Lung mechanics in the aging lung and in acute lung injury. Studies based on sinusoidal flow modulation.

Abstract

Knowledge about lung mechanics is of interest in intensive care to adjust mechanical ventilation and in the lung laboratory for diagnostics and evaluation of patients with various kinds of respiratory diseases.



In mechanical ventilation a single inspiratory elastic pressure-volume (Pel/V) curve is difficult to interpret due to continuing re-expansion of collapsed lung units over a large pressure interval. However, the volume shifts between multiple inspiratory Pel/V curves recorded at different levels of positive end-expiratory pressure (PEEP) give information about lung collapse and re-expansion. Methods based on flow interruption for measurement of Pel/V curves have limitations due to continuing gas exchange, the need for disconnection from the ventilator or the fact that they are time consuming. Recordings during constant or sinusoidal flow can be obtained using a computer-controlled ventilator. Sinusoidal flow modulation provides the possibility to separate the elastic and resistive pressure components of measured pressure, thereby providing more accurate inspiratory Pel/V curves and simultaneous data of resistance (R) in short time. The sinusoidal flow modulation method was further developed to allow recording and analysis of both inspiratory and expiratory limbs of Pel/V loops and to allow automatic recording of Pel/V loops from multiple PEEP levels. Pel/V loops obtained by the sinusoidal flow modulation method and by the flow-interruption method were compared in healthy pigs and in pigs with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Viscoelastic phenomena caused differences in Pel/V loops and influenced hysteresis. Lung collapse and re-expansion at decreasing PEEP levels could, however, be estimated by hysteresis of the Pel/V loops recorded from zero end-expiratory pressure as well as by the volume shifts between multiple inspiratory Pel/V curves recorded at different levels of PEEP. In ALI/ARDS pigs, expiratory R increased during expiration warranting determination of its volume dependence to obtain as accurate dynamic expiratory Pel/V curves as possible.



In the lung laboratory lung parenchyma properties and intrinsic bronchial properties are uniquely reflected in the Pel/V and elastic pressure-resistance (Pel/R) diagrams, respectively, measured at regulated flow rate. The flow-regulation method, previously based on square wave flow modulation (V'square method), was further developed applying sinusoidal flow rate adapted to body size (V'sine method) and iterative parameter estimation for mathematical characterization of Pel/V, Pel/C and Pel/R curves. The quality of results obtained with the V'sine method was equal to that of the more time consuming V'square method. In healthy subjects no effect of heart artefact correction was found. For the V'sine method representative reference values, based on 60 healthy 20 65 year old never-smokers, are presented for Pel/V, Pel/C and Pel/R curves. After normalization to lung size women and men had similar lung mechanics. By relating the Pel/V, Pel/C and Pel/R curves to age and lung size normal ranges were importantly narrowed. Elastic recoil pressure (Pel) decreased with age to an extent in agreement with the higher rates observed in previous studies. The width of the normal range for the Pel/V curve increased with age indicating individual rate of aging as in the skin. At Pel 5 cmH2O, roughly corresponding to functional residual capacity, compliance (C) increased with age as previously observed. At Pel values ? 10 cmH2O C decreased with age. The findings may suggest that the lower part of the Pel/V curve in old subjects is influenced by collapsing alveoli, while in younger subjects airway closure dominates. Expiratory R in relation to Pel decreased with age. When C and R were related to volume rather than to Pel no age dependence was observed. Accordingly, dimension of the lung rather than the distending pressure Pel seems to be a determinant of C and R.

Abstract (Swedish)

Popular Abstract in Swedish

Avhandlingen har fokus på lungornas mekaniska egenskaper hos friska och vid akut lungskada och på metodutveckling för studier av lungmekanik. Kunskap om lungmekanik är av intresse inom intensivvården för att skräddarsy respirator-behandling och i lunglaboratoriet för diagnostik och utvärdering av patienter med olika typer av lungsjukdom.



Vid respiratorbehandling kan föreliggande lungskada förvärras om lungdelar under varje andetag kollaberar och re-expanderas. En kurva som avspeglar lungans elastiska återfjädringstryck mot lungvolym kallas Pel/V-kurva. Jämfört med en enstaka inspiratorisk Pel/V-kurva ger multipla Pel/V-kurvor registrerade från olika trycknivåer säkrare information om sådan kollaps och re-expansion.



I delarbete 1 visades hos friska grisar att dynamiska Pel/V-kurvor registrerade under flöde ger väsentligen samma information som mer tidskrävande registrering av statiska kurvor, som mäts efter avbrott i flödet.



I delarbete 2 automatiserades metoden för registrering av multipla dynamiska Pel/V-kurvor. Hos grisar med akut lungskada visades att sådana kurvor, liksom studier av Pel/V-kurvors skillnad mellan in- och utanding (hysteres), ger god upplysning om lungornas kollapsbenägenhet.



I delarbete 3 presenteras en vidareutveckling och validering av flödesregulator-metoden använd inom klinisk fysiologisk diagnostik. Principer som hämtades från delarbete 1 och 2, omfattar sinusoidal flödesmodulering med matematisk analys och matematisk karakterisering av kurvor som beskriver lungvolym, tänjbarhet och flödesmotstånd i förhållande till lungans elastiska återfjädringstryck. Med den nya metoden erhålles motsvarande information med bibehållen kvalitet från betydligt färre andningsmanövrer jämfört med den tidigare använda flödes-regulatormetoden baserad på ?fyrkant-modulering? av flödet. Den matematiska karakteriseringen av nämnda kurvor underlättar datalagring och forskning.



I delarbete 4 tillämpas ovanstående metod för studier av friska män och kvinnor, 20-65 år gamla. Mera detaljerat än i tidigare studier visas hur normalt åldrande påverkar lungornas mekaniska egenskaper. Studien ger också normalvärden för personer av given ålder och kroppsstorlek att använda i klinisk diagnostik.

• author: Bitzén, Ulrika
• supervisor: Björn Jonson
• opponent: Professor Hedenstierna, Göran, Uppsala Universitet
• organization: Clinical Physiology (Lund)
• publishing date: 2006
• type: Thesis
• publication status: published
• subject: Cardiac and Cardiovascular Systems; Respiratory Medicine and Allergy
• keywords: Diagnostics, Diagnostik, acute lung injury, lung mechanics, acute respiratory distress syndrome, intensivvård, Anestesiologi, intensive care, Anaesthesiology, Andningsorganen, Respiratory system, Fysiologi, Physiology, flow regulation, method, lung resistance, compliance, aging
• defense location: Föreläsningssal 1, Centralblocket, Universitetssjukhuset i Lund
• defense date: 2006-06-14 13:00:00
• ISBN: 91-85559-07-5
• language: English
• LU publication?: yes
• additional info: Ulrika Bitzén, Björn Drefeldt, Lisbet Niklason and Björn Jonson. 2004. Dynamic elastic pressure-volume loops in healthy pigs recorded with inspiratory and expiratory sinusoidal flow modulation. Relationship to static pressure-volume loops. Intensive Care Med, vol 30 pp 481-488.; Ulrika Bitzén, Jens Enoksson, Leif Uttman, Lisbet Niklason, Leif Johansson and Björn Jonson. 2006. Multiple pressure-volume loops recorded with sinusoidal low flow in a porcine acute respiratory distress syndrome model Clin Physiol Funct Imaging, vol 26 pp 113-119.; Ulrika Bitzén, Lisbet Niklason, Björn Drefeldt, Ingegerd Göransson and Björn Jonson. . Sinsuodial flow modulation for studies of bronchial and lung parenchyma mechanics (manuscript); Ulrika Bitzén, Ingegerd Göransson, Lisbet Niklason and Björn Jonson. . Age dependence of elastic and resistive properties of the lung in a reference population (manuscript)
• id: f7f41487-7387-49e9-ba0b-dc79cae119bd (old id 546898)
• date added to LUP: 2016-04-01 16:24:51
• date last changed: 2018-11-21 20:41:13