Vibrating membrane devices deliver aerosols more efficient than standard devices: a study in a neonatal upper airway model

BACKGROUND: Aerosol therapy in preterm infants is challenging, as a very small proportion of the drug deposits in the lungs. AIM: Our aim was to compare efficiency of standard devices with newer, more efficient aerosol delivery devices. METHODS: Using salbutamol as a drug marker, we studied two prototypes of the investigational eFlow(®) nebulizer for babies (PARI Pharma GmbH), a jet nebulizer (Intersurgical(®) Cirrus(®)), and a pressurized metered dose inhaler (pMDI; GSK) with a detergent-coated holding chamber (AeroChamber(®) MV) in the premature infant nose throat-model (PrINT-model) of a 32-week preterm infant (1,750 g). A filter or an impactor was placed below the infant model's "trachea" to capture the drug dose or particle size, respectively, that would have been deposited in the lung. RESULTS: Lung dose (percentage of nominal dose) was 1.5%, 6.8%, and 18.0-20.6% for the jet nebulizer, pMDI-holding chamber, and investigational eFlow nebulizers, respectively (p<0.001). Jet nebulizer residue was 69.4% and 10.7-13.9% for the investigational eFlow nebulizers (p<0.001). Adding an elbow extension between the eFlow and the model significantly lowered lung dose (p<0.001). A breathing pattern with lower tidal volume decreased deposition in the PrINT-model and device residue (p<0.05), but did not decrease lung dose. CONCLUSIONS: In a model for infant aerosol inhalation, we confirmed low lung dose using jet nebulizers and pMDI-holding chambers, whereas newer, more specialized vibrating membrane devices, designed specifically for use in preterm infants, deliver up to 20 times more drug to the infant's lung

Providing feedback on adherence increases use of preventive medication by asthmatic children

This study investigates the impact of measuring adherence and providing feedback on medication usage by children with unstable asthma. Adherence was measured using an electronic monitoring device. Subjects were randomized to either being told of their adherence during review consultations or for their adherence to remain undisclosed to their parents and treating physician. Subjects were reviewed monthly for 4 months. Twenty-six children aged between 6 and 14 years were recruited. Adherence was significantly higher in the intervention group (79% versus 58%,

Usefulness of parental response to questions about adherence to prescribed inhaled corticosteroids in young children

Background Adherence to prescribed inhaled medication is often low in young children. Poor adherence to medication may contribute to lack of symptom control. Doctors are not good at predicting the adherence rates of their patients, and parental report of adherence does not correlate with objective measures of adherence. The objective of this study was to investigate whether parental admission of non-adherence and reasons given for non-adherence correlated with objectively measured adherence

Incentive device improves spacer technique but not clinical outcome in preschool children with asthma

Aim: To investigate the influence of an incentive device, the Funhaler, on spacer technique and symptom control in young children with asthma and recurrent wheeze

Validation of Radiolabeling of Drug Formulations for Aerosol Deposition Assessment of Orally Inhaled Products

Radiolabeling of inhaler formulations for imaging studies is an indirect method of determining lung deposition and regional distribution of drug in human subjects. Hence, ensuring that the radiotracer and drug exhibit similar aerodynamic characteristics when aerosolized, and that addition of the radiotracer has not significantly altered the characteristics of the formulation, are critical steps in the development of a radiolabeling method. The validation phase should occur during development of the radiolabeling method, prior to commencement of in vivo studies. The validation process involves characterization of the aerodynamic particle size distribution (APSD) of drug in the reference formulation, and of both drug and radiotracer in the radiolabeled formulation, using multistage cascade impaction. We propose the adoption of acceptance criteria similar to those recommended by the EMA and ISAM/IPAC-RS for determination of therapeutic equivalence of orally inhaled products: (a) if only total lung deposition is being quantified, the fine particle fraction ratio of both radiolabeled drug and radiotracer to that of the reference drug should fall between 0.85 and 1.18, and (b) if regional lung deposition (e.g., outer and inner lung regions) is to be quantified, the ratio of both radiolabeled drug and radiotracer to reference drug on each impactor stage or group of stages should fall between 0.85 and 1.18. If impactor stages are grouped together, at least four separate groups should be provided. In addition, while conducting in vivo studies, measurement of the APSD of the inhaler used on each study day is recommended to check its suitability for use in man

Validation of Radiolabeling of Drug Formulations for Aerosol Deposition Assessment of Orally Inhaled Products

Radiolabeling of inhaler formulations for imaging studies is an indirect method of determining lung deposition and regional distribution of drug in human subjects. Hence, ensuring that the radiotracer and drug exhibit similar aerodynamic characteristics when aerosolized, and that addition of the radiotracer has not significantly altered the characteristics of the formulation, are critical steps in the development of a radiolabeling method. The validation phase should occur during development of the radiolabeling method, prior to commencement of in vivo studies. The validation process involves characterization of the aerodynamic particle size distribution (APSD) of drug in the reference formulation, and of both drug and radiotracer in the radiolabeled formulation, using multistage cascade impaction. We propose the adoption of acceptance criteria similar to those recommended by the EMA and ISAM/IPAC-RS for determination of therapeutic equivalence of orally inhaled products: (a) if only total lung deposition is being quantified, the fine particle fraction ratio of both radiolabeled drug and radiotracer to that of the reference drug should fall between 0.85 and 1.18, and (b) if regional lung deposition (e.g., outer and inner lung regions) is to be quantified, the ratio of both radiolabeled drug and radiotracer to reference drug on each impactor stage or group of stages should fall between 0.85 and 1.18. If impactor stages are grouped together, at least four separate groups should be provided. In addition, while conducting in vivo studies, measurement of the APSD of the inhaler used on each study day is recommended to check its suitability for use in man

The concentration of iron in real-world geogenic PM₁₀ is associated with increased inflammation and deficits in lung function in mice.

BACKGROUND: There are many communities around the world that are exposed to high levels of particulate matter <10 µm (PM₁₀) of geogenic (earth derived) origin. Mineral dusts in the occupational setting are associated with poor lung health, however very little is known about the impact of heterogeneous community derived particles. We have preliminary evidence to suggest that the concentration of iron (Fe) may be associated with the lung inflammatory response to geogenic PM₁₀. We aimed to determine which physico-chemical characteristics of community sampled geogenic PM₁₀ are associated with adverse lung responses. METHODS: We collected geogenic PM₁₀ from four towns in the arid regions of Western Australia. Adult female BALB/c mice were exposed to 100 µg of particles and assessed for inflammatory and lung function responses 6 hours, 24 hours and 7 days post-exposure. We assessed the physico-chemical characteristics of the particles and correlated these with lung outcomes in the mice using principal components analysis and multivariate linear regression. RESULTS: Geogenic particles induced an acute inflammatory response that peaked 6 hours post-exposure and a deficit in lung mechanics 7 days post-exposure. This deficit in lung mechanics was positively associated with the concentration of Fe and particle size variability and inversely associated with the concentration of Si. CONCLUSIONS: The lung response to geogenic PM₁₀ is complex and highly dependent on the physico-chemical characteristics of the particles. In particular, the concentration of Fe in the particles may be a key indicator of the potential population health consequences for inhaling geogenic PM₁₀