Progression of pulmonary hyperinflation and trapped gas associated with genetic and environmental factors in children with cystic fibrosis

BACKGROUND: Functional deterioration in cystic fibrosis (CF) may be reflected by increasing bronchial obstruction and, as recently shown, by ventilation inhomogeneities. This study investigated which physiological factors (airway obstruction, ventilation inhomogeneities, pulmonary hyperinflation, development of trapped gas) best express the decline in lung function, and what role specific CFTR genotypes and different types of bronchial infection may have upon this process. METHODS: Serial annual lung function tests, performed in 152 children (77 males; 75 females) with CF (age range: 6-18 y) provided data pertaining to functional residual capacity (FRCpleth, FRCMBNW), volume of trapped gas (VTG), effective specific airway resistance (sReff), lung clearance index (LCI), and forced expiratory indices (FVC, FEV1, FEF50). RESULTS: All lung function parameters showed progression with age. Pulmonary hyperinflation (FRCpleth > 2SDS) was already present in 39% of patients at age 6-8 yrs, increasing to 67% at age 18 yrs. The proportion of patients with VTG > 2SDS increased from 15% to 54% during this period. Children with severe pulmonary hyperinflation and trapped gas at age 6-8 yrs showed the most pronounced disease progression over time. Age related tracking of lung function parameters commences early in life, and is significantly influenced by specific CFTR genotypes. The group with chronic P. aeruginosa infection demonstrated most rapid progression in all lung function parameters, whilst those with chronic S. aureus infection had the slowest rate of progression. LCI, measured as an index of ventilation inhomogeneities was the most sensitive discriminator between the 3 types of infection examined (p < 0.0001). CONCLUSION: The relationships between lung function indices, CFTR genotypes and infective organisms observed in this study suggest that measurement of other lung function parameters, in addition to spirometry alone, may provide important information about disease progression in CF.

Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Distribution of intracellular and secreted surfactant during postnatal rat lung development

Pulmonary surfactant prevents alveolar collapse via reduction of surface tension. In contrast to human neonates, rats are born with saccular lungs. Therefore, rat lungs serve as a model for investigation of the surfactant system during postnatal alveolar formation. We hypothesized that this process is associated with characteristic structural and biochemical surfactant alterations. We aimed to discriminate changes related to alveolarization from those being either invariable or follow continuous patterns of postnatal changes. Secreted active (mainly tubular myelin (tm)) and inactive (unilamellar vesicles (ulv)) surfactant subtypes as well as intracellular surfactant (lamellar bodies (lb)) in type II pneumocytes (PNII) were quantified before (day (d) 1), during (d 7), at the end of alveolarization (d 14), and after completion of lung maturation (d 42) using electron microscopic methods supplemented by biochemical analyses (phospholipid quantification, immunoblotting for SP-A). Immunoelectron microscopy determined the localization of surfactant protein A (SP-A). (1) At d 1 secreted surfactant was increased relative to d 7-42 and then decreased significantly. (2) Air spaces of neonatal lungs comprised lower fractions of tm and increased ulv, which correlated with low SP-A concentrations in lung lavage fluid (LLF) and increased respiratory rates, respectively. (3) Alveolarization (d 7-14) was associated with decreasing PNII size although volume and sizes of Lb continuously increased. (4) The volume fractions of Lb correlated well with the pool sizes of phospholipids in lavaged lungs. Our study emphasizes differential patterns of developmental changes of the surfactant system relative to postnatal alveolarization.

Reduction of airspace after lung resection through controlled paralysis of the diaphragm

OBJECTIVES: Residual airspace following thoracic resections is a common clinical problem. Persistent air leak, prolonged drainage time, and reduced hemostasis extend hospital stay and morbidity. We report a trial of pharmacologic-induced diaphragmatic paralysis through continuous paraphrenic injection of lidocaine to reduced residual airspace. The objectives were confirmation of diaphragmatic paralysis and possible procedure related complications. METHODS: Six eligible patients undergoing resectional surgery (lobectomy or bilobectomy) were included. Inclusion criteria consisted of: postoperative predicted FEV1 greater than 1300 ml, right-sided resection, absence of parenchymal lung disease, no class III antiarrhythmic therapy, absence of hypersensitivity reactions to lidocaine, no signs of infection, and informed consent. Upon completion of resection an epidural catheter was attached in the periphrenic tissue on the proximal pericardial surface, externalized through a separate parasternal incision, and connected to a perfusing system injecting lidocaine 1% at a rate of 3 ml/h (30 mg/h). Postoperative ICU surveillance for 24h and daily measurement of vital signs, drainage output, and bedside spirometry were performed. Within 48 h fluoroscopic confirmation of diaphragmatic paralysis was obtained. The catheter removal coincided with the chest tube removal when no procedural related complications occurred. RESULTS: None of the patients reported respiratory impairment. Diaphragmatic paralysis was documented in all patients. Upon removal of catheter or discontinuation of lidocaine prompt return of diaphragmatic motility was noticed. Two patients showed postoperative hemodynamic irrelevant atrial fibrillation. CONCLUSION: Postoperative paraphrenic catheter administration of lidocaine to ensure reversible diaphragmatic paralysis is safe and reproducible. Further studies have to assess a benefit in terms of reduction in morbidity, drainage time, and hospital stay, and determine the patients who will profit.

Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

BACKGROUND: Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R) injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. METHODS: Rats were randomly assigned to a control, Celsior (CE) or Celsior + surfactant (CE+S) group (n = 5 each). In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4 degrees C and 50 min of reperfusion at 37 degrees C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups) or immediately after sacrifice (Control), the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. RESULTS: Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation): CE: 160 mm3 (0.61) vs. CE+S: 4 mm3 (0.75); p < 0.05) and the development of atelectases (CE: 342 mm3 (0.90) vs. CE+S: 0 mm3; p < 0.05) but led to a higher degree of peribronchovascular edema (CE: 89 mm3 (0.39) vs. CE+S: 268 mm3 (0.43); p < 0.05). Alveolar type II cells were similarly swollen in CE (423 microm3(0.10)) and CE+S (481 microm3(0.10)) compared with controls (323 microm3(0.07); p < 0.05 vs. CE and CE+S). The number of lamellar bodies was increased and the mean lamellar body volume was decreased in both CE groups compared with the control group (p < 0.05). CONCLUSION: Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of peribronchovascular edema. Morphological changes of alveolar type II cells due to I/R are not affected by surfactant treatment. The beneficial effects of exogenous surfactant therapy are related to the intraalveolar activity of the exogenous surfactant.

Double-lung transplantation in the rat: an acute, syngeneic in situ model

BACKGROUND. The high rate of reperfusion injury in clinical lung transplantation mandates significant improvements in lung preservation. Innovations should be validated using standardized and low-cost experimental models. METHODS. The model introduced here is analyzed by comparing global lung function after varying ischemic times (2, 4, 8, 16, and 24 hours). A rat double-lung block is flush-perfused, and the main pulmonary artery and left atrium are connected to the left pulmonary artery and vein of a syngeneic recipient using a T-shaped stent. With pressure side ports and incorporated flow crystals, measurement of vascular resistance and graft oxygenation can be performed. The transplant is ventilated separately, and compliance and resistance are determined. RESULTS. The increase in the ischemic interval from 2 to 24 hours caused an increase in the alveolar arterial oxygen difference from 220 +/- 20 to 600 +/- 34 mm Hg, pulmonary vascular resistance from 198 +/- 76 to 638 +/- 212 mm Hg.mL-1.min-1, and resistance to airflow from 274 +/- 50 to 712 +/- 30 cm H2O/L H2O, and a decrease in pulmonary compliance from 0.4 +/- 0.05 to 0.12 +/- 0.06 mL/cm H2O. CONCLUSIONS. This in situ, syngeneic rat lung transplantation model offers an alternative to large animal models for verification of lung preservation solutions and for modification of donor or recipient treatment regimens.

Chest size matching in single and double lung transplantation

We applied predicted vital capacity to chest size matching between donor and recipient in lung transplantation to 15 single-lung transplant recipients with pulmonary fibrosis and to 20 double-lung transplant recipients with emphysema or non-emphysema. The predicted vital capacity of the donor was significantly correlated with the predicted vital capacity of the recipient both in double-lung transplantation (r = 0.79, p = 0.001) and single-lung transplantation (r = 0.71, p = 0.003). In double-lung transplantation, the post-transplant vital capacity was correlated with the predicted vital capacity of the recipient (r = 0.74, p = 0.002). Emphysema patients and non-emphysema patients contributed equally to this correlation. In left single lung transplantation, there was a weak correlation between the post-transplant vital capacity and the predicted vital capacity of the donor in the allograft (r = 0.57, p = 0.1095). In right single lung transplantation, the post-transplant vital capacity of the allograft tended to be correlated with the predicted vital capacity of recipient (r = 0.77, p = 0.0735). We concluded that donors were actually selected based on the comparison of predicted vital capacity between donor and recipient. In double-lung transplantation, the post-transplant vital capacity was limited by the recipient's normal thoracic volume and was not influenced by underlying pulmonary disease. In single-lung transplantation with pulmonary fibrosis, the allograft transplanted in the left chest could expand to its own size, and the allograft transplanted in the right chest could expand to the recipient's normal thoracic volume as in double-lung transplantation.

Does point of care prothrombin time measurement reduce the transfusion of fresh frozen plasma in patients undergoing major surgery? The POC-OP randomized-controlled trial

BACKGROUND: Bleeding is a frequent complication during surgery. The intraoperative administration of blood products, including packed red blood cells, platelets and fresh frozen plasma (FFP), is often live saving. Complications of blood transfusions contribute considerably to perioperative costs and blood product resources are limited. Consequently, strategies to optimize the decision to transfuse are needed. Bleeding during surgery is a dynamic process and may result in major blood loss and coagulopathy due to dilution and consumption. The indication for transfusion should be based on reliable coagulation studies. While hemoglobin levels and platelet counts are available within 15 minutes, standard coagulation studies require one hour. Therefore, the decision to administer FFP has to be made in the absence of any data. Point of care testing of prothrombin time ensures that one major parameter of coagulation is available in the operation theatre within minutes. It is fast, easy to perform, inexpensive and may enable physicians to rationally determine the need for FFP. METHODS/DESIGN: The objective of the POC-OP trial is to determine the effectiveness of point of care prothrombin time testing to reduce the administration of FFP. It is a patient and assessor blind, single center randomized controlled parallel group trial in 220 patients aged between 18 and 90 years undergoing major surgery (any type, except cardiac surgery and liver transplantation) with an estimated blood loss during surgery exceeding 20% of the calculated total blood volume or a requirement of FFP according to the judgment of the physicians in charge. Patients are randomized to usual care plus point of care prothrombin time testing or usual care alone without point of care testing. The primary outcome is the relative risk to receive any FFP perioperatively. The inclusion of 110 patients per group will yield more than 80% power to detect a clinically relevant relative risk of 0.60 to receive FFP of the experimental as compared with the control group. DISCUSSION: Point of care prothrombin time testing in the operation theatre may reduce the administration of FFP considerably, which in turn may decrease costs and complications usually associated with the administration of blood products. TRIAL REGISTRATION: NCT00656396.

Direct combination of nanoparticle fabrication and exposure to lung cell cultures in a closed setup as a method to simulate accidental nanoparticle exposure of humans

The tremendous application potential of nanosized materials stays in sharp contrast to a growing number of critical reports of their potential toxicity. Applications of in vitro methods to assess nanoparticles are severely limited through difficulties in exposing cells of the respiratory tract directly to airborne engineered nanoparticles. We present a completely new approach to expose lung cells to particles generated in situ by flame spray synthesis. Cerium oxide nanoparticles from a single run were produced and simultaneously exposed to the surface of cultured lung cells inside a glovebox. Separately collected samples were used to measure hydrodynamic particle size distribution, shape, and agglomerate morphology. Cell viability was not impaired by the conditions of the glovebox exposure. The tightness of the lung cell monolayer, the mean total lamellar body volume, and the generation of oxidative DNA damage revealed a dose-dependent cellular response to the airborne engineered nanoparticles. The direct combination of production and exposure allows studying particle toxicity in a simple and reproducible way under environmental conditions.

Toxic effects of brake wear particles on epithelial lung cells in vitro

ABSTRACT: BACKGROUND: Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. RESULTS: An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours ("full stop" and "normal deceleration"). The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity), by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p < 0.05) with increasing concentrations of metals on the particles (iron, copper and manganese, which were all strongly correlated with each other). Occludin was also negatively correlated with the intensity of reactive oxidative species. The concentrations of interleukin-8 were significantly correlated with increasing organic carbon concentrations. No correlation was observed between occludin and interleukin-8, nor between reactive oxidative species and interleukin-8. CONCLUSION: These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress.

Lung mechanics and gas exchange in ventilated preterm infants during treatment of hyaline membrane disease with multiple doses of artificial surfactant (Exosurf)

Eight premature infants ventilated for hyaline membrane disease and enrolled in the OSIRIS surfactant trial were studied. Lung mechanics, gas exchange [PaCO2, arterial/alveolar PO2 ratio (a/A ratio)], and ventilator settings were determined 20 minutes before and 20 minutes after the end of Exosurf instillation, and subsequently at 12-24 hour intervals. Respiratory system compliance (Crs) and resistance (Rrs) were measured by means of the single breath occlusion method. After surfactant instillation there were no significant immediate changes in PaCO2 (36 vs. 37 mmHg), a/A ratio (0.23 vs. 0.20), Crs (0.32 vs. 0.31 mL/cm H2O/kg), and Rrs (0.11 vs. 0.16 cmH2O/mL/s) (pooled data of 18 measurement pairs). During the clinical course, mean a/A ratio improved significantly each time from 0.17 (time 0) to 0.29 (time 12-13 hours), to 0.39 (time 24-36 hours) and to 0.60 (time 48-61 hours), although mean airway pressure was reduced substantially. Mean Crs increased significantly from 0.28 mL/cmH2O/kg (time 0) to 0.38 (time 12-13 hours), to 0.37 (time 24-38 hours), and to 0.52 (time 48-61 hours), whereas mean Rrs increased from 0.10 cm H2O/mL/s (time 0) to 0.11 (time 12-13 hours), to 0.13 (time 24-36 hours) and to (time 48-61 hours) with no overall significance. A highly significant correlation was found between Crs and a/A ratio (r = 0.698, P less than 0.001). We conclude that Exosurf does not induce immediate changes in oxygenation as does the instillation of (modified) natural surfactant preparations. However, after 12 and 24 hours of treatment oxygenation and Crs improve significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual energy versus single energy MDCT: measurement of radiation dose using adult abdominal imaging protocols

RATIONALE AND OBJECTIVES: The aim of this study was to measure the radiation dose of dual-energy and single-energy multidetector computed tomographic (CT) imaging using adult liver, renal, and aortic imaging protocols. MATERIALS AND METHODS: Dual-energy CT (DECT) imaging was performed on a conventional 64-detector CT scanner using a software upgrade (Volume Dual Energy) at tube voltages of 140 and 80 kVp (with tube currents of 385 and 675 mA, respectively), with a 0.8-second gantry revolution time in axial mode. Parameters for single-energy CT (SECT) imaging were a tube voltage of 140 kVp, a tube current of 385 mA, a 0.5-second gantry revolution time, helical mode, and pitch of 1.375:1. The volume CT dose index (CTDI(vol)) value displayed on the console for each scan was recorded. Organ doses were measured using metal oxide semiconductor field-effect transistor technology. Effective dose was calculated as the sum of 20 organ doses multiplied by a weighting factor found in International Commission on Radiological Protection Publication 60. Radiation dose saving with virtual noncontrast imaging reconstruction was also determined. RESULTS: The CTDI(vol) values were 49.4 mGy for DECT imaging and 16.2 mGy for SECT imaging. Effective dose ranged from 22.5 to 36.4 mSv for DECT imaging and from 9.4 to 13.8 mSv for SECT imaging. Virtual noncontrast imaging reconstruction reduced the total effective dose of multiphase DECT imaging by 19% to 28%. CONCLUSION: Using the current Volume Dual Energy software, radiation doses with DECT imaging were higher than those with SECT imaging. Substantial radiation dose savings are possible with DECT imaging if virtual noncontrast imaging reconstruction replaces precontrast imaging.

Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury

OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory pressure (PEEP) ventilation. DESIGN: Prospective, randomized, laboratory animal study. SUBJECTS: Twenty-seven male New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits with hydrochloric acid-induced ALI were randomized (n = 9 per group) to 5.5 h NAVA (non-paralyzed), VC (paralyzed; Vt 6-ml/kg), or VC (paralyzed; Vt 15-ml/kg). PEEP was adjusted to hemodynamic goals in NAVA and VC6-ml/kg, and was 1 cmH2O in VC15-ml/kg. MEASUREMENTS AND MAIN RESULTS: PaO2/FiO2; lung wet-to-dry ratio; lung histology; interleukin-8 (IL-8) concentrations in broncho-alveolar-lavage (BAL) fluid, plasma, and non-pulmonary organs; plasminogen activator inhibitor type-1 and tissue factor in BAL fluid and plasma; non-pulmonary organ apoptosis rate; creatinine clearance; echocardiography. PEEP was similar in NAVA and VC6-ml/kg. During NAVA, Vt was lower (3.1 +/- 0.9 ml/kg), whereas PaO2/ FiO2, respiratory rate, and PaCO2 were higher compared to VC6-ml/kg (p<0.05 for all). Variables assessing ventilator-induced lung injury (VILI), IL-8 levels, non-pulmonary organ apoptosis rate, and kidney as well as cardiac performance were similar in NAVA compared to VC6-ml/kg. VILI and non-pulmonary organ dysfunction was attenuated in both groups compared to VC15-ml/kg. CONCLUSIONS: In anesthetized rabbits with early experimental ALI, NAVA is as effective as VC6-ml/kg in preventing VILI, in attenuating excessive systemic and remote organ inflammation, and in preserving cardiac and kidney function.

Preserving middle lobe to improve lung function in non-small-cell lung cancer

When a lung tumor arises in segment 6, the close anatomical relationship to the middle lobe bronchus may make a lower bilobectomy necessary. Sleeve lobectomy may be an alternative. These procedures were compared retrospectively in 36 patients operated on between January 2005 and December 2006 with non-small-cell lung cancer (stage I-IIIB) of the right lower lobe. Sleeve lobectomy was performed in 21 patients and bilobectomy in 15 (41%). Preoperative lung function was comparable in both groups. Radical resection was achieved in 34/36 patients. Operation time was 121 min for sleeve lobectomy and 144 min for bilobectomy. Chest tubes were removed after 5 days in both groups. Postoperative lung function was better after sleeve lobectomy than bilobectomy (forced expiratory volume in 1st sec: 78% vs. 69%). Preservation of the middle lobe by sleeve lobectomy is feasible. There was no evidence that this resection was less radical, and complication rates were similar in both groups.

Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy

The small trees of gas-exchanging pulmonary airways which are fed by the most distal purely conducting airways are called acini and represent the functional gas-exchanging units. The three-dimensional architecture of the acini has a strong influence on ventilation and particle deposition. Due to the difficulty to identify individual acini on microscopic lung sections the knowledge about the number of acini and their biological parameters like volume, surface area, and number of alveoli per acinus are limited. We developed a method to extract individual acini from lungs imaged by high-resolution synchrotron radiation based X-ray tomographic microscopy and estimated their volume, surface area and number of alveoli. Rat acini were isolated by semiautomatically closing the airways at the transition from conducting to gas-exchanging airways. We estimated a mean internal acinar volume of 1.148mm(3), a mean acinar surface area of 73.9mm(2), and a mean of 8470 alveoli per acinus. Assuming that the acini are similarly sized throughout different regions of the lung, we calculated that a rat lung contains 5470±833 acini. We conclude that our novel approach is well suited for the fast and reliable characterization of a large number of individual acini in healthy, diseased, or transgenic lungs of different species including humans.