Search

Objectives: Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS., Methods: A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed., Results: The mass median aerodynamic diameters were 1.4 ± 0.2 versus 0.9 ± 0.2 μm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) μg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume., Conclusions: Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.

In previous studies of the smoke from regular cigarettes and water pipes, we measured aerosol particle sizes in three streams; S1, inhaled by the smoker, S2, released by the device itself and S3, exhaled by the smoker. We used an electrostatic low-pressure impactor (ELPI), giving particle size distributions in real time and calculated median diameters, D50, and dispersion (σg). This allowed us to predict airway deposition. In addition, the aerosol particle half-life in the air was used as a measure of the risk to others from passive smoking. With the same equipment, we measured the particle sizes and persistence in air of the liquid aerosol generated by e-cigarettes (Cigarettec®) containing water, propylene glycol and flavorings with or without nicotine. Aerosol generation was triggered by a syringe or by the inspiration of volunteer smokers. The D50 data obtained in S1, were 0.65 μm with nicotine and 0.60 μm without nicotine. Deposition in the airways could then be calculated: 26% of the total would deposit, of which 14% would reach the alveoli. These data are close to those found with regular cigarettes. For S3, D50 data were 0.34 μm and 0.29 μm with or without nicotine. The half-life in air of the S3 stream was 11 seconds due to a rapid evaporation. The-e-cigarette aerosol, as measured here, is made of particles bigger than those of cigarette and water pipe aerosols. Their deposition in the lung depends on their fate in the airways, which is unknown. Contrary to tobacco smoke, which has a half-life in air of 19 to 20 minutes, the risk of passive "smoking" exposure from e-cigarettes is modest., (Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Marketed since 2004 as an alternative to nicotine delivery and advertised as a valid means to smoking cessation, the electronic (e)-cigarette has been the subject of much controversy but very little experimental study. This review provides a brief summary of the current knowledge of this product. Propylene glycol and glycerol, the main ingredients of the fluid that is vaporized, have proved to be harmless in the fog machines of the entertainment industry. However, in the case of the e-cigarette fluid, the composition is not properly labeled: additives like nicotine and flavors vary between and within brands and contamination with various chemicals has been detected. The short-term toxicity seems low, but the long-term toxicity is unknown. The usefulness of the e-cigarette in smoking cessation has still to be clinically established., (© 2013 S. Karger AG, Basel.)

Background: A simple method for effective bronchodilator aerosol delivery while administering continuing continuous positive airway pressure (CPAP) would be useful in patients with severe bronchial obstruction., Objective: To assess the effectiveness of bronchodilator aerosol delivery during CPAP generated by the Boussignac CPAP system and its optimal humidification system., Methods: First we assessed the relationship between flow and pressure generated in the mask with the Boussignac CPAP system. Next we measured the inspired-gas humidity during CPAP, with several humidification strategies, in 9 healthy volunteers. We then measured the bronchodilator aerosol particle size during CPAP, with and without heat-and-moisture exchanger, in a bench study. Finally, in 7 patients with acute respiratory failure and airway obstruction, we measured work of breathing and gas exchange after a β(2)-agonist bronchodilator aerosol (terbutaline) delivered during CPAP or via standard nebulization., Results: Optimal humidity was obtained only with the heat-and-moisture exchanger or heated humidifier. The heat-and-moisture exchanger had no influence on bronchodilator aerosol particle size. Work of breathing decreased similarly after bronchodilator via either standard nebulization or CPAP, but P(aO(2)) increased significantly only after CPAP aerosol delivery., Conclusions: CPAP bronchodilator delivery decreases the work of breathing as effectively as does standard nebulization, but produces a greater oxygenation improvement in patients with airway obstruction. To optimize airway humidification, a heat-and-moisture exchanger could be used with the Boussignac CPAP system, without modifying aerosol delivery.

Introduction: Second hand cigarette smoke consists predominantly of nanoparticles (with two dimensions less than 100 nanometres). The aim of this study was to examine the aerosol of cigarette smoke suspended in the air of a smoking room, its disappearance over the course of time, and its retention in the airways of passive smokers, as these processes remain poorly characterised., Methods: A smoking machine produced cigarette smoke in a room. A low pressure electrostatic impactor with 13 plates, measured the size distribution and the concentration of the smallest particle sizes in the room air. Healthy adult volunteers (n=14) inhaled and exhaled this air through a nasal mask, allowing calculation of the retention of nanometric particles., Results: The tobacco smoke aerosol was composed of 75% of nanometric particles. The half-life of these particles in the air was 18min. After 2h, 3% of the tobacco smoke particles remained suspended in the air. In passive smokers, the measured airway retention was on average 20%., Conclusion: This work shows that 75% of second hand cigarette smoke aerosol is made up of nanoparticles. When non-smokers inhale this passively, 20% of the particles are retained in their respiratory tract., (Copyright 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: It is a popular perception that narghile (water pipe) smoking is less harmful to the lungs than cigarettes in both active and passive smokers., Methods: Using a sinusoidal pump we simulated water pipe smoking in conditions close to users' habits. The particle sizes and concentrations in the smoke streams were measured with an electrical low pressure impactor (ELPI), sorting particle numbers and size into 12 classes ranging from 0.028 to 10 microm in diameter., Results: Water pipe smoke contains microparticles and nanoparticles. The main inhaled smoke stream (C1) contains particles in a concentration of 3.55 x 10(6) ml(-1) with a median particle diameter (D50) of 0.34microm before bubbling through water. After bubbling, it retains 1.20 x 10(6) ml(-1) particles with a D50 of 0.27 mm, indicating that 2/3 of the particles are retained in the water, the smallest being trapped the less. Compared with C1, the D50 of the side stream smoke (C2) is smaller (0.11mm) while the D50 of the expired stream (C3) is similar (0.25mm)., Conclusion: After bubbling, C1 particle sizes are similar to those measured in cigarette smoke but the volumes inhaled by a water pipe smoker are higher allowing prediction of greater deposition in the respiratory tract than with cigarette smoking.

Introduction: For several decades a more peripheral distribution of the broncho-pulmonary pathologies related to tobacco has been observed., Methods: The aim of this study is to examine whether changes in the particle size of cigarette smoke as the result of new manufacturing technologies could play a part in the observed epidemiologic changes through a more distal disposition of smoke particles in the airways. Using a smoking machine and a low pressure electrostatic impactor we measured the particle size of the smoke from six different types of cigarette, representing old and new manufacturing techniques. The effect of a filter was assessed by a size analyser measuring the electrical mobility of the particles., Results: The results show a difference in particle size between the primary smoke inhaled by the smoker, S1 (0.27 +/- 0.03 microm.) and the secondary smoke, S2 inhaled by passive smokers (0.09 +/- 0.01 microm). There is no difference in particle size between the 6 different types of cigarette. Filters dilute the smoke without altering particle size., Conclusion: The recent alterations in the distribution of tobacco related pathologies cannot be explained by changes in particle size in cigarette smoke. The explanation has to sought elsewhere.

Nebulization of solutions associating gomenol, dexamethasone and framycetin is very widespread in otorhinolaryngology (particularly for the treatment of actue laryngitis and post-traumatic laryngitis and rhinitis and for the tracheotomy care). A rigorous clinical evaluation is however lacking. The aim of this work was to evaluate use of such solutions in comparison with the recommendations issuing from the National Session in April 1997 on good practices for aerosol therapeutics. Stability and granulometry were studied in order to optimize processing. A new formulation and new technical methods of administration are proposed in relation to the results of this study and the national recommendations.

Objective: Various types of filters have been designed to prevent cross contamination of ventilation and respiratory devices. The aim of this study was to experimentally measure the retention efficiency of four simple filters (antibacterial and antiviral and seven combined filters (antibacterial and antiviral plus heat and water exchangers)., Setting: The respiratory function testing (EFR) central department of a university teaching hospital., Measurements and Results: The same aerosol test with a wide range of particle sizes (0.15 to 15 micrometers) was used to compare the retention efficiency of each filter used in various conditions. The particle sizes and the concentration of the aerosol were measured by a laser velocimeter. For all the filters studied, the retention efficiency was found to be higher than 99%. However some of them let large particles let through., Conclusion: These data, performed in vitro, should be assessed also by further clinical studies.

We measured with a laser velocimeter granulometric deposit of an aerosol anti-infectious agent, fusafungin, administered with a controlled inhalator. Total drug deposit was determined on the basis of a granulometric spectrum of the polydispered aerosol (mass mean aerodynamic diameter (MMAD) = 2.8 +/- 1.7 microns) and dispersion in the airways was estimated using the Stahlhofen model. We first compared deposits obtained with oral inhalation in 19 normal subjects and 20 patients with chronic obstructive lung disease. Total deposit in the airways of patients with chronic obstructive lung disease (82%) was not significantly different from that in normal subjects (85%). Estimated dispersion in normal airways was 27% in the alveoles, 8.4% in the tracheobronchic region and 23.5% in the extrathoracic regions. We then compared deposits after nasal inhalation in 22 normal subjects and 21 patients with rhinitis: nasal deposit was significantly greater in patients with rhinitis (54.5%) than in controls (44.7%). We conclude that such an inhalator can be adapted for local treatment of ENT infections and upper respiratory infections. Deposit is not modified in case of obstructive bronchopathy.

The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

We carried out a maximum expiratory flow-volume curve (MEFV) and a spirometric recording with 67 athletes of different ages (15-27 years) and disciplines (rowers, kayakists, cyclists, swimmers) and with 20 adult and 13 adolescent nonathletic controls of matching ages. These recordings were repeated, with athletes only, after 6-10 months of training. Significant differences between the groups of adult athletes and the controls were observed for some parameters, the most discriminating of which were, in order, the peak expiratory flow (PEF), the forced expiratory volume in the first second (FEV1), and the flow at 75% of the vital capacity (V75). The vital capacity (VC) itself was only higher in the rowers group. The adult athletes, when grouped together (n = 47), produced a higher flow at 50% of their VC (V50) than the control group (+15%, P less than 0.05) with no difference in the flow at 25% of VC (V25) nor in the VC. A study of the effects of training showed no evolution among high level athletes while increases of 14% of the PEF, 5% of the V75, and 7% of the FEV1 were found after 7-10 months of training in adolescents; the VC increased during that time by only 2.7%. The reproducibility of these ventilatory parameters after 6-8 months was studied with adult athletes. The upper limit of the variation (95% CLl) was 12% for the FEV1 and forced vital capacity (FVC), 18% for PEF, 21% for V75 and V50, and 40% for V25.(ABSTRACT TRUNCATED AT 250 WORDS)

We have tested the hypothesis that there is a positive relation between arterial elasticity and physical working capacity (PWC) at a given age. The subjects were 28 young men, 16-18 yr old. Arterial elasticity was evaluated by measuring the carotid to femoral pulse-wave velocity (c) at rest. The slope, S(c) of the relation between c and the diastolic blood pressure was studied during a cold pressor test to test vascular reactivity. The relationship between heart rate (HR) and work load was determined using a cycle ergometer; the variables measured were the slope of this relation S(PWC) and the power output at a HR of 170 min-1 (PWC170). The PWC170 ranged from 1.8 to 4.6 W/kg, and values of c ranged from 3.9 to 6.8 m/s. A strong inverse linear relation was found between c and PWC170 (r = -0.76), whereas the HR at rest was positively related to both c (r = 0.68) and PWC170 (r = 0.74). There was no relationship between HR at rest and the slopes S(c) and S(PWC); the latter two variables depend mainly on the sympathetic response. These results show the importance of the intrinsic mechanical properties of the cardiovascular system, particularly arterial elasticity, in human adaptations to muscular exercise.

1. The dynamics of the ventilatory response to carbon dioxide inhalation were studied in ten healthy young men using four different inspired fractions of carbon dioxide (FI, CO2) in air (0.015, 0.030, 0.045 and 0.060) successively increasing and decreasing stepwise. 2. Seven such different progressions were performed for each subject and each of seven different durations of the steps (t) ranging between 0.1 (i.e. one ventilatory cycle) and 10 min ('steady-state' conditions). The overall duration of one test (T) was taken as the sum of the seven successive FI, CO2 steps (t) plus one step, t, of air breathing. Thus, the values of T ranged between 0.8 (i.e. eight ventilatory cycles) and 80 min. Three subjects were tested twice. 3. We measured, as a function of T, the magnitude of the loops formed by the curves PA, CO2-VE and the value of the highest ventilatory response (VE max) to each progression. For all ten subjects, both functions had two maxima, one for T values of 2.6 or 8.0 min and one for T values of 24 or 40 min, and one minimum at T equal to 12 min. 4. The same measurements were made on tidal volume-response curves (PA, CO2-VT) and ventilatory frequency-response curves (PA, CO2-f) and yielded the same results except for the ventilatory frequency-response curves, for which we only found a statistically insignificant single maximum for T values of 24 or 40 min. 5. The locations of the maxima in loop magnitude and VE max were similar in duplicate tests in three subjects, whereas the quantitative values of these variables showed wide differences. 6. We compared our results with what is expected from the current linear dynamic model of ventilatory control submitted to the same forcing function: the first maximum in the loop magnitude is predicted by the model, but the second is not. The model shows no peak in the evolution of VE max. 7. We conclude that controlled system dynamics, which are the only ones included in dynamic models of ventilatory control, cannot by themselves account for our observations, and that one should take into consideration the dynamics of the controlling neuronal network.

1. The dynamics of the ventilatory response to isocapnic hypoxia were studied in seven healthy subjects using four different levels of hypoxia, (inspired oxygen pressures, PI,O2 equal to 110, 100, 80 and 60 mmHg) successively increasing and decreasing stepwise. 2. Five such progressions were performed for each subject, corresponding to five different durations of the steps (t) ranging between 0.33 and 5.00 min. The overall duration of one test (T) was taken as the sum of the seven successive PI,O2 hypoxic steps (t) plus one step t of air breathing. Thus, the values of T ranged between 2.6 and 40.0 min. 3. End-tidal CO2 pressure was maintained constant (+/- 1 mmHg) throughout the test by manipulation of inspired CO2 pressure. 4. We measured, as a function of T, (i) the magnitude of the loops formed by the ventilatory response curves (PA,O2-VE) as measured by their surface area (S), (ii) the magnitude of ventilatory response to each rising hypoxic step, and (iii) the difference between resting VE and VE observed at PA,O2 equal to 50 mmHg (delta V50). On average, we found one maximum in absolute value of S at T = 8 min and one minimum at T = 12 min, along with two maxima of ventilatory response at T values of 8 and 24 min. 5. The same measurements were made on tidal volume response curves (PA,O2-VT) and ventilatory frequency response curves (PA,O2-f): on average we observed two non-significant peaks in the progression with T of VT and S(VT) and two significant peaks in that of delta VT,50 for T = 8 and T = 24 min. No significant peak was observed in the progression with T of f curve parameters. 6. These results are discussed together with the current dynamic model of the ventilatory control system, which includes a central neural controller with no dynamics of its own and a linear response to chemoreceptor inputs. We discuss the physiological meaning of a negative loop area in relation to the previously described depressant effect of hypoxia upon the brain stem. 7. We conclude that the dynamics of the controlling neuronal network are responsible for the observed singularities which result from differential sensitivity properties of the controller. We propose the existence of discrete excitatory states of the controller as a possible explanation of the shape of the steady-state response curve to hypoxia and of the loop variations.

The arterial pulse wave velocity is determined to a large extent by the arterial elastic modulus. We tried to assess the importance of this parameter in cardio-vascular adaptation to exercise by measuring pulse wave velocity (c) in 45 sedentary subjects and 28 competitive cyclists whose ages ranged from 14 to 47 years. The measurements were performed at rest and during the recovery phase after ergometric exercise. At constant diastolic pressure, a positive linear relationship was demonstrated between c and age in both the sedentary and trained subjects. The slope of this relation was significantly different in the two groups. During the recovery phase, at constant diastolic pressure, a linear relationship was also established between c and the relative increase in systolic pressure in the sedentary group classified into six age subgroups. The slope of this relation increased with age. The part taken by diastolic flow velocity during exercise in the increase in c was demonstrated in 8 subjects by simultaneous Doppler ultrasonic recording of contra-lateral femoral arterial velocity. Nevertheless diastolic flow in exercise could not explain entirely the observed increase in c. An increase in arterial elasticity modulus during exercise should be postulated in order to explain the concomitant increase in arterial pulse wave velocity.