Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Patients with an anterior mediastinal mass pose significant risk for cardiorespiratory compromise during surgical procedures and general anesthesia. Several techniques have been described to reverse airway obstruction in these patients. In extreme circumstances, patients may require cardiac bypass or extracorporeal membrane oxygenation (ECMO) until definitive treatment of the mass and patient stabilization is achieved. We present a case in which the RulTract (R) system was used for emergency sternal elevation as a bridge to ECMO in acute respiratory collapse in an 11-year-old female with a minimally symptomatic anterior mediastinal mass. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction: Asthma is a disease that occurs worldwide and approximately 300 million people carry this disease. It is characterized by chronic inflammation, airway obstruction and airway hyper-responsiveness (AHR). This T-lymphocyte controlled disease has symptoms such as coughing, wheezing, and chest tightness. In addition to chronic inflammation, asthma is also caused by overproduction of mucus and airway wall remodelling. The chronic inflammation and airway wall remodelling are suggested to contribute to the AHR and airway obstruction. AHR is a way to measure the reactivity in the airways in asthmatics. IL-13 has been shown to play an important role in the development of AHR, and biopsies from bronchial submucosa and air way smooth muscle (ASM) in humans have shown an increased concentration of IL-13 in severe asthma. Aim: The aim of this work was to evaluate if IL-13 is able to enhance the 5-HT response in mouse tracheal segments, which had been cultured for 2 days and, if so, try to unravel the underlying mechanism for this phenomenon. Literature reports that IL-13 enhanced contractions in mouse trachea in presence of KCl and CCH. Earlier work within this project did not find any clear proof for this observation. However, in this work this observation will be evaluated in a more controlled fashion by correcting for size and location of the trachea. Methods: The trachea was removed from Balp/c mice and cultured in small wells for two days in DMEM medium and various additions were performed to the medium for understanding the effect of e.g. IL-13 on the cells. The contractility change due to IL-13 and various additions in segments challenged with KCL, CCH and 5-HT were measured in a tissue-organ bath. Results and Conclusion: A more enhanced CCH induced contraction of IL-13 treated segments was obtained for the lower part compared to the upper part of the trachea. IL-13 enhanced the response in the ASM to 5-HT after two days of culturing. An increased concentration of the cytokine IL-13 in the airways from TH2-cells enhances the reactivity to 5-HT in the ASM. The underlying mechanism might involve JNK and ERK but more experiments are needed to statistically ensure this claim.

Hematopoietic cells of the myelomonocytic lineage play a central role in orchestrating both innate and adaptive immunity. They are important in the control of infectious agents and in the pathogenesis of diseases characterized by dysregulated immune response. Like allergic asthma in human patients, recurrent airway obstruction (RAO) of horses is a disease exemplified by chronic airway inflammation in the absence of infectious agents. However, unlike allergic asthma, RAO is marked by preponderance of neutrophils rather than eosinophils in the airways. Attempts to understand the immunological basis of RAO by studying lymphocytes produced equivocal results. This thesis examined the possible role of alveolar macrophages (AM) recovered from bronchoalveolar lavage fluid (BALF) in RAO. Since macrophages are predominantly derived from circulating monocytes, the thesis investigated first the phenotypic characteristics of circulating monocytes, second those of macrophages in vitro derived from monocytes, and finally attributes of AM derived in vivo. Flow cytometric analysis following antibody staining of monocytes from 61 horses showed that the clustering pattern of human leukocytes may not always be extrapolated to horses when using this technique since clusters of granulocytes often spill over into the monocyte population. The study showed that DH24A, a monoclonal antibody directed against CD90, which recognizes T cells in other species, will specifically recognize granulocytes in horses and was therefore used to separate neutrophils from monocytes during analysis. In addition, investigation of circulating monocytes showed that expression of the hemoglobin-haptoglobin receptor CD163 on circulating monocytes is significantly increased in horses with systemic inflammation when compared with healthy horses. Evaluating cytokine and chemokine production by macrophages, it was demonstrated that CD163+ macrophages preferentially expressed IL10 while CD163- macrophages showed predominant expression of CCL17. It was, therefore, concluded that CD163+ IL10-producing macrophages of horses are homologues of the alternatively activated anti-inflammatory macrophage subset of humans. Finally, probing of alveolar macrophages for CD163 and CD206 expression showed a significant reduction in the proportion of CD163+ macrophages in horses with RAO. These findings suggest that RAO is associated with a reduction in anti-inflammatory macrophages, an observation that may in part explain the chronic airway inflammation associated with this disease.

Solitary extramedullary plasmacytomas are uncommon neoplasms. They occur most frequently in the upper aerodigestive tract and account for 4% of the nonepithelial tumors in this site. The evolution of a plasmacytoma is unsteady and symptoms at presentation have included dystonia, dysphagia, oral pain, cough, and dyspnea on exertion. Plasmaeytoma of the upper aerodigestive tract has not been previously reported as a cause of obstructive sleep apnea.

Recurrent Airway Obstruction (RAO)-affected horses experience bronchoconstriction and airway inflammation in response to inhalation of irritants including hay molds. Steaming hay reduces fungal content, but the effect on the antigenic potential has not been investigated. We tested the hypothesis that RAO-affected horses develop less severe clinical disease when fed steamed versus non-steamed hay and this reduction coincides with decreased hay fungal content. Six RAO-affected horses in clinical remission were divided in two groups and fed steamed or non-steamed hay for 10 days using a two-way cross-over design. Hay was steamed using a commercial hay-steamer. Clinical assessment was performed daily. Full assessment, including airway endoscopy, tracheal mucous scores and maximal change in pleural pressure, was performed on days 1, 5, and 10. Bronchial fluid sampling and cytology were performed on days 1 and 10. Hay core samples were collected pre- and post-steaming and cultured to determine fungal and bacterial concentrations. Statistical analysis was based on data distribution and quantity and performed using SAS®. P-value <0.05 was significant. Steaming significantly decreased the number of bacterial and fungal colony-forming-units in hay. Horses fed non-steamed hay experienced a significant increase in clinical score and a trend towards airway neutrophilia, while parameters were unchanged in horses fed steamed hay. Only horses fed non-steamed hay experienced a significant increase in tracheal mucous score. Horses fed steamed hay gained significantly more weight compared to horses fed non-steamed hay, even though the amount of hay consumed not greater on a dry matter basis. These results indicate that steaming reduces the RAO-affected horse's response to hay which coincides with a reduction in viable fungal content of hay. / Master of Science

Summer pasture-associated recurrent airway obstruction (SPARAO) is characterized by reversible airway obstruction resulting from airway hyper-reactivity to aeroallergens, mucus accumulation, and airway inflammation. These are key clinical features that are shared with human asthma, suggesting SPARAO’s utility as an animal asthma model. SPARAO affects horses maintained on pasture in conditions of high heat and humidity. Common in the southeastern United States, the cause of SPARAO is unknown, but is presumed to reflect reactivity to seasonally inhaled pasture-associated aeroallergens. This investigation sought to identify well-characterized histopathological lesions of human asthma, collectively termed ‘asthmatic remodeling’, in lung tissue from horses with SPARAO. Two histological staining techniques were used: H&E and Movat’s Pentachrome. Similar to chronic asthma, lung tissue from horses with SPARAO demonstrates statistically significant increases in airway smooth muscle, fibrosis, airway occlusion and inflammation, goblet cell hyperplasia, and remodeling of terminal bronchioles and elastin fibers.

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.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.