[Clinical case of the month. Multiple pulmonary nodules. Epithelioid hemangioendothelioma]. / Le cas clinique du mois. Nodules pulmonaries multiples. L'hémangio-endothéliome épithélioïde.

The epithelioid hemangioendothelioma of the lung is generally detected incidentally by a routine chest radiograph, usually in young asymptomatic woman. This tumor pursues a clinical course intermediate between that of hemangioma and angiosarcoma. Survival over 20 years have already been described in the literature. We report the case of a pulmonary epithelioid hemangioendothelioma diagnosed 16 years ago, with hepatic metastases and a radiologic follow-up that highlights the slow evolution of the pulmonary and hepatic lesions.

Bronchial responsiveness in active steelworkers.

Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.

Evaluation of pleural diseases with FDG-PET imaging: preliminary report.

BACKGROUND: Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) is an accurate method for differentiating benign from malignant disease. The use of FDG-PET for the aetiological diagnosis of pleural disease was investigated in 25 patients. METHODS: PET was performed on each subject before invasive procedures were used to determine the aetiological diagnosis. The PET data were analysed by visual interpretation of coronal, sagittal, and transverse slices. RESULTS: Sixteen patients were found to have malignant pleural disease and nine had benign disease. All patients with histologically confirmed malignant disease showed FDG uptake within the pleural thickening which was intense in 14 cases and moderate in two. PET imaging showed the absence of FDG uptake and correctly categorised seven non-malignant lesions. Two patients with infectious pleural diseases showed a localised and moderate FDG uptake. CONCLUSION: Our preliminary results suggest that FDG-PET could be an effective tool for differentiating between benign and malignant pleural diseases.

[Bronchial reactivity in diabetic patients]. / Réactivité bronchique chez les patients diabétiques.

The data of the literature concerning bronchial reactivity in diabetic patients are controversial. Therefore, we studied the influence of the presence of a diabetic cardiac autonomic neuropathy (CAN) on the ventilatory parameters measured during a methacholine-induced bronchoconstriction test. Ten insulin-dependent diabetic patients without CAN, ten insulin-dependent diabetic patients with CAN and ten healthy volunteers, all non-smokers and free of respiratory symptoms, have undergone a functional respiratory check-up before the methacholine test. The presence of CAN was classically studied by the decrease in heart rate changes during three standardized tests (deep breathing at 6 cycles/min, Valsalva manoeuver, orthostatism) which all mainly explore the parasympathetic function. The bronchial response to methacholine was similar in the healthy subjects and in the diabetic patients without CAN. However, the fall in forced expiratory volume in 1 second induced by the highest dose of methacholine was significantly less marked in the diabetic subjects with CAN than in the two other groups. These results suggest that the diabetic autonomic neuropathy also involves the vagal innervation of the respiratory tract.

[Positron emission tomography in the evaluation of intrathoracic lymphatic extension of non-small cell bronchial cancer. A preliminary study of 30 patients]. / Tomographie à émission de positons dans l'évaluation de l'extension ganglionnaire intrathoracique du cancer bronchique non petites cellules. Etude préliminaire chez 30 patients.

Current methods for evaluating the mediastinum include chest radiography, computed tomography (CT) or magnetic resonance (MR) imaging and mediastinoscopy. Despite advances in morphologic imaging, some lung cancer patients are found to have unresectable disease at surgery. In contrast to CT scan or MR imaging, which depend primarily on anatomic and morphological criteria, positron emission tomography (PET) with 18fluorodeoxyglucose (FDG) depends mainly of the metabolic characteristics of a tissue for the diagnosis of disease. We perform a prospective study to compare FDG-PET and CT of the thorax in the presurgical assessment of the mediastinum in patients with newly diagnosed non-small cell lung cancer. Thirty patients have been included. CT and PET-scans were interpreted separately and results were compared to surgical staging during thoracotomy. In assessing mediastinal involvement, CT scan had a sensitivity of 56% and a specificity of 64%. For diagnosis mediastinal nodal disease, FDG-PET was 87% sensitive and 78% specific. Its positive predictive value was 82%, and the negative value was 83%. In conclusion, our preliminary results show that FDG-PET appears more accurate than CT in staging of mediastinal non-small cell lung cancer.

Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine.

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.

Blood mononuclear cells mobilization and cytokines secretion during prolonged exercises.

This study was designed to compare the effects of three prolonged exercises varying in their intensity and duration, on blood mononuclear cell mobilization and cytokine secretion (IL1(1)-IL(2)). Seven healthy subjects underwent three effort trials (45 % VO(2)max during 4 h - 60% VO(2)max during 3 h - 75 % VO(2)max during 2 h) at one-month intervals. Blood samples were drawn before, different times during exercise and also after exercise. Prolonged exercises induced a transient increase in blood mononuclear cells which occurred across all intensity levels. We also observed a significant increase in plasma IL(1) level during exercise which correlates with the exercise intensity. The mean IL(1) level increased up to 2.5 times after the three proposed exercises (p <0.05). Plasma IL(2) level decreased at the end of prolonged exercises irrespective of the exercise intensity. No correlation was observed between blood mononuclear count and cytokine determination. Our data suggest that blood mononuclear cells mobilization is associated but not correlated with alterations of cytokine levels.

Changes in bronchial responsiveness, circulating leucocytes and ex vivo cytokine production by blood monocytes after PAF inhalation in allergic asthmatics.

We investigated the effects of inhaled platelet-activating factor (PAF) on methacholine bronchial responsiveness, circulating leucocyte counts, and ex vivo tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) production from blood monocytes in eight allergic asthmatics. Bronchial responsiveness was defined as the provocative concentration of methacholine causing a 20% decrease in forced expiratory volume in one second (PC20). Circulating leucocytes were counted by means of an automatic haemocytometer, and cytokines were measured with specific immunoassays. The different variables were measured before and 4, 24, 48, 72 and 168 h after a PAF (225 micrograms), a lyso-PAF (225 micrograms) and a saline bronchial challenge. When compared with lyso-PAF and saline, inhalation of PAF resulted in a significant decrease in PC20 over a period of one week. Two falls in bronchial responsiveness were identified, the first by 4 h and the second beginning 48 h and reaching a maximum by 168 h. The increases in spontaneous TNF alpha and IL-1 production which occurred during the week after both PAF, lyso-PAF and saline, did not differ significantly. Likewise, the changes in circulating neutrophil counts, characterized by a transient rise by 4 h after PAF and lyso-PAF but not saline, followed by a fall by 24 h and a persistent decrease until 168 h, were not significantly different after PAF, lyso-PAF and saline. On the other hand, in comparison with lyso-PAF and saline, inhaled PAF caused a significant protracted augmentation in circulating eosinophil counts, which was maximal by 48 h but did not correlate with the delayed decline in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute bronchial and hematologic effects following inhalation of a single dose of PAF. Comparison between asthmatics and normal subjects.

This study compared the acute bronchial and hematologic effects of inhaled platelet activating factor (PAF) (30 micrograms as a single dose) in 19 patients with mild asthma and 19 normal subjects. Each subject underwent a methacholine bronchial challenge 1 week before PAF challenge to determine the concentration of methacholine causing a 20 percent fall in FEV1 (PC20M). On the day of PAF challenge, specific conductance (SGaw), FEV1, FEF25-75, and platelet and leukocyte counts were measured before, and 5, 10, 15, and 20 min after PAF inhalation. Changes in pulmonary and hematologic parameters were expressed as percent of control (saline solution/ethanol solution). Unlike normal subjects, subjects with asthma had bronchial hyperresponsiveness to methacholine: geometric mean (range): 0.59 mg/ml (0.07 to 9.8) vs > 32 mg/ml. Acute bronchial obstruction over the first 20 min after PAF inhalation was more pronounced in asthmatics than in normal subjects whatever the functional index considered (p < 0.01). In asthmatics (n = 19), mean (SEM) maximal fall in SGaw, FEV1, and FEF25-75 reached 50 percent (6), 11 percent (4), and 19 percent (5), respectively, while in normal subjects (n = 19) the maximal decreases were 24 percent (6), 4 percent (1), and 6 percent (1), respectively. In asthmatics, no correlation was found between log PC20M and log fall in FEV1 after PAF (r = 0.04 p > 0.05). In asthmatics and normal subjects, inhaled PAF caused a transient fall in neutrophils and monocytes by 5 min followed by a full recovery at 15 min and 20 min. These hematologic changes were not significantly different between the two groups. While not correlated with their airway responsiveness to methacholine, asthmatics, compared with normal subjects, develop an exaggerated acute airway obstruction in response to PAF. In contrast, hematologic changes induced by PAF do not differ between asthmatics and normal subjects.

Decrease of T-lymphocyte proliferation in exercise-induced asthma.

The present study was designed to examine the effect of physical exercise on T-lymphocyte proliferation in patients with exercise-induced asthma (EIA). Indeed, a decrease in different immune functions is described in normal man after exercise. Thirty subjects (10 normal and 20 asthmatic subjects with or without EIA) underwent a submaximal exercise test on an electrically driven treadmill. Before and after this test, ventilatory variables were measured, and venous blood was taken to study plasma histamine (RIA) and spontaneous and phytohemagglutinin (PHA)-pulsed T-lymphocyte proliferation (mononuclear cells isolated on Ficoll-Hypaque; tritiated thymidine incorporation). Ten minutes after the end of the exercise, there was a significant FEV1 decrease only in asthmatic subjects with EIA (mean: 24 +/- 5%). In the same group, the mean plasma histamine level was 0.31 ng/ml-1 (+/- 0.06) before the challenge. It rose to 0.62 ng/ml-1 (+/- 0.14) 10 min after the end of the exercise (P < 0.05), and returned to normal limits 20 min after the test. In this group, there was also a significant decrease (by about 35%) of spontaneous and PHA-pulsed T-lymphocyte proliferation 2 and 4 h after the exercise. By contrast, exercise challenge had no effect on either plasma histamine level or T-lymphocyte proliferation in the normal group. Our results show a rapid and transient increase in plasma histamine in EIA. This was followed 2 and 4 h later by a significant decrease of T-lymphocyte proliferation. A possible relationship between these two phenomena is discussed.

Modulation of immunological histamine release from human lung fragments by stem cell factor, IL-3, IL-5 and GM-CSF: comparison with human leukocytes.

Because of the importance of cytokines in the regulation of allergic inflammation, we investigated the effects of SCF, IL-3, IL-5 and GM-CSF on immunological histamine release from sensitized human lung fragments as well as human leukocytes. SCF (0.2-20 ng/ml) caused a concentration-related enhancement of anti-IgE (1/100) induced histamine release from lung fragments reaching maximally 64% at 20 ng/ml. In contrast, enhancement produced by IL-5, IL-3 and GM-CSF (0.2-20 ng/ml) was quite marginal and reached at best around 20% at the higher concentration, IL-5 being slightly more effective than IL-3 and GM-CSF. Further, SCF potentiated histamine release whatever the level of immunological control whereas potentiation by IL-5 primarily occurred when the amount of histamine release induced by the immunological control ranged between 5 and 10%. SCF acted synergistically with IL-5, producing a greater enhancement of histamine release than the sum of each cytokine used alone. Both SCF and, to a lesser extent, IL-5 potentiated anti-IgE-mediated histamine release regardless of passive sensitization of lung fragments. Unlike what was observed with lung fragments, IL-3, GM-CSF and to a lesser extent IL-5, were potent enhancing agents of anti-IgE (1/2,000)-induced histamine release from leukocytes. Maximal enhancement produced by IL-3 (20 ng/ml), GM-CSF (2 ng/ml) and IL-5 (20 ng/ml) reached 92%, 78% and 61%, respectively. By contrast, SCF (0.2-20 ng/ml) was ineffective on human leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of histamine release from human leucocytes by PAF.

Studies on the effects of PAF on histamine release from human leucocytes have yielded conflicting results. We therefore investigated the effects of PAF on leucocytic histamine release (HR) focusing on direct as well as on modulating effects. Peripheral blood leucocytes of normal and atopic subjects were incubated with PAF, anti-IgE and FMP for 30 min at 37 degrees C, and histamine was measured fluorometrically. Unlike anti-IgE (1/2000) and FMP (10(-5) M) which caused histamine release (HR) of 34 +/- 7% and 31 +/- 8%, respectively, PAF by itself (10(-11)-10(-5) M) failed to induce any significant HR from human leucocytes (< 3%) in normal (n = 14) and atopic subjects (n = 6). Nevertheless, in normals as well as atopics, PAF, but not lyso-PAF, enhanced anti-IgE (1/2000) and FMP (10(-5) M)-induced HR in a concentration-related manner. Maximal potentiation of histamine release caused by FMP and anti-IgE was achieved with PAF (10(-7)) (mean +/- SEM: 26 +/- 5%, n = 5, p < 0.01) and PAF (10(-5)) (mean +/- SEM: 20 +/- 7%, n = 7, p < 0.05), respectively. This potentiation was suppressed by WEB2086 (10(-5) M), a specific PAF antagonist. The time course of the enhancing effect produced by PAF was dependent on the type of secretagogue. The enhancement was nearly maximal when PAF and FMP were added simultaneously to the leucocytes, whereas a preincubation of 20 min with PAF was required to get maximal enhancement with anti-IgE. The enhancing activity of PAF on HR induced by both anti-IgE and FMP was reversed by washing the cells after preincubation. While PAF enhancement of FMP-induced HR persisted on mononuclear cell fraction containing basophils, that of anti-IgE-induced HR was considerably reduced under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Asthma and nonspecific bronchial hyperreactivity]. / Asthme et hyperréactivité bronchique non spécifique.

Bronchial hyperresponsiveness is a hallmark of asthma although it can also be present, to a lesser extent, in other diseases. The level of bronchial responsiveness depends on immuno-inflammatory processes modifying the functional status of airway smooth muscle as well as the structure of the bronchial wall. The responsiveness toward a direct constricting pharmacological agent is poorly correlated to the one toward an indirect constricting agent or a physical stimulus which cause airway obstruction through a more complex mechanism. Transversal studies show a relationship between the severity of asthma and the level of methacholine airway responsiveness. Long term treatment with corticoids can reduce the bronchial hyperresponsiveness of asthmatics.

Plasma histamine and bronchial reactivity in allergic asthma.

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic asthmatic patients have yielded controversial results. We therefore measured plasma histamine and bronchial reactivity in 30 nonsmoker volunteers taking no medication. Eleven were normal subjects; 19 were stable, mildly allergic asthmatic patients. Venous blood was taken to measure blood cells and basal plasma histamine by radioimmunoassay. After blood sampling, all subjects underwent a measurement of PC20M (concentration of methacholine causing a 20% fall in FEV1). Mean plasma histamine levels were 0.21 +/- 0.1 ng/ml and 0.44 +/- 0.3 ng/ml in normal and asthmatic subjects, respectively (P < 0.05). We found a significant increase of blood eosinophils and basophils in asthmatic patients, and a positive correlation between plasma histamine and circulating basophils. PC20M was greater than 16 mg in normal volunteers, and mean PC20M was 2.1 +/- 2 mg/ml in asthmatic patients. PC20M did not correlate with plasma histamine levels, but it did so negatively with blood eosinophils. The increased plasma histamine concentration in mildly atopic asthmatic patients might be a consequence of the high basophil releasability of atopics and the higher basophil counts in allergic asthma. Plasma histamine is thus unlikely to be a determinant of BHR in asthma.