[Comparative study of two antitussive drugs in the treatment of acute dry cough of infectious origin (prospective, randomized, single blind study)]. / Etude comparative de deux antitussifs dans le traitement des toux aiguës sèches d'origine infectieuse (étude prospective, randomisée, en simple aveugle).

The objective was to compare, during a 5-day therapy, the efficacy and tolerability of an antihistaminic antitussive syrup, oxomemazine, combining a small quantity of guaifenesine (T), with a centrally acting antitussive, clobutinol (S), in adult patients aged from 18 to 70 years and presenting with a dry cough of infectious origin. This study was performed by 22 general practitioners and 130 ambulatory patients were enrolled. The primary criterion of this multicenter, randomized, single blind study was to compare the evolution of cough intensity using a Visual Analog Squale (VAS) graduated from 0 to 10 cm. Nine secondary criteria including tolerability were also assessed. With regard to cough intensity, the treatments were not equivalent. A greater reduction was observed with T (-5.2 +/- 2.3 versus -4.3 +/- 2.3). This result was confirmed by a further reduction in cough intensity at days: 2 (p = 0.04), 4 (p = 0.05), and 5 (p = 0.02). The frequency of cough disappearance before the end of the study was significantly greater for T than for S: 46% versus 29% (p = 0.05). The time before disappearance of the cough was 4.0 + 1.1 days for both medicines. Induction of sleep and the frequency of nocturnal wakening were significantly better for T from day 4 (p = 0.02). The drowsiness induced by T meant that diurnal quality of life was better with S on days 1 (p = 0.002) and 2 (p = 0.01). Tolerability was similar for both medicines. In conclusion, as a symptomatic treatment of dry cough, T is efficient and well tolerated. Moreover, we have observed a tendency towards superior efficacy of T than S. T is therefore a useful alternative in the therapeutic armamentarium available to the general practitioner.

[Hyperventilation syndrome: evaluation of voluntary hypoventilation programs in two rehabilitation centers]. / Syndrome d'hyperventilation.

PURPOSE: The effectiveness of a voluntary hypoventilation technique was assessed in two rehabilitation centers in patients with hyperventilation syndrome. METHODS: In the first center, 55 patients participated in an open program determining themselves the frequency and number of their consultations. In the second center 158 patients participated in a 10-week program that imposed five 60-min sessions. RESULTS: In the first center, the patients participated in 4.8 30-min sessions over a 6.1 week period. Their cardinal complaints had declined by 48% (range 14% to 67% depending on the type of complaint) at the end of the program. In the second center the patients experienced an improvement in their comfort of life (less sleep disorders, fatigability, symptoms of severe hypocapnia), increasingly so with each new session, those having completed the program reaching a 62% improvement. DISCUSSION: Due to the strong correlation observed between the clinical improvement (with a longer interval between acute episodes) and the quality of patient participation the beneficial effect of these voluntary hypoventilation rehabilitation programs cannot be attributed solely to the psychological effect of patient care.

Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group.

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

[Inhaled corticosteroid therapy in mild and moderate persistent asthma. Acceptability of a new inhalation system: the jet]. / Corticothérapie inhalée dans l'asthme persistant léger à modéré. Acceptabilité en pratique libérale d'un nouveau système d'inhalation: le jet.

The objectives of this study were to assess the acceptability and efficacy of Jet (a metered dose inhaler with a 100 ml chamber giving 250 micrograms beclomethasone dipropionate per puff) in patients with mild to moderate asthma using a dose-for-dose schedule in substitution for their standard metered dose inhaler with or without an inhalation chamber. An open trial was conducted over 5 weeks in 356 asthma patients treated with inhaled corticosteroids at a mean 914 +/- 198 micrograms/24 h dose. beta 2-agonists were used by all patients, either systematically (prescription) or as needed. Prior to the study, 27% of the patients used a standard metered dose inhaler with a large-volume inhalation chamber and 73% used a standard metered dose inhaler alone. The rate of nocturnal, early morning, and diurnal symptoms and cough decreased by 31.4, 33.4, 46.9, and 37.0% respectively and the variability of peak expiratory flow rate fell from 2 +/- 0.08% to 0.9 +/- 0.02% in the group using the metered dose inhaler with the chamber and from 1.3 +/- 0.04 to 0.5 +/- 0.01% in the group using the standard metered dose inhaler. The investigators determined that treatment efficacy was good or excellent in 94.8%. These findings should be confirmed by studies comparing Jet directly with other inhalation chamber systems or with standard metered dose inhalers. For 97.5% of the patients, it was easy to learn to use Jet and 88.2% of the patients felt no discomfort when using Jet; 64.8% of the patients stated they experienced clinical improvement. At the end of the trial, 77.9% of the patients (76.3% of those who used the inhalation chamber during the study and 78.4% of those who used the metered dose inhaler alone) stated they preferred Jet over their prior system.

Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma.

BACKGROUND: Leukotriene receptor antagonists have been shown to protect against bronchoconstriction induced by antigens, exercise, and cold air. There are relatively few clinical studies reported in patients with asthma. The present study is the first clinical evaluation of pranlukast (SB 205312, ONO-1078) outside Japan in patients with asthma. METHODS: A randomised, double blind, placebo controlled, parallel group, multicentre four week study of the safety and tolerability of oral pranlukast, 225 or 337.5 mg twice daily, was performed in patients with mild to moderate asthma. Preliminary efficacy data were obtained; the main efficacy variables evaluated were forced expiratory volume in one second (FEV1) and morning domiciliary (home) peak expiratory flow rates (PEFR). Clinic PEFR and daytime and night-time asthma symptom scores were also recorded. RESULTS: Compared with the placebo group the improvement in morning home PEFR was statistically significant at all time points for patients receiving pranlukast 337.5 mg twice daily and at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg twice daily. Mean morning home PEFR increased by 10.8 to 18.61/min (95% CI 0.2 to 29.3 l/min) in patients treated with pranlukast compared with a slight deterioration in those given placebo. FEV1 significantly increased within one hour after the first dose of pranlukast compared with baseline and this increase was maintained for eight hours. Improvements in trough FEV1-that is, at the end of the dosing interval-were statistically significant for the group treated with pranlukast 225 mg twice daily compared with placebo at week 4. Mean increases in FEV1 ranged from 210 ml to 340 ml (95% CI 60 to 500 ml) at trough in the pranlukast group. Patients treated with pranlukast also showed improvements in summary symptom and night-time asthma scores. Pranlukast was well tolerated, and no drug related changes in haematological and biochemical variables were observed. CONCLUSIONS: Pranlukast, an oral leukotriene receptor antagonist, is well tolerated and is effective for the treatment of asthma. It increased FEV1 within one hour of dosing, improved patient summary symptom and night-time asthma scores, and reduced the use of rescue bronchodilators, thus providing further evidence of a role for leukotrienes in the pathogenesis of asthma.

[Educational diagnosis in asthma. Descriptive results of a questionnaire survey]. / Diagnostic éducatif de l'asthme. Résultats descriptifs d'une enquête par questionnaire.

The object of this work was to carry out an audit on an asthmatic's knowledge of their disease and of the risk factors, their usual therapy and of therapy for acute exacerbations as well as their need for information and education. The study was carried out by a survey of 327 adult asthmatics who were in consultation with specialist physicians in thoracic medicine. The information was gathered using an anonymous questionnaire completed by a nurse. The doctors looking after these patients had given their opinion on the severity of their asthma and the educational needs of their patients. The population studied had an average of 47 +/- 17 years. Forty seven per cent of the subjects were masculine. The general level of education was high. Seventy five per cent of the patients were from an urban environment. The duration of the asthma was on an average of 19 years. Half of these patients had already been in hospital for a serious attack. One third of the patients were considered by their doctors as having severe asthma. The patients were good at distinguishing the level of severity of their acute exacerbations and adapted their therapy on their own initiative in appropriate fashion based on the degree of severity of their disease. The enquiry revealed that patients take some liberties around the basic treatment that they had been prescribed. It also showed some defects or errors in their knowledge of the disease and the appropriate approach vis-à-vis the disease. One noted for example that one third of the asthmatics had already stopped the treatment before the date fixed by their doctor. In a general, patients who were surveyed were interested in their health problems with their health and hoped to be better informed both on asthma and its treatment. This study was biased towards an interest in the understanding of the education in order to manage the asthmatic population better.

[Comparative study of the acceptability of Tilade Syncroner and Tilade Standard by mildly asthmatic patients. Syncroner Trial Research Group]. / Etude comparative de l'acceptabilité du Tilade Syncroner et du Tilade Standard par des patients asthmatiques modérés. Groupe d'investigateurs de l'essai Syncroner.

An open multicenter randomized, cross over study has compared the patients acceptance and preference of nedocromil sodium delivered as metered dose inhaler (MDI) containing 112 puffs and attached to an open tube spacer, the Syncroner with the same product as MDI containing 56 puffs delivered through a standard mouthpiece adaptator. One hundred and forty four patients (67 males) suffering from moderate asthma (mean FEV1: 86%) aged 18 to 70 years received alternatively 2 puffs of 2 mg 4 times a day of nedocromil sodium either by Syncroner or by the standard adaptator for two weeks in random order. The acceptance of each device was assessed by a questionnaire after two weeks of treatment. At the end of the study, the preference was recorded globally by the mean of a visual analog scale and for each of the following criteria: tolerability, shape, efficacy, hygiene, easiness to use, cleaning, contents and confidence. After two weeks of treatment the Syncroner was as well accepted as the standard mouthpiece and even better in terms of contents, cleaning and confidence. At the end of the study, 50.4% of patients prefering the Syncroner and 49.6% the standard mouthpiece. Patients significantly favoured the Syncroner because of its contents, hygiene, and cleaning (p < 0.05 for these 3 criteria) and tolerability (p = 0.07). In conclusion, after two weeks of treatment, the Syncroner was as well accepted as the standard MDI, 50% of patients preferred the new inhalation device. Considering its interest as training aid and the better lung deposition, it can be proposed for drug delivery without risk of a rejection by patients.

Ease-of-use study of pirbuterol acetate in the Autohaler actuator in three countries: the United States, Germany, and France.

The preferred form of acute bronchodilator therapy is to administer aerosolized beta-agonist by a metered-dose inhaler. Many patients cannot use this device efficiently, the major problem being coordination of dose release with inspiration. A new breath-actuated inhaler (the Autohaler actuator) has been developed to overcome this problem. The objective of this study was to evaluate patient's and staff's perceptions of this device. Ninety-eight percent of patients rated the device easy to use and 83% rated the overall use as excellent or good. The staffs rated it as excellent or good for 93% of patients. It was concluded that patients would accept this device, and greater patient compliance could be realized.

Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients.

The aim of this study was to compare the pulmonary effects of a single dose of celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400 mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a double-blind randomized cross-over study in 10 stable asthmatic patients (mean age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5 +/- 0.7 l. A three-day washout period preceded each treatment period. Measurements of respiratory function were done before treatment and after 90, 120 and 180 min. There was a significant increase of FEV1 (+12%) and forced vital capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (-9%) after propranolol. Concerning the combination, celiprolol inhibits the bronchoconstrictor effects of propranolol. We conclude that celiprolol has bronchosparing properties in asthmatic patients, and even improves some of the ventilatory parameters.

Shape change of the occlusion-pressure wave during exercise.

In conscious subjects, the occlusion pressure measured in the initial part of the inspiration (up to 200 ms) appears to be a valid index of output of the respiratory centres. To interpret any relative change in occlusion pressure, the shape of the occlusion-pressure wave must remain absolutely constant. The purpose of this study was to test the hypothesis that the shape of occlusion-pressure wave does not change during exercise. However, we found that the shape changed significantly during cycle incremental-load exercise in five healthy subjects and in 12 of 17 patients with chronic obstructive pulmonary disease. The major change appeared during the second half of the exercise and mainly during the last workloads. This study shows that it is necessary to take into consideration this form change to interpret any relative change in mechanical transforms of the inspiratory neural output such as pressure at 0.1 s (P0.1) and mean inspiratory flow (VT/TI) or their ratio. This finding confirms, in direct fashion, the expected form change from previous data in which P0.1 is thought to measure the rate of change in chest wall muscle pressure (Pmus) over a segment somewhat removed from the onset of neural inspiration.

[A visual analog scale of exercise dyspnea]. / Echelle visuelle analogique de dyspnée à l'exercice.

We have adapted a visual analogue scale (VAS) to make repeated measurements of the sensation of dyspnoea during an exercise test on a bicycle ergometer. We tested the reproducibility of the development of the VAS as a function of work load and its sensitivity in detecting changes in the sensation of dyspnoea induced by the addition of an inspiratory resistance or by a trial of oxygen administration in 13 patients who were dyspnoeic on effort. The reproducibility was acceptable providing to perform a preliminary test and to eliminate the rare subjects who was incapable of performing the test (1/13). The method turned out to be equally sensitive as to the effect of inspiratory resistance for 8/12 patients and for the oxygen enrichment of inspired air for 8/9 patients. This scale thus provides a reproducible and sensitive estimation of the sensation of dyspnoea during effort and thus appears valuable in evaluating the subjective response in therapeutic trials in patients who are dyspnoeic on effort.

Exercise tolerance in chronic obstructive pulmonary disease: importance of active and passive components of the ventilatory system.

We investigated which components of ventilatory function are related to exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. Physical characteristics, usual lung function, timing and neuromuscular components of ventilation were measured in 113 outpatients in whom FEV1/VC was less than 75% of the predicted value and exercise was limited by breathlessness. These variables were used to predict the maximum work load during progressive bicycle exercise. The prediction was obtained using a stepwise procedure in men and women separately. Among the variables selected, age, body weight, FEV1/VC, PImax, and P0.1/VT/TI accounted for 79% of the variability in maximum performance in men. The predictive model was statistically verified and was stable. The mean prediction error was 12 Watts. Among these variables, P0.1/VT/TI, PImax, and FEV1/VC were the main determinants of maximum work load (MWL). These results show that exercise limitation in COPD is related to impairment of both the active (inspiratory muscles) and passive (respiratory impedance) components of the ventilatory system. The same conclusions concerning passive components are proposed for women, despite a smaller population which prevented verification of the prediction.

Treatment compliance and self-medication in asthma in France.

A study was carried out among asthmatic patients in order to determine their compliance to treatment and self-medication. Data collection used a self-administered postal questionnaire as tested in a previous study. The population under study included 450 asthmatic patients; 370 answered; their mean age was 47 +/- 16 yrs and 44% were men. An aerosol was the preferred route of administration (41%). Eighty two percent of the patients tended to reduce the doses following improvement; 80% claimed to know treatment for attacks; 90% had already been using an inhaler, although only 62% had been shown how to use one. Forty eight percent had already bought drugs without prescription, especially patients within the 25-34 yrs age group. This study is consistent with similar surveys performed in other populations. Improved quality of information about treatments and how to use drugs is higher in patients with chronic forms of asthma involving unpredictable acute attacks.

Treatment of bronchial asthma with terfenadine; a randomized controlled trial.

1. Terfenadine, a histamine H1-receptor antagonist, was studied in 52 patients with stable mild perennial asthma with an allergic basis. 2. After a placebo run-in period, patients were randomly allocated to either terfenadine 120 mg twice daily or placebo. After 2 weeks they were crossed over to the other treatment. Forty-six patients completed the study. 3. Terfenadine was significantly more effective than placebo as measured by peak expiratory flows and by symptom scores. 4. These results suggest that histamine may play a more significant role in asthmatic bronchoconstriction than is currently recognised.

[Respiratory handicap. Recognition, evaluation and social benefits]. / Handicap respiratoire. Reconnaissance, évaluation, prestations sociales.

The medico-social aspects of respiratory handicap pose some perplexing problems, notably in their recognition, rigorous evaluation and in the granting of social security benefits. The clinical and respiratory function data should be standardised and classified according to type and significance of respiratory disease and also according to the degree of co-operation and understanding of the patient. The respiratory handicap should be evaluated after considering the functional disability engendered by the disorder and their socio-professional repercussions. The abnormality in the lungs should be measured by resting tests; the degree of disability by exercise studies; the socio-professional handicap by ergonometric tests to assess the scale of the demands and requirements of family and social and professional life, indeed the cultural and economic style of the individual concerned. Such combined studies would enable recognition of severe chronic respiratory handicap leading to decisions for exemption certificates, such as cases of severe respiratory failure in patients requiring supplementary treatment for oxygen therapy or assisted ventilation. The benefits and grants offered to those with respiratory handicaps would involve a number of rights relating to: care, work, costs of replacement of workers in the event of prolonged sick leave or the benefits of an invalidity pension. There will be other allowances such as invalidity cards, lodging special studies and other rights particularly relating to lodging and special equipment. The present scale is difficult to use both because of its lack of specificity and its ill-chosen terminology. For better balance between the handicap and the benefits offered, a common and more flexible system, with a printed table should be at hand for the doctor to use for certain decisions: long term illness, period of invalidity or early retirement because of medical incapacity. Within each table a sub-section should exist to allow for certain aspects of legislation (accidents at work, occupational illness or rights under common law) at the same time certain adjustments may be necessary which take into account the patient, degree of autonomy life style and social and cultural level. A pilot study of respiratory handicap, to standardise tests, and co-ordinate the planning of the medical and social interactions for a better grasp of the disorder and greater uniformity of the regulations within each disablement benefit system as well as between various other social security regimes would be desirable.

[Sudden death during continous electrocardiographic recording by Holter's method]. / Mort subite au cours d'un enregistrement électrocardiographique continu par la méthode de Holter.

The case of a 79 year old patient who died during continuous electrocardiographic recording by Holter monitoring is reported. There was a previous history of respiratory insufficiency, postero diaphragmatic myocardial infarction and left hemiplegia. Death occurred suddenly at home after defecation. Analysis of the recording showed multiple polymorphic ventricular extra-systoles, often occuring in doublets at the beginning of the record. Death was caused by a salvo of three ventricular extrasystoles triggering ventricular tachycardia which rapidly degraded to irreversible ventricular fibrillation. This major arrhythmia may have been due either to adrenergic stimulation from the effort of defecation or to acute myocardial infarction. This case underlies the value of Holter monitoring in the assessment of the gravity of an arrhythmia. It is also of interest because of the absence of an R on T phenomenon before the terminal event.