Idiopathic tracheal stenosis (ITS) is a rare condition, and diagnosis of exclusion should be suspected in patients with exercise intolerance, wheezing, and dyspnea on exertion with a flow-volume loop suggestive of fixed airway obstruction. We report a case of a 32-year-old asthmatic woman with an existing diagnosis of vocal cord dysfunction and previous normal CT scan of the neck. She continued to have fixed upper airway obstruction on repeated flow-volume loops with persistent wheezing and cough along with occasional stridor and hoarseness of voice despite appropriate management of her asthma. She was finally diagnosed with ITS on a repeat CT scan of the neck for which she underwent laser surgery, steroid injection, and controlled radial expansion balloon dilation with a successful reduction of stenosis. This case illustrates the importance of clinical suspicion for early diagnosis of ITS in poorly controlled asthmatic patients and the relevance of non-surgical management of this condition.

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In this dissertation, we examine mechanics of rhythmic tracheal compression (RTC) in the darkling beetle, Zophobas morio. In Chapter 2, we studied the relationship between hemolymph pressure and tracheal collapse to test the hypothesis that pressure is a driving mechanism for RTC. We found that tracheae collapse as pressure increases, but other physiological factors in the body may be affecting tracheal compression in live beetles. Additionally, as the tracheae compress, they do so in varying spatial patterns across the insect body. In chapter 3, we examined spatial variations in the taenidial spacing, stiffness, and tracheal thickness along the length of the tracheae. We related variations in Young's modulus and taenidial spacing with measurements of collapse dimples and found that spatial patterns of Young's modulus correlate with dimensions of collapse dimples. This correlation suggests an intuitive link between tracheal stiffness variations and the unique patterns observed in compressing tracheae. Lastly, in chapter 4, we studied the non-uniform collapse patterns in 3-D. By manually pressurizing the hemocoel and imaging using synchrotron microcomputed tomography (SR-µCT), we reconstructed the tracheal system in its compressed state. While previous studies used 2-D x-ray images to examine collapse morphology, ours is the first to quantify collapse patterns in 3-D and compare with previous 2-D quantification methods. Our method is also the first to make a direct measure of tracheal volume as the tracheal system compresses, similar to the phenomenon that occurs during rhythmic tracheal compression. / Doctor of Philosophy / Insects have long been a source of curiosity and inspiration for scientists and engineers. The insect respiratory system stands as an example of a seemingly complex oxygen delivery system that operates with relative simplicity. As opposed to mammals and other vertebrates, the insect respiratory system does not deliver oxygen using blood. Instead, insects possess a massive network of hollow tracheal tubes that are distributed throughout the body. Air enters spiracular valves along the length of the insect body, travels through the tracheal tube network, and is delivered directly to the tissues. In some insects, the tracheae compress and expand, driving flow of respiratory gasses. However, unlike vertebrate lungs, there are no muscles directly associated with the tracheal system that would drive this tracheal compression, and exactly how this behavior occurs is not fully understood. In this dissertation, we examined pulsatory increases in blood pressure as a possible mechanism that underlies these tracheal compressions in the darkling beetle, Zophobas morio. Additionally, as the tracheae compress, they do so with varying spatial patterns across the insect body. Because tracheae are complex and non-uniform composite tubes, we examined spatial variations in the microstructure, stiffness, and tracheal thickness along the length of the trachea. Lastly, we visualized the variable collapse patterns in three dimensions using synchrotron micro-computed tomography combined with manual pressurization of the hemocoel. While previous studies used two-dimensional x-ray images to quantify tracheal collapse patterns, this work represents the first three-dimensional study. Understanding tracheal collapse mechanics, material properties, and their relationships with the circulatory system can help to gain an understanding of how insects create complex fluid flows within the body using relatively simple mechanisms.

The insect respiratory system serves as a model for both robust microfluidic transport and mate- rial design. In the system, the convective flow of gas is driven through local deformations of the tracheal network, a phenomenon that is dependent on the unique structure and material properties of the tracheal tissue. To understand the underlying mechanics of this method of gas transport, we studied the microstructure and material properties of the primary thoracic tracheal tubes of the American cockroach (Periplaneta americana). We performed quasi-static uniaxial tests on the tissue which revealed a nonlinear stress-strain response even under small deformations. A detailed analysis of the tissue's microstructural arrangement using both light and electron mi- croscopy revealed the primary sources of reinforcement for the tissue as well as heterogeneity on the meso-scale that may contribute to the physiological function of the tracheae during respi- ration. Finally, a custom mechanical testing system was developed with which inflation-extension tests on the tracheae were used to gather data on the biaxial elastic response of the tissue over a wide range of physiologically relevant loading conditions. From information gathered about the material microstructure, a robust constitutive model was chosen to quantify the biaxial response of the tracheae. This model will provide a basis from which to simulate the behavior of tracheal net- works in future computational studies. This study gives the first description of the elastic response of the tracheae which is essential for understanding the mechanics of respiration in insects. Thus it brings us closer to the realization of novel bio-inspired microfluidic systems and materials that utilize mechanical principles from the insect respiratory system. / Ph. D.

Abdominal pumping is a widespread behavior in insects. However, there remains ambiguity surrounding the abdominal pumping behavior, both in terms of describing what exactly abdominal pumping is (i.e., if various modes of operation exist) and also what function(s) abdominal pumping serves (and if function is conserved across groups of insects). In some insects respiratory patterns have been correlated with abdominal movements, although the specific mechanical effects of these movements on the animal\'s respiratory system are generally unknown. Conversely, some insects (such as beetles, ants, and crickets) create convection in the respiratory system by compressing their tracheal tubes, yet the underlying physiological mechanisms of tracheal collapse are also unknown. This study aimed to investigate the relationship between abdominal pumping and the compression of tracheal tubes in the darkling beetle, Zophobas morio. I observed the movements of the abdomen and tracheal tubes using synchrotron x-ray imaging and video cameras, while concurrently monitoring CO2 expiration. I identified and characterized two distinct abdominal movements differentiated by the synchrony (the pinch movement) or lack of synchrony (the wave movement) of abdominal tergite movement. Tracheal tube compressions (and corresponding CO2 pulses) occurred concurrently with every pinch movement. This study provides evidence of a mechanistic linkage between abdominal movements and tracheal tube compressions in the ground beetle, Zophobas morio. / Master of Science

O colapso traqueal é uma obstrução parcial ou total da traqueia caracterizado pelo achatamento dorsoventral dos anéis cartilaginosos e pela frouxidão da membrana traqueal dorsal. Acomete principalmente cães de raças pequenas, de meia idade a idosos, embora também possa ocorrer em cães jovens. O diagnóstico é feito com base nos sinais clínicos e exames complementares. A traqueobroncoscopia permite avaliar o diâmetro da traqueia e dos segmentos brônquicos, principalmente quando as radiografias e fluoroscopia não forem conclusivas e ainda permite a coleta de amostras para citologia, histopatologia e culturas. O objetivo deste estudo foi correlacionar a infecção traqueal com a inflamação da traqueia em cães com colapso de traqueia. A pesquisa foi realizada no HOVET da FMVZ-USP e no Hospital Veterinário Clinivet em Curitiba. A amostra foi constituída por 28 cães, sendo 12 com colapso de traqueia e 16 hígidos para o grupo controle, que propiciou parâmetros de normalidade em relação ao grupo colapso traqueal. Para a coleta de dados utilizou-se a traqueobroncoscopia, com a qual visualizamos a traqueia e graduamos o colapso, colhemos material para cultura bacteriana e citologia. Após a análise dos resultados foi observado diferença estatística significativa nos cães com inflamação e colapso de traqueia. Não foi observado correlação entre a infecção bacteriana e a inflamação na traqueia. Com um teste de dissimilaridade verificou-se que a população bacteriana da orofaringe foi semelhante a da traqueia nos cães do mesmo grupo. Portanto, concluímos que cães com colapso de traqueia tendem a ter a traqueia inflamada, porém não apresentam infecção bacteriana. A composição das bactérias na traqueia pode ser devido à aspiração do conteúdo da orofaringe. / The Tracheal collapse is a partial or total obstruction of the trachea, featured by dorsoventral flattening of the cartilaginous rings and by the laxity of the dorsal tracheal membrane. It mainly affects small breeds, middle-aged and older dogs, although it can also occur in young dogs. The diagnosis is made based on clinical signs and additional exams. The trachealbronchoscopy allows evaluating the trachea diameter and bronchial segments, especially when radiographic and fluoroscopy is not conclusive and still allows the collection of samples for cytology, histopathology and cultures. The objective of this study was correlating the tracheal infection with the tracheal inflammation in dogs with tracheal collapse. The research was conducted in the HOVET FMVZ-USP and Clinivet Veterinary Hospital in Curitiba. The sample consisted of 28 dogs, including 12 with collapsing trachea and 16 healthy subjects in the control group, which allowed normal parameters in relation to the group tracheal collapse. For data collection was used the trachealbronchoscopy, in which was visualized the trachea and the grade of the tracheal collapse was recorded. We also collected samples for cytology and bacterial culture. After analyzing the results we found statistically significant difference in dogs with tracheal collapse and inflammation of the trachea. There was no correlation between bacterial infection and inflammation in the trachea. With dissimilarity test was observed that the bacterial population of the pharynx was similar to the trachea in dogs of the same group. n this study, therefore, concluded that dogs with collapsing trachea tend to have the inflamed trachea, but it does not have bacterial infection. The composition of the bacteria in the trachea may be due to aspiration of pharynx\'s contents.

O colapso traqueal é uma obstrução parcial ou total da traqueia caracterizado pelo achatamento dorsoventral dos anéis cartilaginosos e pela frouxidão da membrana traqueal dorsal. Acomete principalmente cães de raças pequenas, de meia idade a idosos, embora também possa ocorrer em cães jovens. O diagnóstico é feito com base nos sinais clínicos e exames complementares. A traqueobroncoscopia permite avaliar o diâmetro da traqueia e dos segmentos brônquicos, principalmente quando as radiografias e fluoroscopia não forem conclusivas e ainda permite a coleta de amostras para citologia, histopatologia e culturas. O objetivo deste estudo foi correlacionar a infecção traqueal com a inflamação da traqueia em cães com colapso de traqueia. A pesquisa foi realizada no HOVET da FMVZ-USP e no Hospital Veterinário Clinivet em Curitiba. A amostra foi constituída por 28 cães, sendo 12 com colapso de traqueia e 16 hígidos para o grupo controle, que propiciou parâmetros de normalidade em relação ao grupo colapso traqueal. Para a coleta de dados utilizou-se a traqueobroncoscopia, com a qual visualizamos a traqueia e graduamos o colapso, colhemos material para cultura bacteriana e citologia. Após a análise dos resultados foi observado diferença estatística significativa nos cães com inflamação e colapso de traqueia. Não foi observado correlação entre a infecção bacteriana e a inflamação na traqueia. Com um teste de dissimilaridade verificou-se que a população bacteriana da orofaringe foi semelhante a da traqueia nos cães do mesmo grupo. Portanto, concluímos que cães com colapso de traqueia tendem a ter a traqueia inflamada, porém não apresentam infecção bacteriana. A composição das bactérias na traqueia pode ser devido à aspiração do conteúdo da orofaringe. / The Tracheal collapse is a partial or total obstruction of the trachea, featured by dorsoventral flattening of the cartilaginous rings and by the laxity of the dorsal tracheal membrane. It mainly affects small breeds, middle-aged and older dogs, although it can also occur in young dogs. The diagnosis is made based on clinical signs and additional exams. The trachealbronchoscopy allows evaluating the trachea diameter and bronchial segments, especially when radiographic and fluoroscopy is not conclusive and still allows the collection of samples for cytology, histopathology and cultures. The objective of this study was correlating the tracheal infection with the tracheal inflammation in dogs with tracheal collapse. The research was conducted in the HOVET FMVZ-USP and Clinivet Veterinary Hospital in Curitiba. The sample consisted of 28 dogs, including 12 with collapsing trachea and 16 healthy subjects in the control group, which allowed normal parameters in relation to the group tracheal collapse. For data collection was used the trachealbronchoscopy, in which was visualized the trachea and the grade of the tracheal collapse was recorded. We also collected samples for cytology and bacterial culture. After analyzing the results we found statistically significant difference in dogs with tracheal collapse and inflammation of the trachea. There was no correlation between bacterial infection and inflammation in the trachea. With dissimilarity test was observed that the bacterial population of the pharynx was similar to the trachea in dogs of the same group. n this study, therefore, concluded that dogs with collapsing trachea tend to have the inflamed trachea, but it does not have bacterial infection. The composition of the bacteria in the trachea may be due to aspiration of pharynx\'s contents.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22306号 / 医博第4547号 / 新制||医||1040(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 平井 豊博, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第23470号 / 医博第4777号 / 新制||医||1053(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 平井 豊博, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM