Investigation of lung clearance of 99mTc-labelled diethylene triamine penta-acetic acid (DTPA) in smoking sarcoid patients has been impeded by difficulties to differ between pathology of clearance kinetics caused by sarcoidosis and by smoking. This study explores the kinetics of lung clearance of 99mTc-DTPA in 15 current smokers with intrathoracic sarcoidosis. The results are compared with findings from 16 healthy smokers. Measurements of lung clearance over 180 min, i.e. longer than usual, revealed in II of the sarcoid patients a bi-exponential lung clearance course, which is pathologic. All healthy smokers also showed a bi-exponential lung clearance. In the analysis of the bi-exponential curve an initial fast, and a slow clearance component could be separated. The smokers with sarcoidosis had a significantly higher elimination rate of the slow component than the healthy smokers. Thus, analysis of the late part of the lung clearance curve may be rewarding in smoking sarcoid patients. The study shows that lung clearance of 99mTc-DTPA may be a method useful also in smoking patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK In interstitial lung disease lung clearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA) reflects alterations in the alveolar capillary barrier. Our objective was to describe changes in lung clearance during one year in sarcoidosis, and to relate clearance to other data of lung function and disease activity. METHODS Twenty-three newly diagnosed patients were studied with respect to lung DTPA clearance, spirometry, 67Ga scintigraphy and serum angiotensin converting enzyme (SACE). Lung mechanics and arterial PO2 at rest and exercise were studied in patients with radiological parenchymal changes. Six of these patients were prescribed peroral steroids. RESULTS At inclusion lung DTPA clearance measured over 30 minutes was 53 +/- 16 minutes and at follow-up 59 +/- 20 minutes (p > 0.05). The number of pathological clearance curves at inclusion was 10 and at follow-up 6. In treated patients lung DTPA clearance improved as did lung 67Ga score and SACE. However, lung clearance did not correlate significantly with changes in lung function or other activity parameters. CONCLUSIONS Lung DTPA clearance reflects lung function from an aspect different from that of other methods. It seems sensitive to pathology reversed by steroids and may, in some cases, help in the evaluation of disease activity.

In sarcoidosis the lung clearance of inhaled Tc-99m-labelled diethylene triamine pentaacetic acid (DTPA) is often abnormal. Few studies related the lung clearance of Tc-99m-DTPA to the results of other lung function tests and/or disease activity parameters. This study describes the relationship in sarcoidosis between the lung clearance of Tc-99m-DTPA measured over 180 minutes, and a set of function tests comprising lung volumes and lung mechanics as well as arterial blood gases. Disease activity was assessed with serum angiotensin-converting enzyme (SACE) and Ga-67 scintigraphy. Measurements of lung clearance, spirometry and SACE were thus performed in 41 never-smoking patients with radiologic signs of intrathoracic sarcoidosis. In 32 patients a Ga-67 scan was obtained. The clearance of Tc-99m-DTPA was abnormal in 23 patients. Either an abnormally fast mono-exponential clearance or a bi-exponential clearance course was disclosed. In 17 of these patients, dynamic spirometry was normal. The Ga-67 scan was abnormal in 15 patients. There was a significant association between abnormal lung clearance of Tc-99m-DTPA and abnormal pulmonary uptake of Ga-67. This suggests that lung clearance of Tc-99m-DTPA may be used as a means for assessing disease activity in pulmonary sarcoidosis.

The subtle changes often found in interstitial lung disease can be difficult to evaluate at conventional radiography. In order to define the information obtained with digital radiography, it is particularly important to find out to what extent interstitial lung disease can be observed with this technique. Ninety-one patients, 56 with interstitial lung disease and 35 with normal lungs, were examined both with a digital system and with conventional film-screen technique. The examinations were reviewed independently by 4 radiologists with different experience and receiver operating characteristics (ROC) curves were constructed. The 2 systems were equal in diagnostic performance with no statistic difference between the conventional radiographs, the 2 digital images reviewed together or the 2 digital images reviewed separately. There was a significant difference between the 2 observers with the highest and the one with the lowest score only in the review of digital unsharp mask images, but otherwise no differences statistically. A lower number of false negatives and a higher number of false positives were seen with the digital unsharp mask image, producing a higher sensitivity and lower specificity.

Fifteen patients with pulmonary sarcoidosis, representing the functionally most severely affected quartile of referred patients, were prescribed steroids during one year. During this period and after 7 years on average, measurements were made of lung volumes, the static elastic pressure/volume (PstL/V) curve and lung resistance (RL). Lung mechanics and arterial blood gases were studied at exercise. Within months static compliance (CstL) and the arterial partial pressure of oxygen improved along with radiography. A modest positive trend continued throughout the follow-up. The vital capacity followed CstL changes closer than did the total lung capacity, which remained low. Though CstL improved, transpulmonary pressure at maximal inspiration increased and the upper part of the PstL/V curve became flatter. RL remained moderately increased. The course of the physiologic findings may be explained by fairly stable parenchymal and peribronchial fibrosis after cessation of active inflammation, and by regress of reflex inhibition of inspiration. Thus most subjects showed modest improvement during and after treatment. The initial study of lung function provided important prognostic information. The study does not allow conclusive evidence with respect to long term benefit of treatment, but encourages continued use of steroids under the guidance of function tests.

To clarify how lung function at exercise is affected in sarcoidosis, and to analyze how exercise studies compare to testing measurements, 63 patients with pulmonary sarcoidosis were examined with lung mechanics and arterial blood gases during exercise. These findings were compared with simultaneously obtained, but previously reported results of the static lung pressure/volume curve and the lung resistance/static lung pressure curve. While mechanical variables at maximal exercise were as sensitive as those determined by measuring the PstL/V and RL/PstL curves, mechanics during spontaneous breathing at rest was less sensitive. The derangement of mechanics was more evident than that of arterial blood gases. No measurement at rest was a good predictor of working capacity or of arterial PaO2. A comprehensive exercise examination may be an alternative to resting investigations, which are either more elaborate or less sensitive.

Pulmonary sarcoidosis was studied with respect to lung mechanical properties and to the influence of these on lung volumes. Sixty-six patients, with histological support for the diagnosis of sarcoidosis, and radiological signs of pulmonary involvement, i.e., stage II or III, were studied. The static pressure/volume (P/V) curves showed that the static elastic recoil pressure (PelL) tended to be increased at a given percentage of predicted total lung capacity (TLC). Reduction of static lung compliance (CstL) was a typical finding. At maximal inspiration PelL was abnormally low in 20 subjects, including in the main those with recent onset of the disease and older patients. The possibility of a greater inflammatory activity at the site of mechanical receptors in the lungs and airways of these patients is proposed. Pulmonary resistance, measured at a given PelL, was usually increased signifying bronchial involvement. TLC, residual volume (RV) and functional residual capacity (FRC) were lower in current smokers and ex-smokers than in lifelong nonsmokers. This may be due to synergistic effects of the inflammatory processes caused by smoking and sarcoidosis. A reduced vital capacity (VC) mainly reflected a low CstL but also obstruction with increased RV. Forced expiratory volume in one second (FEV1) reflected lung stiffness and obstruction equally. Lung mechanics revealed functional abnormalities which were not obvious from the standard tests, particularly in patients with respiratory symptoms.