Untersuchung zur Bestimmung quantitativer Parameter der Lungenventilation mittels CT und MRT

Die zuverlässige Berechnung von quantitativen Parametern der Lungenventilation ist für ein Verständnis des Verhaltens der Lunge und insbesondere für die Diagnostik von Lungenerkrankungen von großer Bedeutung. Nur durch quantitative Parameter sind verlässliche und reproduzierbare diagnostische Aussagen über den Gesundheitszustand der Lunge möglich. Im Rahmen dieser Arbeit wurden neue quantitative Verfahren zur Erfassung der Lungenventilation basierend auf der dynamischen Computer- (CT) und Magnetresonanztomographie (MRT) entwickelt. Im ersten Teil dieser Arbeit wurde die Frage untersucht, ob das Aufblähen der Lunge in gesunden Schweinelungen und Lungen mit Akutem Lungenversagen (ARDS) durch einzelne, diskrete Zeitkonstanten beschrieben werden kann, oder ob kontinuierliche Verteilungen von Zeitkonstanten die Realität besser beschreiben. Hierzu wurden Serien dynamischer CT-Aufnahmen während definierter Beatmungsmanöver (Drucksprünge) aufgenommen und anschließend aus den Messdaten mittels inverser Laplace-Transformation die zugehörigen Verteilungen der Zeitkonstanten berechnet. Um die Qualität der Ergebnisse zu analysieren, wurde der Algorithmus im Rahmen von Simulationsrechnungen systematisch untersucht und anschließend in-vivo an gesunden und ARDS-Schweinelungen eingesetzt. Während in den gesunden Lungen mono- und biexponentielle Verteilungen bestimmt wurden, waren in den ARDS-Lungen Verteilungen um zwei dominante Zeitkonstanten notwendig, um die gemessenen Daten auf der Basis des verwendeten Modells verlässlich zu beschreiben. Es wurden sowohl diskrete als auch kontinuierliche Verteilungen gefunden. Die CT liefert Informationen über das solide Lungengewebe, während die MRT von hyperpolarisiertem 3He in der Lage ist, direkt das eingeatmete Gas abzubilden. Im zweiten Teil der Arbeit wurde zeitlich hochaufgelöst das Einströmen eines 3He-Bolus in die Lunge erfasst. Über eine Entfaltungsanalyse wurde anschließend das Einströmverhalten unter Idealbedingungen (unendlich kurzer 3He-Bolus), also die Gewebeantwortfunktion, berechnet und so eine Messtechnik-unabhängige Erfassung des Einströmens von 3He in die Lunge ermöglicht. Zentrale Fragestellung war hier, wie schnell das Gas in die Lunge einströmt. Im Rahmen von Simulationsrechnungen wurde das Verhalten eines Entfaltungsalgorithmus (basierend auf B-Spline Repräsentationen) systematisch analysiert. Zusätzlich wurde ein iteratives Entfaltungsverfahren eingesetzt. Aus zeitlich hochaufgelösten Messungen (7ms) an einer gesunden und einer ARDS-Schweinelunge konnte erstmals nachgewiesen werden, dass das Einströmen in-vivo in weniger als 0,1s geschieht. Die Ergebnisse zeigen Zeitkonstanten im Bereich von 4ms–50ms, wobei zwischen der gesunden Lungen und der ARDS-Lunge deutliche Unterschiede beobachtet wurden. Zusammenfassend ermöglichen daher die in dieser Arbeit vorgestellten Algorithmen eine objektivere Bestimmung quantitativer Parameter der Lungenventilation. Dies ist für die eindeutige Beschreibung ventilatorischer Vorgänge in der Lunge und somit für die Lungendiagnostik unerlässlich. Damit stehen quantitative Methoden für die Lungenfunktionsdiagnostik zur Verfügung, deren diagnostische Relevanz im Rahmen wissenschaftlicher und klinischer Studien untersucht werden kann.

Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

PURPOSE To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. MATERIALS AND METHODS Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. RESULTS Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. CONCLUSION AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

Evaluation of two 99mTc-DTPA radioaerosols with different characteristics in lung ventilation studies

Two radioaerosol preparations, TechneScan®-DTPA (99mTc-DTPA, 40 mCi/3 ml; IPEN-CNEN, São Paulo, SP, Brazil) and TechneScan®-DTPA/AEROSOL (99mTc-DTPA/A, 15 mCi/1.5 ml with 0.5 ml ethanol; Mallinckrodt Medical, St. Louis, MO, USA), were compared in pulmonary ventilation studies in terms of total radiocounts and clearance after inhalation. An aerosol with ethanol is supposed to better distribute the radioparticles in the lungs. Twenty normal nonsmoking volunteers (10 men and 10 women), mean age of 23.2 years (range: 20 to 35 years), were studied. Images were obtained immediately and 30, 60 and 90 min after inhalation. Total and regional counts were obtained and the clearance half-lives of both lungs were determined. There was no difference in total counts between the two types of radioaerosol at any time (mean of ~188,000 cpm for male and female subjects at time zero in both aerosols). The highest count was obtained in the middle region of both lungs (P<0.001) with both preparations. The clearance half-life did not differ between aerosols (mean of ~80-88 min for male and female subjects for both aerosols). Small nonsignificant regional differences were observed. No differences between genders or between right and left lung were observed. 99mTc-DTPA/A generated the highest output of radioaerosol. 99mTc-DTPA with alcohol costs approximately five times more than the aerosol without alcohol. The present results show that either kind of aerosol may be adopted routinely for use in pulmonary examinations without affecting diagnosis. We suggest that the amount of 740 mBq (20 mCi) of 99mTc-DTPA in 1.5 ml saline can be used for routine examinations resulting in reduction of costs in pulmonary ventilation studies without diagnostic impairment.

Intravenous versus inhalation anaesthesia for one-lung ventilation

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.ObjectivesThe objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials and quasi-randomized controlled trials of intravenous (e. g. propofol) versus inhalation (e. g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsWe included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.Authors' conclusionsVery little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.

Alternating one lung ventilation using a double lumen endobronchial tube and providing CPAP to the non-ventilated lung in a dog

INTRODUCTION: This case report describes the anaesthetic management of exploratory thoracoscopy and alternating one lung ventilation (OLV) in a dog with a pulmonary bulla, and the application of continuous positive airway pressure (CPAP) to the non-ventilated lung for preventing and treating hypoxia. CASE HISTORY: A 6-year-old, male castrated Border collie was scheduled for exploratory thoracoscopy to investigate spontaneous pnemothorax that had not resolved with repeated suction. Specific requirements for the thoracoscopy were alternating OLV to allow the surgical access to the right middle lobe and its removal, and the examination of the left hemithorax to rule out the presence of other lesions. DIAGNOSIS AND MANAGEMENT: Selective lung ventilation was performed with a double lumen endobronchial tube (DLT), inserted under endoscopic guidance. After a short period of two lung ventilation during preparation of the surgical field, alternating OLV was performed, combining CPAP, provided to the non-ventilated lung via a Mapleson D breathing system, and positive end-expiratory pressure (PEEP) applied to the ventilated lung. Left OLV occurred first and resection of the right middle pulmonary lobe was successfully performed; right OLV followed to allow the examination of the left hemithorax. DISCUSSION AND CONCLUSIONS: The combination of CPAP and PEEP resulted in a satisfactory intra-operative management of hypoxemia. Alternating OLV can be performed successfully by using a DLT. CPAP, commonly employed in human medicine, should be considered an important tool in the anaesthetic management of OLV in small animals.

Multiple training interventions significantly improve reproducibility of PET/CT-based lung cancer radiotherapy target volume delineation using an IAEA study protocol

BACKGROUND AND PURPOSE: To assess the impact of a standardized delineation protocol and training interventions on PET/CT-based target volume delineation (TVD) in NSCLC in a multicenter setting.

MATERIAL AND METHODS: Over a one-year period, 11 pairs, comprised each of a radiation oncologist and nuclear medicine physician with limited experience in PET/CT-based TVD for NSCLC from nine different countries took part in a training program through an International Atomic Energy Agency (IAEA) study (NCT02247713). Teams delineated gross tumor volume of the primary tumor, during and after training interventions, according to a provided delineation protocol. In-house developed software recorded the performed delineations, to allow visual inspection of strategies and to assess delineation accuracy.

RESULTS: Following the first training, overall concordance indices for 3 repetitive cases increased from 0.57±0.07 to 0.66±0.07. The overall mean surface distance between observer and expert contours decreased from -0.40±0.03 cm to -0.01±0.33 cm. After further training overall concordance indices for another 3 repetitive cases further increased from 0.64±0.06 to 0.80±0.05 (p=0.01). Mean surface distances decreased from -0.34±0.16 cm to -0.05±0.20 cm (p=0.01).

CONCLUSION: Multiple training interventions improve PET/CT-based TVD delineation accuracy in NSCLC and reduces interobserver variation.

How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography

Introduction: The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death. Methods: MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH(2)O, at constant driving-pressures of 15 cmH(2)O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP). Results: A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (+/- 5.9 cmH(2)O), and the mean PEEP titrated after MRS was 24.6 (+/- 2.9 cmH(2)O). Mean PaO2/FiO(2) ratio increased from 125 (+/- 43) to 300 (+/- 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver. Conclusions: MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.

[Post-traumatic ARDS--a potential indication for lung transplantation?]

Posttraumatic adult respiratory distress syndrome (ARDS) still involves significant mortality, despite progress in management concepts. Current therapeutic strategies are briefly described, including kinetic therapy, high-frequency jet ventilation and extracorporeal membrane oxygenation. In addition, a spectacular case of the first successful lung transplantation for posttraumatic ARDS after failed ECMO (extracorporeal membrane oxygenation) support is reported. This young man with severe posttraumatic ARDS developed a potentially lethal bilateral pulmonary hemorrhage under treatment with ECMO, and on the basis of this bilateral pulmonary transplantation was considered to be indicated. The patient is alive and well 2 years after the procedure.

Evaluation of deformable image registration for improved 4D CT-derived ventilation for image guided radiotherapy

Recent treatment planning studies have demonstrated the use of physiologic images in radiation therapy treatment planning to identify regions for functional avoidance. This image-guided radiotherapy (IGRT) strategy may reduce the injury and/or functional loss following thoracic radiotherapy. 4D computed tomography (CT), developed for radiotherapy treatment planning, is a relatively new imaging technique that allows the acquisition of a time-varying sequence of 3D CT images of the patient's lungs through the respiratory cycle. Guerrero et al. developed a method to calculate ventilation imaging from 4D CT, which is potentially better suited and more broadly available for IGRT than the current standard imaging methods. The key to extracting function information from 4D CT is the construction of a volumetric deformation field that accurately tracks the motion of the patient's lungs during the respiratory cycle. The spatial accuracy of the displacement field directly impacts the ventilation images; higher spatial registration accuracy will result in less ventilation image artifacts and physiologic inaccuracies. Presently, a consistent methodology for spatial accuracy evaluation of the DIR transformation is lacking. Evaluation of the 4D CT-derived ventilation images will be performed to assess correlation with global measurements of lung ventilation, as well as regional correlation of the distribution of ventilation with the current clinical standard SPECT. This requires a novel framework for both the detailed assessment of an image registration algorithm's performance characteristics as well as quality assurance for spatial accuracy assessment in routine application. Finally, we hypothesize that hypo-ventilated regions, identified on 4D CT ventilation images, will correlate with hypo-perfused regions in lung cancer patients who have obstructive lesions. A prospective imaging trial of patients with locally advanced non-small-cell lung cancer will allow this hypothesis to be tested. These advances are intended to contribute to the validation and clinical implementation of CT-based ventilation imaging in prospective clinical trials, in which the impact of this imaging method on patient outcomes may be tested.

Desfechos tardios de sobreviventes de ensaio clínico randomizado controlado (protocolo ARDSnet vs. Open Lung Approach para o manejo ventilatório da síndrome do desconforto respiratório agudo moderado-grave)

Apesar da utilização da ventilação mecânica protetora como estratégia para o tratamento da síndrome do desconforto respiratório agudo, ao menos um quarto dos pacientes com essa síndrome ainda apresentam redução na função pulmonar após 6 meses de seguimento. Não se sabe se esta redução está relacionada com a gravidade da síndrome ou associada com a forma de ventilar o paciente. Nosso objetivo neste trabalho foi avaliar a associação entre alterações funcionais e estruturais do pulmão com parâmetros de gravidade clínica e de ventilação mecânica. Foi realizada uma análise secundária dos dados obtidos em estudo randomizado e controlado que incluiu pacientes com síndrome do desconforto respiratório agudo moderada/grave, internados em seis unidades de terapia intensiva em um hospital terciário da cidade de São Paulo. Foram analisados dados de pacientes que tinham ao menos um teste de função pulmonar no seguimento. O teste funcional incluiu a medida da capacidade vital forçada, volumes pulmonares e a capacidade de difusão do monóxido de carbono após 1, 2 e 6 meses de seguimento. Foram considerados variáveis independentes o volume corrente, a pressão de distensão e a pressão positiva ao final da expiração (todos medidos após 24 horas da randomização) e um sistema de classificação de prognóstico (APACHE II), a relação PaO2/FIO2 e a complacência respiratória estática (todos medidos antes da randomização). Também foi realizada tomografia de alta resolução do tórax juntamente com os testes de função pulmonar, e posterior análise quantitativa das imagens. Na avaliação de 6 meses também foi realizado teste de caminhada de 6 minutos e um questionário de qualidade de vida (SF-36). Um total de 21 pacientes realizaram o teste de função pulmonar após 1 mês e 15 pacientes realizaram após 2 e 6 meses de seguimento. A capacidade vital forçada foi relacionada inversamente com a pressão de distensão na avaliação de 1, 2 e 6 meses (p < 0,01). A capacidade de difusão do monóxido de carbono relacionou-se inversamente com a pressão de distensão e com o APACHE II (ambos p < 0,01) na avaliação de 1 e 2 meses. Após 6 meses de seguimento, houve correlação inversa entre a pressão de distensão e a capacidade vital forçada independente do volume corrente, da pressão de platô e da complacência estática respiratória após ajustes (R2 = 0,51, p = 0,02). A pressão de distensão também se relacionou com o volume pulmonar total, a densidade pulmonar media e a porcentagem de volume pulmonar não aerado ou pobremente aerado medidos através da análise quantitativa da tomografia computadorizada de tórax realizada na avaliação de 6 meses. Também foi observada relação entre a qualidade de vida após 6 meses de seguimento e a pressão de distensão considerando o domínio estado geral de saúde. Nós concluímos que mesmo em pacientes ventilados com reduzido volume corrente e pressão de platô limitada, maiores valores de pressão de distensão relacionaram-se com menores valores de função pulmonar no seguimento de longo prazo

Detection of an asymptomatic right-ventricle cardiac metastasis from a small-cell lung cancer by F-18-FDG PET/CT.

A right heart metastasis of a small-cell lung cancer was found on the whole-body F-fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG-PET/CT) of a 69-year-old smoker investigated for a right pulmonary mass discovered on chest radiography after a fracture of the right humerus. The PET scan showed an increased FDG uptake by the mass in the right lung and an intense, atypical focal activity of the right ventricle strongly suggestive of a neoplastic process. CT-guided lung biopsy revealed a small-cell lung cancer and myocardial biopsy confirmed the presence of a cardiac metastasis. The patient was treated with six cycles of chemotherapy followed by radiation therapy, which included the heart lesion. At follow-up PET/CT 2 months after the end of treatment, the abnormal cardiac uptake had disappeared, whereas increased FDG uptake persisted in the pulmonary residual mass.

Impact of image quality, radiologists, lung segments, and Gunnar eyewear on detectability of lung nodules in chest CT

BackgroundDespite the increasingly higher spatial and contrast resolution of CT, nodular lesions are prone to be missed on chest CT. Tinted lenses increase visual acuity and contrast sensitivity by filtering short wavelength light of solar and artificial origin.PurposeTo test the impact of Gunnar eyewear, image quality (standard versus low dose CT) and nodule location on detectability of lung nodules in CT and to compare their individual influence.Material and MethodsA pre-existing database of CT images of patients with lung nodules >5 mm, scanned with standard does image quality (150 ref mAs/120 kVp) and lower dose/quality (40 ref mAs/120 kVp), was used. Five radiologists read 60 chest CTs twice: once with Gunnar glasses and once without glasses with a 1 month break between. At both read-outs the cases were shown at lower dose or standard dose level to quantify the influence of both variables (eyewear vs. image quality) on nodule sensitivity.ResultsThe sensitivity of CT for lung nodules increased significantly using Gunnar eyewear for two readers and insignificantly for two other readers. Over all, the mean sensitivity of all radiologist raised significantly from 50% to 53%, using the glasses (P value = 0.034). In contrast, sensitivity for lung nodules was not significantly affected by lowering the image quality from 150 to 40 ref mAs. The average sensitivity was 52% at low dose level, that was even 0.7% higher than at standard dose level (P value = 0.40). The strongest impact on sensitivity had the factors readers and nodule location (lung segments).ConclusionSensitivity for lung nodules was significantly enhanced by Gunnar eyewear (+3%), while lower image quality (40 ref mAs) had no impact on nodule sensitivity. Not using the glasses had a bigger impact on sensitivity than lowering the image quality.

Accidental entrapment of an endo-bronchial blocker tip by a surgical stapler during selective ventilation for lung lobectomy in a dog

OBJECTIVE: To describe the use of an endobronchial blocker (EBB) and to perform selective ventilation during pulmonary lobe resection via thoracotomy in a dog and report its accidental stapling in the resection site. STUDY DESIGN: Clinical case report. ANIMAL: One female dog with a suspected abscess or neoplasia of the right caudal pulmonary lobe. METHODS: One-lung ventilation was performed using a wire-guided EBB to seal the contaminated parenchyma and facilitate surgical access. The affected lung parenchyma was resected and the resection site was closed with staples. RESULTS: Lobar resection was performed successfully, but the loop of the EBB guide wire was inadvertently entrapped in the staple line of the lobectomy. Staples were removed to release the wire loop, and the resulting air leak caused loss of ventilation control until the parenchyma was re-sealed. CONCLUSIONS: We recommend removing the wire guide associate with the EBB after successful lung separation to avoid accidents that could have life-threatening consequences if not recognized. CLINICAL RELEVANCE: One-lung ventilation is useful to isolate healthy parenchyma from diseased parenchyma during lobectomy. Anesthesiologists and surgeons need to be aware of the potential complications associated with use of EBB.

A numerical model for inert gas transport in the lung based on fractal airway morphology

Patients suffering from cystic fibrosis (CF) show thick secretions, mucus plugging and bronchiectasis in bronchial and alveolar ducts. This results in substantial structural changes of the airway morphology and heterogeneous ventilation. Disease progression and treatment effects are monitored by so-called gas washout tests, where the change in concentration of an inert gas is measured over a single or multiple breaths. The result of the tests based on the profile of the measured concentration is a marker for the severity of the ventilation inhomogeneity strongly affected by the airway morphology. However, it is hard to localize underlying obstructions to specific parts of the airways, especially if occurring in the lung periphery. In order to support the analysis of lung function tests (e.g. multi-breath washout), we developed a numerical model of the entire airway tree, coupling a lumped parameter model for the lung ventilation with a 4th-order accurate finite difference model of a 1D advection-diffusion equation for the transport of an inert gas. The boundary conditions for the flow problem comprise the pressure and flow profile at the mouth, which is typically known from clinical washout tests. The natural asymmetry of the lung morphology is approximated by a generic, fractal, asymmetric branching scheme which we applied for the conducting airways. A conducting airway ends when its dimension falls below a predefined limit. A model acinus is then connected to each terminal airway. The morphology of an acinus unit comprises a network of expandable cells. A regional, linear constitutive law describes the pressure-volume relation between the pleural gap and the acinus. The cyclic expansion (breathing) of each acinus unit depends on the resistance of the feeding airway and on the flow resistance and stiffness of the cells themselves. Special care was taken in the development of a conservative numerical scheme for the gas transport across bifurcations, handling spatially and temporally varying advective and diffusive fluxes over a wide range of scales. Implicit time integration was applied to account for the numerical stiffness resulting from the discretized transport equation. Local or regional modification of the airway dimension, resistance or tissue stiffness are introduced to mimic pathological airway restrictions typical for CF. This leads to a more heterogeneous ventilation of the model lung. As a result the concentration in some distal parts of the lung model remains increased for a longer duration. The inert gas concentration at the mouth towards the end of the expirations is composed of gas from regions with very different washout efficiency. This results in a steeper slope of the corresponding part of the washout profile.