[Good practice for aerosol therapy by nebulization in 2020]. / Bonnes pratiques de l'aérosolthérapie par nébulisation en 2020.

Nebulization is a drug delivery mode whose prescription and application remain uncertain. A guide to good practice has been proposed by the work group on aerosol therapy of the French Society for Respiratory Diseases, so-called GAT. The previous recommendations date from 2007. In addition to an update of data on nebulization, these expert recommendations aim to be of real help to the prescriber.

[Comparison of the aerosol produced by electronic cigarettes with conventional cigarettes and the shisha]. / Comparaison de l'aérosol de la cigarette électronique à celui des cigarettes ordinaires et de la chicha.

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.

Electronic cigarettes: a short review.

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.

[Inhalation therapy: provocation tests, infectious risks, acute bronchiolitis and ENT diseases. GAT aerosolstorming, Paris 2011]. / Aérosolthérapie: tests de provocation, risques infectieux, bronchiolites et pathologie ORL. Aérosolstorming du GAT, Paris 2011.

Communications from the 2011 meeting of the GAT are reported in this second article on the practical management of bronchial provocation tests and infectious risks associated with the use of nebulization. Recent advances on the role of nebulized hypertonic saline in the treatment of acute bronchiolitis in infants and of the nebulization in sinusal diseases are also reported.

[Inhalation devices: characteristics, modeling, regulation and use in routine practice. GAT Aerosolstorming, Paris 2011]. / Les dispositifs d'inhalation : propriétés, modélisation, réglementation et utilisation en pratique courante. Aérosolstorming du GAT, Paris 2011.

Aerosoltherapy is a first-line treatment for chronic obstructive respiratory diseases such as asthma and COPD. Treatment modalities and devices are varied and the choice of the device must be adapted to and optimized for every patient. Spacers can be used for some categories of patients for whom the use of other devices turns out to be complicated. The improvement of these treatments requires the optimization of the lung deposition of inhaled particles; lung modeling plays an essential role in the understanding of the mechanisms of flow in the airways. Regulations must frame prescription of inhaled treatments to optimize its quality and, thus, the care for these chronic diseases. Many generally-accepted ideas concerning these treatments turn out to be false. Inhaled treatments are constantly evolving, both pharmacologically and technologically.

[Bronchiolitis obliterans postallogeneic stem cell transplantation: what is new?]. / Bronchiolite oblitérante après allogreffe de cellules souches hématopoïétiques : quels progrès ?

Bronchiolitis obliterans (BO) is a severe complication of hematopoietic stem cell transplantation (HSCT). It is considered as a respiratory manifestation of chronic graft-versus-host disease. It is quite similar to the bronchiolitis obliterans after lung transplantation. Classical therapy associates steroids and immunosuppressive drugs, however theses procedure showed a modest efficacy and have an important morbidity. Recent progresses in the physiopathology of BO post-HSCT allow to use new treatments: mTOR inhibitors, immunotherapy, extra-corporeal photochemotherapy, and bronchial anti-inflammatory effects of azithromycin, statins or antileucotriens. This review will focus on the use of these new therapies in BO post-HSCT.

Reconsidering the arm span-height relationship in patients referred for spirometry.

The interpretation of pulmonary function tests relies on reference values corrected for age, sex and height. Height may be difficult to measure in patients with deformities of the thoracic cage or those unable to stand up properly. Current practice is to substitute arm span to height, once corrected either by a fixed factor or by an age- and sex-dependent regression equation. However arm span may be difficult to measure in some patients. This study evaluated the relationship between arm span, measured height, height as mentioned on an identity document (ID), sex and age in a population of 2,452 Caucasian subjects with no chest or spine deformities. The present study demonstrates that age and sex have to be taken into account to best predict height from arm span or ID height values. The equations predicting height from ID height give the best diagnosis concordance compared to reference in males and females. Age correction does not improve concordance below 70 yrs. The estimation of height from ID height can be substituted to that from arm span when clinically relevant, providing ID height has been measured before the occurrence of stature problems.

Inhaled insulin: a model for pulmonary systemic absorption?

The European Union recently approved a form of insulin intended to be inhaled. This innovative presentation has the potential to partially or completely replace the injections and thus facilitate starting insulin therapy which is considered with apprehension and often differed. On this occasion, we reviewed the issues raised by this pulmonary route for systemic absorption (anatomical and cytological limits, cellular mechanisms, relevant physical parameters, facilitating chemical cofactors, role of tobacco smoking and of common respiratory diseases). The pharmacokinetics of inhaled and injectable insulins are comparable, apart from an appreciably faster absorption of the former, and both show the same intra-individual variability. The total bioavailability is definitely lower with the inhaled route but is notably increased in smokers. These characteristics can vary according to the inhalation system used. A frequent induced cough, the increase in circulating anti-insulin antibodies, and a potentially higher cost are not really determining obstacles. The indications will have to be clearly specified and the long-term innocuousness of repeated inhalation of such a mitogen, especially in children and former smokers, remains to be fully proven.

[Airway deposition of nanoparticles from second hand cigarette smoke]. / Rétention dans les voies aériennes des particules nanométriques de l'aérosol de la fumée de cigarette au cours du tabagisme passif.

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.

Multicentre trial evaluating alveolar NO fraction as a marker of asthma control and severity.

BACKGROUND: Exhaled NO can be partitioned in its bronchial and alveolar sources, and the latter may increase in the presence of recent asthmatic symptoms and in refractory asthma. The aim of this multicentre prospective study was to assess whether alveolar NO fraction and FE(NO) could be associated with the level of asthma control and severity both at the time of measurement and in the subsequent 3 months. METHODS: Asthma patients older than 10 years, nonsmokers, without recent exacerbation and under regular treatment, underwent exhaled NO measurement at multiple constant flows allowing its partition in alveolar (with correction for back-diffusion) and bronchial origins based on a two-compartment model of NO exchange; exhaled NO fraction at 50 ml/s (FE(NO,0.05)) was also recorded. On inclusion, severity was assessed using the four Global initiative for asthma (GINA) classes and control using Asthma Control Questionnaire (ACQ). Participants were followed-up for 12 weeks, control being assessed by short-ACQ on 1st, 4th, 8th and 12th week. RESULTS: Two-hundred patients [107 children and 93 adults, median age (25th; 75th percentile) 16 years (12; 38)], 165 receiving inhaled corticosteroid, were included in five centres. The two-compartment model was valid in 175/200 patients (87.5%). Alveolar NO and FE(NO,0.05) did not correlate to control on inclusion or follow-up (either with ACQ /short-ACQ values or their changes), nor was influenced by severity classes. Alveolar NO negatively correlated to MEF(25-75%) (rho = -0.22, P < 0.01). CONCLUSION: Alveolar and exhaled NO fractions are not indexes of control or severity in asthmatic children and adults under treatment.

[Particle size in water pipe smoke]. / Tailles particulaires de la fumée de chicha.

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.

[Inhaled insulin: a model for pulmonary systemic absorption?]. / L'insuline par voie inhalée: un modèle pour l'absorption systémique pulmonaire?

European Union has recently approved a form of insulin intended to be inhaled. This innovative presentation has the potential to partially or completely replace the injections and thus facilitate starting insulin therapy which is considered with apprehension and too often differed. On this occasion, we reviewed the issues raised by this pulmonary route for systemic absorption (anatomical and cytological limits, cellular mechanisms, relevant physical parameters, facilitating chemical cofactors, role of tobacco smoking and of common respiratory diseases). The pharmacokinetics of inhaled and injectable insulins are comparable, apart from an appreciably faster absorption of the former and both show the same intra-individual variability. The total biodisponibility is definitely lower with the inhaled way but it is notably increased in smokers. These characteristics can vary according to the inhalation system used. A frequent induced cough, the increase in circulating anti-insulin antibodies and a potentially higher cost are not really determining obstacles. The indications will have to be clearly specified and the long-term inocuity of long term inhalation of such a mitogene especially in children and former smokers remains to be formally proven.

[A survey of nebulization practices in France conducted in 2004 by the GAT]. / NUAGES: une enquête sur la pratique de la nébulisation en France.

METHODS: A questionnaire was sent to 50 000 general practicioners (GP) and specialists. RESULTS: 4,898 physicians (9.4%) responded, including 59.1% GP, 16.9% pneumologists, 13% pediatricians and about 10% other specialists, ENT, allergologists, and intensivists. The main reason for pneumologists to prescribe nebulization was the efficiency on long term of approved drugs. GP prescribe nebulization for its local effects, using unapproved drugs, on short periods of time, especially in COPD, asthma, bronchitis and tracheitis/laryningitis. Although pneumologists have been trained during their fellowship and do not ask for further education, MG have learned by their own experience and are asking for further education. CONCLUSION: This study should help to develop teaching programs on nebulization with the aim to optimize its practice.

[Particle size in the smoke produced by six different types of cigarette]. / Tailles particulaires de la fumée produite par six différents types de cigarettes.

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.

N.U.A.G.E.S: a survey of nebulisation practice in France with regard to ERS guidelines.

UNLABELLED: A survey of nebulisation practice in France was conducted under the aegis of the French respiratory society in 2004. METHODS: Analysis of a questionnaire was obtained from 3674 physicians. RESULTS: A total of 2439 physicians were general practitioners (GPs), 698 were chest physicians, and 537 paediatricians. The main reasons to use nebulisation are (1) for chest physicians efficacy in treating various pathologies with long-term administration (1 wk to 1 month) of approved drugs, and (2) for GP's local action properties. While chest physicians learned about nebulisation during their university training and do not ask for additional information, GPs learned by practical experience or from colleagues and ask for further information. CONCLUSION: This study will help to develop targeted educational programmes on nebulisation practice.

Validation of laser diffraction method as a substitute for cascade impaction in the European Project for a Nebulizer Standard.

The project for a European standard testing procedure to characterize nebulizers in terms of particle size distribution has been based on using the Andersen-Marple personal cascade impactor model 298 (A-MPCI) with a sodium fluoride reference solution. In the present study methods based on laser diffraction (Mastersizer-X) and time-of-flight (TOF)(APS) and another cascade impactor (GS1-CI) were compared with the A-MPCI. Two types of nebulizer (Pari LC+ and Microneb) were tested with all apparatuses, and a third type of nebulizer (NL9) was tested with the A-MPCI and Mastersizer-X. Nebulizers were charged with a solution of sodium fluoride in conditions reproducing the European Committee for Normalization (CEN) protocol. There was no difference between the Mastersizer-X and the A-MPCI or between the GS1-CI and the A-MPCI in terms of mass median aerodynamic diameter (MMAD). Comparison between the APS and the A-MPCI showed a significant difference with the Microneb. The geometric standard deviations (GSD) obtained with the A-MPCI were on average 10% greater than GSD obtained with the other apparatuses, but the differences were not statistically significant. We conclude that laser diffraction can be used for particle size distribution in the context of the European standard, and that the Mastersizer-X is particularly interesting for industrial practice in view of its simplicity and robustness.

[Optimization of aerosol therapy in otorhinolaryngology: stability and granulometry of dexamethasone-gomenol-framycetin solution]. / Optimisation de l'aérosolthérapie en ORL: étude de stabilité et de granulométrie d'une solution dexaméthasone-huile gomenolée-framycétine.

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.