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Biomedical subjects

A Denjean

Publications and source records attributed to A Denjean.

At least 19 recordsLinked to original sources

Inhaled salbutamol and beclomethasone for preventing broncho-pulmonary dysplasia: a randomised double-blind study.

UNLABELLED: Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation. We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia (BPD) in ventilator-dependent premature neonates. The study was double-blinded and placebo controlled. We studied 173 infants of less than 31 weeks of gestational age, who needed ventilatory support at the 10th postnatal day. They were randomised to four groups and received either placebo + placebo, placebo + salbutamol, placebo + beclomethasone or beclomethasone + salbutomol, respectively for 28 days. The major criteria for efficacy were: diagnosis of BPD (with score of severity), mortality, duration of ventilatory support and oxygen therapy. The trial groups were similar with respect to age at entry (9.8-10.1 days), gestational age (27.6-27.8 weeks), birth weight and oxygen dependence. We did not observe any significant effect of treatment on survival, diagnosis and severity of BPD, duration of ventilatory support or oxygen therapy. For instance, the odds-ratio (95% confidence interval) for severe or moderate BPD were 1.04 (0.52-2.06) for inhaled beclomethasone and 1.54 (0.78-3.05) for inhaled salbutamol. CONCLUSION: This randomised prospective trial does not support the use of treatment with inhaled beclomethasone, salbutamol or their combination in the prevention of BPD in premature ventilated neonates.

Administration, Inhalation

Influence of correction of flow limitation on continuous positive airway pressure efficiency in sleep apnoea/hypopnoea syndrome.

We evaluated the efficiency of two different treatment procedures with continuous positive airway pressure (CPAP) on sleep, nocturnal breathing characteristics and daytime vigilance in 18 newly diagnosed patients with untreated sleep apnoea/hypopnoea syndrome (SAHS) randomly allocated to two different groups. In group I, the positive pressure (PP) level was set to suppress flow limitation (PFL), while in group II the PP was set at a level that eliminated only apnoea/hypopnoea and snoring (PAHS). At the end of a 3 week period of home CPAP therapy, a follow-up sleep study, vigilance and cognitive tests were made. Overall, PFL was significantly higher than PAHS values (PFL: 10.42.6 cmH2O; PAHS: 8.9+/-2.6 cmH2O; p<0.01, mean+/-SD). We found no difference in sleep quality, nocturnal saturation and apnoea/hypopnoea index, or in daytime vigilance tests between the two groups at the end of the treatment period. However, there was a significantly greater scattering in the changes of sleep latency in group II than in group I. This was associated with a significant difference in the daily duration of nasal CPAP use between the two groups (group I: 7.29+/-0.95 h x day(-1); group II: 6.01+/-0.94 h x day(-1); p=0.01) and with a positive correlation between final maintenance of wakefulness test values and the duration of CPAP use (p<0.05; r=0.55). These results tend to show that correcting flow limitation is associated with a higher observance and a more important efficiency in normalizing daytime vigilance than with conventional nasal continuous positive airway pressure.

Aged

[Assessment of three filters for respiratory function tests].

Several filters specific for respiratory function tests have been on the market for several years. Recommended by the manufacturers to avoid contaminating the equipment and thus improve patient safety, these filters require a considerable financial investment. We studied the passage of diluted blood into artificial saliva in a patient model simulating inspiration tests and rapid forced expiration to assess the retention capacity of three filters used for respiratory function tests: Multi SPIRO MI-90016 (MultiSPIRO), PF 30S (Pall Biomedical) and Spirobac (Dar. S.p.A). The mean percentage of passage was 1.48% through the MI-90016 filter, 57.15% through the PF 30 S filter and 70.45% through the Spirobac filter. These findings provide further elements for choosing filters for respiratory function tests. Indeed, despite the manufacturers' commercial arguments, the technical documents provided do not give necessary information on the filtering capacity of the filters on the market. We have observed that two out of the three filters tested do no meet the standards expected by clinicians.

Blood

Influence of thoracoabdominal pattern of breathing on respiratory resistance.

The purpose of this study was to test the hypothesis that voluntary changes in thoracoabdominal pattern of breathing may increase total respiratory resistance. Thirty-one normal subjects were asked to control their thoracoabdominal pattern of breathing by using a visual feedback. Thoracic and abdominal volume changes were measured by inductance plethysmography. Respiratory resistance and elastance were measured by forced oscillometry. The mean (+/-SD) percent thoracic contributions to tidal volume during thoracic or abdominal breathing were 75 (+/-11) and 25% (+/-9), respectively. These changes induced small but significant increases in resistance (P < 0.005) and elastance (P < 0.002). The increased resistance was observed in 22 subjects for thoracic breathing (P < 0.016) and in 21 subjects for abdominal breathing (P < 0.043). The mean value (+/-SD) of individual increases in resistance during thoracic or abdominal breathing, compared with normal breathing, were 9.2 +/- 17.5 and 9.4 +/- 19.9%, respectively. The fact that departing from spontaneous pattern increases respiratory resistance is consistent with the notion that breathing pattern is optimally adjusted on the basis of mechanical criteria.

Abdomen

Guinea-pig tracheal responsiveness in vitro following general anaesthesia with halothane.

Halothane and isoflurane induce potent bronchodilation during general anaesthesia and have been used successfully during status asthmaticus. The aim of this study was to determine whether airway hyporesponsiveness was prolonged after halothane administration. Sixteen guinea-pigs were submitted for 2 h to either 1.5% halothane in oxygen or 100% oxygen, and were killed 24 h later to elicit isometric tracheal contractions in organ baths with various agonists. Cumulative concentration-response curves to histamine or to KCl and contractions evoked with acetylcholine 1 mM (4.7 +/- 0.8 vs 4.6 +/- 0.5 g) or carbachol 10 microM in calcium-free buffer (4.3 +/- 0.6 vs 4.4 +/- 0.6 g) exhibited no difference between groups. Moreover, when 4% halothane or 4.6% isoflurane were directly bubbled through the organ baths, a significant decrease (13 +/- 1% and 37 +/- 2%) of maximal contractions evoked with acetylcholine and KCI, respectively, was obtained but these relaxant effects did not persist 30 min after cessation of anaesthetic. These results indicate that, even though halothane induces transient airway hyporesponsiveness in vitro, previous halothane anaesthesia in guinea-pigs does not alter subsequent tracheal responsiveness assessed in vitro. Our findings may explain the transient renewal of bronchospasm reported during intermittent periods off halothane in status asthmaticus.

Anesthesia, General

Long-term pulmonary functional outcome of bronchopulmonary dysplasia and premature birth.

Pulmonary function and exercise tolerance were evaluated in late childhood in two groups of prematurely born children: one group with bronchopulmonary dysplasia (BPD) [n = 15; gestational age at birth (GA): 29.6 +/- 2.8 weeks; birth weight (BW): 1,367 +/- 548 g; age at test: 7.9 +/- 0.6 years], and a second group without significant neonatal lung disease [pre-term (PT)] (n = 9; GA: 30.3 +/- 1.7 weeks; BW: 1,440 +/- 376 g; age at test: 7.8 +/- 0.22 years). The results were compared with a control group of children of similar ages and heights, born at term [term born (TB)]. We observed that total lung resistance (RL) was significantly higher in BPD (11 +/- 3 cmH2O/L/s), and in PT (9 +/- 2) than in TB [5 +/- 1; (P < 0.001 and P < 0.05, respectively)]. In BPD RL was higher than in PT (P < 0.05). Dynamic lung compliance (CLdyn) was decreased in BPD (43 +/- 11 mL/cmH2O) and in PT (56 +/- 17) compared with TB (76 +/- 20) (P < 0.001 and P < 0.05), and also in BPD compared with PT (P < 0.05). Forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were lower in BPD (1.07 +/- 0.15 L and 72 +/- 7%) than in PT (1.29 +/- 0.23 L, and 80 +/- 7%) (P < 0.05). Exercise tests were performed in six boys with BPD. The ratio between minute ventilation at maximal workload (VEmax) and the predicted value of maximal voluntary ventilation (MVV) was elevated in the six BPD boys tested, compared with five boys of Group 2 and five TB boys (87 +/- 15% vs. 62 +/- 14% and 65 +/- 13%) (P < 0.05). We conclude that: 1) prematurity and BPD is followed by long-term airway obstruction and a mild degree of exercise intolerance and; 2) premature birth without BPD may be followed by a milder degree of airway obstruction in childhood than in infants who developed BPD during the neonatal period.

Analysis of Variance

Lack of bronchodilator effect after administration of subanaesthetic concentration of isoflurane in mild asthmatic subjects challenged with methacholine.

Volatile anaesthetics used in high concentrations are potent bronchodilators. The effect of lower subanaesthetic concentrations is less documented, particularly in humans with provoked bronchial obstruction. We have studied seven mild asthmatic subjects twice, 1 week apart, during an asymptomatic period. A provocative test with methacholine was performed to produce a decrease in forced expiratory volume in 1 s (FEV1) of at least 20%. The subjects then inhaled either 100% oxygen or 0.75% isoflurane in oxygen for 8 min, via a face mask. During isoflurane inhalation, the subjects lost consciousness but recovered quickly. There was no significant improvement in FEV1 and maximum expiratory flow at 50% vital capacity (MEF50) recorded 3, 6, 9, 14 and 19 min after the end of isoflurane inhalation compared with time-control values. We conclude that lung function in mild asthmatic subjects challenged with methacholine was not improved after administration of a low subanaesthetic concentration of isoflurane. This may be important during recovery from general anaesthesia.

Adult

Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin.

To investigate the capacity of the pulmonary vascular bed to acutely vasodilate, we examined in 35 consecutive patients with primary pulmonary hypertension (PPH), the hemodynamic effects of incremental inhalation periods of an air-NO mixture at different concentrations (10, 20, and 40 ppm), and compared them with those of an acute infusion of prostacyclin (PGI2). An individual pulmonary vasodilator response was defined by a fall in total pulmonary resistance (TPR) > or = 30% relative to mean TPR baseline value. Thirteen patients were responders and 22 were nonresponders to both drugs, and they did not significantly differ in overall baseline characteristics except for mean right atrial pressure (p < 0.03). In responders, both drugs produced similar individual vasodilator response. Changes in mean pulmonary arterial pressure and TPR observed during NO and PGI2 were closely correlated (r2 = 0.9, p < 0.001, and r2 = 0.7, p < 0.01, respectively). The vasodilator response to NO was not concentration-related with a maximal effect obtained at 10 ppm. Combination of both drugs did not lead to any additive vasodilator response. Unlike PGI2, NO did not induce any systemic effect, no adverse reaction, but a moderate increase in methemoglobin. Inhaled NO at low dose (10 ppm) appears to be an effective, safe, and reliable substitute for PGI2 in screening for acute pulmonary vasodilator responsiveness during therapeutic assessment of patients with PPH.

Adult

[Non-allergenic bronchial hyperreactivity. Measurement methods and reproducibility].

Different methods are available to measure non-allergic airway responsiveness. In the last years, efforts have been made to improve standardization of these methods, in order to allow comparison of data from different sources. The most currently used bronchial provocation tests are those with nebulisation of histamine or methacholine either a tidal volume or from a dosimeter, a dose-response curve being obtained in measuring expiratory flows or airway resistance. Inhalation of non-iso-osmolar solutions, cold air hyperventilation, exercise or other agents and stimuli may be used to estimate airway response, but they are more useful as a research tool than for clinical purposes. The reproducibility of bronchial provocation tests is dependent of different factors such as those related to the subject (asthma stability, performance of tests, medications, circadian variations), technical factors (type and calibration of the apparatus, nebulizer output, measurements, solutions) and to the methods of calculation of the bronchial response. Short-term reproducibility of the different types of bronchial provocation tests is usually good although long-term stability needs to be further assessed. A correlation has been reported between the response to most of the different bronchoconstrictor agents, although variable.

Administration, Inhalation

[Risk factors for gastroesophageal reflux in chronic asthma].

In order to study risk factors for gastroesophageal reflux (RGO), we have analysed the clinical particulars, the spirometry and the different therapies of chronic asthmatics with and without RGO. RGO has been studied using 24 hour pH manometry in 53 patients suffering from chronic asthma. 70% of these patients had RGO, defined as oesophageal pH below 4, for 4.2% or more of the total time. The only predictive factor for the presence of RGO (log regression) was the dose of theophylline (P is equal to 0.02) whose average dose was higher in cases of RGO (9.1 plus or minus 2.3 mg/kg against 6.3 plus or minus 1.7 mg/kg, P is less than 0.03). Although the severity of the asthma and the spirometric parameters were similar. On the other hand, the severity of RGO, assessed as the percentage of the total time passed with a pH below 4 or correlated (multiple regression) with longevity of the disease (P is equal to 0.02) and the dose of theophylline (P is equal to 0.001). These results suggest that the treatment with theophylline and the duration of the asthma could constitute risk factors for RGO in chronic asthma.

Adolescent

Dose-related bronchodilator response to aerosolized salbutamol (albuterol) in ventilator-dependent premature infants.

We used a placebo-controlled standardized protocol to define the dose-response relationship to the beta-adrenergic bronchodilator salbutamol (albuterol) in 10 ventilator-dependent premature infants at a postnatal age of 13.3 +/- 4.9 days. Passive respiratory system resistance and compliance were measured at baseline and 10 minutes after administration of salbutamol via a metered-dose inhaler and spacer device. Salbutamol caused a significant dose-related response with a 33% mean decrease in respiratory system resistance (p less than 0.05) and a 67% mean increase in respiratory system compliance (p less than 0.001). In seven and six patients, respectively, 100 micrograms of salbutamol caused significant improvement in resistance and compliance; 200 micrograms was required in the remainder, but one patient had no improvement in compliance. Oxygen saturation increased linearly with the increase in compliance. In 7 of the 10 infants, the duration of action of 200 micrograms of salbutamol on the following day was 3 hours. We conclude that bronchodilator treatment may be useful in the management of ventilator-dependent neonates with respiratory distress syndrome.

Aerosols

Accuracy of measurements of HbF with OSM3 in neonates and infants.

The accuracy of the Radiometer OSM3 oxymeter for measurement of fetal haemoglobin (HbF) in infants was investigated, and compared to one of the standard reference methods using alkali electrophoresis of haemoglobin. Blood samples of 37 infants with different gestational (27-41 weeks) and postnatal (1-198 days) ages were analysed. The two methods gave very close results but a significant mean difference (range -4.5-16.5%). However, agreement between the two methods was judged clinically acceptable (95% limits of agreement -7.5-15.5%). A rapid determination of HbF percentage, using OSM3, is an important determinant for correct assessment of oxygen saturation in newborn infants in intensive care units.

Electrophoresis

Hypoxia-induced bronchial responsiveness in awake sheep: role of carotid chemoreceptors.

Hypoxia enhances bronchial responsiveness in sheep and dogs and we recently reported a similar effect in asthmatic subjects. Activation of a reflex arc due to stimulation of peripheral chemoreceptors has been suggested to explain this finding. We evaluated the contribution of carotid body chemoreceptors to hypoxia-induced bronchial responsiveness in conscious sheep. Incremental concentrations of aerosolized methacholine were given to each of seven sheep ventilated successively (in a random order) with a normoxic and a hypoxic gas mixture (15% O2 in N2), both before and after peripheral surgical chemodenervation. Hypoxia alone did not affect lung mechanics in intact or chemodenervated animals. Bronchial responsiveness to methacholine was significantly increased by hypoxia in intact sheep, as compared to chemodenervated sheep. We conclude that hypoxia has a stimulating effect on bronchial responsiveness in awake sheep similar to that seen in human patients with asthma. This increased responsiveness may be mediated by hypoxic stimulation of carotid body chemoreceptors, which in turn may influence the nervous control of airway calibre.

Airway Resistance

Interaction between tracheal sound and flow rate: a comparison of some different flow evaluations from lung sounds.

We simultaneously recorded tracheal sound and air flow from nine normal subjects (seven males and two females). Sound was picked up at the supra sternal notch with an air-coupled sensitive microphone held in a small airtight probe. Flow was measured at the mouth using a pneumotachograph Fleisch n degrees 2. Both sound and flow were directly digitized at a sampling rate of 5120 Hz and then divided in 128-sample blocks. For each sound block the frequency spectrum was computed using the fast Fourier transform. In order to evaluate instantaneous flow-rate from tracheal sounds we investigated eight methods divided in two groups of four. In the first group (i.e., reference curves methods), we assumed that a relationship existed between sound and flow and was thus reflected by the variations of certain parameters. We chose to use simple straightforward relationships, already known and published. We tested four different parameters. During a calibration phase, we built for each parameter P a reference curve representing the variations of P versus flow and being specific to each subject. Then, an unknown flow was evaluated in calculating P on a 128-sample block, and the reference curve gave the corresponding flow. In the second group, we made a hierarchial clustering analysis of sound spectra for revealing the frequency modifications, induced by the flow. We tested two kinds of spectra as well as two ways of associating a flow to a given cluster. This led us to four other methods for calculating the flow. All the eight methods but one gave a mean uncertainty in the measure of flow of about 15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Accumulation of platelets and eosinophils in baboon lung after paf-acether challenge. Inhibition by ketotifen.

Intratracheal administration of platelet-activating factor (paf-acether) induced transient bronchoconstriction in baboons. Using an automated isotopic monitoring system, we found that intratracheal administration of paf-acether also elicited transient accumulation of platelets labeled with 111In oxine within the pulmonary vasculature after the increase in maximal peak inspiratory pressure. Bronchoalveolar eosinophilia were inhibited by prophylactic administration of the antiasthma drug ketotifen but not by pyribenzamine, suggesting that the effects of ketotifen are unrelated to H-1 receptor antagonism. Platelet accumulation was not affected by ketotifen or pyribenzamine. This study suggests that paf-acether may be a mediator of the eosinophil recruitment in bronchial asthma and that inhibition of this phenomenon by ketotifen may contribute to the therapeutic efficacy of this drug.

Animals

Mild isocapnic hypoxia enhances the bronchial response to methacholine in asthmatic subjects.

We studied the effect of mild isocapnic hypoxia (FIO2 = 15.5%) on lung mechanics, heart rate, circulating plasma catecholamines, and bronchial responsiveness to methacholine in ten asthmatic adults. Hypoxia did not alter lung mechanics (i.e., dynamic pulmonary compliance [CLdyn], pulmonary resistance [RL]) nor did it increase plasma catecholamines, but it significantly increased bronchial responsiveness to aerosolized methacholine, as assessed by the fall in forced expiratory volume in one second (FEV1: 1.2 +/- 0.18 versus 0.9 +/- 0.14 L/s, p less than 0.05), the rise in RL (RL: 19.1 +/- 1.4 versus 8.4 +/- 1 cm H2O/L/s, p less than 0.05), and the steeper slope of the dose-response curve to methacholine. We concluded that the hypoxic characteristic of asthmatic attacks may aggravate airflow obstruction.

Adult

Postoperative pulmonary complications: general anesthesia with postoperative parenteral morphine compared with epidural analgesia.

In a prospective study, patients undergoing abdominal cancer surgery were randomly allocated to receive either general anesthesia with fentanyl intravenously and postoperative analgesia with parenteral morphine (GA group) or general anesthesia combined with epidural bupivacaine and epidural morphine for postoperative pain relief (EP group). Analgesia was tested on a visual pain scale. Pulmonary complications were evaluated by clinical complications, blood gas analysis, x-ray film changes, and pulmonary volumes (vital capacity, forced expiratory volume in 1 second). Measurements were performed on the day before the operation and on the first 5 postoperative days. In the EP group the pain relief was significantly better on the first day (p less than 0.03). Whatever the criteria used, the rates of pulmonary complications were similar in the two groups: clinical complications 21% versus 26%, radiologic complications 50% versus 64% for GA and EP groups, respectively. Postoperative PaO2 and spirometric values were similar in the two groups. Postoperative epidural analgesia may improve the patient's comfort but does not decrease the incidence of pulmonary complications.

Abdomen