Bulletin europeen de physiopathologie respiratoire最新文献

The pulmonary effects of chronic exposure to isocyanates (mainly MDI) at low levels (less than 0.02 ppm) were studied in a five year longitudinal survey of workers from two factories producing polyurethane foam. A respiratory questionnaire, flow volume curves and a single breath CO diffusion test were done at the beginning of the survey and repeated five years later; 318 workers (214 men, 104 women) of whom 83 (group I) were unexposed, 117 indirectly exposed (group II) and 118 directly exposed to isocyanates (group III) were examined. Five years later, half of the initial cohort only was still active and re-examined. The longitudinal analysis distinguished unexposed workers at both examinations (group A), indirectly at both examinations (group. B), directly exposed at both examinations (group. C) and workers exposed directly at first examination and retired from risk at the second (group. D). The decline of VC and FEV1 was not significantly different between exposed and unexposed. On the contrary, DLCO declined significantly in group C compared to the others. The results indicate that even at 'safe levels', chronic exposure to isocyanates involved a respiratory risk.

The importance of airways inflammation for the development of bronchial hyperresponsiveness and for exacerbation of asthma was investigated in subjects with occupational asthma. We examined subjects sensitized to isocyanates, a small molecular weight compound that causes occupational asthma. Studies in asthmatic subjects sensitized to toluene diisocyanate (TDI) demonstrated that late, but not early, asthmatic reactions induced by TDI were associated with an acute increase in bronchial responsiveness, and with a marked infiltration of neutrophils and a slight infiltration of eosinophils into the airways, both prevented by steroids. As the late asthmatic reactions and the increase in responsiveness induced by TDI were prevented by steroids, but not by indomethacin, we speculated that cell membrane phospholipid metabolites, which are inhibited by steroids but not by indomethacin, may be involved in TDI induced hyperresponsiveness. The results of these studies suggest that bronchial hyperresponsiveness and exacerbation of asthma may be related to inflammation of the airways and that cell membrane phospholipid metabolites may be involved.

Several studies on the prognosis of isocyanate-induced asthma show that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work, and that further exposure to isocyanates in sensitized subjects leads almost invariably to persistence of respiratory symptoms and of bronchial hyperresponsiveness and the deterioration of airway function. Specific bronchial reactivity to isocyanates may change after cessation of work; however, some subjects continue to be sensitive to TDI several months after cessation of work. The determinants of an unfavourable prognosis for asthma seem to be the same as those for other types of occupational asthma due to low molecular weight compounds (i.e. red cedar asthma): long duration of exposure before the onset of asthma, long duration of symptoms before diagnosis, airway obstruction, and dual airway response after specific challenge tests. Also, single acute exposure to high levels of TDI in the workplace (spills) can result in persistent nonspecific bronchial hyperresponsiveness. Potential mechanisms of persistence of symptoms and of nonspecific bronchial hyperresponsiveness may be chronic inflammation, bronchial smooth muscle alteration, autonomic nervous system disregulation.

Sera from 99 subjects exposed to the industrial gas leak in Bhopal on December 2, 1984 were studied along with sera from guinea pigs exposed to methyl isocyanate (MIC) to determine the production of antibodies specific to (MIC). Each of the four guinea pigs injected with the reactive isocyanate produced MIC-specific antibodies in titres of 1:5120 to 1:10240, when tested with MIC-guinea pig albumin antigen conjugate. Analogous antigens prepared by reaction of MIC with human serum albumin were used to probe production of antibodies in 264 serially obtained human sera from 99 subjects from Bhopal. MIC-specific antibodies belonging to IgG, IgM and IgE classes were detected in eleven subjects. Though titres were low and transient (declining after several months) these findings indicate that the single large exposure to MIC resulted in an immunologic response. This finding was concomitant with chronic respiratory effects following MIC exposure.

Airway conductance (Gaw) depends on lung volume (TGV). An approximate correction for this volume dependence can be obtained by calculating specific airway conductance (sGaw = Gaw-TGV). In this study, Gaw-TGV curves were compared with sGaw in 30 healthy and 20 asthmatic subjects who were studied by body plethysmography. Gaw, TGV and sGaw were measured five times at three to five different lung volumes. sGaw was dependent on TGV, the regression having a negative slope (-0.24 and -0.27 kPa-1.s-1.l-1, in the group without and with asthma, respectively). A change in TGV by 1 l caused a 9 and 11% decrease in sGaw, respectively. Bronchial obstruction induced by histamine inhalation in the asthmatic subjects increased the dependence on TGV by sGaw, now with a positive slope. Thus, a change in TGV by 1 l caused a 20-100% increase in sGaw, depending on the degree of airway obstruction. The Gaw-TGV curve was approximately linear around the resting lung volume. The coefficient of variation in determining the slope of the Gaw-TGV curve was as high as 110 and 153% in health and asthmatic subjects, respectively. It is concluded that sGaw, although rapidly determined, has a systematic error in its correction of lung volume dependence, which the Gaw-TGV curve does not. The Gaw-TGV curve therefore has advantages in research work, but since its construction is time consuming it is hardly suitable in clinical practice.

Pulmonary haemodynamics and blood gas tensions were investigated in eight healthy volunteers, breathing room air and at the 15th min of an acute inspiratory hypoxia (fraction of inspired oxygen, (FIO2), 0.125) before and after administration of ibuprofen, a cyclooxygenase inhibitor, and of dazoxiben, a thromboxane A2 (TxA2) synthetase inhibitor; both drugs either with or without an infusion of prostaglandin E1. Hypoxia decreased arterial oxygen tension (PaO2) to below 50 mmHg in every subject and increased pulmonary vascular resistance by an average of 100-150% from baseline values. Acute and chronic dazoxiben or ibuprofen administration markedly reduced serum thromboxane B2 (TxB2), the stable metabolite of TxA2, but had no effect on pulmonary haemodynamics and blood gas tensions in both normoxic and hypoxic conditions. Prostaglandin E1 given in addition to ibuprofen or to dazoxiben did not inhibit hypoxia-induced increases in pulmonary vascular resistance. The stability of this hypoxic pressor response on repetition of an acute hypoxic exposure was established in six additional healthy subjects. Although obtained on a small number of subjects, these results do not suggest that products of the cyclooxygenase pathway of arachidonic acid metabolism play an important role in modulating normoxic or hypoxic pulmonary vascular tone in man.

In 403 healthy subjects, 4 to 20 years of age, we measured total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz. When possible, vital capacity and forced expiratory volume in one second were also determined. The Rrs and Xrs vs frequency data depend on age or height, on sex, and slightly on weight. During growth, Rrs and the frequency dependence of Rrs decrease while Xrs increases. Only part of these changes may be explained entirely by a size effect. The variations with growth of ventilation unevenness, of airway wall compliance and of the topographic distribution of airway resistances probably also play a role. The influence of the interactions between height and age, and height and weight on Rrs and Xrs differ between sexes. Adult values for Rrs and Xrs are attained at the age of 15 years in girls and 18 years in boys.