Dynamics of aerosol size during inhalation : Hygroscopic growth of commercial nebulizer formulations

We thank the Elizabeth Blackwell Institute (EBI) for financial support through the EBI Early Career Research Fellowship awarded to AEH, and the EPSRC for financial support through a Leadership Fellowship awarded to JPR (grant reference EP/G007713/1). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are creditedThe size of aerosol particles prior to, and during, inhalation influences the site of deposition within the lung. As such, a detailed understanding of the hygroscopic growth of an aerosol during inhalation is necessary to accurately model the deposited dose. In the first part of this study, it is demonstrated that the aerosol produced by a nebulizer, depending on the airflows rates, may experience a (predictable) wide range of relative humidity prior to inhalation and undergo dramatic changes in both size and solute concentration. A series of sensitive single aerosol analysis techniques are then used to make measurements of the relative humidity dependent thermodynamic equilibrium properties of aerosol generated from four common nebulizer formulations. Measurements are also reported of the kinetics of mass transport during the evaporation or condensation of water from the aerosol. Combined, these measurements allow accurate prediction of the temporal response of the aerosol size prior to and during inhalation. Specifically, we compare aerosol composed of pure saline (150 mM sodium chloride solution in ultrapure water) with two commercially available nebulizer products containing relatively low compound doses: Breath, consisting of a simple salbutamol sulfate solution (5 mg/2.5 mL; 1.7 mM) in saline, and Flixotide Nebules, consisting of a more complex stabilized fluticasone propionate suspension (0.25 mg/mL; 0.5 mM in saline. A mimic of the commercial product Tobi (60 mg/mL tobramycin and 2.25 mg/mL NaC1, pH 5.5-6.5) is also studied, which was prepared in house. In all cases, the presence of the pharmaceutical was shown to have a profound effect on the magnitude, and in some cases the rate, of the mass flux of water to and from the aerosol as compared to saline. These findings provide physical chemical evidence supporting observations from human inhalation studies, and suggest that using the growth dynamics of a pure saline aerosol in a lung inhalation model to represent nebulizer formulations may not be representative of the actual behavior of the aerosolized drug solutions. (C) 2014 Published by Elsevier B.V.Peer reviewe

EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on public health risks represented by certain composite products containing food of animal origin

This Opinion reviews the factors that affect microbial survival and growth in composite products, and in foods in general. It concludes that the main factors to be considered are: water activity, pH, temperature and duration of storage, processing, and intensity and duration of other non-thermal physical processes applied. Prevalence and concentration of the pathogens in food are important to determine the risk for consumers. The opinion presents a review of the quantitative microbiology models and databases that can be used to provide quantitative estimations of the impact of the above factors on the survival and growth of the main bacterial pathogens. In composite products, migration and diffusion of moisture and substances among the ingredients may change their physico-chemical parameters, particularly at the interfaces. Therefore, the assessment of the risk posed by composite products needs to consider the combinations of parameters most permissive to survival and growth of pathogens. Two complementary approaches are proposed for the identification and profiling of microbiological hazards in different specific composite products. The first one is based on past outbreaks and prevalence of hazards in the products and leads to the conclusion that the most frequent hazard-composite product combinations are Salmonella in cakes and bakery products. The second one consists in decision tools based on the impact on the pathogens of food composition and food processing. Categorisation of the risk for composite products requires information on their composition, processing and further handling, which can largely differ for foods belonging to the same category. Further conditions may influence the risk and should be verified, i.e. hygienic conditions during preparation of the composite products and their ingredients, shelf-life conditions, and reliability of cooking by consumers to inactivate pathogens. The decision tools developed apply to all composite products considered by the mandate, as well as to all other foods. © European Food Safety Authority, 201

Characterisation of aerosol delivery devices and their influence on deposition in humans and animals

One way of administrating pharmaceutical drugs in the development phase and in the clinical situation is by inhalation. It is essential to ensure an accurate delivered dose, as the prediction of the effect and side effects of the drug action is dependent on a precise estimation of the given dose. During inhalation as compared to other techniques (oral or intravenous) this becomes more complicated as the dose is dependent on device performance and patient interaction during inhalation, both which influence the site of deposition which can be of interest for specific drug applications. This thesis will try to explain some of the main underlying factors involved, and how to control, or measure, the effect of them in order to achieve a more accurate dosing to patients. Initially six different commercially available nebulisers were investigated in order to try to explain the nebuliser droplet generation and separation properties. The results obtained in this study indicate that the mass median diameters (MMD) of the investigated nebulisers were dependent on air velocity, and the ratio of liquid to air volumetric flow rate (QI/Qa). It was also found that changes in air velocity affects QI/Qa, and both air velocity and QI/Qa separately influence the size distribution and thus the output A novel inhalation system, called FIDO, was developed to enable a more accurate estimate of the inhaled dose than previously used methods. The data obtained supports the hypothesis that FIDO is more accurate in delivering and estimating a predefined inhaled dose compared to conventional indirect filter methods used today. The effect of turbulence on regional deposition of Evans Blue dye tracer aerosol in normal and constricted airways was investigated using an animal (rabbit) model. This was achieved by using different aerosol carrier gases consisting of either Helium-Oxygen (80% He/ 20% 02) or air (79% N2/21% 02) in histamine-provoked and non-provoked rabbits. The results showed that bronchial provocation gave more central deposition (0.55 ± 0.11 expressed as ratio central/total deposition) compared to the non-provoked control group (0.80 ± 0.09). The He-O2 ventilated rabbits also had a significantly higher peripheral deposition compared with air ventilated rabbits when provoked. The effect of the relative humidity of entrained ambient air on nebulised aerosol size properties was assessed in a study where two jet nebuliser designs were investigated using the proposed CEN standard. The first one was a conventional constant output nebuliser, the second one a breath enhanced nebuliser. The study showed a droplet size distribution dependency related to the relative humidity (RH) of the entrained air when using the conventional nebuliser, an effect which was not apparent for the breath enhanced nebuliser. An inhalation study using sodium chromoglycate was performed on light to moderate asthmatic children. The effect on deposition was investigated by changing the droplet size distribution inhaled through alteration of the relative humidity (RH) (low RH corresponding to 13% and a high RH corresponding to >90% RH) of the entrained air. The droplet size was monitored with an impactor and was found to be 1.2 mm for the low RH and 2.0 mm for the high RH. A difference in the total deposition between the low and high RH, 34% and 41% respectively, was found. The results were compared with the results obtained by a lung deposition software, TGLD2, developed at Karolinska Institute. The software could differentiate between lung and extrathorasic deposition and could explain the difference in the total deposition obtained at different RH. The study also showed a correlation between the tidal volume inhaled and the total amount deposited. There was also a correlation between the RH (e.g. droplet size) and the amount deposited

Specialpedagogers arbete i fo?rskolan med fokus pa? inkludering. Special educators work in preschool with focus on inclusion

How do special educators work to include children with special needs in preschool? That was the question that our thesis proceeded from, and the purpose was to get an insight in the methods used by the special educators to achieve inclusion. Our questions were: • Is Swedish preschool a place for inclusion? • How are special educators work organized and focused? • Which experiences do special educators have working with children with special needs in preschool, and what role do they mean that inclusion plays in this work? Our procedure in this enquiry was to perform semi-structured interviews with 5 different special educators in two different cities. Interpretation and analyis proceeded from three different theories: Urie Bronfenbrenner’s ecological systems theory, John Bowlby’s theory of attachment and Karsten Hundeide’s sociocultural theory. The result showed support for the idea of the Swedish preeschool as a place with many opportunities for inclusion. We have also seen how both money and political decisions has an impact on which possibilities the preschools receive to work with inclusion. In addition it became apparent that the methods used by special educators differed depending on both cities and districts. One of the main purposes of the special educators consisted in finding different ways to include children in the everyday activities

Effect of humidity on constant output and breath enhanced nebulizer designs when tested in the EN 13544-1 EC standard

Aqueous aerosols produced by nebulizers used in clinical situations can rapidly change size as the patient inhales. This is caused by air with a relative humidity (RH) lower than inside the nebulizer being entrained and mixed with nebulized aerosol during the inhalation maneuver. A way to assess the change in size is to measure the aerosol in a test method that reflects the clinical situation. The EC standard, EN 13544-1, offers a first step towards this assessment. In this paper we have tested two nebulizer designs, one conventional constant output nebulizer and one breath-enhanced nebulizer, using the proposed standard in order to assess the effect of the relative humidity of entrained ambient air on nebulized aerosol size properties. The results indicate that aerosol size from the conventional nebulizer is greatly affected by the RH of the entrained air, while the breath-enhanced nebulizer is not affected. The results agree with theoretical expectations of how the entrained air interacts with nebulized aerosol. In the breath-enhanced nebulizer, the air is passed through the nebulizer interior and becomes saturated with moisture drawn from the relatively large nebulizer reservoir solution. With the conventional constant output nebulizer, ambient air is drawn over the nebulizer and draws its moisture from the relatively small volume of nebulized aerosol released from the nebulizer. For the conventional nebulizer design, we found a large decrease in measured nebulized aerosol size with decreasing relative humidity-3.1 mum MMAD at 75% RH fell to 1.9 mum MMAD at 20% RH. For the breath-enhanced nebulizer design, the MMAD was stable between a similar humidity range. The results indicate that aerosol size is dependent on relative humidity of the entrained air for the constant output jet nebulizer design that has no air entrainment through the nebulizer. We found no significant effect of ambient humidity of entrained air on nebulized aerosol size from the breath-enhanced nebulizer design