Introduction: The slope of phase III of the capnogram (S_III) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. S_III depends not only on the airway geometry, but also on the dynamic respiratory compliance (Crs); this latter effect has not been evaluated. Accordingly, we established the value of S_III for monitoring airway resistance during mechanical ventilation. Methods: Sidestream capnography was performed during mechanical ventilation in patients undergoing elective cardiac surgery (n = 144). The airway resistance (Raw), total respiratory resistance and Crs displayed by the ventilator, the partial pressure of arterial oxygen (PaO₂) and S_III were measured in time domain (S_T-III) and in a smaller cohort (n = 68) by volumetry (S_V-III) with and without normalization to the average CO₂ phase III concentration. Measurements were performed at positive end-expiratory pressure (PEEP) levels of 3, 6 and 9 cmH₂O in patients with healthy lungs (Group HL), and in patients with respiratory symptoms involving low (Group LC), medium (Group MC) or high Crs (Group HC). Results: S_T-III and S_V-III exhibited similar PEEP dependencies and distribution between the protocol groups formed on the basis of Crs. A wide interindividual scatter was observed in the overall Raw-S_T-III relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in S_III in Group HC, and in moderate decreases in S_III in Group MC, whereas S_T-III was insensitive to changes in airway caliber in Groups LC and HL. Conclusions: S_III assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although S_T-III may be of value for bedside monitoring of the airway properties, its sensitivity depends on Crs. Thus, assessment of the capnogram shape should always be coupled with Crs when the airway resistance or oxygenation are evaluated.

Capnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation–perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. Simultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (S_II,T) and III slopes (S_III,T). The volumetric method was applied to estimate phase II (S_II,V) and III slopes (S_III,V), together with the dead space values according to the Fowler (V_DF), Bohr (V_DB), and Enghoff (V_DE) methods and the volume of CO₂ eliminated per breath ($VCO2$). The partial pressure of end-tidal CO₂ ($PETCO2$) was registered. Excellent correlation and good agreement were observed in S_III,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R²=0.92, P<0.0001]. Although the sidestream technique significantly underestimated $VCO2$ and overestimated S_III,V [1.32 (0.28), R²=0.93, P<0.0001], V_DF, V_DB, and V_DE, the agreement between the mainstream and sidestream techniques in the difference between V_DE and V_DB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R²=0.92, P<0.0001]. The $PETCO2$ exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. Sidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation–perfusion mismatching, because it allows reliable assessments of the phase III slope, $PETCO2$ and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO₂ volumes) requires the application of a mainstream device.

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 (Z_rs) at 0, 3, and 6 cmH₂O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Z_rs into pulmonary (Z_L) and chest wall (Z_cw) components. A model containing a frequency-independent Newtonian resistance (R_N), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Z_rs, Z_L, and Z_cw spectra. The contribution of Z_cw to R_N was negligible in all species and PEEP levels studied. However, the participation of Z_cw 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.

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.

Background: To characterize the impact of lung volume changes in the lung function impairment after the surgical repair of congenital heart diseases, combined measurements of functional residual capacity, lung clearance index, and respiratory mechanics were performed in children with hypoperfused lungs (tetralogy of Fallot [TOF]) or with pulmonary hyperperfusion (ventricular septal defect [VSD]). Methods: Lung volume and clearance were assessed by using a sulfur hexafluoride washout technique, and the mechanical properties of the respiratory system were assessed using a low-frequency oscillation technique. Lung volume and oscillatory measurements were made preoperatively, before and after cardiopulmonary bypass and aortic clamping (AC), and after chest closure. Results: Impairments in airway (36 +/- 2%) and tissue mechanics (22 +/- 3%) were observed in the children with TOF after bypass; AC and chest closure were associated with marked decreases in functional residual capacity (-24 +/- 3% and -13 +/- 2% for TOF and VSD after AC, respectively) and increases in lung clearance index (-60 +/- 6% and -24 +/- 3% for TOF and VSD after AC, respectively). Smaller impairments in lung mechanics were observed after bypass and AC in children with VSD. Conclusions: These findings suggest that the lung volume loss and lung mechanical deteriorations are probably caused by a diminished tethering effect of the lung periphery through a reduced filling of the pulmonary capillaries. This effect seems to be more pronounced in children with hypoperfused lungs (TOF) than in those with pulmonary hyperperfusion (VSD). The beneficial postoperative changes in children with VSD are consequences of the reversal of the pulmonary vascular engorgement after surgical repair.

Diabetes mellitus increases smooth muscle tone and causes tissue remodeling, affecting elastin and collagen. Although the lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body shapes were divided into the control nondiabetic ( n = 73) and diabetic ( n = 31) groups. The other two groups included obese patients without diabetes ( n = 43) or with diabetes ( n = 30). The mechanical properties of the respiratory system were determined by forced oscillation technique. Airway resistance (Raw), tissue damping (G), and tissue elastance (H) were assessed by forced oscillation. Capnography was applied to determine phase 3 slopes and dead space indices. The intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO₂/FIO₂) were estimated from arterial and central venous blood samples. Compared with the corresponding control groups, diabetes alone increased the Raw (7.6 ± 6 cmH₂O.s/l vs. 3.1 ± 1.9 cmH₂O.s/l), G (11.7 ± 5.5 cmH₂O/l vs. 6.5 ± 2.8 cmH₂O/l), and H (31.5 ± 11.8 cmH₂O/l vs. 24.2 ± 7.2 cmH₂O/l ( P < 0.001 for all). Diabetes increased the capnographic phase 3 slope, whereas PaO₂/FIO₂ or Qs/Qt was not affected. Obesity alone caused similar detrimental changes in respiratory mechanics and alveolar heterogeneity, but these alterations also compromised gas exchange. We conclude that diabetes-induced intrinsic mechanical abnormalities are counterbalanced by hypoxic pulmonary vasoconstriction, which maintained intrapulmonary shunt fraction and oxygenation ability of the lungs.