Objectives 1. To define the normative airway of Chinese population using three-dimensional imaging and computer analysis 2. To evaluate the upper airway differences in patients with normal facial profile and those with skeletal class III deformity 3. To evaluate the differences in upper airway models among patients with different dentofacial deformities and describe the role of computational fluid dynamics (CFD) in the human upper airway Materials and Methods Part I : Three-Dimensional Analysis of the Normative Upper Airway in Chinese This was a cross-sectional observational study. Cone beam computerized tomography (CBCT) scans of one hundred patients were analyzed. Computer analysis of the different upper airway parameters were studied including airway length and volume, as well as airway dimensions at the axial level of the soft palate, hard palate, base of tongue, and epiglottis. The most constricted airway location was identified and correlation analysis with variables of interest was done. Part II: A Cone Beam Computerized Tomography Study of Airway in Skeletal Class I and Class III Cone-beam computed tomography (CBCT) records of 200 patients were used to evaluate the upper airway dimensions. This sample consisted of patients with normal facial profile (Class I) and those demonstrating skeletal class III deformities. Computer analysis of the upper airway parameters such as airway length, airway volume, airway anterior-posterior and cross-sectional area dimensions at the hard palate, soft palate, base of tongue and epiglottis were performed. The most constricted airway sites were identified. Part III: Computational fluid dynamics study of upper airway in different dentofacial deformities Cone-beam computed tomography records of 12 patients were used to evaluate the upper airway. This sample consisted of facial skeletal Class I, II and III subjects. The upper airway models were constructed to allow CFD simulations in the airway from the epiglottis to the hard palate. Cross-sectional area, pressure, velocity and resistance were measured based on the reconstructed meshed models. Results Part I : Three-Dimensional Analysis of the Normative Upper Airway in Chinese In 100 subjects (40 males, 60 females) aged 16-40 years with normal facial profile, we found that the most constricted site occurs at the level of the soft palate. This surface area of this site was found to be linearly correlated to the airway volume, suggesting a significant relationship between the most constricted area and the total airway volume. Gender differences were found in airway length, volume, and in the dimensions at the base of tongue and epiglottis region. The mean airway length was 54.12 mm + 6.19 for males and 49.25 mm + 4.86 for females; airway volume of 15.09 cm3 + 4.92 for males and 13.12 cm3 + 4.72 for females. Part II: A Cone Beam Computerized Tomography Study of Airway in Skeletal Class I and Class III The sample consisted of 100 Class I (41 males, 59 females) with a mean age of 25.4 years and 100 Class III (38 males, 62 females) with a mean age of 23.5 years. Gender differences were noted in the airway length, airway volume and dimensions at the base of tongue and epiglottis for both groups. Males showed longer airway length, larger airway volume, larger airway dimensions at the base of tongue and epiglottis compared to females. Significant differences in all the airway parameters between the two groups were found except for airway length. The soft palate was found to be the most constricted airway site observed in the Class I subjects while Class III subjects showed restriction in both the soft palate and epiglottis region. Part III: Computational fluid dynamics study of upper airway in different dentofacial deformities The airflow was variable among airway in different skeletal deformities. The pressure changes along airway of Class II were the largest, followed by Class I. The pressure drop in the airway of Class III subjects were the smallest. The larger pressure differences would cause greater resistance in the airway. The highest resistance was observed in the airway of Class II subjects. Conclusion Part I : Three-Dimensional Analysis of the Normative Upper Airway in Chinese This airway data provide a normative reference that can be used in various dentofacial analysis as well as for diagnosis and treatment planning for related dentofacial deformities and in understanding the pathophysiology for sleep-related breathing disorders. Part II: A Cone Beam Computerized Tomography Study of Airway in Skeletal Class I and Class III The upper airway is larger in patients with Class III deformity than those with a normal facial profile. The site of restriction is commonly observed at the soft palate in the Class I group whereas patients with Class III deformity, the airway restriction sites are at both the soft palate and epiglottis. Understanding of the upper airway differences in between class I and class III facial deformities can have implications on treatment planning for orthognathic surgery. Part III: Computational fluid dynamics study of upper airway in different dentofacial deformities The results in this study suggest that skeletal pattern showed a significant correlation with pressure and resistance along the upper airway. / published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

Epithelial cells lining the upper airways are characterized by low sodium absorption and elevated chloride secretion. Together, the movement of these ions creates the osmotic drive to hydrate the airways. Recent studies indicate that influenza is capable of directly modulating the vectorial transport of sodium and chloride ions. However, the direct impact of influenza has not been studied with respect to potassium channels. This is significant because potassium conductance creates the driving force for chloride secretion. Disruptions to this process leads to edema formation in the lungs and can subsequently cause Acute Respiratory Distress Syndrome. Additionally, it has been demonstrated that the induction of pro-inflammatory cytokines in infected cells may contribute to altered ion channel function, further exacerbating edema formation. The purpose of this study was to assess the direct and indirect effects of influenza virus infection on potassium and chloride ion channel function in a secretory epithelial cell model. In order to assess the direct effects we exposed polarized epithelial cell monolayers to varying doses of H1N1 virus. Potassium and chloride channel function was measured by means of short-circuit current in an Ussing chamber. The immune response to viral infection was determined by RT-qPCR and Bioplex suspension array. Virus conditioned media (CM), and IL-8 were used to characterize the indirect effects on non-infected cells. We observed an increase in chloride secretion, consistent with edema formation, when 60% of the epithelium was infected, and after CM treatment. This observation correlated with increased potassium channel conductance through the calcium-activated (KCNN4) and cAMP-activated potassium channels (KCNQ1), which was ameliorated upon specific inhibition of these channels. The data suggest that the mixture of pro-inflammatory cytokines induced by viral infection directly up-regulate these potassium channels. However, treatment with IL-8 also appears to increase chloride secretion, although the underlying mechanism remains to be determined, as it is not mediated through KCNN4 and KCNQ1. We conclude that the strong induction of cytokines in infected cells act in a paracrine manner on non-infected cells to increase potassium channel conductance. This up-regulation of potassium channels subsequently drives an increase in chloride secretion, leading to fluid build-up in the lungs and edema formation.

The purpose of this study was to explore nurses' experiences of obstructed airways in the prehospital work. A qualitative interview study with a descriptive and explorative design was used. The sample consisted of nine registered nurses whereof three were women and six were men, with or without further education and varying length of experience in the ambulance service. Prehospital personnel builds up a vast plan of action based on the emergency information provided by SOS. Simple methods for managing obstructed airways were stated often enough. Problems with obstructed airways are considered so unusual that it never becomes a routine. Several factors affect the identification and managing of obstructed airways, both external factors and the different patient categories are considered important. The study found that the bystanders rarely perceived to be performing actions for the creation of a free airway. While obstructed airways perceived to be stressful for ambulance nurses, however, they are not worried to face such a situation. For the coping of what has happened during an emergency, ambulance crew talk through the whole situation of what could have been done better or if something could be done differently. Many factors affect the identification and managing of obstructed airways in prehospital nurses' work. While obstructed airways perceived to be stressful for ambulance nurses they are not concerned to face such a situation. The tools and techniques available for managing airways are usually considered to be adequate and well-functioning

Tracheal epithelium is organized along two axes: apicobasal, seen through apical ciliogenesis, and planar seen through organized ciliary beating, which moves mucus out of the airway. Diseased patients with affected ciliary motility have serious chronic respiratory infections. The standard method to construct epithelium is through air liquid interface culture which creates apicobasal polarization, not planar organization. Nanogrooved surface topography created in diffusible substrates for use in air liquid interface culture will induce planar organization of the cytoskeleton. We have created a nanogrooved gelatin device which allows basal nutrient diffusion. Multiple epithelial cells have been found to align in the direction of the nanogrooves in both sparse and confluent conditions. This device is also congruent with ALI culture as seen through formation of tight junctions and ciliogenesis. Thus, we have created nanogrooved surface topography in a diffusible substrate that induces planar alignment of epithelial cells and cytoskeleton.

Tracheal epithelium is organized along two axes: apicobasal, seen through apical ciliogenesis, and planar seen through organized ciliary beating, which moves mucus out of the airway. Diseased patients with affected ciliary motility have serious chronic respiratory infections. The standard method to construct epithelium is through air liquid interface culture which creates apicobasal polarization, not planar organization. Nanogrooved surface topography created in diffusible substrates for use in air liquid interface culture will induce planar organization of the cytoskeleton. We have created a nanogrooved gelatin device which allows basal nutrient diffusion. Multiple epithelial cells have been found to align in the direction of the nanogrooves in both sparse and confluent conditions. This device is also congruent with ALI culture as seen through formation of tight junctions and ciliogenesis. Thus, we have created nanogrooved surface topography in a diffusible substrate that induces planar alignment of epithelial cells and cytoskeleton.

Thesis (M.Tech.: Emergency Medical Care)-Dept. of Emergency Medical Care and Rescue, Durban University of Technology, 2008. xii, 301 leaves, Annexures A-0 to A-7 / Paramedic clinical decision making (CDM) surrounding emergency airway management of the critically ill or injured patient in the pre-hospital environment is poorly understood. In order to deliver pre-hospital care effectively it is necessary to understand how paramedics make clinical decisions in this area and determine what influences clinical practice. This study primarily investigated the factors influencing paramedic CDM in the context of advanced emergency airway management with specific focus on the newly introduced skill of rapid sequence intubation (RSI). An evaluation of the correct application of RSI guidelines, the determination of the need for their review and the identification of measures to enhance CDM around RSI were secondary research questions.

Cardiac surgery incisional pain can decrease inspiratory effort, alter normal respiratory mechanics, and increase the potential for post-operative pulmonary complications. Post-surgical atelectasis is the most frequent complication after coronary artery bypass grafting (CABG), ranging from 54% to 92%. All types of therapy such as an incentive spirometry (IS), deep breathing exercises (DBE) or continuous positive airway pressure (CPAP) have a valuable role to play in the prevention or the treatment of post-surgical atelectasis. However, the type of therapy that should be used is not completely clear yet. The present research aims to evaluate the benefit of early use of CPAP via mask therapy to treat or prevent post-surgical atelectasis after CABG, particularly in smokers and elderly patients, as compared to regular (IS) therapy. Also, it aims to evaluate the patients' and medical staff's experience about the use of the new method of CPAP via mask therapy. The present research was conducted at King Fahd Armed Forces Hospital in Saudi Arabia between March 2010 and December 2011. It used a mixed methods approach. The first two studies were intervention quantitative studies, which investigated the benefit of CPAP via mask therapy. The others were qualitative studies that evaluated the experience of patients and medical staff regarding CPAP therapy use.A total of 180 patients (male and female) (36 in each group) participated in the two quantitative studies. Ninety two participants (male and female) participated in the qualitative studies. The first quantitative study results showed an improvement in CPAP via mask therapy for half hours every two hours group measurements as compared to IS therapy groups. IC was increased significantly in the "CPAP every two hours group" as compared to control group (IS) (baseline mean for IS group 1.34L and "CPAP every two hours group" 1.42L, post- therapy mean 1.59L and 1.88L respectively, p= 0.037). In addition, when chest physiotherapy was added to the two regimens, the improvement of CPAP therapy measurements became more than IS therapy. Moreover, the patient’s acceptance rate for CPAP therapy every two hours was 93% and the medical staff acceptance rate was 86%. CPAP via mask therapy for half hour every two hours had better outcomes in treating or preventing post-surgical atelectasis after CABG, particularly in smokers and elderly patients. Adding chest physiotherapy led to even better outcomes. The use of the new method of CPAP therapy had high acceptance rate by the participants and medical staff.

In surgery for airway obstruction, the anesthetist and the ear-nose-throat surgeon share the approach to the airway and jet ventilation (JV) is a mutually convenient ventilation technique for both parties. As a consequence of the open system jet ventilation is applied in, bedside measurements of lung volumes are cumbersome to perform and thus, there is a lack of studies comparing different modes of JV or investigating the influence of ventilator settings on lung volumes and gas exchange. In this thesis, single frequency jet ventilation and superimposed high frequency jet ventilation (SHFJV) at different frequencies are systematically compared with respect to lung volume changes, underlying airway pressure variations and the resulting gas exchange. We compared three single-frequency JV modalities with SHFJV in patients. Moreover, we performed a systematic investigation of single frequency JV and SHFJV in a porcine model. Single frequency JV and SHFJV were compared frequency-wise in intact airways and in a newly developed model of tracheal obstruction. This model was also used to assess the influence of variable airway diameter on ventilation effectiveness during SHFJV. We measured chest wall volume variations with opto-electronic plethysmography and obtained airway pressures as well as gas exchange parameters. In unobstructed airways, both single-frequency JV and SHFJV provided adequate oxygenation, despite differences in lung volumes. Carbon dioxide removal was most effective using single frequency JV at a frequency of 150 min-1. During SHFJV, for both intact and obstructed airways, the choice of frequency for the high frequency component had little influence on lung volumes, airway pressures and gas exchange. With decreasing airway diameter and SHFJV, we observed air trapping and lower tidal volumes and acceptable oxygenation. Carbon dioxide removal, however, was insufficient at the narrowest airway diameter. In single frequency JV, very high frequencies resulted in negligible tidal volume and inacceptable gas exchange. Airway obstruction potentiated this frequency dependence. In conclusion, in intact airways, single frequency JV at sufficiently low frequencies provided adequate oxygenation and better CO2 removal than SHFJV. With decreasing airway diameter, SHFJV provided better oxygenation and CO2 removal and may therefore be the mode of choice in more complicated cases.

The prevalence and economic burden of chronic airway disorders such as asthma is on the rise annually. Allergic asthma is characterized by chronic airway inflammation, airway hyper-responsiveness (AHR), and structural airway remodeling due to increased smooth muscle mass. Most allergic asthma occurs due to the overproduction of immunoglobulin E (IgE) antibodies against common allergens. Classically, IgE has been shown to modulate airway smooth muscle (ASM) contraction/relaxation which is believed to be the underlying cause of airway hyperreactivity. However, the molecular mechanisms underlying IgE effects on ASM cell are not established. Recently, the high-affinity Fc receptor for IgE (FcεRI) has been identified in human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthma patients. However, it is unknown whether FcεRI activation on ASM can modulate the immune response within the airways. We hypothesized that the IgE-FcεRI interaction plays a key role in inducing phenotypic and functional changes in ASM cells that eventually contributes to the establishment of airway inflammation, AHR, and remodeling. We sought to investigate the regulation, effector functions, and underlying mechanisms of FcεRI activation in ASM cells. Our work shows that the proinflammatory tumor necrosis factor (TNF) and T helper type 2 (Th2) cytokine interleukin (IL)-4 enhanced the FcεRI abundance and amplified the IgE-induced chemokine (eotaxin-1/CCL11, RANTES/CCL5, IL-8/CXCL8, and IP-10/CXCL10) release in ASM cells via transcriptional mechanisms. Both TNF and IgE induced a novel, Th2-favoring cytokine thymic stromal lymphopoietin (TSLP) through the activation of spleen tyrosine kinase (Syk), and nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1). In addition, IgE induced de novo DNA synthesis and ASM cell proliferation via mitogen-activated protein kinases (MAPKs) and signal-transducer and activator of transcription 3 (STAT3) activation. Collectively, our data suggest that the IgE-induced FcεRI activation leads to the expression of multiple chemokines in ASM which may indirectly recruit inflammatory cells and promote allergic airway inflammation; IgE induces TSLP which can promote the Th2 immune responses within the airways; and IgE may potentially induce airway remodeling by directly inducing ASM cell proliferation. Therefore, targeting the IgE-FcεRI network on ASM may offer a novel therapeutic strategy in allergic asthma.

The prevalence and economic burden of chronic airway disorders such as asthma is on the rise annually. Allergic asthma is characterized by chronic airway inflammation, airway hyper-responsiveness (AHR), and structural airway remodeling due to increased smooth muscle mass. Most allergic asthma occurs due to the overproduction of immunoglobulin E (IgE) antibodies against common allergens. Classically, IgE has been shown to modulate airway smooth muscle (ASM) contraction/relaxation which is believed to be the underlying cause of airway hyperreactivity. However, the molecular mechanisms underlying IgE effects on ASM cell are not established. Recently, the high-affinity Fc receptor for IgE (FcεRI) has been identified in human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthma patients. However, it is unknown whether FcεRI activation on ASM can modulate the immune response within the airways. We hypothesized that the IgE-FcεRI interaction plays a key role in inducing phenotypic and functional changes in ASM cells that eventually contributes to the establishment of airway inflammation, AHR, and remodeling. We sought to investigate the regulation, effector functions, and underlying mechanisms of FcεRI activation in ASM cells. Our work shows that the proinflammatory tumor necrosis factor (TNF) and T helper type 2 (Th2) cytokine interleukin (IL)-4 enhanced the FcεRI abundance and amplified the IgE-induced chemokine (eotaxin-1/CCL11, RANTES/CCL5, IL-8/CXCL8, and IP-10/CXCL10) release in ASM cells via transcriptional mechanisms. Both TNF and IgE induced a novel, Th2-favoring cytokine thymic stromal lymphopoietin (TSLP) through the activation of spleen tyrosine kinase (Syk), and nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1). In addition, IgE induced de novo DNA synthesis and ASM cell proliferation via mitogen-activated protein kinases (MAPKs) and signal-transducer and activator of transcription 3 (STAT3) activation. Collectively, our data suggest that the IgE-induced FcεRI activation leads to the expression of multiple chemokines in ASM which may indirectly recruit inflammatory cells and promote allergic airway inflammation; IgE induces TSLP which can promote the Th2 immune responses within the airways; and IgE may potentially induce airway remodeling by directly inducing ASM cell proliferation. Therefore, targeting the IgE-FcεRI network on ASM may offer a novel therapeutic strategy in allergic asthma.