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Usefulness of Pulmonary Vascular Leakiness Assessment in Interstitial Pneumonitis

Usefulness of Pulmonary Vascular Leakiness Assessment in Interstitial PneumonitisInflammatory alteration in the function of the barrier of the alveolar septum is one of the main pathophysiologic events leading to destruction of the pulmonary architecture and to pulmonary fibrosis. Increased pulmonary epithelial permeability following alveolar septal injury has been demonstrated in several studies of interstitial lung diseases. While the assessment of pulmonary vascular leakiness has been found useful to estimate lung injury in the ARDS,- its value in interstitial pneumonitis (IP) remains unclear. We have previously reported that pulmonary vascular leakage of In-transferrin was increased in an animal model of acute lung injury induced by bacterial peritonitis or IV oleic acid administration. In addition, Raijmakers et al were able to show, by IV injection of Ga citrate, which is expected to bind to circulating transferrin, that the pulmonary leak index (LI) is increased after noncar-diogenic pulmonary edema and cardiopulmonary bypass surgery. In this study, pulmonary vascular leakiness to IV-injected Ga citrate, thereafter referred to as LI, was estimated in patients with IP by our previously reported method. A quantitative estimate of pulmonary Ga uptake (gallium index) was also performed 48 h after the measurements of LI to compare both indexes, and to clarify the correlation between pulmonary Ga uptake and vascular leakiness in IP. Finally, the contribution of LI in the assessment of disease activity in IP was examined.
Materials and Methods
All study participants were admitted between July 1998 and November 1999 to the Departments of Medicine at either the National Minami-Yokohama Hospital or the Tokyo Electric Power Company Hospital. This study was reviewed by the ethics committee of our institutions and was performed in accordance with the ethical standards expressed in an appropriate version of the 1964 Declaration of Helsinki. Informed consent was obtained from each participant prior to the study.
The index population consisted of 14 men and 6 women, 25 to 79 years of age. Idiopathic IP was diagnosed in 17 patients, 2 patients had IP associated with collagen vascular diseases, and 1 patient had eosinophilic pneumonia. Four serial Ga examinations were performed in a single patient with acute interstitial pneumonia, for a total of 23 measurements. The diagnosis of IP was histologically confirmed by specimens from transbronchial lung biopsy, open lung biopsy, thoracoscopic lung biopsy, or at autopsy in 17 of the 20 patients. On the basis of the pathologic and radiographic findings, and from the clinical course, including rate of disease progression, usual interstitial pneumonia was diagnosed in 13 of these 17 patients, acute interstitial pneumonia was diagnosed in 1 patient, nonspecific interstitial pneumonia was diagnosed in 2 patients, and bronchiolitis obliterans organizing pneumonia was diagnosed in 1 patient (Table 1). The pathologic findings in the two patients with IP associated with collagen vascular diseases resembled those of usual interstitial pneumonia.
In four febrile patients who had marked decreases in Pao2 and progression of infiltrates on chest radiographs, BAL was performed with 50 mL of saline solution after the pulmonary gallium uptake measurement, in search of an infectious process.
In addition to symptoms and radiographic findings consistent with IP, the disease was considered to be active when (1) either a > 5 mm Hg decrease in arterial O2 tension or > 3% decrease in arterial O2 saturation under stable O2 therapy was observed within 3 months preceding or following the Ga study, and (2) in absence of clear evidence of pulmonary infection. Measurements of gas exchange were made after at least 10 min of the patient being in the supine position and at normal body temperature. When a significant decrease in either Pao2 or arterial O2 saturation was observed, radiographic examinations, blood tests, including leukocyte counts, lactate dehydrogenase, and C-reactive protein, and sputum examinations were performed. In addition, whenever possible, pulmonary function tests were also obtained. Ultimately, a pertinent microorganism was identified in none of these IP patients.
The control population consisted of 15 men and 2 women, 34 to 75 years of age, who underwent Ga scintigraphy in search of a cause of prolonged low-grade fever. In 14 of these patients, the low-grade fever resolved within 3 weeks, and the ultimate diagnosis was a nonpulmonary infection in 8 patients. In three patients, the clinical presentation fulfilled the criteria of fever of unknown origin. One patient had a malignant lymphoma located in the abdomen. In two other patients, the source of fever of unknown origin remained unidentified. In all control patients, the chest CT scans was free of diffuse interstitial lung infiltrates, and results of pulmonary function tests and arterial blood gas analyses were normal.
Seventy-four millibecquerels of Ga citrate (Daiichi Radioisotope; Tokyo, Japan) was injected IV, and anterior chest dynamic imaging was performed with the patient in a supine position. Gamma-ray data collection by a gamma camera (GCA901A; Toshiba; Tokyo, Japan) equipped with a medium energy collimator began at the time of injection and continued for 30 min (frame time, 1 min; matrix size, 128 X 128). Static lung imaging was performed 48 h after the injection of Ga for 3 min.
Table 1—Clinical Characteristics of Patients With Interstitial Pneumonia

Diagnostic Decrease in Decrease in Steroid
Groups/Patient No. Age, yr Sex Diagnosis Method Pao2, mm Hg Sao2, % Therapy
Active disease
1 54 M BOOP TB 21.7 > 3 Yes
2 25 F EP TBLB 19.2 > 3 Yes
3 62 F UIP Autopsy 14.8 >3 Yes
4 78 M UIP TBLB 11.2 >3 Yes
5 58 M UIP OLB 13.8 >3 No
6 55 M UIP TB 10.1 >3 No
7 59 M UIP TBLB NM >3 Yes
8 63 F NSIP TB 17.8 >3 Yes
9 42 M NSIP TBLB 16.4 >3 Yes
10 79 M UIP Clinical 19.2 >3 No
11 69 F AIP TBLB 20.3 >3 Yes
Stable disease
13 63 M UIPf TBLB NM 0 Yes
14 78 M UIP Clinical 3.2 0 No
15 74 M UIPf Clinical NM 1 No
16 61 M UIP TBLB NM 0 Yes
17 59 M UIP TBLB NM 1 No
18 64 M UIP TBLB NM 0 Yes
19 61 F UIP TBLB NM 2 Yes
20 66 M UIP TBLB NM 0 No