More Realistic Face Model Surface Improves Relevance of Pediatric In-Vitro Aerosol Studies.

BACKGROUND: Various hard face models are commonly used to evaluate the efficiency of aerosol face masks. Softer more realistic "face" surface materials, like skin, deform upon mask application and should provide more relevant in-vitro tests. Studies that simultaneously take into consideration many of the factors characteristic of the in vivo face are lacking. These include airways, various application forces, comparison of various devices, comparison with a hard-surface model and use of a more representative model face based on large numbers of actual faces. AIM: To compare mask to "face" seal and aerosol delivery of two pediatric masks using a soft vs. a hard, appropriately representative, pediatric face model under various applied forces. METHODS: Two identical face models and upper airways replicas were constructed, the only difference being the suppleness and compressibility of the surface layer of the "face." Integrity of the seal and aerosol delivery of two different masks [AeroChamber (AC) and SootherMask (SM)] were compared using a breath simulator, filter collection and realistic applied forces. RESULTS: The soft "face" significantly increased the delivery efficiency and the sealing characteristics of both masks. Aerosol delivery with the soft "face" was significantly greater for the SM compared to the AC (p< 0.01). No statistically significant difference between the two masks was observed with the hard "face." CONCLUSIONS: The material and pliability of the model "face" surface has a significant influence on both the seal and delivery efficiency of face masks. This finding should be taken into account during in-vitro aerosol studies.

Computerized Dead-Space Volume Measurement of Face Masks Applied to Simulated Faces.

BACKGROUND: The dead-space volume (VD) of face masks for metered-dose inhaler treatments is particularly important in infants and young children with asthma, who have relatively low tidal volumes. Data about VD have been traditionally obtained from water displacement measurements, in which masks are held against a flat surface. Because, in real life, masks are placed against the face, VD is likely to differ considerably between masks depending upon their contour and fit. The aim of this study was to develop an accurate and reliable way to measure VD electronically and to apply this technique by comparing the electronic VD of commonly available face masks. METHODS: Average digital faces were obtained from 3-dimensional images of 270 infants and children. Commonly used face masks (small and medium) from various manufacturers (Monaghan Medical, Pari Respiratory Equipment, Philips Respironics, and InspiRx) were scanned and digitized by means of computed tomography. Each mask was electronically applied to its respective digital face, and the VD enclosed (mL) was computerized and precisely measured. RESULTS: VD varied between 22.6 mL (SootherMask, InspiRx) and 43.1 mL (Vortex, Pari) for small masks and between 41.7 mL (SootherMask) and 71.5 mL (AeroChamber, Monaghan Medical) for medium masks. These values were significantly lower and less variable than measurements obtained by water displacement. CONCLUSIONS: Computerized techniques provide an innovative and relatively simple way of accurately measuring the VD of face masks applied to digital faces. As determined by computerized measurement using average-size virtual faces, the InspiRx masks had a significantly smaller VD for both small and medium masks compared with the other masks. This is of considerable importance with respect to aerosol dose and delivery time, particularly in young children. (ClinicalTrials.gov registration NCT01274299.).

Nasal versus oral aerosol delivery to the "lungs" in infants and toddlers.

OBJECTIVES: The oral route has been considered superior to the nasal route for aerosol delivery to the lower respiratory tract (LRT) in adults and children. However, there are no data comparing aerosol delivery via the oral and nasal routes in infants. The aim of this study was to compare nasal and oral delivery of aerosol in anatomically correct replicas of infants' faces containing both nasal and oral upper airways. METHODS: Three CT-derived upper respiratory tract ("URT") replicas representing infants/toddlers aged 5, 14 and 20 months were studied and aerosol delivery to the "lower respiratory tract" (LRT) by either the oral or nasal route for each of the replicas was measured at the "tracheal" opening. A radio-labeled (99mDTPA) normal saline solution aerosol was generated by a soft-mist inhaler (SMIRespimat® Boehringer Ingelheim, Germany) and aerosol was delivered via a valved holding chamber (Respichamber® TMI, London, Canada) and an air-tight mask (Unomedical, Inc., McAllen, TX). A breath simulator was connected to the replicas and an absolute filter at the "tracheal" opening captured the aerosol representing "LRT" dose. Age-appropriate mask dimensions and breathing patterns were employed for each of the airway replicas. Two different tidal volumes (Vt ) were used for comparing the nasal versus oral routes. RESULTS: Nasal delivery to the LRT exceeded that of oral delivery in the 5- and 14-month models and was equivalent in the 20-month model. Differences between nasal and oral delivery diminished with "age"/size. Similar findings were observed with lower and higher tidal volumes (Vt ). CONCLUSION: Nasal breathing for aerosol delivery to the "LRT" is similar to, or more efficient than, mouth breathing in infant/toddler models, contrary to what is observed in older children and adults. Pediatr Pulmonol. 2015; 50:276-283. © 2014 Wiley Periodicals, Inc.

Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study.

OBJECTIVES: Delivery of inhaled medications to infants is usually very demanding and is often associated with crying and mask rejection. It has been suggested that aerosol administration during sleep may be an attractive alternative. Previous studies in sleeping children were disappointing as most of the children awoke and rejected the treatment. The SootherMask (SM) is a new, gentle and innovative approach for delivering inhaled medication to infants and toddlers. The present pilot study describes the feasibility of administering inhaled medications during sleep using the SM. DESIGN: Prospective observational study. SETTING: Out patients. PARTICIPANTS: 13 sleeping infants with recurrent wheezing who regularly used pacifiers and were <12 months old. INTERVENTION: Participants inhaled technetium99mDTPA-labelled normal saline aerosol delivered via a Respimat Soft Mist Inhaler (SMI) (Boehringer-Ingelheim, Germany) and SM + InspiraChamber (IC; InspiRx Inc, New Jersey, USA). OUTCOMES: The two major outcomes were the acceptability of the treatment and the lung deposition (per cent of emitted dose). RESULTS: All infants who fulfilled the inclusion criteria successfully received the SM treatment during sleep without difficulty. Mean lung deposition (±SD) averaged 1.6±0.5% in the right lung. CONCLUSIONS: This study demonstrated that the combination of Respimat, IC and SM was able to administer aerosol therapy to all the sleeping infants who were regular pacifier users with good lung deposition. Administration of aerosols during sleep is advantageous since all the sleeping children accepted the mask and ensuing aerosol therapy under these conditions, in contrast to previous studies in which there was frequent mask rejection using currently available devices. CLINICAL TRIAL REGISTRY: NCT01120938.

Design of aerosol face masks for children using computerized 3D face analysis.

BACKGROUND: Aerosol masks were originally developed for adults and downsized for children. Overall fit to minimize dead space and a tight seal are problematic, because children's faces undergo rapid and marked topographic and internal anthropometric changes in their first few months/years of life. Facial three-dimensional (3D) anthropometric data were used to design an optimized pediatric mask. METHODS: Children's faces (n=271, aged 1 month to 4 years) were scanned with 3D technology. Data for the distance from the bridge of the nose to the tip of the chin (H) and the width of the mouth opening (W) were used to categorize the scans into "small," "medium," and "large" "clusters." RESULTS: "Average" masks were developed from each cluster to provide an optimal seal with minimal dead space. The resulting computerized contour, W and H, were used to develop the SootherMask® that enables children, "suckling" on their own pacifier, to keep the mask on their face, mainly by means of subatmospheric pressure. The relatively wide and flexible rim of the mask accommodates variations in facial size within and between clusters. CONCLUSIONS: Unique pediatric face masks were developed based on anthropometric data obtained through computerized 3D face analysis. These masks follow facial contours and gently seal to the child's face, and thus may minimize aerosol leakage and dead space.

A cell chip for sequential imaging of individual non-adherent live cells reveals transients and oscillations.

Advances in molecular cell biology, medical research, and drug development are driving a growing need for technologies that enable imaging the dynamics of molecular and physiological processes simultaneously in numerous non-adherent living cells. Here we describe a platform technology and software--the CKChip system--that enables continuous, fluorescence-based imaging of thousands of individual living cells, each held at a given position ("address") on the chip. The system allows for sequential monitoring, manipulation and kinetic analyses of the effects of drugs, biological response modifiers and gene expression in both adherent and non-adherent cells held on the chip. Here we present four specific applications that demonstrate the utility of the system including monitoring kinetics of reactive oxygen species generation, assessing the intracellular enzymatic activity, measuring calcium flux and the dynamics of target cell killing induced by conjugated cytotoxic T-lymphocytes. We found large variations among individual cells in the overall amplitude of their response to stimuli, as well as in kinetic parameters such as time of onset, initial rate and decay of the response, and frequency and amplitude of oscillations. These variations probably reflect the heterogeneity of even cloned cell populations that would have gone undetected in bulk cell measurements. We demonstrate the utility of the system in providing kinetic parameters of complex cellular processes such as Ca++ influx, transients and oscillations in numerous individual cells. The CKChip opens up new opportunities in cell-based research, in particular for acquiring fluorescence-based, kinetic data from multiple, individual non-adherent cells.