An alternative approach to define reference values of whole-body plethysmography in infants, children and adults Richard Kraemer1, and Hans-Jürgen Smith2,

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An alternative approach to define reference values of whole-body plethysmography in infants, children and adults Richard Kraemer1, and Hans-Jürgen Smith2, 1Department of Clinical Research, University of Berne, CH-3010 Berne, Switzerland, and 2CarFusion LTD, Würzburg, Germany Rational and Aims Parameters of Airway Mechanics CONCLUSIONS Predicting equations defining reference values of lung function in infants, children and adults are usually based on algorithms using the subject’s anthropometric measures, such as age, body weight, body height or a combination of them, as independent variables. However, the seminal work of Weibel [1] and later several other authors demonstrated, that the bronchial tree is a fractal structure [2-5]. The airflow signal propagating over this type of structure may expect a rather complex behaviour. Aim. To determine this complexity recovered in parameters such as the effective specific airway resistance (sReff), its reciprocal parameter, the effective specific airway conductance (sGeff), and the specific resistive work of breathing (sWOB), we developed a model, which, independent from age and height also included potential co-determinants of the breathing pattern and the control of breathing As previously postponed by Hesser CM et al. [6], we can demonstrate that parameters of airway mechanics have to be predicted not only by anthropometric, but also by parameters defining the pattern and timing of breathing, as well as ventilation in relation to EELV. Discussion The major step in the assessment of parameters evaluating the entire “breathing loop”, and its mathematical comprehension of its entire “loop shaping” was certainly elaborated and introduced by Matthys and Orth, defining the so call effective specific airway resistance (sReff). The aim was to analyse the contribution of these disturbances given by a dissociation between the body-box shift volume and tidal flow observed in patients with, mainly expiratory, intra-bronchial ventilation disturbances. They extended the dimensional analysis applied by Jaeger and Otis to integrate these contributions to an "effective resistance" that included the effects of the entire range of variable flows during tidal breathing and nonlinearities in the breathing loop. During tidal breathing sReff is computed as ratio of the integrated shift volume–tidal volume loop, the specific flow resistive work of breathing (sWOB) and the integrated tidal flow - volume loop, which is now readily calculated by digital algorithms in modern computer-assisted plethysmo-graphs. The outstanding characteristic of sReff is its reflection of an integrative assessment of airway behaviour throughout the entire tidal breath. sGeff is obtained as reciprocal procedure. In our multi-level linear mixed model approach working on the interaction of 1)anthropometric data, 2)ventilation 4)ventilation in relation to EELV) and 4)timing of tidal breathing, we became aware, that most interrelations were high power functions. best fits were obtained by sWOB. It follows that sGeff and sReff, the latter especially presenting with high power functions, can much better be defined with sWOB as natural logarithm within the equation. Deduction. The present approach features the possibility to calculate normative values and z-scores customized to the subjects breathing. The integral method computing airway mechanics throughout the whole breathing cycle, presented on a print-screen of the MasterLab-BabyBody Results Methods The study collective consisted of 322 measurements-set obtained from a total of 292 control subjects (136 males, 46.6%; 156 females 53.4%) with an age distribution of 0.5-83.2 years. sWOB was evaluated first, and is part of the equations for sGeff and sReff.   sWOB males: Ln(sWOB)= -.0566+(.1559*Ln(Age))+(.5322*ln(VT))-(.4612*VT/FRC)+(1.0186*Ln(VT/TI))) ±.177 sWOB females: Ln(sWOB)= -.2135+(.1861*Ln(Age))+(.4984*ln(VT))-(.5748*VT/FRC) +(.8900*Ln(VT/TI))) ±.158 sGeff males: Ln(sGeff) = -.6550+(.1398*Ln(Age)-(.4723*Ln(sWOB)+(.3895*VT)+(.3855*VT/TI) ± .182 sGeff females: Ln(sGeff) = -.2376+(.0416*Ln(Age) -(.3484*Ln(sWOB)+(.4000*VT)+(.2291*VT/TI) ± .221 sReff males: Ln(sReff) = -.6550+(.1398*Ln(Age)+(.4723*Ln(sWOB)+(.3895*VT)+(.3855*VT/TI) ± .182 sReff females: Ln(sReff) = -.2376+(.0416*Ln(Age) +(.3484*Ln(sWOB)+(.4000*VT)+(.2291*VT/TI) ± .211 From five Swiss databases using a Jaeger plethysmograph (CareFusion, Würzburg, Germany) lung function data were exported and analysed by a multi-level linear mixed model utilizing SPSS version 24. The independent variables for prediction of sReff, sGeff and sWOB were age, weight and height (anthropometric data), BF, VT, MV (ventilation), VT/FRC (ventilation in relation to end-expiratory volume, EELV), and TI, TE, VT/TI and VT/TE ()timing of tidal breathing). References Weibel ER. Morphometry of the human lung. Academic Press, New York, 1963. Weibel ER, Gomez DM. Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 1962; 137: 577-585. West BJ, Bhargava V, Goldberger AL. Beyond the principle of similitude: renormalization in the bronchial tree. J Appl Physiol (1985) 1986; 60: 1089-1097. Thamrin C, Frey U. Complexity and respiratory growth: a developing story. Journal of applied physiology 2009; 106: 753-754. Glenny RW. Emergence of matched airway and vascular trees from fractal rules. J Appl Physiol (1985) 2011; 110: 1119-1129. Hesser CM, Lind F, and Linnarsson D. Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans. J Appl Physiol (1985) 68: 1875-1882, 1990.