[Long-term treatment with corticoids in respiratory disorders]. / Chronische behandeling met corticoïden bij respiratoire aandoeningen.

In a first chapter the author reviews the mechanisms of action of corticoids in respiratory diseases. Moreover the causes and the prevalence of unwanted side-effects are discussed. The advantages of synthetic glucocorticoids with short half-life time in pneumology are stressed. In the following chapters, the rationale of long-term corticoid treatments of asthma, in non allergic obstructive chronic lung diseases, in sarcoidosis and in the thoracic localisations of some collagen diseases is presented in detail. Regarding the treatment of asthma the author discusses the advantages of the alternate-day therapy, the use of corticoids in aerosols and the ratioale of ACTH. The usefulness of alternate-day therapy in sarcoidosis is also advocated.

Contribution to the natural history of chronic bronchitis in coal-miners.

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.

[Conclusions of an international symposium held at Aachen on 4 and 5 May about mucolytic agents, especially oral acetylcysteine]. / Conclusies an een internationaal symposium over mucolytica, in het bijzonder acetylcysteine per os, gehouden te Aken op 4 en 5 mei 1979.

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.

Clinical effects of mucolytics associated with bronchodilators in treating exacerbation of chronic bronchitis in coal miners.

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.

[Ventilatory effect and side effects of oral bamifylline]. / Ventilatorische werking en neveneffekten van oraal bamifylline.

The results are in agreement with the hypothesis that 900 mg oral bamifylline, as a unique dose, should produce slight and temporarily bronchodilating effects. This phenomen may be discussed from the 30th minute after intake. It was significant after 2 hours and remained significant till the 4th hour. It is interesting to stress that this conclusion is in agreement with some isolated observations we could make before in our laboratory by means of injections or suppositories with the same product [9]. We did not observe facts suggesting a possible cumulative effect of the drug, when taken at a dosage of 3 times 900 mg regularly spread over the day. The drug seems to be perfectly tolerated. A 10 days' treatment with the above mentioned posology did not produce neither haematological, haepatic, renal, nor vascular side-effects which could be identified by the techniques classically used in these respective fields.

Lung function changes in smokers with normal conventional spirometry.

The comparative ability to detect early abnormalities in smokers by commonly used lung function tests was studied. Sixty-five healthy male nonsmokers served as a reference group and provided standards for 1-sec forced expiratory volume, vital capacity, end-tidal spirometry, spirometric forced mid-and end-expiratory flows, single-breath diffusing capacity, static lung volumes (helium method), and single-breath N2 closing volume measurements, In the present series of 80 male smokers, the measurements of forced mid-expiratory flow and forced end-expiratory flow did not improve the ability of the more conventional indices, 1-sec forced expiratory volume and the ratio of 1-sec forced expiratory volume to vital capacity, to detect obstructive lung disease. In 71 smokers with normal 1-sec forced expiratory volume and ratio of 1-sec forced expiratory volume to vital capacity, the end-tidal spirometry, diffusing capacity, and residual volume indices revealed 14,20, and 21 per cent of abnormalities. respectively. The single-breath N2 closing volume test (Phase IV/vital capacity and slope of Phase III) detected the greatest number of subtle changes in lung function; this was abnormal in 32 per cent of smokers with normal conventional spirometry. In young or light smokers, Phase IV/vital capacity was more frequently increased than the slope of Phase III; an incerse trend was observed in older or heavier smokers. The single-breath N2 closing volume test also provided the greatest number of abnormal results when other indices were impaired in the same subjects.

[The importance of epidemiology for research on pneumoconiosis in Belgium]. / L'importance de l'épidémiologie pour la recherche sur les pneumoconioses en Belgique.

Epidemiological surveys of coal workers' pneumoconiosis are only possible by means of periodic X-ray examinations, repeated with a reasonable frequency in order to allow an identification of the first X-ray anomalies of simple pneumoconiosis in exposed workmen. Incidence studies to detect simple pneumoconiosis at its first stages and its progressive increase in cohorts of coal-miners whose dust exposure is known are indeed theoretically the best way to approach these problems. For many reasons, discussed in this paper, such incidence studies are nowadays impossible in Belgium. The survey technique used in our country is based on repeated transversal surveys. Its results are illustrated and commented.

Oxitropium bromide (Ba 253), an advance in the field of anticholinergic bronchodilating treatments. Preliminary results.

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.

[Dyspnea symptoms in coalminers]. / Contribution à l'étude des plaintes de dyspnáee chez les mineurs de charbon.

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.

[Treatment of bronchial obstruction with beta-2-mimetic and anticholinergic agents in aerosol. Advantages of the combination of both groups of pharmaceuticals]. / Behandeling van bronchusobstructie met bêta 2-mimetica en anticholinergica in aërosol. Voordelen van het associëren van beide groepen farmaca.

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.

[Current aspects of clinical bronchopulmonary and cardiovascular clinical pharmacology. Talampicillin in acute bronchopulmonary diseases in mine workers]. / Aktualiteiten van bronchopulmonaire en cardiovasculaire klinische farmacologie. Talampicilline in acute borncho-pulmonaire aandoeningen bij mijnwerkers.

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.

The relationship between host factors of allergic nature and respiratory symptoms.

Respiratory symptoms and personal history of allergy were examined in 1659 children, including the entire elementary school population of four villages of the Belgian Ardennes. Levels of atmospheric pollution were monitored during the survey and proved to be very low. It is suggested that socio-economic factors produce a small increase in respiratory symptoms, particularly in cough symptoms. A personal history of eczema and of hay fever was highly associated with dyspnea and wheezing.

Diurnal variations and reproducibility of the N2 closing volume test in healthy subjects.

To assess the diurnal variation of closing volume measurements, 11 non-smokers and 10 somkers, all healthy, were tested with the single-breath nitrogen test. In each subject, 3 satisfactory tracings were recorded at 9:a.m., 11:a.m., 1:p.m., 3:p.m. and 5:p.m. on each of two consecutive days. Duplicate copies of the tracings were read in radom order by two independent observers. The "best+ and the mean values of closing volume to vital capacity ratio (CV/VC or phase 4/VC) and of the slppe of phase 3 were calculated. The study shows that: (1) the time of the day may be a source of variation of the closing volume measurements. Meals and cigarette smoke did not appear to be responsible for this diurnal variation, (2) values obtained with the "best" tracing method can, at least in some readers, give systematic differences with the mean of several traces, (3) individual variations in CV/VC and in the slope of phase 3 are the highest with the "best" trace analysis, and (4) the vlaues obtained by two independent readers may significantly differ. The differences observed between hours, although significant, were nevertheless small in magnitude and did not explain most of the variation of the measurements. Variations in trace aspect were small in some subjects. The reproducibility of the test was remarkable in them, at least when the junction of phase 4 with phase 3 was well defined. In other subjects, the coefficient of variation was high mainly because of varying curve shape and/or poorly defined departure of phase 4. This explains for a great part the intra-and interreader variations observed in this study.

[Cardiorespiratory function in young bronchitis patients, mostly mineworkers, before and after kinesitherapy and exertion training. Comparison with a control group (Preliminary results)]. / Cardiorespiratoire functie bij jonge bronchitislijders, voor het merendeel mijnwerkers, vóór en na kinesitherapie en inspanningstraining. Vergelijking met een controlegroep (Preliminaire resultaten).

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.

[Mineworker's dyspnea. 2. Evaluation of blood gas analysis using arterialized blood from the earlobe]. / Bijdrage tot de studie van de mijnwerkersdyspnoe. Tweede deel. Validatie van de bepalingen van de bloedgaswaarden met gearterialiseerd bloed uit de oorlel.

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.

Carbuterol, fenoterol, orciprenaline, salbutamol and terbutaline per os in reversible obstructive chronic bronchitis.

The effects of tablets of carbuterol, orciprenaline, salbutemol, terbutaline and fenoterol at two dosages were studied using FEV1 and specific airway conductance as parameters. A placebo was used as a reference. Carbuterol and fenoterol proved to be more potent than the other sympathomimetic competitors. Fenoterol 5 mg was on the average somewhat less potent than 3 mg carbuterol. This differnce was not statistically significant for FEV1; it was significant three hours after intake for airway conductance. None of the drugs produced significant changes of the blood pressure. Carbuterol and 12 mg fenoterol caused a statistically significant increase in heart rate. ECG changes were observed in eight patients with the different beta-sympathomimetics, with the exception of 5 mg fenoterol.

Contribution to the standardization of pharmacodynamic tests in lung function.

By bringing the aerosols in a spirometrical bell from which a constant volume aerosol was thereafter inhaled by each subject through a bi-directional valve, we observed more consistent and reproducible ventilatory results than by giving the aerosols by means of a classical device via a face mask. Moreover the results were significantly higher with the first technique; this fact suggests that the quantity of inhaled broncho-active drug with suitable granulometry would have been on the average greater per minute with the first method.

[Effect of almitrine on arterial gases in patients with chronic respiratory insufficiency. Comparison with doxapram. Preliminary results]. / Invloed van almitrine op de arteriële gassen bij patiënten met chronische respiratoire insufficiëntie. Vergelijking met doxapram. Voorlopige resultaten.

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.

[Reflections on 19 cases of asbestosis discovered by chance in the population of an industrial region in the Basse-Sambre]. / Réflexions à propos de 19 cas d'asbestose fortuitement découverts dans la population d'une collectivité industrielle de la Basse-Sambre

The authors describe 19 cases of definite or highly probable asbestosis which were observed among unselected out-patients at a hospital in the industrial area of the "Basse-Sambre". These cases were of various types and were, almost exclusively, of occupational origin. The variety and severity of the asbestosis in many of the cases justify a more thorough survey in this area. Those people who have handled and inhaled asbestos fibres at work will be examined in the first place. A radiological pulmonary survey will also be organized among the people living in the neighbourhood of factories using asbestos. Precise information about the origin, quality and characteristics of the inhaled dust as well as the intensity and duration of exposure will be obtained. Cases discovered in the survey will be investigated systematically by means of an extensive range of techniques: frontal and oblique X-rays with an appropriate kilovoltage for the detection of pleural calcifications and of the reticular thickening of the parenchyma; spirometry and measurement of the transfer factor for CO; arterial blood gases at rest and during exercise; search for ferruginous bodies in sputum; pathological studies of pulmonary and pleural tissues and of the ultrastructure of pleural tumours.

[Double blind study of the effect of alveolar air distribution influenced by RG 033 in chronic bronchitis]. / Etude en double aveugle des effets de la distribution de l'air alvéolaire sous l'effet du RG 033 dans la bronchite chronique.

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.