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      Noninvasive assessment for acute allograft rejection in a rat lung transplantation model

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          Abstract

          After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung mechanics correlate with disease severity, especially with pathological rejection grade. In this study, we examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. To this end, we assessed lung resistance and elastance ( R L and E L) from implanted left lung of these animals. The perivascular/interstitial component of rejection severity grade (A‐grade) was also quantified from histological images using tissue fraction (TF; tissue + cell infiltration area/total area). We found that TF, R L, and E L increased according to A‐grade. There was a strong positive correlation between E L at the lowest frequency ( E low; E L at 0.5 Hz) and TF ( r 2 = 0.930). Furthermore, the absolute difference between maximum value of E L ( E max) and E low ( E het; E maxE low) showed the strong relationship with standard deviation of TF ( r 2 = 0.709), and A‐grade (Spearman's correlation coefficients; r s = 0.964, P < 0.0001). Our results suggest that the dynamic elastance as well as its frequency dependence have the ability to predict A‐grade. These indexes should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection.

          Abstract

          After lung transplantation, early detection of acute allograft rejection is important for both in timely treatment and prediction of chronic rejection which is a major cause of late death. We examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. Our results suggest that the dynamic elastance as well as its frequency dependence reflect the perivascular‐interstitial component of rejection severity grade (A‐grade), and this method should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection.

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          Most cited references 49

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          The forced oscillation technique in clinical practice: methodology, recommendations and future developments.

           ,  K Desager,  E Oostveen (2003)
          The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres. The present European Respiratory Society Task Force Report describes the basic principle of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations. FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be confirmed in future studies. Forced oscillation technique is a reliable method in the assessment of bronchial hyperresponsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed, forced oscillation technique does not modify the airway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimal requirement for the subject's cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and field studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.
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            Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation.

            Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT 50% (p = 0.001) and a lower FIO2 at the day of death (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed a higher weaning rate in NA (p = 0.014) but not a significantly improved survival (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.
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              The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report--2011.

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                Author and article information

                Journal
                Physiol Rep
                Physiol Rep
                physreports
                phy2
                Physiological Reports
                Wiley Periodicals, Inc.
                2051-817X
                December 2014
                18 December 2014
                : 2
                : 12
                Affiliations
                [1 ]Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
                [2 ]Department of Thoracic Surgery, Kobe City Medical Center General Hospital, Hyogo, Japan
                [3 ]Department of Surgery, Graduate school of Medicine, Kyoto University, Kyoto, Japan
                Author notes
                CorrespondenceHiroaki Sakai, Department of Thoracic Surgery, Graduate school of Medicine, Kyoto University, 54 Shogoin Kawahara‐cho, Sakyo‐ku, Kyoto‐shi, Kyoto 606‐8507, Japan. Tel: +81‐75‐751‐4975 Fax: +81‐75‐751‐4974 E‐mail: hsakai@ 123456kuhp.kyoto-u.ac.jp
                Article
                phy212244
                10.14814/phy2.12244
                4332222
                25524280
                © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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                Original Research

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