Individual benefit in heart sparing during DIBH-supported left breast radiotherapy.

Introduction: Deep-inspirational breath hold (DIBH) is an option for heart protection in breast radiotherapy; we intended to study its individual benefit. Materials and Methods: 3DCRT treatment planning was performed in a cohort of 103 patients receiving radiotherapy of the whole breast (WBI)/chest wall (CWI) ± nodal regions (NI) both under DIBH and free breathing (FB) in the supine position, and in the WBI only cases prone (n = 45) position, too. A series of patient-related and heart dosimetry parameters were analyzed. Results: The DIBH technique provided dramatic reduction of all heart dosimetry parameters the individual benefit, however, varied. In the whole population the best predictor of benefit was the ratio of ipsilateral lung volume (ILV)FB and ILVDIBH. In the WBI cohort 9-11 patients and 5-8 patients received less dose to selected heart structures with the DIBH and prone positioning, respectively; based on meeting various dose constraints DIBH was the only solution in 6-13 cases, and prone positioning in 5-6 cases. In addition to other excellent predictors, a small ILVFB or ILVDIBH with outstanding predicting performance (AUC ≥ 0.90) suggested prone positioning. Detailed analysis consistently indicated the outstanding performance of ILVFB and ILVDIBH in predicting the benefit of one over the other technique in lowering the mean heart dose (MHD), left anterior descending coronary artery (LAD) mean dose and left ventricle(LV)-V5Gy. The preference of prone positioning was further confirmed by anatomical parameters measured on a single CT scan at the middle of the heart. Performing spirometry in a cohort of 12 patients, vital capacity showed the strongest correlation with ILVFB and ILVDIBH hence this test could be evaluated as a clinical tool for patient selection. Discussion: Individual lung volume measures estimated by spirometry and anatomical data examined prior to acquiring planning CT may support the preference of DIBH or prone radiotherapy for optimal heart protection.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Comparison of the respiratory effects of commonly utilized general anaesthesia regimes in male Sprague-Dawley rats.

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared. Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6 cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness. Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p < 0.001), no between-group differences were observed (p > 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups. Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar-capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Lung and chest wall mechanical properties in metformin-treated and untreated models of type 2 diabetes.

The adverse respiratory consequences of type 2 diabetes mellitus (T2DM) may reflect compromised lung function and/or alterations of the chest wall because of skeletal muscle stiffening. We assessed the separate contributions of these compartments to respiratory complications in diabetes and explored the effects of metformin on respiratory abnormalities. Experiments were performed in untreated rats (control, n = 7), high-fat diet-fed rats receiving streptozotocin (T2DM, n = 7), and metformin-treated diabetic rats (MET, n = 6). Newtonian resistance, tissue damping, and elastance were separately assessed for lung and chest wall components by measuring the esophageal pressure during forced oscillations at low (0 cmH2O), medium (3 cmH2O), and high positive end-expiratory pressure (PEEP) (6 cmH2O). Tissue hysteresivity was calculated as damping/elastance. Blood gas parameters were used to assess gas exchange, and lung histology was performed to characterize collagen expression. T2DM at low PEEP compromised airway and lung tissue mechanics in association with gas-exchange defects and collagen overexpression. Abnormal chest wall mechanics in T2DM was indicated only by decreased tissue hysteresivity. No difference in lung or chest wall mechanics, gas exchange, or lung histology was observed between the MET and control groups. These findings suggest the primary involvement of the pulmonary system in the respiratory consequences of T2DM, with chest wall properties only disturbed by a shift toward the dominance of elastic forces at low PEEP. The adequacy of metformin to treat the adverse respiratory consequences of diabetes was also revealed, in addition to its well-established beneficial effects on other organs.NEW & NOTEWORTHY The present study examined the contributions of the lungs and chest wall to respiratory complications in a rat model of diabetes and clarified the effects of metformin on these changes. At low positive end-expiratory pressure, type 2 diabetes was linked to dysfunctional airway and lung tissue mechanics in relation with gas-exchange defects and collagen overexpression, whereas decreased tissue hysteresivity was manifested in the chest wall abnormalities. Metformin treated all adverse respiratory consequences of diabetes.

Respiratory consequences of obesity and diabetes / Az elhízás és a cukorbetegség légzorendszeri következményei

Összefoglaló. Bevezetés: A cukorbetegségben no a simaizmok tónusa, és megváltozik az elasztin és a kollagén szerkezete. Mivel a tüdoszövetben ezek a strukturális elemek meghatározóak, a cukorbetegség várhatóan módosítja a légutak és a tüdoszövet mechanikai és funkcionális viselkedését. Célkituzés: Vizsgálatunk során diabetesben szenvedo, elhízott és nem elhízott betegeink körében tanulmányoztuk a légzésmechanikai elváltozásokat és a gázcserefunkciót. Módszer: Elektív szívsebészeti beavatkozásra kerülo, normál testalkatú betegeket diabetesben nem szenvedo (n = 80), illetve cukorbeteg (n = 35) csoportokra osztottuk. További két betegcsoportba elhízott és nem cukorbeteg (n = 47), valamint elhízott és diabetesben szenvedo (n = 33) betegek kerültek. A légzorendszer mechanikai tulajdonságait kényszerített oszcillációs technikával határoztuk meg, mellyel a légúti ellenállás (Raw), valamint a szöveti csillapítás (G) és rugalmasság (H) tényezoi jellemezhetok. Volumetriás kapnográfia segítségével a kapnogram 3. fázisának meredekségét és a légzési térfogat különbözo ventilációs/perfúziós illeszkedési zavaraiból adódó holttérfrakciókat határoztuk meg. Az intrapulmonalis shuntfrakciót és az oxigenizációs indexet (PaO2/FiO2) artériás és centrális vénás vérgázmintákból határoztuk meg. Eredmények: A megfelelo kontrollcsoportokhoz hasonlítva a cukorbetegség önmagában is növelte az Raw (7,4 ± 5 vs. 3,0 ± 1,7 H2Ocm.s/l), a G (11,3 ± 4,9 vs. 6,2 ± 2,4 H2Ocm/l) és a H (32,3 ± 12,0 vs. 25,1± 6,9 H2Ocm/l) értékét (p<0,001 mindegyik betegcsoportnál), de ez nem járt együtt a gázcserefunckció romlásával. Hasonló patológiás elváltozásokat észleltünk elhízás során a légzésmechanikában és az alveolaris heterogenitásban, amelyek azonban a gázcsere hatékonyságát is rontották. Következtetés: Cukorbetegségben a légzésmechanika romlását a fokozott hypoxiás pulmonalis vasoconstrictio ellensúlyozni képes, ezzel kivédve az intrapulmonalis shunt növekedését és az oxigenizációs képesség romlását. Orv Hetil. 2022; 163(2): 63-73. INTRODUCTION: While sustained hyperglicemia affects the smooth muscle tone and the elastin-collagen network, the effect of diabetes mellitus on the function and structure of the airways and the lung parenchyma has not been characterized, and the confounding influence of obesity has not been elucidated. OBJECTIVE: To reveal the separate and additive roles of diabetes mellitus and obesity on the respiratory function. METHOD: Non-obese mechanically ventilated patients were categorized as control non-diabetic (n = 80) and diabetic (n = 35) groups. Obese patients with (n = 33) or without (n = 47) associated diabetes were also enrolled. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and tissue elastance (H). Capnography was utilized to determine phase 3 slopes and ventilation dead space parameters. Arterial and central venous blood samples were analyzed to assess intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FiO2). RESULTS: Diabetes without obesity increased the Raw (7.4 ± 5 cmH2O.s/l vs. 3.0 ± 1.7 cmH2O.s/l), G (11.3 ± 4.9 cmH2O/l vs. 6.2 ± 2.4 cmH2O/l), and H (32.3 ± 12.0 cmH2O/l vs. 25.1 ± 6.9 cmH2O/l, (p<0.001 for all), compared with the corresponding control groups. Capnographic phase 3 slope was increased in diabetes without significant changes in PaO2/FiO2 or Qs/Qt. While similar detrimental changes in respiratory mechanics and alveolar heterogeneity were observed in obese patients without diabetes, these alterations also compromised gas exchange. CONCLUSION: The intrinsic mechanical abnormalities in the airways and lung tissue induced by diabetes are counterbalanced by hypoxic pulmonary vasoconstriction, thereby maintaining intrapulmonary shunt fraction and oxygenation ability of the lungs. Orv Hetil. 2022; 163(2): 63-73.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange.

OBJECTIVE: To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. DESIGN: A prospective, nonrandomized clinical investigation. SETTING: A university hospital. PARTICIPANTS: One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. INTERVENTIONS: Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. MEASUREMENTS AND MAIN RESULTS: Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. CONCLUSION: Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Lung volume dependence of respiratory function in rodent models of diabetes mellitus.

BACKGROUND: Diabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters. METHODS: Rats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology. RESULTS: The rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained. CONCLUSIONS: These findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.

Different contributions from lungs and chest wall to respiratory mechanics in mice, rats, and rabbits.

Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

Volumetric but Not Time Capnography Detects Ventilation/Perfusion Mismatch in Injured Rabbit Lung.

Whereas time capnography (Tcap) is routinely displayed during mechanical ventilation, the volumetric representation (Vcap) is seldom used. We compared the diagnostic value of indices derived from Tcap and Vcap following ventilation to perfusion ratio () mismatch subsequent to experimentally induced acute respiratory distress syndrome (ARDS), and alveolar recruitment by elevating the positive end-expiratory pressure (PEEP). Lung injury was induced by iv lipopolysaccharide, whole lung lavage and injurious ventilation in anesthetized, mechanically ventilated rabbits (n = 26). Mainstream Tcap and Vcap were performed to assess normalized phase 2 (Sn2T, Sn2V) and phase 3 slopes (Sn3T, Sn3V) in the time and volumetric domains. Vcap was also used to estimate Enghoff's physiological dead space (VDE). Lung oxygenation index (PaO2/FiO2) and intrapulmonary shunt (Qs/Qt) were derived from arterial and central venous blood gas samples. All measurements were made under baseline conditions, and, following lung injury, under moderate (6 cmH2O) and high PEEP levels (9 cmH2O). Lung injury deteriorated the PaO2/FiO2 (baseline vs. injured 466 ± 10.2 [95% confidence interval] vs. 77.3 ± 17.1 mmHg, p < 0.05) and compromised all mechanical parameters significantly, whereas Tcap parameters exhibited contradictory or inconsistent changes. Conversely, Vcap indices exhibited consistent changes and provided excellent diagnostic value in detecting lung-function deterioration subsequent to lung injury [area under the receiver operating characteristic (ROC) curve of 1.0 ± 0.0, 0.87 ± 0.22 and 0.86 ± 0.22 for VDE, Sn3V and Sn3V/Sn2V, respectively]. Elevated PEEP increased PaO2/FiO2 and decreased Qs/Qt, which was reflected only in the Vcap slope ratio (Sn3V/Sn2V, p < 0.05). Our findings demonstrate the limited value of Tcap to detect ventilation to perfusion ratio () mismatch, following severe lung injury. Conversely, indices derived from Vcap proved to be sensitive for detecting lung volume loss and alveolar recruitment. Therefore, promotion of Vcap is of paramount importance as a real-time, non-invasive, bedside monitoring modality to detect the development of and to follow-up the progression of lung injury in a model of ARDS.

Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics.

BACKGROUND: Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB). METHODS: Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. RESULTS: Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and -0.57; P < 0.0001, respectively), whereas SIII correlated most strongly (P < 0.0001) with Raw (r = 0.63; P < 0.0001). CPB induced significant elevations in Raw and G and H (P < 0.0001). These adverse mechanical changes were reflected consistently in SII, SIII, and D2min, with weaker correlations with the dead-space indices (P < 0.0001). The intrapulmonary shunt expressed as the difference between the Enghoff and Bohr dead-space parameters was increased after CPB (95% ± 5% [SEM] vs 143% ± 6%; P < 0.001). CONCLUSIONS: In mechanically ventilated patients, the capnographic parameters from the early phase of expiration (SII and D2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.

Estimating the diameter of airways susceptible for collapse using crackle sound.

Airways that collapse during deflation generate a crackle sound when they reopen during subsequent reinflation. Since each crackle is associated with the reopening of a collapsed airway, the likelihood of an airway to be a crackle source is identical to its vulnerability to collapse. To investigate this vulnerability of airways to collapse, crackles were recorded during the first inflation of six excised rabbit lungs from the collapsed state, and subsequent reinflations from 5, 2, 1, and 0 cmH(2)O end-expiratory pressure levels. We derived a relationship between the amplitude of a crackle sound at the trachea and the generation number (n) of the source airway where the crackle was generated. Using an asymmetrical tree model of the rabbit airways with elastic walls, airway vulnerability to collapse was also determined in terms of airway diameter D. During the reinflation from end-expiratory pressure = 0 cmH(2)O, the most vulnerable airways were estimated to be centered at n = 12 with a peak. Vulnerability in terms of D ranged between 0.1 and 1.3 mm, with a peak at 0.3 mm. During the inflation from the collapsed state, however, vulnerability was much less localized to a particular n or D, with maximum values of n = 8 and D = 0.75 mm. Numerical simulations using a tree model that incorporates airway opening and closing support these conclusions. Thus our results indicate that there are airways of a given range of diameters that can become unstable during deflation and vulnerable to collapse and subsequent injury.