Several epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 μm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 μm and 2.5 μm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats. Rats were either exposed for 6 weeks to 100 μg/m3 (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed. No significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology. Our findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R² = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

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.

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K_ATP) in vascular smooth muscle. Because airway smooth muscle also expresses K_ATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone ( group L), levosimendan after pretreatment with a K_ATPchannel blocker (glibenclamide, group LG), glibenclamide only ( group G), or solvent alone (dextrose, group C). Airway resistance (R_aw), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in groups L and LG or glucose in groups G and C. Sham treatments in groups C and G had no effect on lung responsiveness. However, levosimendan treatment in group L elevated CO and inhibited the MCh-induced airway responses [R_awchanges of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 μg·kg⁻¹·min⁻¹MCh, P < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, P < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a K_ATP-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.

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 (S_II) and phase III slopes (S_III), their transition (D_2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. RESULTS: Before CPB, S_II and D_2min exhibited the closest (P = 0.006) associations with H (0.65 and −0.57; P < 0.0001, respectively), whereas S_III 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 S_II, S_III, and D_2min, 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 (S_II and D_2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on S_III dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.