Academic literature on the topic 'Forced oscillation technique (FOT)'

The forced oscillation technique (FOT) is a non-volitional assessment that is used during tidal breathing. A variant of FOT uses a pseudorandom noise (PRN) signal which we postulated might have utility in assessing lung function in prematurely born children. We, therefore, undertook a systematic review to evaluate the evidence regarding PRN FOT. A comprehensive search of the literature was conducted by using the following databases: Medline, Embase, Web of Science and CINAHL. Observational studies, case series/reports and randomized-controlled trials were eligible for inclusion. Article abstracts and full texts were screened independently by two reviewers, with disagreements resolved by discussion or a third reviewer if necessary. Five studies were included (n = 587 preterm children). Three compared PRN FOT with spirometry, and two compare it to the interrupter technique. Most studies failed to report comprehensive methodology of the frequency spectra used to generate the PRN signal. There was evidence that poorer lung function, as assessed by PRN FOT, was associated with a greater burden of respiratory symptoms, but there was insufficient evidence to determine whether PRN FOT performed better than other lung-function tests. Detailed methodological documentation, in accordance with ERS guidance, is needed to assess the benefits of PRN FOT prior to routine clinical incorporation to assess prematurely born children.

AbstractThe forced oscillation technique (FOT) is a non-invasive pulmonary function test which is based on the measurement of respiratory impedance. Recently, promising results were obtained by the application of FOT on patients with respiratory failure and obstructive sleep apnea (OSA). By using a nasal mask instead of a mouthpiece, the influences of the nasal passage and upper shunt alter the measured mechanical impedance. In this paper, we investigated the effects of the nasal passage and mask on FOT measurements from eight healthy subjects. A method for flow correction has been developed, which contains a pressure-flow characteristics compensation of the undetermined flow leakage at the face-mask interface. Impedance calculation and parameter estimation were performed in the frequency domain using fast Fourier transform (FFT). Average nasal parameters were

Abstract There is a lack of noninvasive pulmonary function tests which can assess regional information of the lungs. Electrical impedance tomography (EIT) is a radiation-free, non-invasive real-time imaging that provides regional information of ventilation volume regarding the measurement of electrical impedance distribution. Forced oscillation technique (FOT) is a pulmonary function test which is based on the measurement of respiratory mechanical impedance over a frequency range. In this article, we introduce a new measurement approach by combining FOT and EIT, named the oscillatory electrical impedance tomography (oEIT). Our oEIT measurement system consists of a valve-based FOT device, an EIT device, pressure and flow sensors, and a computer fusing the data streams. Measurements were performed on five healthy volunteers at the frequencies 3, 4, 5, 6, 7, 8, 10, 15, and 20 Hz. The measurements suggest that the combination of FOT and EIT is a promising approach. High frequency responses are visible in the derivative of the global impedance index $\Delta {Z_{{\text{eit}}}}(t,{f_{{\text{os}}}}).$ The oEIT signals consist of three main components: forced oscillation, spontaneous breathing, and heart activity. The amplitude of the oscillation component decreases with increasing frequency. The band-pass filtered oEIT signal might be a new tool in regional lung function diagnostics, since local responses to high frequency perturbation could be distinguished between different lung regions.

Background: The bronchial provocation test (BPT) performed by using the forced oscillation technique (FOT) is cooperated without forced expiratory effort. However, a comparison of the application value and safety of BPTs measured by using the FOT and the standardized dosimeter method is lacking, which limits its clinical practice. Objective: We aimed to analyze the diagnostic value and safety of the BPT as measured by the FOT in patients with asthma and in healthy subjects. Methods: This was a randomized cross-over clinical study. Airway responsiveness was measured by using the FOT and the aerosol provocation system (APS) dosimeter method in all the participants. The between-test interval was 24 hours. The diagnostic value and safety of the two tests were analyzed. Results: Asthma control status was assessed based on ACT scores, and patients with asthma (including 27 uncontrolled, 34 partially controlled, and 32 controlled) were collected, and 69 healthy subjects were recruited. Receiver operating characteristic curves revealed slightly superior screening capability of cumulative dose of methacholine causing a 20% decrease (PD20)‐forced expiratory volume in the first second of expiration when measured by using the APS-dosimeter method (area under the curve [AUC] 0.981 [95% confidence interval {CI}, 0.952‐1.000]) over that of cumulative dose of inhaled methacholine at the inflection point when respiratory resistance began to increase continuously (Dmin) by using the FOT (AUC 0.959 [95% CI, 0.924‐0.994]). The sensitivity and specificity were 98.9% and 98.6%, respectively, with the APS-dosimeter method, and 100% and 87.0%, respectively, with the FOT. It took an average of 9.0 minutes (range, 6.0‐11.0 minutes) when using the FOT and an average of 17.0 minutes (range, 14.0‐25.0 minutes) when using APS-dosimeter method (p < 0.01) in all the participants. The measurement time for the FOT was reduced by 47.1% than the APS-dosimeter. The incidence rate of the adverse events with the FOT was slightly higher than that with the APS-dosimeter method (p < 0.05). Both tests were well tolerated. No serious adverse event was found. Conclusion: The FOT, characterized as being simple, safe, and time saving, could be used to assess airway hyperresponsiveness in patients with asthma and worthy of clinical application.

Anti-tumor necrosis factor alpha (TNFα) therapy is widely used to treat various inflammatory conditions. Paradoxically, there are several case reports describing the development of bronchocentric granulomatosis treated with TNFα inhibitors, and it is difficult to determine the effect of treatment using conventional spirometry because the lesions are located in small airways. However, it has been reported that the forced oscillation technique (FOT) is useful in the evaluation of small airway disease in bronchial asthma or chronic obstructive pulmonary disease. We performed the FOT to determine the effect of treatment on bronchocentric granulomatosis and found it to be useful. We report the case of a 55-year-old female with ulcerative colitis who was treated with golimumab and who developed bronchocentric granulomatosis as a sarcoid-like reaction to golimumab. She was successfully treated with prednisone, and the treatment efficacy was confirmed by the FOT. The FOT may be useful in the evaluation of small airway disease in bronchocentric granulomatosis. This case may help inform clinicians of the usefulness of the FOT to assess small airway disease in various diseases.

This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3–6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease.

The forced oscillation technique (FOT) is a non-invasive method to assess airway function by emitting oscillatory signals into the respiratory tract during tidal ventilation. This opinion piece discusses the current use, trialled modification and future directions in utilizing FOT as a novel diagnostic tool for early detection of small airway changes in smokers. The published evidence to date has shown that FOT parameters could be a sensitive diagnostic tool to detect early respiratory changes in smokers. Multiple frequencies and the frequency dependence of resistance and reactance can provide the most valuable and early information regarding smoking induced changes in airways. Considering its non-invasiveness, lower level of discomfort to patients than spirometry, feasibility, and cost effectiveness, it could be the first-choice diagnostic technique for detection of early respiratory changes in smokers. The finding of FOT could further be supported and correlated with inflammatory markers.

The forced oscillation technique (FOT) requires minimal patient cooperation and is useful for children. However, comprehensive values of respiratory impedance at baseline and after the reversibility test have not been definitively confirmed. The aim of this study was to evaluate the basic parameters of FOT reactance (Xrs) and resistance (Rrs) in groups of healthy children and children with controlled and uncontrolled asthma. The second aim was the assessment of the reversibility bronchial test using the forced oscillation method in children with bronchial asthma. Materials and Methods. One hundred and six children aged from 2 to 6 years diagnosed with early-onset controlled or uncontrolled asthma and healthy controls were included in this single-center, prospective, randomized study. All asthmatic patients and healthy controls underwent basic FOT as one measurement according to the recommendation of Resmon Pro FOT. The reversibility test was then performed 15 min after the administration of 200 mcg salbutamol by MDI in all patients. Results. Basic Rrs showed significantly higher mean values in patients with uncontrolled asthma compared to patients with controlled asthma, which were in turn higher than the values for patients in the control group (11.14 ± 1.29 versus 15.71 ± 2.6 versus 9.21 ± 0.98, resp.; p<0.05). The data analysis showed similar relationships in terms of the Xrs between the studied groups (−4.76 ± 1.19 versus −7.31 ± 2.33 versus −2.11 ± 0.48, resp.; p<0.05). According to the changes in the Rrs values, 35 (66%) positive bronchial reversibility tests were obtained in 53 subjects with controlled asthma and in 39 (74%) subjects with uncontrolled asthma. Conclusions. Rrs and Xrs obtained by FOT well-discriminate patients with asthma from healthy children. A bronchial reversibility test involving the use of FOT is valuable for the diagnosis of bronchial asthma.

The forced oscillation technique (FOT) can provide unique and clinically relevant lung function information with little cooperation with subjects. However, FOT has higher variability than spirometry, possibly because strategies for quality control and reducing artifacts in FOT measurements have yet to be standardized or validated. Many quality control procedures rely on either simple statistical filters or subjective evaluation by a human operator. In this study, we propose an automated artifact removal approach based on the resistance against flow profile, applied to complete breaths. We report results obtained from data recorded from children and adults, with and without asthma. Our proposed method has 76% agreement with a human operator for the adult data set and 79% for the pediatric data set. Furthermore, we assessed the variability of respiratory resistance measured by FOT using within-session variation (wCV) and between-session variation (bCV). In the asthmatic adults test data set, our method was again similar to that of the manual operator for wCV (6.5 vs. 6.9%) and significantly improved bCV (8.2 vs. 8.9%). Our combined automated breath removal approach based on advanced feature extraction offers better or equivalent quality control of FOT measurements compared with an expert operator and computationally more intensive methods in terms of accuracy and reducing intrasubject variability. NEW & NOTEWORTHY The forced oscillation technique (FOT) is gaining wider acceptance for clinical testing; however, strategies for quality control are still highly variable and require a high level of subjectivity. We propose an automated, complete breath approach for removal of respiratory artifacts from FOT measurements, using feature extraction and an interquartile range filter. Our approach offers better or equivalent performance compared with an expert operator, in terms of accuracy and reducing intrasubject variability.

Respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) is theoretically and experimentally related to lung volume. In chronic obstructive pulmonary disease (COPD), the absolute volume measured by body plethysmography includes a proportion that is inaccessible to pressure oscillations applied via the mouth, that is, a “noncommunicating” lung volume. We hypothesized that in COPD the presence of noncommunicating lung would disrupt the expected Xrs-volume relationship compared with plethysmographic functional residual capacity (FRCpleth). Instead, Xrs would relate to estimates of communicating volume, namely, expiratory reserve volume (ERV) and single-breath alveolar volume (VaSB). We examined FOT and lung function data from people with COPD ( n = 51) and from healthy volunteers ( n = 40). In healthy volunteers, we observed an expected inverse relationship between reactance at 5 Hz (X5) and FRCpleth. In contrast, there was no such relationship between X5 and FRCpleth in COPD subjects. However, there was an inverse relationship between X5 and both ERV and VaSB. Hence the theoretical Xrs-volume relationship is present in COPD but only when considering the communicating volume rather than the absolute lung volume. These findings confirm the role of reduced communicating lung volume as an important determinant of Xrs and therefore advance our understanding and interpretation of FOT measurements in COPD. NEW & NOTEWORTHY To investigate the determinants of respiratory system reactance (Xrs) measured by the forced oscillation technique (FOT) in chronic obstructive pulmonary disease (COPD), we examine the relationship between Xrs and lung volume. We show that Xrs does not relate to absolute lung volume (functional residual capacity) in COPD but instead relates only to the volume of lung in communication with the airway opening. This communicating volume may therefore be fundamental to our interpretation of FOT measurements in COPD and other pulmonary diseases.

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.

This chapter first theorizes as if each system leader has been similar in terms of the resource foundations it has brought to the arena and what it has been able to do with those foundations. Earlier leaders were much weaker than later leaders. What accounts for the difference? Our answer is that system leaders have had variable claims to leads in commerce, technology, and energy. When they combined all three, they became very powerful. The chapter then addresses one of the central issues of Big History: the swinging of the socioeconomic, military, and political lead from western Eurasia to eastern Eurasia and back to western Eurasia and North America in what is sometimes referred to as the “Great Divergence.” This oscillation was put in motion by the discovery of agricultural techniques that gave the West a lead to innovate all sorts of things. Gradually the East caught up, until at one point Rome and Han China were roughly equal. After Rome declined and the Han Empire fragmented, China came back in the Sui–Tang–Song dynasty period, while western Europe remained fragmented. However, the medieval Chinese lead did not persist. Ultimately, the West was able to forge ahead by combining new energy sources and technology. Now, China may be catching up once again.

The induction of acoustic-mechanical oscillations to virus particles by illuminating them with microwave signals is analyzed theoretically. Assuming the virus particle is of spherical shape, its capsid consisting primarily of glycoproteins, a viscous fluid model is adopted while the outside medium of the sphere is taken to be the ideal fluid. The electrical charge distribution of virus particles is assumed to be spherically symmetric with a variation along the radius. The generated acoustic-mechanical oscillations are computed by solving a boundary value problem analytically, making use of Green’s function approach. Resonance conditions to achieve maximum energy transfer from microwave radiation to acoustic oscillation to the particle are investigated. Estimation of the feasibility of the technique to compete with virus epidemics either for sterilization of spaces or for future therapeutic applications is examined briefly.

This paper proposes a generalized dynamics model and a leader-follower control architecture for skid-steered tracked vehicles towing polar sleds. The model couples existing formulations in the literature for the powertrain components with the vehicle-terrain interaction to capture the salient features of terrain trafficability and predict the vehicles response. This coupling is essential for making realistic predictions of the vehicles traversing capabilities due to the power-load relationship at the engine output. The objective of the model is to capture adequate fidelity of the powertrain and off-road vehicle dynamics while minimizing the computational cost for model based design of leader-follower control algorithms. The leader-follower control architecture presented proposes maintaining a flexible formation by using a look-ahead technique along with a way point following strategy. Results simulate one leader-follower tractor pair where the leader is forced to take an abrupt turn and experiences large oscillations of its drawbar arm indicating potential payload instability. However, the follower tractor maintains the flexible formation but keeps its payload stable. This highlights the robustness of the proposed approach where the follower vehicle can reject errors in human leader driving.