Cat allergen exposure in a naturalistic exposure chamber: A prospective observational study in cat-allergic subjects.

BACKGROUND: To determine the proportion and reproducibility of cat-allergic mild asthmatics with early asthmatic response (EAR) during cat allergen exposure in a naturalistic exposure chamber (NEC). METHODS: This was a prospective, observational study in 30 cat-allergic mild asthmatics who received two 180-min cat-allergen (Felis domesticus allergen 1 [Fel d 1]) challenges 27 days apart in an NEC. RESULTS: An EAR (≥20% reduction from baseline in forced expiratory volume in 1 s [FEV1]) was observed in 67% and 52% of subjects at first and second NEC exposure, respectively, with similar median time to EAR; 44% of subjects had an EAR on days 1 and 28. Late asthmatic response (≥15% reduction in FEV1 within 24 h of NEC exit) was observed in 33% of subjects following either exposure. Average FEV1 and total nasal symptom score during NEC exposure were highly correlated within subjects between NEC exposures (r = 0.91, p < 0.0001; r = 0.73, p < 0.001), but total ocular symptom score was not. Time to EAR, but not average FEV1, was significantly associated with NEC Fel d 1 concentration, which was variable. There were no serious adverse events; 12/30 subjects experienced 20 adverse events (including asthma, 10%; headache, 10%). CONCLUSIONS: The NEC model demonstrates that average FEV1 change is highly reproducible and has a low correlation with cat allergen levels. However, time to EAR and incidence of EAR are less reproducible and are highly correlated with NEC allergen levels. Average FEV1, rather than incidence of EAR or time to EAR, could be considered as an endpoint for interventional trials testing cat-specific anti-allergy therapies using an NEC.

Numerical investigations of anisotropic structures of red blood cell aggregates on ultrasonic backscattering.

Although quantitative ultrasound techniques based on the parameterization of the backscatter coefficient (BSC) have been successfully applied to blood characterization, theoretical scattering models assume blood as an isotropic scattering medium. However, the red blood cell (RBC) aggregates form anisotropic structures such as rouleaux. The present study proposes an anisotropic formulation of the effective medium theory combined with the local monodisperse approximation (EMTLMA) that considers perfectly aligned prolate-shaped aggregates. Theoretical BSC predictions were first compared with computer simulations of BSCs in a forward problem framework. Computer simulations were conducted for perfectly aligned prolate-shaped aggregates and more complex configurations with partially aligned prolate-shaped aggregates for which the size and orientation of RBC aggregates were obtained from blood optical observations. The isotropic and anisotropic EMTLMA models were then compared in an inverse problem framework to estimate blindly the structural parameters of RBC aggregates from the simulated BSCs. When considering the isotropic EMTLMA, the use of averaged BSCs over different insonification directions significantly improves the estimation of aggregate structural parameters. Overall, the anisotropic EMTLMA was found to be superior to the isotropic EMTLMA in estimating the scatterer volume distribution. These results contribute to a better interpretation of scatterer size estimates for blood characterization.

In Vitro Measurements of Spiriva Respimat Dose Delivery in Mechanically Ventilated Tracheostomy Patients.

Background: For patients with severe chronic obstructive pulmonary disease under invasive mechanical ventilation, medication for aerosol therapy is delivered through tracheostomy or endotracheal airways. Typically, these medications (such as bronchodilators) are long-acting formulations that are delivered through Soft Mist™ Inhalers (SMI), or Pressurized Metered-Dose Inhalers. The Respimat® SMI has been shown to have increased efficiency because of its slow and prolonged aerosol mist and has gained popularity in clinical settings. However, the Respimat was not designed for drug delivery through artificial airways. Therefore, there is a need for SMI adapters in intensive care for use in mechanical ventilator circuits. The purpose of this study was to evaluate the performance of a new Respimat adapter (ODAPT™ for mechanical ventilator [ODAPT MV]) for use in mechanical ventilator circuits which, in combination with a Pulmodyne T-piece adapter, allows use without interruption of the circuit in case of medication replacement. Methods: Tiotropium delivery to the lungs, using Respimat, was assessed using the ODAPT MV adapter within an in vitro setup, including a three-dimensional printed trachea model and a mechanical ventilator. Medication deposition and losses were investigated using two commonly used tracheostomy tube (TT) sizes (6 and 8 mm inner canula) for two flow rates (45 and 60 L/min) under different conditions (30%-50%. and 100% relative humidity [RH]). Medication delivery using the ODAPT MV adapter was compared with the RTC-26C in-line adapter under similar conditions (8 mm TT size, 100% RH at 45 L/min). Results: It was found that 7.1%-13.4% of the nominal dose (ND) was lost in the ODAPT MV adapter for different TT size, RH, and flow rates used. Higher losses were found in the inhaler's mouthpiece ranging from 15.7% to 29.1% ND. The percentage of the delivered medication reaching the lungs was determined to be 13.7%-18.5% ND delivered without significant differences between the experimental conditions tested. The ODAPT MV performed well compared with the RTC-26C under similar conditions (17.9% and 16.6% ND, respectively). Conclusion: The medication delivered through mechanical ventilation using the ODAPT MV adapter represents about one third the dose delivered directly through the Respimat SMI in vivo.

In vitro investigation of the Flusso™ Bypass adapter efficiency upon ventilator circuit disconnect in a clinical simulated environment.

RATIONALE: Mechanically ventilated patients must be disconnected from the ventilator during intra-facility transfers. Intentional and accidental circuit disconnections represent a potential hazard to patients (sudden collapse and re-expansion of the alveoli) as well as to clinical staff (exposure to patient's unfiltered exhalation). Therefore, avoiding abrupt circuit disconnections could better protect the patient's health and reduce or eliminate contamination risks around clinical staff. OBJECTIVE: The purpose of this in-vitro work was to investigate and evaluate the potential for environmental exposure of Nitric Oxide (NO, as an indicator of any contamination exposure) before and after implementing the novel Flusso™ Bypass adapter during the disconnect procedure of a mechanical ventilator system. METHODS: A mechanical ventilator delivering NO was connected to a breathing simulator with and without the Flusso™ Bypass adapter. The ambient NO concentration was measured when the circuit was briefly disconnected (3 s) during inhalation and exhalation. Both volume and pressure ventilation modes were used. MEASUREMENTS AND MAIN RESULTS: Disconnecting the standard ventilator circuit (pressure-controlled mode) without the Flusso™ Bypass adapter produced higher NO escape to the surroundings (compared with the volume-controlled mode), leading to a longer NO dissipation time. No ambient NO traces were detected when the Flusso™ adapter was used. CONCLUSION: The usage of the Flusso™ adapter drastically decreases the unwanted exposure among clinical staff dealing with potentially hazardous airborne biological aerosols emanating from the circuit. Avoiding abrupt disconnection in the ventilator circuit could reduce lung injuries and alveolar over distension and collapse.

Experimental Study of Spiriva Respimat Soft Mist Inhaler Spray Characterization: Size Distributions and Velocity.

Background: Respiratory illnesses such as asthma, bronchitis, and chronic obstructive pulmonary disease (COPD) are considered to be debilitating diseases. A variety of inhalation devices have been used to deliver aerosol medication to patients in the treatment of those diseases. Soft Mist Inhalers (SMIs, for example, the Spiriva Respimat) are a new generation of propellant-free inhalers. In this type of inhalation device, inhalable droplets are generated from an aqueous solution. Droplet size and velocity are two of the most substantial factors that impact the deposition of SMI aerosol medication into the patient lungs. Methods: In this study, size and velocity of droplets generated from the Spiriva Respimat inhaler were measured using phase Doppler anemometry (PDA). Measurements were taken at four locations along the centerline of the Spiriva Respimat inhaler, in addition to three cross sections (free-spray configuration). In addition, measurements were also performed at a single cross section in confined spray configurations using two separate idealized mouth cavities. Results and Conclusions: Measurements along the centerline of the aerosol mist generated using the Spiriva Respimat inhaler (6.5, 25, 100, and 125 mm downstream of the inhaler nozzle' orifice) showed that droplets at the mouthpiece have the highest velocity of 10.95 m/s, decreasing to 1.33 m/s at the 125 mm location away from the nozzle. The mean diameter D10 values ranged from 3.97 to 3.67 µm at 6.5 and 125 mm locations, respectively. In addition, of the three probability density functions (PDFs) that were tested, the log-normal PDF showed better curve fitting for the empirical data (droplet size distributions) that were measured. The effect of spray confinement using two idealized mouth cavities shows that there was a drop in the particles' velocity for both models on each axes compared with the open-air environment (free-spray configuration).

Red blood cell aggregates and their effect on non-Newtonian blood viscosity at low hematocrit in a two-fluid low shear rate microfluidic system.

Red blood cells (RBCs) are the most abundant cells in human blood. Remarkably RBCs deform and bridge together to form aggregates under very low shear rates. The theory and mechanics behind aggregation are, however, not yet completely understood. The main objective of this work is to quantify and characterize RBC aggregates in order to enhance the current understanding of the non-Newtonian behaviour of blood in microcirculation. Suspensions of human blood were flowed and observed in vitro in poly-di-methyl-siloxane (PDMS) microchannels to characterize RBC aggregates. These microchannels were fabricated using standard photolithography methods. Experiments were performed using a micro particle image velocimetry (µPIV) system for shear rate measurements, coupled with a high-speed camera for flow visualization. RBC aggregate sizes were quantified in controlled and measurable shear rate environments for 5, 10 and 15% hematocrit. Aggregate sizes were determined using image processing techniques, while apparent viscosity was measured using optical viscometry. For the samples suspended at 5% H, aggregate size was not strongly correlated with shear rate. For the 10% H suspensions, in contrast, lowering the shear rate below 10 s-1 resulted in a significant increase of RBC aggregate sizes. The viscosity was found to increase with decreasing shear rate and increasing hematocrit, exemplifying the established non-Newtonian shear-thinning behaviour of blood. Increase in aggregation size did not translate into a linear increase of the blood viscosity. Temperature was shown to affect blood viscosity as expected, however, no correlation for aggregate size with temperature was observed. Non-Newtonian parameters associated with power law and Carreau models were determined by fitting the experimental data and can be used towards the simple modeling of blood's non-Newtonian behaviour in microcirculation. This work establishes a relationship between RBC aggregate sizes and corresponding shear rates and one between RBC aggregate sizes and apparent blood viscosity at body and room temperatures, in a microfluidic environment for low hematocrit. Effects of hematocrit, shear rate, viscosity and temperature on RBC aggregate sizes have been quantified.

Aerosolization of Zn-DTPA Decorporation Agent Using Jet and Ultrasonic Nebulizers.

BACKGROUND: Chelating agents such as diethylenetriamine pentaacetic acid (DTPA) can be used as a decorporation drug in the zinc (Zn) form to treat internal radioactive contamination after exposure to plutonium or americium in a nuclear accident. Although Zn-DTPA is normally administered intravenously, inhalation of Zn-DTPA in aerosol form is a better route for direct delivery to the lungs. This work investigates the feasibility of synthesizing Zn-DTPA from three common chemicals and aerosolizing it using a jet or ultrasonic nebulizer. METHODS: The particle size distribution (PSD) of this decorporation agent at different concentrations were tested in vitro using two different methods: inertial impaction and aerodynamic time of flight. The particles were generated using either a jet nebulizer or an ultrasonic nebulizer. Two parameters, namely the mass median aerodynamic diameter and the geometric standard deviation, were assessed to determine the PSD of the generated aerosols. These parameters were obtained for different concentrations of Zn-DTPA using both nebulizers. RESULTS AND CONCLUSIONS: Zn-DTPA was successfully synthesized for decorporation purposes. Aerosol particles within the inhalable range were successfully generated by both nebulizers from four different concentrations of Zn-DTPA. It was found that the medication concentration did not affect the PSD of Zn-DTPA. The ultrasonic nebulizer was observed to produce a slightly larger aerosol particle size and required slightly longer treatment periods to deliver an effective dose to the lungs when compared with the jet nebulizer. Both nebulizers can be sustainably run to administer the agent for effective decorporation treatment of a large population after any major nuclear accident.

Controlled Microfluidic Environment for Dynamic Investigation of Red Blood Cell Aggregation.

Blood, as a non-Newtonian biofluid, represents the focus of numerous studies in the hemorheology field. Blood constituents include red blood cells, white blood cells and platelets that are suspended in blood plasma. Due to the abundance of the RBCs (40% to 45% of the blood volume), their behavior dictates the rheological behavior of blood especially in the microcirculation. At very low shear rates, RBCs are seen to assemble and form entities called aggregates, which causes the non-Newtonian behavior of blood. It is important to understand the conditions of the aggregates formation to comprehend the blood rheology in microcirculation. The protocol described here details the experimental procedure to determine quantitatively the RBC aggregates in microcirculation under constant shear rate, based on image processing. For this purpose, RBC-suspensions are tested and analyzed in 120 x 60 µm poly-dimethyl-siloxane (PDMS) microchannels. The RBC-suspensions are entrained using a second fluid in order to obtain a linear velocity profile within the blood layer and thus achieve a wide range of constant shear rates. The shear rate is determined using a micro Particle Image Velocimetry (µPIV) system, while RBC aggregates are visualized using a high speed camera. The videos captured of the RBC aggregates are analyzed using image processing techniques in order to determine the aggregate sizes based on the images intensities.