracy of high resolution computed tomography (CT) in the diagnosis of centrilobular emphysema has been hampered by a lack of pathologic correlation. We applied high resolution computed tomography to 20 postmortem lung specimens fixed by a method that allows for direct one-to-one pathologic-radiologic correlation. The degree of centrilobular emphysema was assessed radiologically on a visual grading system based on nonperipheral low-attenuation areas. The lungs were then sectioned along the plane of the CT image, and the degree of centrilobular emphysema was graded pathologically by scoring against a panel of standards. A significant correlation (r = 0.91, p less than 0.005) was found between the pathologic grade and the in vitro CT score.

Centrilobular emphysema: CT-pathologic correlation.

Over a 5-year period, 25 patients who had undergone chest computed tomography (CT) died and were autopsied. Their lungs were fixed in the inflated state and were assessed for the presence and severity of centrilobular emphysema (CLE). Three radiologists independently evaluated the CT scans for nonperipheral low-attenuation areas, peripheral low-attenuation areas, pulmonary vascular pruning, pulmonary vascular distortion, and pulmonary density gradient. The CT criterion that best correlated with the presence and severity of CLE was the nonperipheral low-attenuation area. With this CT criterion, lung destruction was correctly identified in 13 of 15 cases. The absence of this criterion resulted in correct identification of eight of ten normal lungs. These preliminary data suggest that CLE can be reliably identified and quantified with current CT scanners.