Dissertations / Theses on the topic 'Forced oscillation technique (FOT)'

Thesis (M.S.) -- University of Maryland, College Park, 2005.
Thesis research directed by: Dept. of Aerospace Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Background: Measurements of lung function are routinely used in patients with cystic fibrosis (CF) to provide information that may be clinically relevant. Spirometry is the conventional lung function measurement used, however young children find spirometry difficult to perform and often cannot achieve the strict acceptability criteria for the test. The forced oscillation technique (FOT) is a lung function measurement that only requires tidal breathing and is easy for young children to perform. However, there is limited information about the utility of this technique in the clinical assessment of young children with CF who are unable to perform spirometry. Aims: The aim of this project was to evaluate the FOT for clinical assessment in 2 to 7 year old children with CF. Specifically this involved: 1. Technical assessment of the FOT in children with CF; 2. Comparisons of lung function using the FOT in children with CF and healthy children; 3. Evaluation of associations with factors known to be associated with lung disease including: i) inflammation ii) infection and iii) structural damage. Methods Lung function was measured in a cohort of 59 children between the ages of 2 and 7 years with CF at the time of quarterly clinic visits. Resistance and reactance at 6, 8 and 10Hz (Rrs6, Rrs8, Rrs10, Xrs6, Xrs8, Xrs10, respectively) were reported and expressed as Z scores. Children were classified as asymptomatic or symptomatic based on a respiratory questionnaire and physical examination at the time of testing. Bronchoalveolar lavage and high resolution computed tomography (HRCT) were performed annually under general anaesthesia annually. BAL fluid was assessed for the presence of micro-organisms and quantification of a range of inflammatory markers and HRCT used to determine the extent of structural abnormalities. Results: The between test repeatability (n=25) for lung function was within limits previously described in healthy children. No systematic bias was observed and repeatability was not affected by the presence of respiratory symptoms. Children with CF (n=57) had significantly increased Rrs6-10 (p<0.0001) and decreased Xrs6-10 (p<0.004) compared to healthy children. Rrs6 and Xrs6-10 were significantly worse in the presence of respiratory symptoms, and Rrs6-10 progressively worsened from an asymptomatic to a symptomatic clinic visit. Children with CF (n=48) had no greater bronchodilator response (BDR) compared to healthy children. BDR was not influenced by the presence of an infection or respiratory symptoms. No relationships between inflammatory markers and lung function (n=39) were identified when the presence of an infection was adjusted for. Children with a current infection (n=20) had increased Rrs6-10 (p<0.01) and decreased Xrs6-10 (p<0.04) compared to children who were uninfected (n=23). These relationships were most marked for children infected with Pseudomonas aeruginosa, with children having a reduced lung function between 0.95 and 1.47 of a Z score. No relationships with the presence or absence of mild structural abnormalities (bronchiectasis, bronchial wall thickening and air trapping) and lung function at the time of HRCT were identified (n=34). Conclusion: The FOT is a repeatable measurement of lung function in children with CF and reliable results can be obtained in children as young as 2 years old. Young children with CF exhibit altered respiratory function which was affected by the presence of factors known to be associated with lung disease. The FOT has the potential to provide useful information about changes in clinical status in young children with CF and may be used to direct management of patient lung disease.

Mechanical ventilation saves lives, but it is an intervention fraught with the potential for serious complications. Prevention of these complications has become the focus of research and critical care in the last twenty years. This thesis presents the first use, or the application under new conditions, of three technologies that could contribute to optimization of mechanical ventilation. Optoelectronic plethysmography was used in Papers I and II for continuous assessment of changes in chest wall volume, configuration, and motion in the perioperative period. A forced oscillation technique (FOT) was used in Paper III to evaluate a novel positive end-expiratory pressure (PEEP) optimization strategy. Finally, in Paper IV, FOT in conjunction with an optical sensor based on a self-mixing laser interferometer (LIR) was used to study the oscillatory mechanics of the respiratory system and to measure the chest wall displacement. In Paper I, propofol anesthesia decreased end-expiratory chest wall volume (VeeCW) during induction, with a more pronounced effect on the abdominal compartment than on the rib cage. The main novel findings were an increased relative contribution of the rib cage to ventilation after induction of anesthesia, and the fact that the rib cage initiates post-apneic ventilation. In Paper II, a combination of recruitment maneuvers, PEEP, and reduced fraction of inspired oxygen, was found to preserve lung volume during and after anesthesia. Furthermore, the decrease in VeeCW during emergence from anesthesia, associated with activation of the expiratory muscles, suggested that active expiration may contribute to decreased functional residual capacity, during emergence from anesthesia. In the lavage model of lung injury studied in Paper III, a PEEP optimization strategy based on maximizing oscillatory reactance measured by FOT resulted in improved lung mechanics, increased oxygenation, and reduced histopathologic evidence of ventilator-induced lung injury. Paper IV showed that it is possible to apply both FOT and LIR simultaneously in various conditions ranging from awake quiet breathing to general anesthesia with controlled mechanical ventilation. In the case of LIR, an impedance map representing different regions of the chest wall showed reproducible changes during the different stages that suggested a high sensitivity of the LIR-based measurements.

Carmen Klein: Sonographie der Lunge und Analyse der Atmungsmechanik mittels Impuls-Oszilloresistometrie beim lungengesunden und pneumoniekranken Ferkel und Läuferschwein Institut für Bakteriologie und Mykologie der Veterinärmedizinischen Fakultät der Universität Leipzig Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin (BgVV), Fachbereich 4 in Jena eingereicht im Mai 1999, verteidigt am 16. November 1999 (157 Seiten, 52 Abbildungen, 34 Tabellen, 285 Literaturstellen; Anhang mit: 62 Seiten, 15 Abbildungen und 50 Tabellen) Mit der Sonographie der Lunge und der Impuls-Oszilloresistometrie (IOS - engl.: Impulse Oscilloresistometry System) wurden erstmals zwei nichtinvasive diagnostische Verfahren auf ihre Anwendbarkeit und Aussagefähigkeit bei lungengesunden und pneumoniekranken Absatzferkeln und Läuferschweinen bis zu einer Körpermasse von ca. 50 kg geprüft. Die sonographische Untersuchung der Lunge wurde an insgesamt 45 lungengesunden bzw. pneumoniekranken Schweinen durchgeführt. Dazu wurden die Tiere mit 2,0 mg/kg KM Diazepam sediert. Eine Studie an sechs klinisch gesunden Schweinen gab Aufschluß über die Ausdehnung des bei dieser Tierart sonographisch erreichbaren Lungenfeldes. Die bei Pneumonien häufig betroffenen kranioventral gelegenen Lungenabschnitte waren sonographisch gut zu erreichen. Die bei der sonographischen Untersuchung der Lunge des Schweines nachgewiesenen Befunde zeigten eine gute Übereinstimmung mit den in der Literatur an anderen Spezies beschriebenen Resultaten. Beim Schwein wurden folgende Befundbilder abgegrenzt: ? keine Veränderungen : sonographisch o.b.B. ? geringgradige Veränderungen: Kometenschweifartefakte in geringer Ausprägung ? mittelgradige Veränderungen: Kometenschweifartefakte und Konsolidierungen oder echogenes Grundmuster mit Kometenschweifartefakten ? hochgradige Veränderungen: echogenes Grundmuster oder echogenes Grundmuster mit Abszeß oder Nekrose Die Befunde der sonographischen Untersuchung der Lunge wurden bei 34 Schweinen den entsprechenden pathologisch-anatomischen Befunden zugeordnet. Pathologisch-anatomisch unverändertes Gewebe stellte sich mit einer Wahrscheinlichkeit (Sensitivität) von 95,65 % ohne bzw. mit nur geringradigen sonographischen Veränderungen dar. Bei pathologisch-anatomisch verändertem Gewebe wurden mit einer Wahrscheinlichkeit von 74,62 % (Sensitivität) mittel- und hochgradig veränderte sonographische Befundbilder festgestellt. In die histologische Untersuchung wurden insgesamt 49 Gewebeproben einbezogen. Rückschlüsse vom sonographischen Befund auf die Art der histologisch diagnostizierten Pneumonie waren beim Schwein nicht möglich. Es wurde jedoch eine statistisch gesicherte Beziehung zwischen dem Ausprägungsgrad der histologischen Veränderung und den sonographischen Befunden festgestellt. Der Ausprägungsgrad der histologischen Veränderung stand u.a. in direkter Beziehung zum Luftgehalt im Lungengewebe. Die Impuls-Oszilloresistometrie ist ein Verfahren zur Analyse der Atmungsmechanik und wurde am Schwein ebenfalls unter Sedation mit Diazepam (1,5 bis 2,0 mg/kg KM) oder aber nach entsprechendem Training der Tiere ohne jede medikamentelle Ruhigstellung vorgenommen. Die Schweine wurden in einer Hängematte streßarm fixiert und das Meßsystem über eine starre, luftdicht am Kopf abschließende Atemmaske an das Tier adaptiert. Insgesamt 26 Schweine wurden in die Studien zur Untersuchung verschiedener Einflüsse auf das Verhalten der IOS-Parameter einbezogen. Folgende Parameter wurden berücksichtigt: Atmungsfrequenz (Af), Atemzugvolumen (Vt), die Spektralparameter Resistance (R), Reactance (X) und Kohärenz (K) jeweils bei 5, 10, 15 und 20 Hz (R5, ...R20, X5, ...X20, K5, ...K20) sowie die Modellparameter zentrale (Rz) und periphere (Rp) Resistance, Lungencompliance (Cl) und zentrale Inertance (Lz). In einer Variabilitätsanalyse an fünf nicht sedierten, klinisch gesunden Schweinen wurde die Reproduzierbarkeit der Ergebnisse bei drei unmittelbar innerhalb weniger Minuten aufeinander folgend sowie bei an drei Tagen nacheinander zur selben Tageszeit durchgeführten IOS-Messungen überprüft. Innerhalb des kurzen Zeitraumes von wenigen Minuten wurde die Variabilität der Meßergebnisse der meisten IOS-Parameter überwiegend durch inter-individuelle Einflüsse verursacht, während bei der über mehrere Tage reichenden Betrachtungsweise der intra-individuell bedingte Anteil der Variabilität zunahm. Die Entwicklung von Alter und Körpermasse konnten im Rahmen der an elf klinisch gesunden, sedierten Schweinen über einen Zeitraum von 62 Tagen vorgenommenen IOS-Messungen nur teilweise die mit dem Wachstum einhergehenden Veränderungen der IOS-Parameter erklären. Der an acht klinisch gesunden, sedierten Schweinen festgestellte Einfluß der Tageszeit auf die IOS-Parameter war nur gering, stimmte aber von der Tendenz her mit den in der Literatur beschriebenen Angaben überein. An 16 klinisch gesunden Schweinen wurde der Einfluß der Sedation mit Diazepam auf die IOS-Parameter überprüft. Dieses Medikament führte zu einer signifikanten Verringerung von Af und Vt und zu einer Verbesserung der Qualität der IOS-Messungen (K5, K10, K20). An sieben klinisch gesunden, nicht sedierten Schweinen wurden durch Inhalation von Aerosolen mit bestimmten pharmakologisch wirksamen Substanzen (Carbachol, Fenoterolhydrobromid) definierte Zustände am respiratorischen System wie Bronchospasmus und Bronchodilatation ausgelöst und mittels IOS-Messungen nachgewiesen. Die während der bronchospastischen Reaktion vorgefundenen Veränderungen der IOS-Parameter, insbesondere der starke Anstieg der Resistance im unteren Frequenzbereich (R5), das deutliche Absinken der Reactance, insbesondere bei 5 Hz, und die beträchtliche Erhöhung des Modellparameters Rp sind für diesen Zustand des Bronchialsystems charakteristisch. Neun klinisch gesunde, sedierte Schweine wurden zunächst bei physiologischer und anschließend bei stark distal abgebeugter Kopfhaltung untersucht. Durch die starke Flexion im Kopf-Hals-Bereich wurde eine extrathorakal gelegene Obstruktion erzeugt. Hierbei waren die spektrale Resistance (R5 bis R20) und der Modellparameter Rz bei abgebeugter Kopfhaltung signifikant erhöht. Am Beispiel einer experimentell ausgelösten Infektion mit Actinobacillus pleuropneumoniae wurde der Verlauf einer respiratorischen Erkrankung an sieben sedierten Schweinen unter regelmäßiger Durchführung von IOS-Messungen, über einen Zeitraum von 23 Tagen verteilt, beobachtet. Die Resultate der IOS-Messungen 3 Tage p.i. (Resistance im gesamten Frequenzbereich erhöht, starker Anstieg von Rz und Lz ) wiederspiegelten vor allem eine Beteiligung der extrathorakal und zentral gelegenen Bereiche des Respirationstraktes. Durch die zumindest tendenziell vorhandenen Veränderungen bestimmter IOS-Parameter (Verstärkung der negativen Frequenzabhängigkeit, Erhöhung von Rp, Abnahme von Cl) wurde zusätzlich eine Beteiligung der peripheren Bereiche in der Lunge angezeigt. Für einen definierten Zeitraum wurden die IOS-Meßergebnisse den Befunden der sonographischen Untersuchung der Lunge gegenübergestellt. Dabei wurden hohe Korrelationen zwischen auf periphere Veränderungen verweisenden IOS-Parametern und sonographisch ermittelten Veränderungen an der Lunge nachgewiesen. Abschließend ist festzustellen: 1.) Beide getesteten diagnostischen Verfahren sind beim Schwein anwendbar und liefern eine wertvolle Ergänzung der konventionellen Diagnostik am Respirationstrakt dieser Tierart. 2.) Nach sonographischer Untersuchung der Lunge sind mit hoher Wahrscheinlichkeit Aussagen über das Vorhandensein pathologisch-anatomisch sichtbarer pneumonischer Verän-derungen und deren Ausdehnung im sonographisch erreichbaren Lungenfeld möglich. 3.) Die Impuls-Oszilloresistometrie liefert in einem Parameter-Komplex Informationen über den funktionellen Zustand des gesamten respiratorischen Systems. Dieser ist von zahlreichen physiologisch wirkenden Faktoren (u.a. Kopfhaltung, Wachstum, Tageszeit), applizierten pharma-kologisch wirksamen Substanzen (z.B. Diazepam, Carbachol, Fenoterolhydrobromid) und dem Vorhandensein einer Erkrankung des respiratorischen Systems (z.B. Actinobacillus pleuropneumoniae) abhängig. 4.) Da beide Verfahren verschiedene Sachverhalte, den morphologischen (Sonographie) bzw. den funktionellen Zustand (Impuls-Oszilloresistometrie) des respiratorischen Systems widerspiegeln, liefern sie einander ergänzende Aussagen. 5.) Beide diagnostischen Verfahren bieten sich beim Schwein vor allen Dingen für den Einsatz zu wissenschaftlichen Zwecken an. Aufgrund ihres nichtinvasiven Charakters ist ein schonender Umgang mit den Probanden möglich. 6.) Die Anwendung der Sonographie der Lunge ist auch in ausgewählten Fällen der tierärztlichen Praxis, z.B. beim Ankauf von Zuchttieren, denkbar
Carmen Klein: Lung Sonography and Analysis of the Respiratory Mechanics by means of Impulse Oscilloresistometry in Healthy and Pneumonic Piglets and Porkers Institute of Bacteriology and Mycology Faculty of Veterinary Medicine University of Leipzig Germany Federal Institute for Health Protection of Consumers and Veterinary Medicine Jena Branch Germany submitted in May 1999 (157 pages, 52 figures, 34 tables, 285 references, appendix with 62 pages, 15 figures, 50 tables) Two non-invasive diagnostic methods, i.e. lung sonography and impulse oscillometry, were examined for the first time with regard to their applicability and evidence in clinically healthy as well as pneumonic weaned piglets and porkers of up to ca. 50 kg b.w. A total of 45 healthy or pneumonic swine was subjected to lung sonography. For this purpose, the animals were sedated with 2.0 mg/k b.w. diazepam. Six clinically healthy swine were studied to establish the lung area accessible to sonography in this animal species. Sonography was found to cover well the cranioventral sections of the lung often affected by pneumonias. The findings established by lung sonography in the swine showed a good coincidence with results described in literature for other species. The findings in swine revealed the following picture. ? No changes: sonography NAD ? Low-grade changes: little pronounced comet-tail artefacts ? Moderate changes: Comet-tail artefacts and consolidations or echogenic basic pattern including comet-tail artifacts ? High-degree changes: basic echogenic pattern or basic echogenic pattern plus abscess or necrosis Lung sonography findings in 34 swine were assigned to the corresponding pathological-anatomical findings. Tissue considered as unchanged from the pathological-anatomical angle was found to be without or with only minor sonographic changes, with a probability (sensitivity) of 95.65 %. In tissue exhibiting pathological-anatomical changes, sonographic findings showed pictures of moderate and high-degree changes, with a probability (sensitivity) of 74.62 % A total of 49 tissue samples was subjected to histological examination. It was not possible to infer, from the sonographic findings, the type of pneumonia diagnosed histologically in the swine. Nevertheless, a statistically confirmed correlation between the degree of pronouncedness of the histological changes and the sonographic findings was established. The pronouncedness of the histological changes was, like other factors, directly related to the air content of the lung tissue. Impulse oscillometry being a method used to analyze respiratory mechanics was applied to swine either sedated by means of diazepam (1.5 - 2.0 mg/kg b.w.) or non-sedated by medication but trained correspondingly. The animals were fixed in a canvas sling with openings for the limbs, avoiding stress, and the measuring system was adapted to the animal using a rigid face mask hermetically fitting to the animal's head. A total of 26 animals was included in the studies to examine a variety of factors influencing the IOS parameters. The following parameters were considered: Respiratory rate (Af), tidal volume (Vt), the spectral parameters resistance (R), reactance (X) and coherence (K) at 5, 10, 15 and 20 Hz each (R5, ...R20, X5, ...X20, K5, ...K20) as well as the model parameters, central (Rz) and peripheral (Rp) resistance, lung compliance (Cl) and central inertance (Lz). A variability analysis involving five non-sedated, clinically healthy swine served to examine the reproducibility of the results of three IOS measurements either performed consecutively within a few minutes, or on three consecutive days at the same time of the day. During the brief period of a few minutes, the variability of the results of measurements, for most parameters, was due to inter-individual factors while in the case of an analysis over several days, the intra-individual share of variability increased. In the context of the IOS measurements performed in eleven clinically healthy, sedated swine over a period of 62 days, development in terms of age and body weight could only partially explain the variations of the IOS parameters taking place with growth. The influence of the time of the day on IOS parameters studied in eight clinically healthy, sedated swine was found to be small; coincidence with data given in literature, however, was seen as a tendency. The influence of diazepam sedation on the IOS parameters was examined in 16 clinically healthy swine. This medication resulted in a significant reduction of Af and Vt and improved quality of IOS measurements (K5, K10, K20). In seven clinically healthy, non-sedated swine, defined respiratory situations, i.e. bronchospasm and bronchodilatation were generated by aerosol inhalation of pharmacologically active substances such as carbachol and fenoterolhydrobromide and demonstrated by IOS measurements. This state of the bronchial system is characterized by the changes in IOS parameters found at the time of the bronchospasmic reaction, in particular the vehement rise of resistance in the lower frequency range (R5), the obvious drop in reactance, especially at 5 Hz and the noteworthy rise in the model parameter, Rp. Nine clinically healthy, sedated swine were examined first with their heads in a physiological and then, in a vertical position of their heads. The severe bending in the head-neck area produced an extrathoracic obstruction. Spectral resistance (R5 - R20) and the model parameter, Rz were significantly higher at a vertical position of the head. An experimental infection of seven sedated swine with Actinobacillus pleuropneumoniae served as a model to study the course of respiratory disease. The animals were subjected to regular IOS measurements over a period of 23 days. The results of IOS measurements performed 3 days p.i. (elevated resistance over the entire frequency range, vehement rise of Rz and Lz) reflected, above all, an involvement of the extrathoracic and central areas of the respiratory tract. As a result, the modifications of defined IOS parameters (intensification of negative frequency dependency, rise in Rp, drop in Cl) which were present at least as a tendency, indicated an additional involvement of the peripheral lung areas. The results of IOS measurements over a defined period were compared with the findings from lung sonography. High correlations between IOS parameters indicating peripheral changes and lung changes detected by sonography were demonstrated. Conclusions 1.) Both diagnostic methods studied may be used in swine and will provide a valuable completion of conventional diagnosis in the respiratory tract of this species. 2.) With a high probability, lung sonography will provide evidence of the presence of visible pathological-anatomical changes in the lung and their extent in the lung area that is accessible to sonography. 3.) Impulse oscillometry provides a complex of parameters that contain information about the functional state of the entire respiratory system. This state is dependent upon numerous physiological factors (among them position of the head, growth, time of the day), pharmacologically active substances administered (e.g. diazepam, carbachol, fenoterolhydrobromide) and the presence of respiratory disease (e.g. caused by Actinobacillus pleuropneumoniae). 4.) Since the two methods reflect different facts, i.e. the morphological (sonography) and the functional (impulse oscillometry) state of the respiratory system, they supply mutually supplementing information. 5.) Both diagnostic methods offer themselves above all for use in scientific research on swine. Owing to their non-invasive character, it is possible to handle test animals in a non-offensive way. 6.) In specific cases, lung sonography may also be used in the veterinary practitioner's surgery, e.g. for the examination of animals kept for breeding

Doctor of Philosophy (PhD)
Asthma is a chronic inflammatory disease of the airways. Corticosteroid medication is the most effective currently available treatment. Complications of corticosteroid therapy are dose-dependent, however, the clinical efficacy of varying doses of inhaled corticosteroids has been studied with mixed results. A randomized, double-blind, parallel group study was used to evaluate the inhaled corticosteroid dose-response relationship for clinical endpoints and in vitro parameters of underlying airway inflammation and remodelling. The mannitol provocation test with Forced Oscillation Technique (FOT) was used to derive potential dose-differentiating endpoints. In vitro inflammatory markers were measured in alveolar macrophages from bronchoalveolar lavage. Basement membrane thickness was measured from bronchial biopsies. Eleven nonasthmatic subjects were enrolled for comparison. This thesis addresses the null hypothesis that there is no significant difference in clinical and biological effects between low dose (200mcg/day, n=11) and high dose (1000mcg/day, n=11) treatment (for 6-7 weeks) with inhaled fluticasone propionate (FP) for a range of clinical outcomes and in vitro markers of airway inflammation and remodelling. Significant changes after FP included increased FEV1, reduced airway hyperresponsiveness (AHR) (by FOT and FEV1), exhaled nitric oxide and Juniper symptom score. In addition, significant reductions occurred in expression of GM-CSF, TNF-alpha and IL-1ra in macrophages. A lower baseline FOT-derived respiratory system conductance was predictive of a greater degree of improvement in symptoms. No statistically significant differences in the changes after treatment between low and high dose FP were found in spirometry, exhaled nitric oxide, symptom scores, AHR, alveolar macrophage cytokine levels (GM-CSF, TNF-alpha, IL-1ra, IL-10) and basement membrane thickness, although there were trends towards greater improvements in many of the parameters after high dose FP. Basement membrane thickness appeared to be reduced by high dose FP, although this reduction was not statistically significant. There was a weak, but statistically significant, negative correlation between basement membrane thickness and FOT-derived conductance (r2=0.135, p=0.042). With the recognition of the limitations in the interpretation of these data, the results suggest that, in previously steroid naïve mild to moderate asthmatics, there may be only minimal benefit derived from an additional 800µg/day of inhaled fluticasone above the low dose of 200µg/day.

Background: Asthma is a heterogeneous disease. Diagnosis relies on symptom evaluation and lung function tests using spirometry. Symptoms can be vague. Spirometry is effort-dependent and does not reliably evaluate small airways. Allergic asthma in preschool children is not easily separated from episodic wheeze. Exhaled NO (FeNO) is a marker of allergic Th2-cytokine-driven airway inflammation. However, FeNO is not feasible in preschoolers with current devices and algorithms. Alveolar NO is an estimate of small airway involvement. Forced oscillometry (FOT) is an effort-independent lung function test assessing both large and small airways. Aims: To study clinical and methodological aspects of FeNO, alveolar NO and lung function indices by FOT. Methods: Asthmatic children and young adults and healthy controls, were included in the studies. FeNO at 50 mL/s was performed in all studies (in study III with an adapted single-breath method with age-adjusted exhalation times). FeNO at multiple exhalation flow rates were performed in studies I, II and IV to calculate alveolar NO, as was spirometry. FOT indices were assessed in study IV. Results: The exhalation time needed to reach steady-state NO was < 4 s in subjects aged 3-4 years, and was related to subject height. FeNO was higher in ICS-naïve asthmatic children than in controls. ICS-naïve asthmatic preschool children had FeNO < 20 ppb. The oral contribution to FeNO was similar in asthmatic and healthy youths. Multiple flow rates and modelling of alveolar NO were feasible in children aged 10-18 years. Alveolar NO correlated to asthma characteristics, though not when axial diffusion correction was applied. FOT resistance measures were associated with asthma diagnosis, and small airway FOT measures were associated with asthma control, in adolescents. Conclusion: An adapted FeNO method is feasible from 4 years, and exhalation time is related to child height. Our findings emphasise the need to refine clinical cut-offs for FeNO in younger children. FOT variables discriminate between asthmatics and controls, much like spirometry. The information provided by FOT is additive to that from spirometry. Further studies of exhaled NO dynamics and FOT indices of small airways are warranted to evaluate new treatment options and possibly improve asthma control.

The forced Oscillation Technique (FOT) can be used to measure lung impedance continuously during breathing. However, spectral overlap between the breathing waveform and the applied flow oscillation can be problematic if the frequency content of spontaneous breathing is unknown. This problem motivated us to develop a modification to the FOT system called the Tracked Breathing Trainer. The modification uses biofeedback to constrain subjects to breathe at a single predetermined frequency. This thesis investigates the engineering and physiological aspects of the modification we made. We studied 8 adult non-asthmatic and 8 adult asthmatic subjects. Three 16 s perturbatory flow oscillation signals ranging from 1-40 Hz were used on the subjects. Each subject received three trials per perturbation for both spontaneous and tracked breathing. We then fitted a resistance-elastance-inertance model of the lung to each data set. For non-asthmatic subjects, the average resistance (R) and elastance (E) values for the first spontaneous breathing trial were 2.5±0.15 cmH2O.s.ml-1 and 18.1±3.55 cmH2O.ml-1, and for the third spontaneous breathing trial were 2.4±0.12 cmH2O.s.ml-1 and 21.8±4 cmH2O.ml-1. R and E for the first tracked breathing trial were 2.3±0.21 cmH2O.s.ml-1 and 33.6±7.4 cmH2O.ml-1, and for the third tracked breathing trial were 2.4±0.14 cmH2O.s.ml-1 and 25.75±4.3 cmH2O.ml-1, respectively. For asthmatic subjects, the average R and E values for the first spontaneous breathing trial were 3.32±0.68 cmH2O.s.ml-1 and 39.13±9.8 cmH2O.ml-1, and for the third spontaneous breathing trial were 3.12±0.15 cmH2O.s.ml-1 and 39.91±6.2 cmH2O.ml-1. R and E for the first tracked breathing trial were 2.86±0.15 cmH2O.s.ml-1 and 32.47±4.1 cmH2O.ml-1, and for the third tracked breathing trial were 2.86±0.21 cmH2O.s.ml-1 and 33.89±10 cmH2O.ml-1, respectively. These results show that R was consistently lower during tracked breathing than spontaneous breathing in both non-asthmatic and asthmatic subjects. However, an increase in E was observed during tracked breathing. We suspect this effect may have resulted from dynamic hyperinflation. These results also show that R and E are reproducible with both spontaneous and tracked breathing, and that R and E were not noticeably different between both breathing maneuvers. We conclude that using biofeedback to control the breathing pattern during application of the FOT in normal subjects does not significantly affect impedance measurements, and thus may be useful for avoiding spectral overlap between FOT perturbations and the breathing pattern.

O crescimento do percentual de idosos na população ocorre mundialmente tornando necessário conhecer o impacto do processo de envelhecimento, neste contexto, do sistema respiratório. O desconhecimento do impacto do envelhecimento associado a diferentes graus de exposição a poluentes e a presença de comorbidade(s) dificulta a diagnose das pneumopatias acarretando aos idosos piora da qualidade de vida. São vantagens da Técnica de Oscilações Forçadas (FOT): alto potencial de aplicação em idosos, fácil realização, análise detalhada da mecânica respiratória, desempenho de papel complementar, bem como de alternativa na impossibilidade de realização dos exames tradicionais. Foi realizado um estudo experimental comparativo que objetivou investigar o impacto do envelhecimento no sistema respiratório pela FOT e pela espirometria entre grupos de diferentes faixas etárias, sendo a idade a variável independente e as variáveis dependentes, os parâmetros oscilométricos resistência em regime contínuo (R0) e das vias aéreas centrais (Rm), inclinação da resistência (S), frequência de ressonância (fr), reatância média (Xm), complacência dinâmica (Cdin,sr) e os parâmetros espirométricos (VEF1, CVF, VEF1/CVF e FEF/CVF). Foram realizados entrevista, exame clínico, radiografia torácica, avaliação da mecânica respiratória pela FOT e da função pulmonar pela espirometria. 255 indivíduos com idades entre 20 e 86 anos foram entrevistados. Destes, 175 foram excluídos, restando os 80 voluntários analisados, que foram divididos em 6 grupos de acordo com a faixa etária (A: 20 a 29 anos; B: 30 a 39 anos; C: 40 a 49 anos; D: 50 a 59 anos; E: 60 a 69 anos; F: 70 anos ou mais). Foram utilizados os testes de Shapiro-Wilkins, na avaliação da normalidade dos dados biométricos em cada grupo, Oneway ANOVA, na comparação entre os grupos, e Tukey HSD na comparação entre as classes subjacentes. A análise da associação entre duas variáveis foi realizada inicialmente pela regressão univariada entre os parâmetros oscilométricos, a idade e a altura. A regressão múltipla entre os parâmetros oscilométricos, idade e altura foi realizada em conjunto. Foi realizada a análise de confundimento ou modificação de efeito sobre o parâmetro altura na relação entre a idade e os parâmetros oscilométricos. A correção pelo fator altura foi realizada quando sua análise apresentava fator de confundimento. Quanto aos parâmetros resistivos, não foram observadas alterações em R0 e Rm com o envelhecimento enquanto que o declínio observado em S é discreto e não-significativo. Em relação aos parâmetros reativos, verificouse que Cdin,sr e Xm diminuem enquanto que fr aumenta com o processo de envelhecimento. Todas estas alterações são significativas. Todavia, a diminuição da Cdin,sr não apresenta relação com a idade e sim com a altura, que constituiu modificação do efeito. Nos demais parâmetros oscilométricos, a altura constituiu fator de confundimento. Quanto à espirometria, observou-se declínio significativo do VEF1, do VEF1/CVF e da CVF. O índice FEF/CVF apresentou declínio nãosignificativo. Concluindo, a resistência do sistema respiratório e a complacência dinâmica não se modificam enquanto a homogeneidade do sistema respiratório diminui com o processo de envelhecimento.
The increase in the elderly percentage in the population occurs worldwide. To know the impact of the aging process, in this context, on the respiratory system, is crucial. The unawareness of the impact of aging, with different exposure degrees to pollution and the presence of commorbities introduces difficulty in the pneumopathies diagnosis make worsen the elderlys quality of life. The Forced Oscillation Technique (FOT) has as advantages a high application potential in elderly people, detailed analysis of the respiratory mechanics, plays complementary role and alternative in the impossibility to perform the traditional exams, as well. A comparative experimental study was done with the purpose of analyze the impact of aging in the respiratory system by FOT and spirometry between groups of different ages. Age is the independent variable and the dependent variables are the oscillometric parameters continuum regime resistance (R0), central airways resistance (Rm), slope of resistance (S), resonant frequency (fr), average reactance (Xm), dynamic compliance (Cdin,sr) and the spirometry parameters (FEV1, FVC, FEV1/CVF and FEF/FVC). Interviews, clinical examination, thoracic roentgenograms, mensuration of the respiratory mechanics by FOT and of the pulmonary function by spirometry were performed. 255 individuals aged from 20 to 86 years were interviewed. From these, 175 were excluded and the 80 remaining volunteers were analyzed and divided into six groups according to age (A: 20-29 years old; B: 30-39 years old; C: 40-49 years old; D: 50-59 years old; E: 60-69 years old; F: 70 or more years old). The Shapiro-Wilkins test was used in the analysis of the normality of the biometric data in each group. Oneway ANOVA was used in the comparison between groups and the Tukey HSD test was used in the comparison between the underlying classes. The analysis of the association between two variables was done initially between the oscilometric parameters, age and height. Multiple regressions between oscilometric parameters, age and height was performed in conjunction. Confounding analysis or effect modification over height and oscilometric parameters was done. The correction by the height factor was done when its analysis presented confounding factor. There were not changes in the resistive parameters R0 and Rm with age while the decrease seen in S is slight and not significant. In the reactive parameters, it was found that Cdin,sr and Xm decrease while fr increases with the aging process. All of these changes are significant. However, the decrease in Cdin,sr is not related to the aging process but with height, which was a confounding factor. It was found that the spirometric parameters FEV1, FVC and CVF presented a significant decrease and the index FEF/CVF presented a not significant decrease. Concluding, the resistance and the dynamic compliance of the respiratory system do not change while the homogeneity of the respiratory system decreases with the aging process.

O termo silicose refere-se ao processo de fibrose pulmonar causado pela inalação de poeira contendo sílica. É uma doença ocupacional, incurável, que se inicia nas vias aéreas distais e pode progredir independente do término da exposição. Os testes de função pulmonar, apesar de não serem utilizados como ferramenta diagnóstica para silicose, são amplamente empregados para acompanhar longitudinalmente esses indivíduos. Estudos recentes sugerem que a Técnicas de Oscilações Forçadas (FOT) pode ser aplicada para detecção de alterações pulmonares precoces em indivíduos com silicose. Contudo, existem poucos estudos descrevendo as alterações de mecância respiratória associada com a silicose através da FOT. Neste contexto, os objetivos deste estudo são: (1) analisar as alterações de mecânica respiratória de indivíduos portadores de silicose com diferentes graus de obstrução e (2) avaliar a capacidade da FOT em detectar alterações na função pulmonar decorrentes da silicose. Trata-se de um estudo transversal controlado com avaliação de casos prevalentes, tendo como unidade de avaliação o indivíduo. Os exames realizados incluíram medidas de espirometria e FOT. Foi selecionado um total de 67 indivíduos, 46 portadores de silicose e 21 sadios, caracterizando o grupo controle. Os indivíduos com diagnóstico de silicose foram divididos em três grupos classificados de acordo com o nível de obstrução sugerido pela espirometria. Essa classificação resultou em três categorias: Indivíduos normais ao exame espirométrico (NE), n= 12; com distúrbio ventilatório obstrutivo leve (DVOL), n=22; com distúrbio ventilatório obstrutivo moderado ou acentuado (DVOMA), n= 12. Todos os indivíduos realizaram exames da FOT para análise das propriedades resistivas e reativas do sistema respiratório. Posteriormente aos exames da FOT os indivíduos foram submetidos à espirometria. Considerando os grupos divididos a partir da espirometria, os parâmetros resistivos e reativos e a impedância do sistema respiratório em 4Hz (Z4Hz) se modificaram significativamente com a progressão da distúrbio obstrutivo. Na análise do poder diagnóstico da FOT os parâmetros R0, Rm, Rsr4 e |Z4Hz| mostraram-se precisos para identificar as modificações de mecânica respiratória em pacientes com silicose apresentando distúrbio ventilatório obstrutivo leve. Para distúrbio ventilatório obstrutivo moderado e acentuado todos os parâmetros analisados apresentaram habilidade para identificar essas alterações. Na análise entre o grupo controle e normal ao exame, nenhum parâmetro da FOT apresentou valor de acurácia adequado para uso clínico. Esses resultados são coerentes com as alterações fisiopatológicas relacionadas à silicose, confirmando o potencial da FOT na avaliação das modificações de mecânica respiratória em doentes com silicose.
The term silicosis is the name given to the pulmonary fibrosis caused by inhalation of dust containing crystalline silica. Is a typical occupational disease, chronic, incurable, starting in the peripheral airways and that can progress independently of the end of exposure. The pulmonary function tests, although not used as a diagnostic tool for silicosis, are widely employed to follow these individuals. Recent works suggests that the Forced Oscilation Technique (FOT) may be applied in the detection of early respiratory changes in silicosis. However, few studies have been analyzing the changes on respiratory mechanics associated with silicosis through the FOT. In this context, the aims of this study were (1) to analyze changes respiratory mechanics in subjects with silicosis with different degrees of obstruction by FOT, and (2) to evaluate the potential of the FOT to detect alterations in the lung function resulting from silicosis. This is a sectional study evaluation of prevalent cases, with the evaluation unit the individual. The examinations included measurement of FOT and spirometry. Sixty-seven volunteers were analyzed: 21 healthy subjects and 46 with silicosis. Spirometry was used to classify airway obstruction in the silicosis groups. This classification resulted in three categories: normal spirometric exam (n = 12); mild obstruction (n = 22); moderate or severe obstruction (n = 12.). All subjects performed FOT exam for the analysis of resistive and reactive properties of the respiratory system. The order of the examinations was FOT, followed by spirometry. Considering the groups classified according to the spirometry, the resistive and reactive the parameters and the impedance of the respiratory system at 4Hz (|Z4Hz|), have changed significantly with the progression of obstructive. The analysis of the diagnostic power of FOT parameters R0, Rm, and Rsr4 |Z4Hz| showed to be accurate to identify the changes of respiratory mechanics in silicosis patients with mild obstructive lung disease. To the moderate and severe obstructions, all the parameters analyzed showed adequate to identify these changes. In the analysis between the control and normal exam, no parameters of the FOT showed adequate measure to use to correctly identify these subjects. The FOT parameters adequately described the pathophysiological changes associated with silicosis and presented adequate accuracy for clinical use, indicating that this technique can be helpful in the evaluation respiratory mechanics in this disease.

O aprofundamento de nosso conhecimento acerca das alterações da mecânica respiratória e da resposta ao uso do broncodilatador em crianças com asma pode contribuir para o melhor entendimento desta doença. A técnica de oscilações forçadas (FOT) apresenta elevado potencial neste sentido, pois permite uma avaliação detalhada da mecânica respiratória de crianças asmáticas. Desta maneira, os objetivos deste estudo são: (1) aprofundar nosso conhecimento sobre as alterações de mecânica respiratória em crianças asmáticas; (2) investigar o potencial de utilização clínica da FOT e (3) analisar as alterações de mecânica respiratória decorrentes da resposta broncodilatadora em crianças asmáticas. No presente estudo foram analisadas 93 crianças, separadas em grupo controle (n=31) e grupo de crianças asmáticas divididas de acordo com o grau de obstrução ao fluxo aéreo determinado pela espirometria em: normal ao exame espirométrico (n=31) e com distúrbio ventilatório obstrutivo leve (n=31). Pela FOT foram analisados os parâmetros relacionados às propriedades resistivas do sistema respiratório R0 (resistência no intercepto), Rm (resistência média) e S (inclinação da reta de resistência). R0 e Rm aumentaram com a obstrução ao fluxo aéreo (p<0,002 e p<0,02, respectivamente) e S apresentou redução (p<0,0007) caracterizando, este último, aumento da não-homogeneidade do sistema respiratório. Observou- se uma redução nos parâmetros relacionados às propriedades reativas do sistema respiratório, Cdin,sr (complacência dinâmica, p<0,03) e Xm (reatância média, p<0,02) com o aumento da obstrução. Também foi analisado o módulo da impedância em 4 Hz (׀Zrs4Hz׀), parâmetro relacionado com a carga mecânica total no sistema respiratório, que mostrou- se aumentado com a obstrução(p<0,001). Na análise do desempenho diagnóstico, os parâmetros R0, Rm, Cdin,sr e ׀Zrs4Hz׀ apresentaram área sob a Curva (AUC), sensibilidade (Se) e especificidade (Sp) adequados ao uso clínico no grupo com distúrbio ventilatório obstrutivo leve. Estes valores foram mais elevados do que no grupo de crianças asmáticas normais ao exame espirometrico, o que está relacionado com as maiores alterações no grupo com obstrutrução leve. A resposta broncodilatadora foi estudada observando- se as diferenças dentro do mesmo grupo de crianças e mensurando as alterações em cada grupo antes e após o uso do broncodilatador. Os parâmetros relacionados às propriedades resistivas, R0, Rm e S apresentaram melhora significativa com redução das resistências no grupo controle (p<0,00001, p<0,0003 e 0,00001), normal ao exame espirometrico (p<0,000002, p<0,00008 e 0,0006) e grupo com distúrbio ventilatório obstrutivo leve (p<0,0001, p<0,0007 e 0,000001). Estas alterações ocorreram no grupo controle e nos grupos de crianças asmáticas. Crs,din e Xm também apresentaram alterações significativas em todos os grupos estudados: no grupo controle (p<0,0001, p<0,00001), normal ao exame (p<0,00006, p<0,00001) e no grupo com distúrbio ventilatório obstrutivo leve (p<0,0001, p<0,00001), fato também observado na análise de ׀Zrs4Hz׀ no grupo controle (p<0,00001), normal ao exame (p<0,00001) e grupo com distúrbio ventilatório obstrutivo leve (p<0, 00001). Concluímos que a asma introduz alterações nos parâmetros resistivos e reativos do sistema respiratório com o aumento do grau de obstrução ao fluxo aéreo. Essas alterações foram identificadas nas crianças com obstrução leve. A FOT detectou as alterações ocorridas após a utilização da medicação broncodilatadora. Estes resultados indicam que a FOT pode ser um exame sensível para avaliar as alterações fisiopatológicas decorrentes da asma em crianças.
The increase of our knowledge about changes in respiratory mechanics and response to bronchodilator use in asthmatic children may contribute to a better understanding of this disease. The forced oscillation technique (FOT) has high potential in this sense, since it allows a detailed assessment of respiratory mechanics in asthmatic children. Thus, the objectives of this study are: (1) increase our understanding of the changes in respiratory mechanics of asthma in children, (2) investigate the clinical potential of FOT and (3) analyze the changes in respiratory mechanics resulting from bronchodilator response in asthmatic children. The present study examined 93 children, separated in the control group (n=31) and the asthmatic group divided according to the degree of airflow obstruction determined by spirometry in normal spirometry results (n=31) and with mild airway obstruction (n=31). Using the FOT we analyzed parameters related to the resistance of the respiratory system R0 (intercept resistance), Rm (resistance average) and S (slope of the resistance). R0 and Rm increased with airflow obstruction (p<0.002 and p<0.02, respectively) and S decreased (p<0.0007), indicating increased respiratory system non-homogeneity. There was a reduction in parameters related to the reactive properties of the respiratory system, Cst,sr (dynamic compliance, p<0.03) and Xm (reactance average, p<0,001) with increasing obstruction. The module of the respiratory system impedance at 4 Hz (| Zrs4Hz |) was also studied. This parameter is related to the total mechanical load on the respiratory system, and increased significantly with obstruction (p<0,001). Analyzing the diagnostic performance of FOT parameters, R0, Rm, Cst,sr and |Zrs4Hz| presented adequate values for clinical use in the identification of mild airway obstruction (AUC>0.7). These values were higher than that observed in the identification of the normal to the spirometric exam group, which may be related to the higher modifications in the group of children with mild airway obstruction. The bronchodilator response was studied by observing the differences within the same group of children, measuring the changes in each group before and after bronchodilator use. The parameters related to the resistance, R0, Rm and S showed significant improvement indicating reduced resistance in control group (p<0.00001,p<0.0003 e 0.00001), normal spirometry results (p<0.000002, p<0.00008 e 0.0006) and with mild airway obstruction (p<0.0001, p<0.0007 e 0.000001). These changes occurred in the control group and groups of children with asthma. Crs,din and Xm also showed significant changes in all groups studied in control group p<0.0001, p<0.00001), normal spirometry results (p<0.00006, p<0.00001) and with mild airway obstruction (p<0.0001, p<0.00001), a fact also observed in the analysis of | Zrs4Hz |, with showed a significant decrease in control group (p<0.00001), normal spirometry results(p<0.00001) and with mild airway obstruction (p<0.00001). We conclude that the increase of the degree of airflow obstruction in asthmatic children introduces increases in the resistance of the respiratory system, reductions in the dynamic compliance, reduction in homogeneity, as well as increase in the total respiratory system mechanical load. The FOT is able to detect respiratory changes in patients with mild airway obstruction. The use of bronchodilator medication introduces changes in asthmatic children, as well as in normal children. The results of the present study indicate that the FOT can be a sensitive test to evaluate the changes associated with asthma in children.

Allergic asthma is an inflammatory disease of the airways and is characterized by eosinophilic inflammation and increased airway reactivity. In the studies presented in this thesis, lung mechanics and measurements of airway reactivity were assessed in anaesthetized tracheostomized mice by using an animal ventilator (flexiVent®). A forced oscillation technique makes it possible to measure of both airway and tissue mechanics with a potential to distinguish between central and peripheral airways. The results of the experiments on lung mechanics imply that it is important to understand how altered lung mechanics can affect the airway physiology in order to assess the relevance of different animal models of asthma. We have investigated the effects of changing different components of the lung mechanical measurements, such as administering bronchoconstrictive agents via inhalation or intravenously and implementing deep inhalation in animals with airway inflammation. We have also investigated the relation between airway inflammation and oxidative stress. We found that the formation and time-course of F2-isoprostanes, a marker of oxidative stress, and tissue damage were associated with the degree of inflammation and with the degree of heterogeneous airway airflow. Finally we wished to investigate the hypothesis that nitric oxide (NO) may interact with glucocorticoid (GC) treatment because we see a potential for finding new strategies to increase the therapeutic effect in poor responders or patients resistant to GC treatment. NO plays a central role in physiological regulation of the airway function, and is involved in asthma. We found that the concomitant administration of NO and GC attenuated the airway reactivity more than either treatment alone. In conclusion, with the information presented in this thesis, we hope to contribute to the development of better experimental tools and to improved understanding of murine models of asthma for investigating and understanding the underlying pathophysiology of asthma.

The use of forced oscillation technique (FOT) to study the mechanical properties of the respiratory system was proposed by Dubois (1956). This technique allows studying the mechanical behavior of the respiratory system, and from models, extracting features of pulmonary mechanics that would be barely noticeable by other methods. The object of this work was to build a portable device that uses the forced oscillation technique so that tests could be performed in locations with limited space. The device of TOF2 was remodeled from an early version called TOF1. Its components are integrated by replacing the set of equipment, power, signal generator, pressure transducers and data acquisition board with a single portable system. It was also developed a processing system for the collected data. In the validation process of TOF2 the pressure transducers were calibrated, the acquisition and data processing approach were defined, a standard resistance-inertance-compliance (RIC) model was built (analogue), and compared to the known value of impedance with the measured values in TOF2. The resulting procedure is analogous to that used in characterization of electric resistances. The reproducibility of the resistance measurements with TOF2 coupled to the analogue, along with the coherence function was greater than 95%, which indicates a good reliability. We conclude that the developed device, called TOF2, includes all the instrumentation needed to perform the measurements of a conventional TOF instrument, and meets the general recommendations for the design and implementation of the measurement system.
O uso da Técnica de Oscilações Forçadas (TOF) no estudo das propriedades mecânicas do sistema respiratório foi proposto por DUBOIS (1956). Essa técnica permite estudar o comportamento mecânico do sistema respiratório e, a partir de modelos, extrair características da mecânica pulmonar que seriam pouco perceptíveis por outros métodos. O objeto deste trabalho foi a construção de um aparelho portátil que utiliza a técnica de oscilações forçadas para que os exames pudessem ser realizados em locais com pouco espaço. O aparelho da TOF2 foi remodelado a partir de uma versão inicial denominada TOF1. Seus componentes foram integrados substituindo o conjunto de aparelhos, fonte, gerador de sinais, transdutores de pressão e placa de aquisição de dados por um único sistema portátil. Foi desenvolvido também um sistema de processamento dos dados coletados. No processo de validação do TOF2 foram calibrados os transdutores de pressão, definidos a aquisição e o processamento dos dados, foi construído um modelo resistência-inertância-complacência (RIC) padrão (analogue) e comparou-se o valor de impedâncias conhecidas com os valores mensurados no TOF2. Os resultados foram compatíveis aos valores obtidos na caracterização das resistências. A reprodutibilidade das medidas de resistência com o TOF2 acoplado ao analogue, juntamente com a função de coerência foi superior a 95%,o que indica uma boa confiabilidade dos dados. Conclui-se que o aparelho desenvolvido, denominado TOF2, inclui toda a instrumentação necessária para realizar as medições convencionais de um aparelho TOF, e cumpre as recomendações gerais para a elaboração e implementação do sistema de medidas.

L'étude expérimentale du transfert de matière est réalisée pour 3 systèmes ternaires mettant en jeu principalement des molécules plutôt que des ions. Deux phénomènes sont observés: un effet électrostatique (orientation des molécules) et un effet électrodynamique (modification de la tension interfaciale). Un contacteur à électrode externe, soumis à des oscillations forcées est utilisé pour l'extraction de l'acide acétique. Lorsque la fréquence des oscillations est égale à la fréquence de résonance naturelle des gouttes on observe une diminution de la vitesse de chute et une augmentation du coefficient de transfert. La taille des gouttes a aussi une influence.

Carmen Klein: Sonographie der Lunge und Analyse der Atmungsmechanik mittels Impuls-Oszilloresistometrie beim lungengesunden und pneumoniekranken Ferkel und Läuferschwein Institut für Bakteriologie und Mykologie der Veterinärmedizinischen Fakultät der Universität Leipzig Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin (BgVV), Fachbereich 4 in Jena eingereicht im Mai 1999, verteidigt am 16. November 1999 (157 Seiten, 52 Abbildungen, 34 Tabellen, 285 Literaturstellen; Anhang mit: 62 Seiten, 15 Abbildungen und 50 Tabellen) Mit der Sonographie der Lunge und der Impuls-Oszilloresistometrie (IOS - engl.: Impulse Oscilloresistometry System) wurden erstmals zwei nichtinvasive diagnostische Verfahren auf ihre Anwendbarkeit und Aussagefähigkeit bei lungengesunden und pneumoniekranken Absatzferkeln und Läuferschweinen bis zu einer Körpermasse von ca. 50 kg geprüft. Die sonographische Untersuchung der Lunge wurde an insgesamt 45 lungengesunden bzw. pneumoniekranken Schweinen durchgeführt. Dazu wurden die Tiere mit 2,0 mg/kg KM Diazepam sediert. Eine Studie an sechs klinisch gesunden Schweinen gab Aufschluß über die Ausdehnung des bei dieser Tierart sonographisch erreichbaren Lungenfeldes. Die bei Pneumonien häufig betroffenen kranioventral gelegenen Lungenabschnitte waren sonographisch gut zu erreichen. Die bei der sonographischen Untersuchung der Lunge des Schweines nachgewiesenen Befunde zeigten eine gute Übereinstimmung mit den in der Literatur an anderen Spezies beschriebenen Resultaten. Beim Schwein wurden folgende Befundbilder abgegrenzt: ? keine Veränderungen : sonographisch o.b.B. ? geringgradige Veränderungen: Kometenschweifartefakte in geringer Ausprägung ? mittelgradige Veränderungen: Kometenschweifartefakte und Konsolidierungen oder echogenes Grundmuster mit Kometenschweifartefakten ? hochgradige Veränderungen: echogenes Grundmuster oder echogenes Grundmuster mit Abszeß oder Nekrose Die Befunde der sonographischen Untersuchung der Lunge wurden bei 34 Schweinen den entsprechenden pathologisch-anatomischen Befunden zugeordnet. Pathologisch-anatomisch unverändertes Gewebe stellte sich mit einer Wahrscheinlichkeit (Sensitivität) von 95,65 % ohne bzw. mit nur geringradigen sonographischen Veränderungen dar. Bei pathologisch-anatomisch verändertem Gewebe wurden mit einer Wahrscheinlichkeit von 74,62 % (Sensitivität) mittel- und hochgradig veränderte sonographische Befundbilder festgestellt. In die histologische Untersuchung wurden insgesamt 49 Gewebeproben einbezogen. Rückschlüsse vom sonographischen Befund auf die Art der histologisch diagnostizierten Pneumonie waren beim Schwein nicht möglich. Es wurde jedoch eine statistisch gesicherte Beziehung zwischen dem Ausprägungsgrad der histologischen Veränderung und den sonographischen Befunden festgestellt. Der Ausprägungsgrad der histologischen Veränderung stand u.a. in direkter Beziehung zum Luftgehalt im Lungengewebe. Die Impuls-Oszilloresistometrie ist ein Verfahren zur Analyse der Atmungsmechanik und wurde am Schwein ebenfalls unter Sedation mit Diazepam (1,5 bis 2,0 mg/kg KM) oder aber nach entsprechendem Training der Tiere ohne jede medikamentelle Ruhigstellung vorgenommen. Die Schweine wurden in einer Hängematte streßarm fixiert und das Meßsystem über eine starre, luftdicht am Kopf abschließende Atemmaske an das Tier adaptiert. Insgesamt 26 Schweine wurden in die Studien zur Untersuchung verschiedener Einflüsse auf das Verhalten der IOS-Parameter einbezogen. Folgende Parameter wurden berücksichtigt: Atmungsfrequenz (Af), Atemzugvolumen (Vt), die Spektralparameter Resistance (R), Reactance (X) und Kohärenz (K) jeweils bei 5, 10, 15 und 20 Hz (R5, ...R20, X5, ...X20, K5, ...K20) sowie die Modellparameter zentrale (Rz) und periphere (Rp) Resistance, Lungencompliance (Cl) und zentrale Inertance (Lz). In einer Variabilitätsanalyse an fünf nicht sedierten, klinisch gesunden Schweinen wurde die Reproduzierbarkeit der Ergebnisse bei drei unmittelbar innerhalb weniger Minuten aufeinander folgend sowie bei an drei Tagen nacheinander zur selben Tageszeit durchgeführten IOS-Messungen überprüft. Innerhalb des kurzen Zeitraumes von wenigen Minuten wurde die Variabilität der Meßergebnisse der meisten IOS-Parameter überwiegend durch inter-individuelle Einflüsse verursacht, während bei der über mehrere Tage reichenden Betrachtungsweise der intra-individuell bedingte Anteil der Variabilität zunahm. Die Entwicklung von Alter und Körpermasse konnten im Rahmen der an elf klinisch gesunden, sedierten Schweinen über einen Zeitraum von 62 Tagen vorgenommenen IOS-Messungen nur teilweise die mit dem Wachstum einhergehenden Veränderungen der IOS-Parameter erklären. Der an acht klinisch gesunden, sedierten Schweinen festgestellte Einfluß der Tageszeit auf die IOS-Parameter war nur gering, stimmte aber von der Tendenz her mit den in der Literatur beschriebenen Angaben überein. An 16 klinisch gesunden Schweinen wurde der Einfluß der Sedation mit Diazepam auf die IOS-Parameter überprüft. Dieses Medikament führte zu einer signifikanten Verringerung von Af und Vt und zu einer Verbesserung der Qualität der IOS-Messungen (K5, K10, K20). An sieben klinisch gesunden, nicht sedierten Schweinen wurden durch Inhalation von Aerosolen mit bestimmten pharmakologisch wirksamen Substanzen (Carbachol, Fenoterolhydrobromid) definierte Zustände am respiratorischen System wie Bronchospasmus und Bronchodilatation ausgelöst und mittels IOS-Messungen nachgewiesen. Die während der bronchospastischen Reaktion vorgefundenen Veränderungen der IOS-Parameter, insbesondere der starke Anstieg der Resistance im unteren Frequenzbereich (R5), das deutliche Absinken der Reactance, insbesondere bei 5 Hz, und die beträchtliche Erhöhung des Modellparameters Rp sind für diesen Zustand des Bronchialsystems charakteristisch. Neun klinisch gesunde, sedierte Schweine wurden zunächst bei physiologischer und anschließend bei stark distal abgebeugter Kopfhaltung untersucht. Durch die starke Flexion im Kopf-Hals-Bereich wurde eine extrathorakal gelegene Obstruktion erzeugt. Hierbei waren die spektrale Resistance (R5 bis R20) und der Modellparameter Rz bei abgebeugter Kopfhaltung signifikant erhöht. Am Beispiel einer experimentell ausgelösten Infektion mit Actinobacillus pleuropneumoniae wurde der Verlauf einer respiratorischen Erkrankung an sieben sedierten Schweinen unter regelmäßiger Durchführung von IOS-Messungen, über einen Zeitraum von 23 Tagen verteilt, beobachtet. Die Resultate der IOS-Messungen 3 Tage p.i. (Resistance im gesamten Frequenzbereich erhöht, starker Anstieg von Rz und Lz ) wiederspiegelten vor allem eine Beteiligung der extrathorakal und zentral gelegenen Bereiche des Respirationstraktes. Durch die zumindest tendenziell vorhandenen Veränderungen bestimmter IOS-Parameter (Verstärkung der negativen Frequenzabhängigkeit, Erhöhung von Rp, Abnahme von Cl) wurde zusätzlich eine Beteiligung der peripheren Bereiche in der Lunge angezeigt. Für einen definierten Zeitraum wurden die IOS-Meßergebnisse den Befunden der sonographischen Untersuchung der Lunge gegenübergestellt. Dabei wurden hohe Korrelationen zwischen auf periphere Veränderungen verweisenden IOS-Parametern und sonographisch ermittelten Veränderungen an der Lunge nachgewiesen. Abschließend ist festzustellen: 1.) Beide getesteten diagnostischen Verfahren sind beim Schwein anwendbar und liefern eine wertvolle Ergänzung der konventionellen Diagnostik am Respirationstrakt dieser Tierart. 2.) Nach sonographischer Untersuchung der Lunge sind mit hoher Wahrscheinlichkeit Aussagen über das Vorhandensein pathologisch-anatomisch sichtbarer pneumonischer Verän-derungen und deren Ausdehnung im sonographisch erreichbaren Lungenfeld möglich. 3.) Die Impuls-Oszilloresistometrie liefert in einem Parameter-Komplex Informationen über den funktionellen Zustand des gesamten respiratorischen Systems. Dieser ist von zahlreichen physiologisch wirkenden Faktoren (u.a. Kopfhaltung, Wachstum, Tageszeit), applizierten pharma-kologisch wirksamen Substanzen (z.B. Diazepam, Carbachol, Fenoterolhydrobromid) und dem Vorhandensein einer Erkrankung des respiratorischen Systems (z.B. Actinobacillus pleuropneumoniae) abhängig. 4.) Da beide Verfahren verschiedene Sachverhalte, den morphologischen (Sonographie) bzw. den funktionellen Zustand (Impuls-Oszilloresistometrie) des respiratorischen Systems widerspiegeln, liefern sie einander ergänzende Aussagen. 5.) Beide diagnostischen Verfahren bieten sich beim Schwein vor allen Dingen für den Einsatz zu wissenschaftlichen Zwecken an. Aufgrund ihres nichtinvasiven Charakters ist ein schonender Umgang mit den Probanden möglich. 6.) Die Anwendung der Sonographie der Lunge ist auch in ausgewählten Fällen der tierärztlichen Praxis, z.B. beim Ankauf von Zuchttieren, denkbar.
Carmen Klein: Lung Sonography and Analysis of the Respiratory Mechanics by means of Impulse Oscilloresistometry in Healthy and Pneumonic Piglets and Porkers Institute of Bacteriology and Mycology Faculty of Veterinary Medicine University of Leipzig Germany Federal Institute for Health Protection of Consumers and Veterinary Medicine Jena Branch Germany submitted in May 1999 (157 pages, 52 figures, 34 tables, 285 references, appendix with 62 pages, 15 figures, 50 tables) Two non-invasive diagnostic methods, i.e. lung sonography and impulse oscillometry, were examined for the first time with regard to their applicability and evidence in clinically healthy as well as pneumonic weaned piglets and porkers of up to ca. 50 kg b.w. A total of 45 healthy or pneumonic swine was subjected to lung sonography. For this purpose, the animals were sedated with 2.0 mg/k b.w. diazepam. Six clinically healthy swine were studied to establish the lung area accessible to sonography in this animal species. Sonography was found to cover well the cranioventral sections of the lung often affected by pneumonias. The findings established by lung sonography in the swine showed a good coincidence with results described in literature for other species. The findings in swine revealed the following picture. ? No changes: sonography NAD ? Low-grade changes: little pronounced comet-tail artefacts ? Moderate changes: Comet-tail artefacts and consolidations or echogenic basic pattern including comet-tail artifacts ? High-degree changes: basic echogenic pattern or basic echogenic pattern plus abscess or necrosis Lung sonography findings in 34 swine were assigned to the corresponding pathological-anatomical findings. Tissue considered as unchanged from the pathological-anatomical angle was found to be without or with only minor sonographic changes, with a probability (sensitivity) of 95.65 %. In tissue exhibiting pathological-anatomical changes, sonographic findings showed pictures of moderate and high-degree changes, with a probability (sensitivity) of 74.62 % A total of 49 tissue samples was subjected to histological examination. It was not possible to infer, from the sonographic findings, the type of pneumonia diagnosed histologically in the swine. Nevertheless, a statistically confirmed correlation between the degree of pronouncedness of the histological changes and the sonographic findings was established. The pronouncedness of the histological changes was, like other factors, directly related to the air content of the lung tissue. Impulse oscillometry being a method used to analyze respiratory mechanics was applied to swine either sedated by means of diazepam (1.5 - 2.0 mg/kg b.w.) or non-sedated by medication but trained correspondingly. The animals were fixed in a canvas sling with openings for the limbs, avoiding stress, and the measuring system was adapted to the animal using a rigid face mask hermetically fitting to the animal''s head. A total of 26 animals was included in the studies to examine a variety of factors influencing the IOS parameters. The following parameters were considered: Respiratory rate (Af), tidal volume (Vt), the spectral parameters resistance (R), reactance (X) and coherence (K) at 5, 10, 15 and 20 Hz each (R5, ...R20, X5, ...X20, K5, ...K20) as well as the model parameters, central (Rz) and peripheral (Rp) resistance, lung compliance (Cl) and central inertance (Lz). A variability analysis involving five non-sedated, clinically healthy swine served to examine the reproducibility of the results of three IOS measurements either performed consecutively within a few minutes, or on three consecutive days at the same time of the day. During the brief period of a few minutes, the variability of the results of measurements, for most parameters, was due to inter-individual factors while in the case of an analysis over several days, the intra-individual share of variability increased. In the context of the IOS measurements performed in eleven clinically healthy, sedated swine over a period of 62 days, development in terms of age and body weight could only partially explain the variations of the IOS parameters taking place with growth. The influence of the time of the day on IOS parameters studied in eight clinically healthy, sedated swine was found to be small; coincidence with data given in literature, however, was seen as a tendency. The influence of diazepam sedation on the IOS parameters was examined in 16 clinically healthy swine. This medication resulted in a significant reduction of Af and Vt and improved quality of IOS measurements (K5, K10, K20). In seven clinically healthy, non-sedated swine, defined respiratory situations, i.e. bronchospasm and bronchodilatation were generated by aerosol inhalation of pharmacologically active substances such as carbachol and fenoterolhydrobromide and demonstrated by IOS measurements. This state of the bronchial system is characterized by the changes in IOS parameters found at the time of the bronchospasmic reaction, in particular the vehement rise of resistance in the lower frequency range (R5), the obvious drop in reactance, especially at 5 Hz and the noteworthy rise in the model parameter, Rp. Nine clinically healthy, sedated swine were examined first with their heads in a physiological and then, in a vertical position of their heads. The severe bending in the head-neck area produced an extrathoracic obstruction. Spectral resistance (R5 - R20) and the model parameter, Rz were significantly higher at a vertical position of the head. An experimental infection of seven sedated swine with Actinobacillus pleuropneumoniae served as a model to study the course of respiratory disease. The animals were subjected to regular IOS measurements over a period of 23 days. The results of IOS measurements performed 3 days p.i. (elevated resistance over the entire frequency range, vehement rise of Rz and Lz) reflected, above all, an involvement of the extrathoracic and central areas of the respiratory tract. As a result, the modifications of defined IOS parameters (intensification of negative frequency dependency, rise in Rp, drop in Cl) which were present at least as a tendency, indicated an additional involvement of the peripheral lung areas. The results of IOS measurements over a defined period were compared with the findings from lung sonography. High correlations between IOS parameters indicating peripheral changes and lung changes detected by sonography were demonstrated. Conclusions 1.) Both diagnostic methods studied may be used in swine and will provide a valuable completion of conventional diagnosis in the respiratory tract of this species. 2.) With a high probability, lung sonography will provide evidence of the presence of visible pathological-anatomical changes in the lung and their extent in the lung area that is accessible to sonography. 3.) Impulse oscillometry provides a complex of parameters that contain information about the functional state of the entire respiratory system. This state is dependent upon numerous physiological factors (among them position of the head, growth, time of the day), pharmacologically active substances administered (e.g. diazepam, carbachol, fenoterolhydrobromide) and the presence of respiratory disease (e.g. caused by Actinobacillus pleuropneumoniae). 4.) Since the two methods reflect different facts, i.e. the morphological (sonography) and the functional (impulse oscillometry) state of the respiratory system, they supply mutually supplementing information. 5.) Both diagnostic methods offer themselves above all for use in scientific research on swine. Owing to their non-invasive character, it is possible to handle test animals in a non-offensive way. 6.) In specific cases, lung sonography may also be used in the veterinary practitioner''s surgery, e.g. for the examination of animals kept for breeding.