Fibrosing alveolitis (FA) is a frequent and often fatal complication of systemic sclerosis (SSC). Alveolar inflammation has been recognized as a primary event in the pulmonary manifestation of SSC. To evaluate the significance of the alveolitis in SSC, we performed bronchoalveolar lavage (BAL) and correlated the generated data with changes in lung function over time. Seventy nine SSC patients with pulmonary involvement were followed for 56.8 +/- 3.1 wk (mean +/- SEM) with a repeat lung function test at the end of the follow-up period. During follow-up, 38 patients were treated with a systemic immunosuppressive regimen. For evaluation, patients were assigned to two groups according to whether their BAL cell differential was normal (inactive BAL) or abnormal (active BAL: i.e., polymorphonuclear leukocytes > 5% and/or lymphocytes > 15%). Active BAL was associated with more severe lung function impairment than was inactive BAL, and patients with active BAL deteriorated during follow-up if untreated. In contrast, treated patients with active BAL stabilized or improved. In summary, active alveolitis as characterized by BAL is associated with progressive pulmonary disease in SSC patients, and a significant positive effect of immunosuppressive therapy on the course of pulmonary disease was observed in patients with active BAL.

Aerosol bolus dispersion is a physiological test of lungs, which uses monodisperse submicron particles to measure intrapulmonary convective gas mixing. In this study, aerosol bolus dispersion was measured in healthy subjects in order to assess reference values for possible clinical applications, to assess the reproducibility of these values, and to identify physical and physiological factors influencing aerosol bolus dispersion.Aerosol bolus dispersion was measured in 79 healthy subjects using 20 cm 3 aerosol boluses consisting of monodisperse di-2-ethylhexyl sebacate (DEHS) particles.The reproducibility of parameters characterizing the width of the exhaled bolus was of the same order as that of parameters of the flow-volume curve (10%). Aerosol bolus dispersion was independent of the level of lung inflation, and the slope of the relationship between flow rate and dispersion was on average not significantly different from zero (range 100-700 cm 3 ·s -1 ). Multiple linear regression showed that aerosol bolus dispersion increased with increasing total lung capacity of the subject.We conclude that differences in total lung capacity between individuals should be taken into account when using measures of aerosol bolus dispersion for possible clinical applications. Eur Respir J 1997; 10: 460-467 Changes in lung ventilation distribution are presumed to be an early indication of lung disease. Such changes have been observed in patients with various lung diseases [1, 2], and in smokers [3]. A simple and noninvasive diagnostic test, which is sensitive to such ventilatory disturbances, could efficiently supplement conventional methods used in lung diagnosis, occupational and environmental medicine, and epidemiology. The aerosol bolus dispersion test is a technique with the potential to meet these requirements. This technique employs monodisperse submicron aerosol particles as tracers of the convective gas transport in the lungs. Its diagnostic capabilities have been shown in several studies: ventilatory disturbances in patients with cystic fibrosis [4]; papaininduced peripheral lung injury in excised animal lungs [5]; and changes in lung ventilation distribution due to ozone exposure [6]. Recently, it has been shown that this technique has higher sensitivity and specificity than conventional lung function tests in detecting early lung impairment due to cigarette smoking [7].This study addresses one requirement for the possible clinical application of this technique, namely the reliable assessment of individual specific reference values for the healthy state. Respiratory experiments were conducted on a sample of 79 nonsmokers with normal, healthy lungs. The variability of the measurements over time was tested in two of these subjects over a period of 6 months. To characterize physical and physiological factors influencing aerosol bolus dispersion, the effect of lung inflation and flow rate was investigated in subgroups of these subjects. SubjectsSeventy nine healthy nonsmokers (38 males and 41 females) were includ...

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An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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A Ae er ro os so ol l d de er ri iv ve ed d a ai ir rw wa ay y m mo or rp ph ho om me et tr ry y i in n h he ea al lt th hy y s su ub bj je ec ct ts s Airspace dimensions were in good agreement with morphometric lung data. Airspace dimensions increased with increasing lung inflation. Interindividual variation of airspace dimensions was lowest in the lung periphery, at high levels of lung inflation, and when the volumetric lung depth was normalized to the endinspiratory lung volume. Analysis of variance showed an increase of airspace dimensions with age.The results of this study indicate that aerosol-derived airway morphometry is dependent on the level of lung inflation and the age of the subject. These results suggest that in contrast to conventional lung function techniques, aerosol-derived airway morphometry might be a powerful tool for the detection of small changes in peripheral airway geometry. Eur Respir J., 1995Respir J., , 8, 1639Respir J., -1646

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Recently, in addition to the detection of circulating tumor cells in peripheral blood of patients with solid tumors, the presence of free circulating nucleic acids in the plasma and serum has also been described. We have focused on the possibility of isolating and amplifying intact extracellular, tumor-related mRNA from the plasma/serum of patients with lung cancer. For this purpose, we established several RT-PCR-based amplification systems for the detection of a panel of five different genes. The expression of these genes was either shown to be restricted to lung tissue or associated with malignancy. We examined two small groups of 18 patients with lung cancer before and during chemotherapy, respectively. The message for ␤-actin (control for integrity of the RNA) was detected in all of the analyzed sera from the control group and patients with lung cancer. Analysis of CK-19 expression was positive in the majority of tumor patients, but positive results were also shown in all of the control sera. The expression of MAGE-2 and TTF-1 genes was not observed in any of the patients in either the lymphocyte preparations or serum samples. Expression of the PGP 9.5 gene was observed in the cells of all 18 patients, but mRNA in the serum was only detectable in one case. The hnRNP-B1 mRNA was detectable in 14/18 sera, and Her2/neu-specific mRNA could be amplified from the serum of 7/18 patients. Combining the last two markers, we were able to detect all patients with a malignant lung tumor.