Biomedical subjects
Publications and source records attributed to A Minette.
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Treatments combining acetylcysteine by mouth and beta 2-agonists aerosols were given to 293 coal-miners or ex-coal miners suffering from chronic bronchitis presenting an acute phase of their illness and complaining of an increased sputum production. None of them related complaints nor showed objective signs of atopy. From the whole group, 41 cases carefully followed during periods of time varying from 17-26 days having taken in this period a regular treatment combining both types of drugs. This group could be compared to another group comprising 37 cases receiving only acetylcysteine. In both groups the author observed a general tendency to a better pourability after treatment than before. This resulted in an increase of the sputum production without concomitant increased cough. These facts were associated with an improvement in the auscultatory findings. It is not possible to ascertain whether these results were due to acetylcysteine alone. Indeed all patients received during different periods of time other drugs in combination, in particular antimicrobial substances. When comparing answers concerning the opinion on general respiratory improvement, there was no significant difference between both groups.
The authors compared the results of measurements of blood gases on arterialized blood taken at the earlobe and on arterial blood collected at the brachial artery. The measurements were made at rest and during exercise with the main pre-occupation of the respective feasibility and relevance of both techniques in epidemiology. Ninety-four in-patients suffering from respiratory diseases at various stages of their evolution were concerned by this investigation. The techniques of blood collection were standardized. In particular the authors took care that the blood samples were collected simultaneously at the brachial artery and at the earlobe. All blood samples were taken by the same trained experimenter. All the measurements were performed by the same experienced medical analyst. Both types of samples were compared by means of an apparatus Corning 165. As the authors also had a Corning 175 at their disposal, it was possible to investigate the importance of the factor "apparatus" in the differences which were stated. An approach of the role played by the measurement cells in these differences was possible by studying simultaneously by means of the Corning 165 a same sample of arterial blood before and after transfer in a heparinized capillary. The results suggest that the measurements on arterial and arterialized blood are concordant in in-patients at rest with the applied normalisation. During exercise, the differences are greater; nevertheless they are not large enough to reject the technics on arterialized blood in epidemiology. On the other hand the authors confirmed the observation of numerous other investigators showing that the method on arterialized blood gives on the average rise to underestimation. This might result from the technical characteristics of the measurement cells.
We have studied the effects of respiratory physiotherapy and physical training on the cardiopulmonary function of patients with early chronic bronchitis and broncho-obstruction presumably at the beginning stages. The trained group was compared with a control group who was treated with infra-red rays on the thorax. Both groups were treated during four weeks. All patients were less than 50 years old and all were smokers. They complained of dyspnea on exertion (stage 2 ECCS), cough and expectoration for at least one year. Their spirometry and airway resistance values were normal or near normal but at least two of the following functional indices were altered in all: the He residual volume, the slope of N2 phase III and/or the He bolus phase IV. In the trained group, functional indices of central or peripheral airway obstruction did not change after the four weeks of treatment. On the contrary, the slow vital capacity (SVC) and the peak expiratory flow (PEF), which are presumably more influenced by the force of respiratory muscles, were significantly increased after respiratory rehabilitation. During steady-state exercise of moderate intensity 1.) a slight increase of pH (P less than 0.1 at a VO2 of 1.5 l/min and 1.75 l/min), perhaps due to a lessened lactacidemia, 2.) a decrease in ventilation (VE) (P less than 0.1 at a VO2 of 1.25 l/min) and 3.) a reduction in the alveolo-arterial gradient (AaDO2) (P less than 0.1 at a VO2 of 1.25 l/min) were observed. In the control group there was no change of respiratory functional indices at rest or during exercise after treatment. The reduction of AaDO2 observed in the trained group could be due to an improvement of pulmonary gas exchange. This was small, however, and probably without clinical significance. We believe that the improvement of dyspnea noted in the trained group could be due to the increase in ventilatory performance (SVC, PEF and VE) and to a better O2 extraction in the peripheral muscles.
The authors remind the fundamental items of the bronchodilating treatments by means of pressurized aerosols using beta 2-agonists and parasympatholytics; a review of the literature on the toxicity of the different propellants used in the cartridges is presented. The problems proceeding from inequalities of deposition of the aerosols in the normal subjects and in lung diseases are stressed. Results regarding the prevalence of positive responses to aerosols of atropine methonitrate and to aerosols of a beta-agonist given to a group of patients with reversible broncho-obstruction are presented and discussed. The advantages of oxitropium bromide, a recently synthetized parasympatholitic drug which appears more interesting than ipratropium bromide, are discussed by means of the ventilatory results observed with both drugs in 19 patients with reversible broncho-obstruction. The interest of associating atropinics and beta 2-agonists in the same cartridges is discussed. The efficacy of a recently commercialized preparation associating fenoterol and ipratropium bromide is commented.
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One of the authors observed an excess of dyspnea complaints in coalminers without bronchitis, massive fibrosis or emphysema in different epidemiological surveys. An abnormally high prevalence of dyspnea complaints in coalminers has also been reported by other investigators in different countries. It seems therefore necessary to study whether the type of complaints observed in our country can be validated by appropriate functional investigations. A research on this problem is in progress in our laboratory. In this preliminary publication a review of the literature concerning the mechanisms of dyspnea is presented. Such a study was necessary in order to make an adequate choice of the functional measurements usable for our validation study.
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The changes in FEV1 and in specific conductance induced by 200 micrograms oxitropium bromide given as pressurized aerosol were measured at 8 time intervals during 7 hours after inhalation in a group of 19 patients with reversible broncho-obstruction. The working of the drug was compared to the functional values observed at the same time intervals after placebo, 40 micrograms ipratropium bromide and 400 micrograms fenoterol. Both oxitropium and ipratropium were definitely and significantly superior to placebo at all time intervals. Oxitropium was superior to ipratropium at the 7th hour. At this time interval the difference was significant At the 7th hour oxitropium gave higher mean results than fenoterol, but this difference was not significant. The drug was also compared to its competitors regarding its subjective and cardiovascular tolerance. No unfavourable side-effects were observed.
We compared the effects of almitrine and doxapram on the arterial blood gases and ventilation of patients with chronic respiratory insufficiency and chronic hypercapnia and hypoxemia. Sixteen long-term in-patients were randomly allocated to one of the following treatment groups: the first group (8 patients) received IV almitrine 0.5 mg/kg and the second group (8 patients) IV doxapram 1 mg/kg by IV perfusion during 30 min. All gave their informed consent. Arterial blood gases and ventilation were measured 10 min and 5 min before treatment, at the 5th, 15th and 25th min of perfusion time, and 5, 10 and 15 min after infusion. There was a marked increase in paO2 in almitrine-treated patients, which was maximum at the 25th min of infusion (+ 14.6 mm Hg, p < 0.001), but only a slight improvement was observed in the doxapram group (+ 3.3 mm Hg, p < 0.05). After almitrine the maximum mean paCO2 decrease was at the 10th min after perfusion (-6.9 mm Hg, p < 0.001); after doxapram the maximum decrease, although highly significant, was much less (-2.8 mm Hg, p < 0.01). Thus, at the presently used and well-tolerated doses, almitrine is much more efficient than doxapram in improving gas exchange in patients with chronic hypoxemia and hypercapnia. However, complementary studies using higher dosage of doxapram are warranted.
Two epidemiological surveys were made by the same research team on the prevalence and the aetiological factors of chronic bronchitis symptoms in coalminers. The first study was made in a coalminers' community of Belgian Limburg, the other one in a representative sample of coalminers regularly at work. In both surveys an excess of dyspnea complaints was observed in comparison to the prevalence of this symptom in controls. These dyspnea complaints often presented themselves as isolated symptoms, without chronic cough or phlegm production. Dyspnea in excess could not be explained by massive fibrosis. The prevalence of the symptom was not linked, neither to the spirometric values, nor to the results of respiratory challenge tests with acetylcholine, tobacco use, or the length of exposure at the coalface. When dyspnea was associated with cough and phlegm production there was on the contrary a statistically significant relation with the spirometric values and the effect of acetylcholine. It seems therefore reasonable to explain at least partially the isolated dyspnea complaints in coalminers by specific mechanisms not related to bronchitis but resulting from the pathological lesions characteristic of simple pneumoconiosis. Complaints of cough and phlegm production appear as a rule later in the coalminer's life. In the groups taken into consideration in the study they were linked with cigarette smoking which appeared as the predominant aetiological factor for these complaints; in a subgroup a synergic action of coaldust, tobacco use and air pollution could be discussed in this respect. Notwithstanding the pathogenic independence of some dyspnea complaints versus cough and expectoration, it is quite clear that when productive bronchitis develops and causes broncho-obstruction, it may aggravate pre-existing dyspneic patterns.
The results observed with talampicilline in our clinical study confirmed the observations made by others regarding the activity and the improved tolerance for this drug versus ampicilline. The use of a high daily dosage of 3 g per day was neither a cause of more frequent nor more severe side-effects than the usually smaller posology used in other studies published in the literature.
RG 033 is a compound consisting of betametasone in resinic microcapsules which allow a slow and continuous dialysis of the active drug through the membrane in the digestive tract. The drug was studied with regard to its effects on the distribution of alveolar air and its gastric tolerance. In a preliminary study the drug release from the capsules in the pH-conditions of the digestive tract was studied by means of a physico-chemical model. Two groups of 15 patients with broncho-obstruction reversed by salbutamol, a potent beta 2-sympathomimetic, were included in the trial. One group received 1 mg and the other 2 mg of the drug. An alternate scheme was used for the treatments. The functional methods used to assess the ventilatory results were chosen according to the conclusions of a previous comprehensive study by one of the authors [7] [8]. The ventilatory results of both dosages were quite similar. This observation suggests that a maximum effect on alveolar air distribution was obtained with 1 mg. No unfavourable side-effect on the gastric mucosa was observed.
The usefulness of mucolytics for clinical purposes remains controversial. Although many authors agree with the opinion that some of these drugs, above all aerosols of acetylcysteine at convenient dosages, provided they are associated with beta 2-sympathomimetics, may be useful in the treatment of bronchial obstruction due to inspissated mucus in excess in the lumens, many specialists remain reluctant concerning the activity of mucolytics given by mouth. It seemed therefore interesting to organize an international meeting on this topic. First of all, I would like to pay honour to the initiative of the Zambon Laboratories who organized this symposium. I would also like to express my gratitude for having been involved in the preparation of the programme of these days and having been asked to present the general conclusions of the meeting. The following pages are devoted to these conclusions. We shall repeatedly make reference to the works which were presented in extenso during the meeting. The general report of the symposium will shortly appear in a special supplement of the European Journal of Respiratory Diseases. It seems however useful to give at the end of our text the complete list of the presented lectures.
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