A theoretical model of the application of RF energy to the airway wall and its experimental validation

<p>Abstract</p> <p>Background</p> <p>Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF) energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall.</p> <p>Methods</p> <p>An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model.</p> <p>Results</p> <p>Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations.</p> <p>The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty.</p> <p>Conclusions</p> <p>The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest that comparing model results to RF generator electrical measurements may be a useful tool in the early evaluation of a model.</p

Effect of Parenchymal Stiffness on Canine Airway Size with Lung Inflation

Although airway patency is partially maintained by parenchymal tethering, this structural support is often ignored in many discussions of asthma. However, agonists that induce smooth muscle contraction also stiffen the parenchyma, so such parenchymal stiffening may serve as a defense mechanism to prevent airway narrowing or closure. To quantify this effect, specifically how changes in parenchymal stiffness alter airway size at different levels of lung inflation, in the present study, we devised a method to separate the effect of parenchymal stiffening from that of direct airway narrowing. Six anesthetized dogs were studied under four conditions: baseline, after whole lung aerosol histamine challenge, after local airway histamine challenge, and after complete relaxation of the airways. In each of these conditions, we used High resolution Computed Tomography to measure airway size and lung volume at five different airway pressures (0, 12, 25, 32, and 45 cm H2O). Parenchymal stiffening had a protective effect on airway narrowing, a fact that may be important in the airway response to deep inspiration in asthma. When the parenchyma was stiffened by whole lung aerosol histamine challenge, at every lung volume above FRC, the airways were larger than when they were directly challenged with histamine to the same initial constriction. These results show for the first time that a stiff parenchyma per se minimizes the airway narrowing that occurs with histamine challenge at any lung volume. Thus in clinical asthma, it is not simply increased airway smooth muscle contraction, but perhaps a lack of homogeneous parenchymal stiffening that contributes to the symptomatic airway hyperresponsiveness

Instillation and Fixation Methods Useful in Mouse Lung Cancer Research

The ability to instill live agents, cells, or chemicals directly into the lung without injuring or killing the mice is an important tool in lung cancer research. Although there are a number of methods that have been published showing how to intubate mice for pulmonary function measurements, none are without potential problems for rapid tracheal instillation in large cohorts of mice. In the present paper, a simple and quick method is described that enables an investigator to carry out such instillations in an efficient manner. The method does not require any special tools or lighting and can be learned with very little practice. It involves anesthetizing a mouse, making a small incision in the neck to visualize the trachea, and then inserting an intravenous catheter directly. The small incision is quickly closed with tissue adhesive, and the mice are allowed to recover. A skilled student or technician can do instillations at an average rate of 2 min/mouse. Once the cancer is established, there is frequently a need for quantitative histologic analysis of the lungs. Traditionally pathologists usually do not bother to standardize lung inflation during fixation, and analyses are often based on a scoring system that can be quite subjective. While this may sometime be sufficiently adequate for gross estimates of the size of a lung tumor, any proper stereological quantification of lung structure or cells requires a reproducible fixation procedure and subsequent lung volume measurement. Here we describe simple reliable procedures for both fixing the lungs under pressure and then accurately measuring the fixed lung volume. The only requirement is a laboratory balance that is accurate over a range of 1 mg–300 g. The procedures presented here thus could greatly improve the ability to create, treat, and analyze lung cancers in mice

Individual Canine Airway Response Variability to a Deep Inspiration

In healthy individuals, a DI can reverse (bronchodilation) or prevent (bronchoprotection) induced airway constriction. For individuals with asthma or COPD, these effects may be attenuated or absent. Previous work showed that the size and duration of a DI affected the subsequent response of the airways. Also, increased airway tone lead to increased airway size variability. The present study examined how a DI affected the temporal variability in individual airway baseline size and after methacholine challenge in dogs using High-Resolution Computed Tomography. Dogs were anesthetized and ventilated, and on 4 separate days, HRCT scans were acquired before and after a DI at baseline and during a continuous intravenous infusion of methacholine (Mch) at 3 dose rates (17, 67, and 200 μg/min). The Coefficient of Variation was used as an index of temporal variability in airway size

Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice

BACKGROUND: This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice. METHODS: Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF(50 )in another group of anesthetized, orotracheally intubated mice. RESULTS: With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage. CONCLUSION: We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF(50 )method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice

Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice

Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect in antioxidant responses has been speculated to exacerbate asthma severity, this has been difficult to demonstrate with certainty. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive basic leucine zipper transcription factor that is involved in the transcriptional regulation of many antioxidant genes. We show that disruption of the Nrf2 gene leads to severe allergen-driven airway inflammation and hyperresponsiveness in mice. Enhanced asthmatic response as a result of ovalbumin sensitization and challenge in Nrf2-disrupted mice was associated with more pronounced mucus cell hyperplasia and infiltration of eosinophils into the lungs than seen in wild-type littermates. Nrf2 disruption resulted in an increased expression of the T helper type 2 cytokines interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid and in splenocytes after allergen challenge. The enhanced severity of the asthmatic response from disruption of the Nrf2 pathway was a result of a lowered antioxidant status of the lungs caused by lower basal expression, as well as marked attenuation, of the transcriptional induction of multiple antioxidant genes. Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma

Understanding the Use of Crisis Informatics Technology among Older Adults

Mass emergencies increasingly pose significant threats to human life, with a disproportionate burden being incurred by older adults. Research has explored how mobile technology can mitigate the effects of mass emergencies. However, less work has examined how mobile technologies support older adults during emergencies, considering their unique needs. To address this research gap, we interviewed 16 older adults who had recent experience with an emergency evacuation to understand the perceived value of using mobile technology during emergencies. We found that there was a lack of awareness and engagement with existing crisis apps. Our findings characterize the ways in which our participants did and did not feel crisis informatics tools address human values, including basic needs and esteem needs. We contribute an understanding of how older adults used mobile technology during emergencies and their perspectives on how well such tools address human values.Comment: 10 page

Bronchial Thermoplasty in Asthma

In this review we discuss the potential of a new procedure, termed Bronchial Thermoplasty to prevent serious consequences resulting from excessive airway narrowing. The most important factor in minimizing an asthmatic attack is limiting the degree of smooth muscle shortening. The premise that airway smooth muscle can be either inactivated or obliterated without any long-term alteration of other lung tissues, and that airway function will remain normal, albeit with reduced bronchoconstriction, has now been demonstrated in dogs, a subset of normal subjects, and mild asthmatics. Bronchial Thermoplasty may thus develop into a useful clinical procedure to effectively impair the ability for airway smooth muscle to reach the levels of pathologic narrowing that characterizes an asthma attack. It may also enable more successful treatment of asthma patients who are unresponsive to more conventional therapies. Whether this will remain stable for the lifetime of the patient still remains to be determined, but at the present time, there are no indications that the smooth muscle contractility will return. This successful preliminary experience showing that Bronchial Thermoplasty could be safely performed in patients with asthma has led to an ongoing clinical trial at a number of sites in Europe and North America designed to examine the effectiveness of this procedure in subjects with moderately severe asthma