Fractal analysis reveals functional unit of ventilation in the lung

Ventilation is inhomogeneous in the lungs across species. It has been hypothesized that ventilation inhomogeneity is largely determined by the design of the airway branching network. Because exchange of gases at the alveolar barrier is more efficient when gas concentrations are evenly distributed at subacinar length scales, it is assumed that a 'functional unit' of ventilation exists within the lung periphery, where gas concentration becomes uniform. On the other hand, because the morphology of pulmonary airways and alveoli, and the distribution of inhaled fluorescent particles show self-similar fractal properties over a wide range of length scales, it has been predicted that fractal dimension of ventilation approaches unity within an internally homogeneous functional unit of ventilation. However, the existence of such a functional unit has never been demonstrated experimentally due to lack of in situ gas concentration measurements of sufficient spatial resolution in the periphery of a complex bifurcating network. Here, using energy-subtractive synchrotron radiation tomography, we measured the distribution of an inert gas (Xe) in the in vivo rabbit lung during Xe wash-in breathing manoeuvres. The effects of convective flow rate, diffusion and cardiac motion were also assessed. Fractal analysis of resulting gas concentration and tissue density maps revealed that fractal dimension was always smaller for Xe than for tissue density, and that only for the gas, a length scale existed where fractal dimension approached unity. The length scale where this occurred was seen to correspond to that of a rabbit acinus, the terminal structure comprising only alveolated airways. Key points Gas ventilation is inhomogeneous in the lung of many species. However, it is not known down to what length scales this inhomogeneity persists. It is generally assumed that ventilation becomes homogeneous at subacinar length scales, beyond the spatial resolution of commonly available imaging techniques, hence this has not been demonstrated experimentally. Here we measured the distribution of inhaled Xe gas in the rabbit lung using synchrotron radiation energy-subtractive imaging and used fractal analysis to show that ventilation becomes internally uniform within regions about the size of rabbit lung acini.Peer reviewe

Change in capnogram waveform is associated with bronchodilator response and asthma control in children

International audienceBackgroundAirway hyper-reactivity, inflammation and remodeling contribute to inhomogeneity of ventilation-perfusion ratio VAQ in asthma. Short-term variations in V.AQ can cause changes in expired capnographic indices. ObjectivesTo measure acute changes in the phase 3 slope of the volumetric capnogram after beta 2-agonist inhalation (Delta SIII), for comparison with airway response based on FEV1 (Delta FEV1), and asthma control. Subjects and MethodsAfter ethical approval and informed consent, 72 children aged 6-18y, followed up for asthma underwent spirometry and capnography before and after beta-agonist inhalation through a spacer, using a side-stream rapid infrared analyzer. Asthma control was assessed using the GINA questionnaire. ResultsChildren with positive reversibility tests (defined as Delta FEV1>12%) had a significantly higher Delta SIII (mSE: 87.4 +/- 41.4) versus those with negative tests (31.3 +/- 14.0%, P=0.001). Uncontrolled asthma was associated with a significantly larger Delta SIII (103.4 +/- 64.0%, n=7) compared to partly controlled (52.0 +/- 26.1, n=24; P=0.009) and controlled asthma (30.8 +/- 16.3, n=41; P=0.003). Neither Bohr dead space nor Delta FEV1 were different between asthma control groups. Conclusions Delta SIII was significantly larger in children with positive response to beta 2-agonist, and in uncontrolled asthmatics. To our knowledge these are the first data on exhaled CO2 phase III volumetric slope change and asthma control. The observed Delta SIII could be due to an increased ventilation of inhomogeneous peripheral lung units, and merits further evaluation as a potential phenotypic biomarker in asthma

Change in phase 3 slope of exhaled CO2 in response to beta 2 agonist inhalation is associated with asthma control in children

European-Respiratory-Society (ERS) International Congress, Milan, ITALY, SEP 09-13, 2017International audienc

CT Density Distribution Analysis in Patients with Cystic Fibrosis: Correlation with Pulmonary Function and Radiologic Scores

International audienceRationale and Objectives: The progressive changes in lung morphology observed in cystic fibrosis (CF) can potentially affect the statistical distribution of computed tomography (CT) density values. This study aimed to characterize the lung CT density distributions by quantifying indices of the kurtosis and skewness of the lung density distribution and to compare these indices to radiologic scores and lung function parameters in children and young adults with CF. Materials and Methods: CT scans and lung function of 26 patients with CF were retrospectively examined. The Bhalla radiologic scoring was performed separately, in random order, by two expert radiologists, blinded to the patient's identity, age, clinical status, results of lung function tests, and the other paired observer's score. Results: Positive relations were evidenced between the log indices of lung density distribution kurtosis (iKurtosis) and the overall radiologic scores (RS) of both observers (R = 0.58; P<.001 vs RS1 and R = 0.71; P<.001 vs RS2). A similar relationship was evidenced with the log index of the degree of distribution asymmetry (iSkewness; R = 0.62; P<.001 vs RS1 and R = 0.62; P <.001 vs RS2). Log-iKurtosis and log-iSkewness were related to FEV1 (R = -0.56; P <10(-5) and R = -0.55;P<10(-5)) and to residual volume (R = 0.40; P<.001 and R = 0.45; P<.001, respectively). Both radiologic scores showed significant relation with lung function. The correlation between RS1 and RS2 was excellent (R = 0.93), with a Cohen weighted kappa of 0.43. Conclusions: Characteristic indices of lung CT density distribution are correlated to lung function and radiologic scores in patients with CF and merit further evaluation as part of more comprehensive automated methods for quantifying CF lung CT data

Polyethylene bag wrapping to prevent hypothermia during percutaneous central venous catheter insertion in the preterm newborn under 32 weeks of gestation

International audienceAim: In preterm neonates, during nursing procedures, body temperature decreases. This study evaluates the interest of polyethylene bag wrapping to prevent this decrease during percutaneous central venous catheter (PCVC) insertion procedure, in preterm neonates under 32 weeks of gestation nursed in closed incubators. Methods: This prospective observational study compared two periods: [May 2009-September 2009]: ``without polyethylene bag wrapping'' and [October 2009-March 2010]: ``with polyethylene bag wrapping''. The main criterion was newborn skin temperature at the end of the procedure. Results: There was no difference between the two groups for skin temperature before the procedure (36.9 +/- 0.3 degrees C versus 36.9 +/- 0.3 degrees C; p = NS). The skin temperature at the end of the procedure was lower in the ``without bag wrapping'' group (36.0 +/- 0.5 degrees C) compared to the ``bag wrapping'' group (36.4 degrees C +/- 0.5 degrees C; p = 0.01). Furthermore, no skin temperature at the end was higher than 37.4 degrees C in the bag wrapping group. Conclusion: The use of a polyethylene bag was effective in decreasing skin temperature fall during a PCVC insertion procedure in our population. No side effects were observed. The benefit of prolonged wrapping or for shorter procedure should be evaluated

Fractal dimension of pulmonary gas and blood distribution assessed by synchrotron K-edge subtraction imaging: effect of bronchoconstriction

We analyzed the fractal dimension (Df) of lung gas and blood distribution imaged with synchrotron radiation K-edge subtraction (KES), in six anesthetized adult New Zealand White rabbits. KES imaging was performed in upright position during stable Xe gas (64% in O2) inhalation and iodine infusion (Iomeron, 350 mg/mL), respectively, at baseline and after induced bronchoconstriction by aerosolized methacholine (125 mg/mL, 90 s) and bronchodilator (salbutamol, 10 mg/mL, 90 s) inhalation, at two axial image levels. Lung Xe and iodine images were segmented, and maps of regional lung gas and blood fractions were computed. The Df of lung gas (DfXe) and blood (DfIodine) distribution was computed based on a log-log plot of variation coefficient as a function of region volume. DfXe decreased significantly during bronchoconstriction (P < 0.0001), and remained low after salbutamol. DfIodine depended on the axial image level (P < 0.0001), but did not change with bronchoconstriction. DfXe was significantly associated with arterial PaO2 (R = 0.67, P = 0.002), and negatively associated with PaCO2 (R = -0.62, P = 0.006), respiratory resistance (R = -0.58, P = 0.011), and elastance (R = -0.55, P = 0.023). These data demonstrate the reduced Df of gas distribution during acute bronchoconstriction, and the association of this parameter with physiologically meaningful variables. This finding suggests a decreased complexity and space -filling properties of lung ventilation during bronchoconstriction, and could serve as a functional imaging biomarker in obstructive airway diseases.NEW & NOTEWORTHY Here, we used an energy-subtractive imaging technique to assess the fractal dimension (Df) of lung gas and blood distribution and the effect of acute bronchoconstriction. We found that Df of gas significantly decreases in broncho-constriction. Conversely, Df of blood exhibits gravity-dependent changes only, and is not affected by acute bronchoconstriction. Our data show that the fractal dimension of lung gas detects the emergence of clustered rather than scattered loss of ventilatory units during bronchoconstriction

Failing to meet relative humidity targets for incubated neonates causes higher heat loss and metabolic costs in the first week of life

International audienceAim: Frequent nursing procedures can modify a newborn infant's thermal environment when their incubator is opened. This study evaluated the impact of relative humidity (RH) on preterm infants in closed incubators and calculated their heat loss and additional metabolic cost. Methods: We studied 45 preterm infants born before 32 + 0 weeks, nursed at the neonatal intensive care unit at Amiens University Hospital, France from January 2009 to November 2011. Their body, skin and air temperatures and the incubator's RH were continuously recorded from day 1 to 8 of life, and the differences between the measured and target RH were calculated. Body heat loss (BHL) was also calculated. Results: On day one, the measured RH (68.7 +/- 1.0%) was significantly lower than the target RH (75%, p < 0.05), but this difference, together with BHL (p < 0.001) and evaporative heat loss (p < 0.001), fell significantly over time (p < 0.05). The additional metabolic cost correlated with the difference between measured and target RH (p < 0.001). Conclusion: RH from day 1 to 8 was below the recommended target value for preterm infants and resulted in high evaporative and greater total BHL and additional metabolic cost. The findings pose numerous challenges, including nursing care and incubator design

Regional distribution of lung inflammation in a multiple-hit model of ARDS assessed by micro-PET-CT imaging in juvenile rabbits

European-Respiratory-Society (ERS) International Congress, Madrid, SPAIN, SEP 28-OCT 02, 2019International audienc

Physiologically variable ventilation reduces regional lung inflammation in a pediatric model of acute respiratory distress syndrome

Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS)

Regional dynamic lung strain and specific elastance imaged by synchrotron computed tomography

International audienc