Bulletin europeen de physiopathologie respiratoire最新文献

The over production of toxic oxygen species (TOS) by the phagocytic cells involved in inflammatory processes plays a crucial role in generating the immune defects which characterize both infections and neoplastic diseases. Since the thiol containing drugs, and N-acetylcysteine possess a high capacity for scavenging and inhibiting TOS, the question of whether these substances are able to protect, in vivo as well as in vitro, the function of lymphocytes isolated from the peripheral blood in patients suffering from chronic pulmonary diseases (CPD) was investigated. The lymphocytes isolated from healthy donors as well as those from CPD patients exposed in vitro to TOS showed a reduced viability and an impairment of functions in: (a) the ability to express HLA Class II and TAC antigens and (b) the capacity to stimulate and proliferate in allogenic (MLR) and autologous mixed lymphocyte reactions (AMLR). The presence of NAC or CAT blocked this toxicity. Cells isolated from healthy donors and patients following treatment with NAC were less sensitive to the in vitro toxicity of TOS.

Paf-acether, whose role has been suggested in asthma, is a mediator released by stimulated neutrophils, platelets and other cells. Neutrophils and platelets are activated in vivo during exercise or allergen-induced asthma. Upon in vitro stimulation, macrophages from mice treated with an inflammatory stimulus, such as thioglycoccollate, release less paf-acether than macrophages from non-treated mice. We hypothesized that upon in vitro activation platelets and neutrophils should produce less paf-acether after exercise- or allergen-induced asthma. To test this hypothesis, we measured the production of paf-acether by neutrophils and platelets obtained before, 15 and 75 min after exercise in seven normal subjects and five asthmatic subjects with exercise-induced asthma, and in five other asthmatic subjects after specific challenge with Dermatophagoides Pteronyssinus. Purified neutrophils and washed platelets were incubated independently for 10 min at 37 degrees C with no specific activator, with a platelet activator (thrombin, 1 IU.ml-1), a neutrophil activator (opsonized zymosan, 1 mg.ml-1), and both together. We found no significant difference between asthmatic and normal subjects in the amount of paf-acether synthesized by platelets or neutrophils and no fall in the production of paf-acether after exercise- or allergen-induced asthma. However, our method may lack sensitivity in detecting partial activation of these cells and is based on the assumption that changes in peripheral blood cells are representative of changes of these cells in lungs.

It is becoming increasingly clear that certain types of pulmonary injury may be closely related to oxidant-antioxidant imbalance in the lung, resulting from the production of reactive oxygen species within the lung during endogenous metabolism and xenobiotic insult. We have investigated the role of glutathione in pneumoprotection from such reactive species and, in particular, methods of manipulating the resident antioxidant capacity of lung glutathione. One such approach has been the use of the thiol-containing drug N-acetylcysteine. We have shown that N-acetylcysteine is able to both support intracellular glutathione biosynthesis and act as a 'scavenger' of reactive electrophilic species through the chemical reactivity of its thiol group. N-acetylcysteine reduces hydrogen peroxide to water, with the commensurate formation of N-acetylcysteine disulphide both when the peroxide was supplied directly or generated enzymatically. This basal reduction of hydrogen peroxide by N-acetylcysteine was greatly enhanced by the inclusion of catalytic amounts of the selenium-containing heterocycle, Ebselen, in the incubations. Thus, Ebselen mimics the activity of glutathione peroxidase but, unlike the enzyme, is able to use N-acetylcysteine as a co-substrate. Thus, the combination of N-acetylcysteine and Ebselen may provide a useful therapeutic tool in conditions of pulmonary toxicity associated with oxidant insult.

We have performed bronchoprovocation tests with methacholine in 41 patients with asthma due to Western red cedar dust and in 56 office-workers without known respiratory illness. Our purpose was to define a summary statistic for useful bronchial hyperresponsiveness in epidemiologic surveys. We found a significant linear relationship between the concentration of methacholine and the FEV1 response. We noted, in addition, a positive relation between the rate of the FEV1 response per concentration and the level of FEV1. We conclude that a linear dose-response slope, which can be calculated for each individual, provides a comprehensive summary of methacholine bronchoprovocation tests and is useful in epidemiologic surveys.

Thoracic gas volume (TGV) and specific airway resistance (sRaw) are commonly measured using pressure type and flow type body plethysmographs. Within-subject variability of the data, defined as the coefficient of variation of eight to ten measurements during the same session, was assessed with the two kinds of instruments and compared in fifteen normal subjects. The reproducibility of data obtained several days apart was also compared. All measurements were made in a 480-l body chamber, which could be used in both the pressure and the flow mode. The signals were processed digitally using three different algorithms: 1) simple linear regression (LR); 2) linear regression with drift correction achieved by adding to, or subtracting from the plethysmographic signal a term proportional to time (LRC); 3) Fourier analysis (FFT). Within-subject variability of TGV was much larger with flow than with pressure plethysmography when the signals were processed by LR (14.5 +/- 7.5 vs 6.3 +/- 3.0%; p less than 0.001), but almost the same using LRC (6.7 +/- 3.2 vs 5.4 +/- 2.7%) and FFT (6.1 +/- 2.4 vs 5.0 +/- 2.4%). For sRaw, variabilities were larger and less influenced by methodological factors. Adequate digital processing may therefore largely remedy the inherently greater variability of TGV measurements with flow plethysmographs.

To evaluate the toxic effects of various oxidants on alveolar macrophages (O2, NO2, tobacco smoke and silica), we used an original method of cell culture in aerobiosis, which permitted direct contact between the atmosphere and the target cells. Our results demonstrated that the variations of cell sensitivity to the cytotoxic effects of oxidants were associated with various levels in cellular antioxidant equipment. A significant correlation was found between cytotoxicity and antioxidant enzymes (superoxide dismutase and catalase) and/or cellular glutathione. Addition of N-acetylcysteine, a polypeptide known to have an antioxidant activity and to be a precursor of glutathione, was responsible for a decrease of oxidant-mediated cytotoxicity. Whether this protective effect was due to an increase in glutathione cell content or to a scavenger effect of N-acetylcysteine still needs to be elucidated.

A methacholine bronchial provocation test was administered to 290 subjects obtained from the 1,900 male volunteers participating in the Normative Aging Study. A positive response (less than 20% decline in FEV1) was obtained in 83 subjects. A positive response was associated with current smoking, presence of wheeze and reduced FEV1. Bronchial responsiveness, cigarette smoking, normal subjects, FEV1.

A system for continuous long-term measurement of respiratory gas exchange in ventilated patients is presented. The method is noninvasive and may be applied in a clinical setting over a period of several days without adversely affecting the patient's wellbeing. The set-up was designed exclusively as a research tool. It registers oxygen uptake and CO2 elimination at 5 min intervals; breath-averaged measurements are carried out every 30 s. Expired minute volume is measured with a pneumotachograph equipped with an automatic drift compensation. A newly developed gas mixer insures that the inspiratory oxygen concentration remains constant. Expired gases are analysed for O2 and CO2 concentrations by mass spectrometer. The effect of the compressible gas volume is eliminated by segregating the inspiratory gas from the expired gas. The basic accuracy of measurement of the method is +/- 2.5% for oxygen uptake and +/- 2.0% for CO2 elimination. This result is based on a comparison of the individual components of the system with standard methods. The system's time constant (t90) for changes in O2 and CO2 concentrations is about 50 s. Based on the results of a case study, we will discuss oxygen uptake, CO2 elimination and the oxygen uptake profile of a patient measured over a period of seven days.

We have studied the mechanism underlying the increase in end-expiratory lung volume (VEEL) after vagotomy in dogs anaesthetized with thiopentone and gluco-chloralose. Dogs (n = 10) were studied during three phases: a) baseline, b) after bilateral vagotomy, and c) during paralysis with suxamethonium after vagotomy. To examine the influence of posture, dogs were randomly studied either in the upright (n = 5) or in the supine (n = 5) position. After vagotomy, VEEL, as determined by spirometry, increased by 27.8 +/- 13.6% (SD) and 15.3 +/- 9.6% in upright and supine dogs, respectively. After paralysis, further small increases in VEEL were observed in all upright and three supine dogs. Static lung compliance did not change after vagotomy or paralysis. Chest wall compliance decreased after vagotomy, but returned towards baseline values during paralysis. The rectus abdominis electromyogram recorded expiratory muscle activity during the expiratory pause; vagotomy markedly reduced it in upright dogs and it was undetectable in supine dogs. We conclude that VEEL is actively maintained by expiratory muscles, predominantly under reflex vagal control. This reflex may serve to minimize the increase in VEEL that occurs on assuming the upright posture. We suggest that reflex vagal mechanisms are also involved in the inhibition of expiratory muscle activity during lung inflation.

A quasi steady-state noninvasive, radioisotopic technique for measuring regional lung water distribution in man is described. The method depends upon the dilution principle. 123I labelled human serum albumin (HSA) and sodium iodide (NaI) were injected intravenously, allowed to mix completely within the body fluids and then counted externally over the chest. The size of each compartment to which the markers are confined was calculated from the external count rate and the isotopic concentration of the marker in plasma. 123I-HSA was used to estimate intravascular water and 123I-NaI extracellular water. Ratio analysis of the differential attenuation of the two photoenergies of 123Iodine (29 keV, 159 keV) by the lung and chest wall was used to estimate the absolute amount of isotope in the lung, independent of chest wall contribution, after validation by phantom studies. Regional pulmonary plasma (PPVr) and interstitial (PIVr) fluid volumes in normal subjects were 7.1 +/- 1.4 and 7.6 +/- 1.3 ml.100 cm-3 lung (mean +/- SD; n = 13) at mid-tidal volume, respectively. In patients with the adult respiratory distress syndrome, PPVr and PIVr were 7.0 +/- 2.9 and 15.9 +/- 4.6 ml.100 cm-3 lung (n = 18), respectively. The pulmonary artery wedge (Paw) pressure was normal (12.5 +/- 2.5 mmHg; n = 5). In patients with pulmonary oedema due to left heart disease, PPVr and PIVr were 7.2 +/- 2.7 and 12.1 +/- 3.7 ml.100 cm-3 lung (n = 8), respectively. The mean Paw pressure in this group was high (28.5 +/- 3.9 mmHg).