Search

Oscillometric measurements of respiratory system resistance (Rrs) in infants are usually made via the nasal pathways, which not only significantly contribute to overall Rrs but also introduce marked flow (V')-dependent changes. We employed intrabreath oscillometry in casts of the upper airways constructed from head CT images of 46 infants. We examined oscillometric nasal resistance (Rn) in upper airway casts with no respiratory flow (R0) and the effect of varying V' on Rn by simulating tidal breathing. A characteristic nonlinear relationship was found between Rn and V', exhibiting segmental linearity and a prominent breakpoint (V'bp) after log-log transformation. V'bp was linearly related to the preceding value of end-expiratory volume acceleration (V″eE ; on average r2 = 0.96, P < 0.001). Rn depended on V', and R at end-expiration (R eE) showed a strong dependence on V″eE in every cast (r2 = 0.994, P < 001) with considerable interindividual variability. The intercept of the linear regression of ReE) versus V″eE was found to be a close estimate of R0. These findings were utilized in reanalyzed Rrs data acquired in vivo in a small group of infants (n = 15). Using a graphical method to estimate R0 from ReE), we found a relative contribution of V'-dependent nonlinearity to total resistance of up to 33%. In conclusion, we propose a method for correcting the acceleration-dependent nonlinearity error in ReE) . This correction can be adapted to estimate R0 from a single intrabreath oscillometric measurement, which would reduce the masking effects of the upper airways on the changes in the intrathoracic resistance. NEW & NOTEWORTHY Oscillometric measurements of respiratory system resistance (Rrs) in infants are usually made via the nasal pathways, which not only significantly contribute to overall Rrs but also introduce marked flow acceleration-dependent distortions. Here, we propose a method for correcting flow acceleration-dependent nonlinearity error based on in vitro measurements in 3D-printed upper airway casts of infants as well as in vivo measurements. This correction can be adapted to estimate Rrs from a single intrabreath oscillometric measurement. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and objective: Selecting ‘healthy’ preschool‐aged children for reference ranges may not be straightforward. Relaxing inclusion criteria for normative data does not affect spirometry z‐scores. We therefore investigated the effect of similarly relaxing inclusion criteria in preschoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT). Methods: The International Study of Asthma and Allergies in Childhood questionnaire classified 585 children into a healthy and five mutually exclusive groups. Zrs was measured between 4 and 26 Hz and resistance (R) and compliance (C) obtained by model fitting. Prediction models were determined using mixed effect models and z‐scores compared between healthy children and the five groups. Results: Zrs data were obtained for 494 participants (4.30 ± 0.7 years) on 587 occasions. Comparison of the Zrs z‐scores between the healthy children and the health groups found significant differences in children with asthma, current wheeze and respiratory symptoms, but not in children born preterm or with early‐life wheeze. Adding these two groups to the healthy dataset had no significant effect on the distribution of z‐scores and increased the size of the dataset by 22.3%. Conclusion: Our data suggest that preschool‐aged children born preterm or with early‐life wheeze can be included in FOT reference equations, while those with asthma, current wheeze and respiratory symptoms within 4 weeks of testing should be excluded. This more inclusive approach results in more robust FOT reference ranges. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Mannitol challenge testing is an established tool for clinical asthma diagnosis, and can be performed outside of specialized respiratory laboratories. Despite applicability in both clinical and non-clinical populations, with different pre-test asthma probabilities, differences in diagnostic properties have not been well explored. This study aimed to quantify the diagnostic utility of mannitol challenge testing for asthma in a community cohort and a symptomatic wheezing subset of this cohort. Methods During the 22-year follow-up of the Western Australian Pregnancy (Raine) Cohort, 772 participants (384 males) completed mannitol challenge and skin prick testing and respiratory health questionnaires, of whom 148 reporting wheeze in the past 12 months were included in a wheezing subset. Results Responsiveness to mannitol had low sensitivity (19%) and high specificity (97%) to identify current asthma in the complete cohort, with positive and negative predictive values ( PPV and NPV) of 45% and 92%, respectively. Within the wheezing subset, sensitivity (19%) and specificity (94%) remained similar, but PPV increased to 79%, and NPV decreased to 52%. Conclusion Our findings support previously reported high specificity and good PPV for mannitol challenge testing in symptomatic wheezing populations, and highlight the need for caution when interpreting mannitol test results in non-clinical populations. [ABSTRACT FROM AUTHOR]

Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field. [ABSTRACT FROM AUTHOR]

The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALT). Viral-induced ALT is poorly studied, and this study aimed to determine whether ALT induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 104.5 plaque-forming units of influenza AIMem/1/71 in 50 μl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, TL-6, TNF-α, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation. [ABSTRACT FROM AUTHOR]

Studies the volume dependence of airway and tissue impedances in mice. Use of model fitting to obtain parameters for airway and tissue mechanics; Pattern of changes in respiratory mechanics with increasing lung volume; Progressive fall in airway resistance; Increase in coefficients of tissue damping and elastance.

Abstract: In a variety of physico-chemical reactions, the actual process takes place in a reactive zone, called the “active surface”. We define the active surface of the lung as the set of airway segments that are closed but connected to the trachea through an open pathway, which is the interface between closed and open regions in a collapsed lung. To study the active surface and the time interval between consecutive openings, we measured the sound pressure of crackles, associated with the opening of collapsed airway segments in isolated dog lungs, inflating from the collapsed state in 120s. We analyzed the sequence of crackle amplitudes, inter-crackle intervals, and low frequency energy from acoustic data. The series of spike amplitudes spans two orders of magnitude and the inter-crackle intervals spans over five orders of magnitude. The distribution of spike amplitudes follows a power law for nearly two decades, while the distribution of time intervals between consecutive crackles shows two regimes of power law behavior, where the first region represents crackles coming from avalanches of openings whereas the second region is due to the time intervals between separate avalanches. Using the time interval between measured crackles, we estimated the time evolution of the active surface during lung inflation. In addition, we show that recruitment and instabilities along the pressure–volume curve are associated with airway opening and recruitment. We find a good agreement between the theory of the dynamics of lung inflation and the experimental data which combined with numerical results may prove useful in the clinical diagnosis of lung diseases. [Copyright &y& Elsevier]

Abstract: There is a growing interest in imaging techniques as non-invasive means of quantitatively measuring regional lung structure and function. Abnormalities in lung ventilation due to alterations in airway function such as those observed in asthma and COPD are highly heterogeneous, and experimental methods to study this heterogeneity are crucial for better understanding of disease mechanisms and drug targeting strategies. In severe obstructive diseases requiring mechanical ventilation, the optimal ventilatory strategy to achieve recruitment of poorly ventilated lung zones remains a matter of considerable debate. We have used synchrotron radiation computed tomography (SRCT) for the in vivo study of regional lung ventilation and airway function. This imaging technique allows direct quantification of stable Xenon (Xe) gas used as an inhaled contrast agent using K-edge subtraction imaging. Dynamics of Xe wash-in can be used to calculate quantitative maps of regional specific lung ventilation. More recently, the development of Spiral-CT has allowed the acquisition of 3D images of the pulmonary bronchial tree and airspaces. This technique gives access to quantitative measurements of regional lung volume, ventilation, and mechanical properties. Examples of application in an experimental model of allergic asthma and in imaging lung recruitment as a function of mechanical ventilation parameters will be presented. The future orientations of this tecnique will be discussed. [Copyright &y& Elsevier]