<p><strong>Bakgrund:</strong> Nya tekniska lösningar för att intubera patienter börjar bli tillgängliga för operationsavdelningar. Glidescope är ett videolaryngoskop som visar lovande resultat när det gäller underlättande av intubationer för personal framförallt vid svåra luftvägar och intubationer. Forskningen pekar på att Glidescope reducerar antalet intubationsförsök och ökar andelen lyckade förstagångsintubationer. Studier pekar på att det för patienten är fördelaktigt med så få intubationsförsök som möjligt.</p><p><strong>Syfte: </strong>Att undersöka anestesipersonals erfarenheter av att arbeta med Glidescope.</p><p><strong>Metod: </strong>Semistrukturerade individuella intervjuer genomfördes med nio anestesisjuksköterskor och två läkare. En kvalitativ beskrivande ansats med en kvalitativ innehållsanalys som analysmetod har använts. Intervjuerna genomfördes våren 2010 på ett sjukhus i södra norrland.</p><p><strong>Resultat: </strong>Glidescope är ett enkelt och lättanvänt redskap för intubation och detta gäller även för personer med begränsad erfarenhet av Glidescope. Det underlättar intubationer men kan förlänga tiden för att placera tuben. Det reducerar patienttraumat som förknippas med en intubation och ökar patientsäkerheten. Ur ett hygienperspektiv behövs bättre rutiner för användning av Glidescopet. En begränsning för Glidescopet är pågående blödning i svalget.</p><p><strong>Slutsats: </strong>Glidescope är i de flesta fall ett enkelt och lättanvänt redskap för intubation som underlättar främst vid svåra intubationer. Glidescope förbättrar patientsäkerheten. Glidescope är användbart vid studenthandledning. Glidescope begränsas av pågående blödning i svalget och är sämre ur ett hygienperspektiv jämfört med Macintoshlaryngoskopet.</p> / <p><strong>Background:</strong> New technical solutions for patient intubation are becoming available for surgical wards. Glidescope is a video laryngoscope which shows promising results for easy intubation for staff, especially in difficult airways and intubations. Research shows that Glidescope reduces the number of tries and increases the proportion of successful first try intubations. Studies show that the patient benefits from a reduced number of tried intubations.</p><p><strong>Purpose: </strong>To examine anaesthesia staffs experience of working with Glidescope.</p><p><strong>Method: </strong>Semi structured personal interviews were conducted with nine anaesthetic nurses and two anaesthesiologists. A qualitative descriptive approach with a qualitative content analysis as an analysis method was used. The interviews were conducted at a hospital in the middle part of Sweden during the spring of 2010.</p><p><strong>Results: </strong>Glidescope is an easy to use tool for intubation and this is also true for staff with limited experience with Glidescope. It makes intubation easier but may prolong the time to place the tube. Glidescope reduces the trauma for the patient associated with intubation and increases patient safety. From a hygiene perspective better routines are needed for the use of the Glidescope. Glidescope is limited by ongoing bleeding in the throat area.</p><p><strong>Conclusion: </strong>Glidescope is for the most part an easy to use tool which eases difficult intubations. Glidescope improves patient safety. Glidescope is useful in student instruction. Glidescope is limited by on going bleeding in the throat area and is less hygienic than the Macintoshlaryngscope.</p>

<p>We have developed a methacholine provocation method, which detects bronchial responsiveness in more than 80% of healthy subjects. The method enables us to detect differences in bronchial responsiveness within the normal range. </p><p>With this method FEV1 and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness. Differences, between protocols when using doubling or fourfold concentration steps emphasize the importance to strictly adhere to a predefined protocol. </p><p>Deep inhalation associated with the FEV1 manoeuvre decreases bronchial tone induced by methacholine for up to 6 minutes, which emphasizes the importance of exact timing between successive FEV1 measurements in bronchial provocation tests. There is a substantial overlap in bronchial responsiveness between healthy and asthmatic subjects and a deep inhalation at the end of the methacholine test challenge could not discriminate between asthmatic and non-asthmatic subjects.</p><p>Inhalation of dust in a swine confinement building causes an intense airway inflammatory reaction with an extensive migration of inflammatory cells, predominantly neutrophils, into the upper and lower airways. Bronchial responsiveness to methacholine increased by about 3 doubling concentration steps and was normalized one week after exposure. However, exposure to dust in a swine confinement building did not yield increased bronchial responsiveness to eucapnic hyperventilation with dry air which is often observed in asthmatic subjects. Exhaled NO was approximately doubled five hours after exposure and in the present study we found no relationship between exhaled NO levels and bronchial responsiveness in healthy subjects. </p><p>Protection with half-mask inhibited the dust induced increase of exhaled NO whereas the increase in bronchial responsiveness was influenced only to a minor extent.</p><p>These findings, do not support the hypothesis that the increased bronchial responsiveness following organic dust exposure is directly caused by the inflammation. Instead, a possible direct effect on the smooth muscle and swelling of the airway mucosa and increased secretions due to the general inflammatory reaction probably leads to airway narrowing enhancing the post-exposure bronchial response to methacholine. </p>

The lactoperoxidase (LPO) antimicrobial system has been shown to play an important role in maintaining sterile conditions in several tissues including the mammary gland, the salivary gland, and the airway. The LPO system in the airway consists of the enzyme LPO and its substrates hydrogen peroxide and an anion. LPO catalyzes the oxidation of a halide or pseudohalide ion for example SCN-or I- by hydrogen peroxide producing a product, OSCN- or OI- which have antibacterial, antifungal, and antiviral properties. In order to have a functional antimicrobial system all the components need to be present at appropriate concentrations. The LPO system has been suggested to be deficient in cystic fibrosis. There are three possible regulatory mechanism of this antimicrobial system and these involve the secretion and availability of the three components of the LPO system in the luminal fluid. The studies presented in this dissertation examine two of the possible regulatory mechanisms of the LPO system in the airway; the availability and transport of SCN- to the luminal surface, and the expression of LPO. The knowledge obtained from these studies could be utilized to develop treatments to control infection in diseases characterized by chronic infections such as cystic fibrosis.

It is well established that air pollution has detrimental effects on both human health as well as the environment. Exposure to ozone and particulate matter pollution, is associated with an increase in cardiopulmonary mortality and morbidity. Asthmatics, elderly and children have been indicated as especially sensitive groups. With a global increase in use of vehicles and industry, ambient air pollution represents a crucial health concern as well as a political, economical and environmental dilemma. Both ozone (O3) and diesel exhaust (DE) trigger oxidative stress and inflammation in the airways, causing symptoms such as wheezing, coughing and reduced lung function. The aim of this thesis was to further examine which pro-inflammatory signaling pathways that are initiated in the airways by ozone, as compared to diesel exhaust. Furthermore, to study the effects of these two ambient air pollutants in a sequential exposure, thus mimicking an urban profile. In order to investigate this in healthy as well as asthmatic subjects, walk-in exposure chambers were utilized and various airway compartments were studied by obtaining induced sputum, endobronchial biopsies, or airway lavage fluids. In asthmatic subjects, exposure to 0.2 ppm of O3 induced an increase in the cytokines IL 5, GM-CSF and ENA-78 in the bronchial epithelium six hours post-exposure. The healthy subjects, however, displayed no elevations of bronchial epithelial cytokine expression in response to the ozone exposure. The heightened levels of neutrophil chemoattractants and Th2 cytokines in the asthmatic airway epithelium may contribute to symptom exacerbations following air pollution exposure. When examining an earlier time point post O3 exposure (1½ hours), healthy subjects exhibited a suppression of IL-8 as well as of the transcription factors NFκB and c-jun in the bronchial epithelium, as opposed to after filtered air exposure. This inhibition of early signal transduction in the bronchial epithelium after O3 differs from the response detected after exposure to DE. Since both O3 and DE are associated with generating airway neutrophilia as well as causing direct oxidative damage, it raises the query of whether daily exposure to these two air pollutants creates a synergistic or additive effect. Induced sputum attained from healthy subjects exposed in sequence to 0.2 ppm of O3 five hours following DE at a PM concentration of 300 µg/m3, demonstrated significantly increased neutrophils, and elevated MPO levels, as compared to the sequential DE and filtered air exposure. O3 and DE interactions were further investigated by analyses of bronchoalveolar lavage and bronchial wash. It was demonstrated that pre-exposure to DE, as compared to filtered air, enhances the O3-induced airway inflammation, in terms of an increase in neutrophil and macrophage numbers in BW and higher EPX expression in BAL. In conclusion, this thesis has aspired to expand the knowledge of O3-induced inflammatory pathways in humans, observing a divergence to the previously described DE initiated responses. Moreover, a potentially adverse airway inflammation augmentation has been revealed after exposure to a relevant ambient combination of these air pollutants. This provides a foundation towards an understanding of the cumulative airway effects when exposed to a combination of ambient air pollutants and may have implications regarding future regulations of exposure limits.

We have developed a methacholine provocation method, which detects bronchial responsiveness in more than 80% of healthy subjects. The method enables us to detect differences in bronchial responsiveness within the normal range. With this method FEV1 and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness. Differences, between protocols when using doubling or fourfold concentration steps emphasize the importance to strictly adhere to a predefined protocol. Deep inhalation associated with the FEV1 manoeuvre decreases bronchial tone induced by methacholine for up to 6 minutes, which emphasizes the importance of exact timing between successive FEV1 measurements in bronchial provocation tests. There is a substantial overlap in bronchial responsiveness between healthy and asthmatic subjects and a deep inhalation at the end of the methacholine test challenge could not discriminate between asthmatic and non-asthmatic subjects. Inhalation of dust in a swine confinement building causes an intense airway inflammatory reaction with an extensive migration of inflammatory cells, predominantly neutrophils, into the upper and lower airways. Bronchial responsiveness to methacholine increased by about 3 doubling concentration steps and was normalized one week after exposure. However, exposure to dust in a swine confinement building did not yield increased bronchial responsiveness to eucapnic hyperventilation with dry air which is often observed in asthmatic subjects. Exhaled NO was approximately doubled five hours after exposure and in the present study we found no relationship between exhaled NO levels and bronchial responsiveness in healthy subjects. Protection with half-mask inhibited the dust induced increase of exhaled NO whereas the increase in bronchial responsiveness was influenced only to a minor extent. These findings, do not support the hypothesis that the increased bronchial responsiveness following organic dust exposure is directly caused by the inflammation. Instead, a possible direct effect on the smooth muscle and swelling of the airway mucosa and increased secretions due to the general inflammatory reaction probably leads to airway narrowing enhancing the post-exposure bronchial response to methacholine.

Bakgrund: Nya tekniska lösningar för att intubera patienter börjar bli tillgängliga för operationsavdelningar. Glidescope är ett videolaryngoskop som visar lovande resultat när det gäller underlättande av intubationer för personal framförallt vid svåra luftvägar och intubationer. Forskningen pekar på att Glidescope reducerar antalet intubationsförsök och ökar andelen lyckade förstagångsintubationer. Studier pekar på att det för patienten är fördelaktigt med så få intubationsförsök som möjligt. Syfte: Att undersöka anestesipersonals erfarenheter av att arbeta med Glidescope. Metod: Semistrukturerade individuella intervjuer genomfördes med nio anestesisjuksköterskor och två läkare. En kvalitativ beskrivande ansats med en kvalitativ innehållsanalys som analysmetod har använts. Intervjuerna genomfördes våren 2010 på ett sjukhus i södra norrland. Resultat: Glidescope är ett enkelt och lättanvänt redskap för intubation och detta gäller även för personer med begränsad erfarenhet av Glidescope. Det underlättar intubationer men kan förlänga tiden för att placera tuben. Det reducerar patienttraumat som förknippas med en intubation och ökar patientsäkerheten. Ur ett hygienperspektiv behövs bättre rutiner för användning av Glidescopet. En begränsning för Glidescopet är pågående blödning i svalget. Slutsats: Glidescope är i de flesta fall ett enkelt och lättanvänt redskap för intubation som underlättar främst vid svåra intubationer. Glidescope förbättrar patientsäkerheten. Glidescope är användbart vid studenthandledning. Glidescope begränsas av pågående blödning i svalget och är sämre ur ett hygienperspektiv jämfört med Macintoshlaryngoskopet. / Background: New technical solutions for patient intubation are becoming available for surgical wards. Glidescope is a video laryngoscope which shows promising results for easy intubation for staff, especially in difficult airways and intubations. Research shows that Glidescope reduces the number of tries and increases the proportion of successful first try intubations. Studies show that the patient benefits from a reduced number of tried intubations. Purpose: To examine anaesthesia staffs experience of working with Glidescope. Method: Semi structured personal interviews were conducted with nine anaesthetic nurses and two anaesthesiologists. A qualitative descriptive approach with a qualitative content analysis as an analysis method was used. The interviews were conducted at a hospital in the middle part of Sweden during the spring of 2010. Results: Glidescope is an easy to use tool for intubation and this is also true for staff with limited experience with Glidescope. It makes intubation easier but may prolong the time to place the tube. Glidescope reduces the trauma for the patient associated with intubation and increases patient safety. From a hygiene perspective better routines are needed for the use of the Glidescope. Glidescope is limited by ongoing bleeding in the throat area. Conclusion: Glidescope is for the most part an easy to use tool which eases difficult intubations. Glidescope improves patient safety. Glidescope is useful in student instruction. Glidescope is limited by on going bleeding in the throat area and is less hygienic than the Macintoshlaryngscope.

Air pollutants, such as ozone (O3) and diesel exhaust particles, elicit oxidative stress in the lung. Antioxidants within the respiratory tract lining fluid (RTLF) protect the underlying tissue from oxidative injury. Supplementation with vitamins has been shown to modulate the acute ozone-induced effects, but the mechanisms behind this have not been fully clarified. The aim of this thesis was to investigate the airway responses to diesel exhaust and ozone exposure in healthy humans, with the emphasis on inflammatory and antioxidant responses. Furthermore, to study whether oral supplementation with vitamin C could increase ascorbate concentration in the RTLF and whether vitamin supplementation could modulate the negative effects induced by ozone exposure. Diesel exhaust (100 µg/m3 PM10 for 2h), evaluated 18 hours post exposure (PE), induced a neutrophilic airway inflammation and an increase in bronchoalveolar (BAL) urate and reduced glutathione. During O3 exposure (0.2 ppm for 2h), significant losses of nasal RTLF urate and ascorbate concentrations were observed. Six hours PE, a neutrophilic inflammation was evident in the bronchial wash (BW), together with enhanced concentrations of urate and total glutathione. In the bronchoalveolar lavage (BAL), where vitamin C, urate and glutathione concentrations were augmented, no inflammatory response was seen. In alveolar lavage leukocytes, there was a significant loss of glutathione and cysteine, whereas an increase in ascorbate was found in bronchial tissue samples. Following supplementation with increasing doses of vitamin C (60-1,000 mg/day, for 14 days), evaluated 24 hours after the last dose, ascorbate concentrations were unchanged in the nasal RTLF, despite elevated concentrations in plasma and urine. In contrast, following a single dose of 1g of vitamin C, vitamin C concentrations increased significantly in both plasma and nasal lavage two hours post supplementation, before returning to baseline levels at 24 hours. Notably, dehydroascorbate (DHA) accounted for the largest part of RTLF vitamin C and a number of control experiments were performed to ensure the authenticity of this finding. Healthy O3 responders were exposed to O3 (0.2 ppm for 2 h) and air, following seven days of supplementation with vitamin C and E or placebo. No protective effect on lung function or airway inflammation was observed following supplementation. BW and BAL-DHA were enhanced after O3, with further increases following supplementation. In conclusion, oxidative air pollutants induce airway inflammation, as well as a broad spectrum of antioxidant adaptations, which could ultimately limit the airway inflammatory responses. Oral vitamin supplementation was shown to augment RTLF-vitamin C concentrations, but it did not provide protection from the ozone-induced airway responses following a single insult of ozone. The finding of high concentrations of DHA in the RTLF could indicate that DHA represents an important transport form of vitamin C onto the surface of the lung.

Cystic fibrosis (CF) is an inherited disease with symptoms mainly in the respiratory tract. The airway epithelium is covered with a thin layer of fluid, the airway surface liquid (ASL). The volume and composition of ASL are important in the pathogenesis of cystic fibrosis. The composition of ASL was determined. Firstly, pig airways were analyzed by X-ray microanalysis in the frozen-hydrated state. Secondly, small Sephadex beads were left to absorb the ASL in situ and were analyzed by X-ray microanalysis. The Na and Cl concentrations in the ASL of the pig were close to those of these ions in serum. Rat tracheal ASL was hypotonic. However, rat nasal fluid was hypertonic with an extremely high concentration of K. The composition of the ASL could be influenced by pharmacological stimulation. The development of transgenic mouse models for CF may help to develop therapies for the disease. The composition of mouse ASL was investigated using different collection techniques. (1) beads mounted on filter paper, (2) beads randomly spread over the airway epithelium, and (3) beads spread over the epithelium with a syringe. No significant difference could be detected between these techniques, and mouse ASL was hypotonic. Calibration curves had to be made for each element of interest. Nasal fluid from healthy human volunteers was collected with: (1) a pipette, (2) filter paper, (3) cotton wool, or (4) Sephadex beads. Collection on filter paper and equilibration with Sephadex beads gave reliable results. The Na and Cl concentrations in nasal fluid of control subjects were about the same as in serum, but the K concentration was higher. Rhinitis or primary ciliary dyskinesia patients and CF heterozygotes had abnormally high concentrations of Na and Cl in their nasal fluid (probably due to inflammation of the nasal epithelium), and CF homozygotes had even higher concentrations of Na and Cl.

Background: Ambient air pollution is associated with adverse health effects, but the sources and components, which cause these effects is still incompletely understood. The aim of this thesis was to investigate the pulmonary effects of a variety of common air pollutants, including diesel exhaust, biomass smoke, and road tunnel and subway station environments. Healthy non-smoking volunteers were exposed in random order to the specific air pollutants and air/control, during intermittent exercise, followed by bronchoscopy. Methods and results: In study I, exposures were performed with diesel exhaust (DE) generated at transient engine load and air for 1 hour with bronchoscopy at 6 hours post-exposure. Immunohistochemical analyses of bronchial mucosal biopsies showed that DE exposure significantly increased the endothelial adhesion molecule expression of p-selectin and VCAM-1, together with increased bronchoalveolar lavage (BAL) eosinophils. In study II, the subjects were exposed for 1 hour to DE generated during idling with bronchoscopy at 6 hours. The bronchial mucosal biopsies showed significant increases in neutrophils, mast cells and lymphocytes together with bronchial wash neutrophils. Additionally, DE exposure significantly increased the nuclear translocation of the aryl hydrocarbon receptor (AhR) and phosphorylated c-jun in the bronchial epithelium. In contrast, the phase II enzyme NAD(P)H-quinone oxidoreductase 1 (NQO1) decreased after DE. In study III, the 2-hour exposures took place in a road tunnel with bronchoscopy 14 hours later. The road tunnel exposure significantly increased the total numbers of lymphocytes and alveolar macrophages in BAL, whereas NK cell and CD56+/T cell numbers significantly decreased. Additionally, the nuclear expression of phosphorylated c-jun in the bronchial epithelium was significantly increased after road tunnel exposure. In study IV, the subjects were exposed to metal-rich particulate aerosol for 2 hours at a subway station with bronchial biopsy and BAL sampling at 14 hours. The subway exposure significantly increased the concentration of glutathione disulphide (GSSG) in BAL, with no airway inflammatory responses. In contrast, the number of neutrophils in the bronchial mucosa and the nuclear expression of phosphorylated c-jun in the bronchial epithelium tended to decrease after the subway exposure. In study V, the exposure to biomass smoke lasted 3 hours. Bronchoscopy was conducted 24 hours post exposure. The investigated biomass combustion emissions resulted in a significant increase in total glutathione and reduced glutathione in BAL, without any evident acute airway inflammatory responses.     Conclusion: The present thesis presents data from exposures of healthy subjects to a variety of common air pollutants, as compared with an air reference. Oxidative as well as bronchial mucosal and bronchoalveolar responses differed between these air pollutants, with the most pronounced airway effects seen after exposure to diesel exhaust. This may be due to differences in pulmonary deposition, physicochemical characteristics, toxicological pathways and potency. Additional studies will assist in addressing dose-response and time kinetic aspects of the airway responses.

We report herein that IL-10-treated dendritic cells (DC) can be used effectively to reverse established severe asthma-like disease in a mouse model. Our lab had shown previously that allergen-presenting splenic CD8¦Á+ DCs could ¡Ö50% reduce airway hyper responsiveness (AHR), eosinophilia, and Th2 responses in asthma-phenotype mice, but only marginally reduce IgE/IgG1 levels. We now show that bone marrow-derived DCs that have been differentiated in the presence of IL-10 (DCIL-10) are effective in reversing the asthma phenotype. Co-culture of DCIL-10 with T memory (TM) cells from asthma-phenotype mice was associated with lack of Th2 responses, and this was partially reversed by IL-2. Immunostimulatory DC activated these Th2 cells. <i>In vivo</i>, delivery of allergen-pulsed DCIL-10, either into the airway or intraperitoneally abrogated AHR from weeks 3-10 post-treatment, and ameliorated lung eosinophilia and Th2 (IL-4, -5, -9, & -13, IgE) responses, as well as circulating allergen-specific IgE responses for at least 32 weeks following treatment. Repeated OVADCIL-10 treatments kept AHR normalized for 8 weeks as well as Th2 responses significantly low. In vivo, delivery of anti-IL-10R, but not anti-TGF-¦Â from day 12-21 after treatment had moderate effects on DCIL-10-driven tolerance, but 1-methyl tryptophan (inhibitor of indoleamine-2,3-dioxygenase) treatment had significant effects on Th2 responses. The mechanisms mediating tolerance in vivo are likely complex, but we speculate that infectious tolerance sustains this regulatory activity during the 32-week period in which we have observed tolerance to be in place.