How important is the separate contribution of airway (Raw) and lung tissue (RT) resistance to energy dissipation during physiological breathing? Recent animal studies invoking the alveolar capsule technique have indicated that RT amount to about 80% of the total lung resistance (RL) when ventilated around 0.3 HZ. With a constrictive agonist, there is often a greater percent increase in RT than in Raw. These findings appear in striking contrast to the earlier views regarding parenchymal mechanics, i.e., they imply that rather than bronchoconstriction the correct term is""""""""pulmonary constriction"""""""". It seems intuitive, then, that during breathing, tissue resistance should be important in man as well. If so, specific treatment modalities (eg., systemic versus topical (airway) steroid treatment for the asthmatic inflammatory condition) should be re- evaluated. Previous measurements in human asthmatics have been possible primarily at 1.0-1.5 HZ and have reported that RT was 6+35% of RL. However, between the spontaneous breathing frequency (-0.15 HZ) and 2 HZ the RT decreases while Raw remains fairly constant. Consequently, it is highly likely that in asthmatic RT is much higher during normal breathing. This proposal will test the following hypothesis: The tissue is a more dominant constricted lungs. In man one cannot use alveolar capsules. We have developed a new approach called an optimal ventilator waveform (OVW) for measuring RL and lung elastance (EL). The OVW contains energy at several frequencies and by novel design maintains ventilation while eliminating nonlinear distortion on the RL and EL from 0.1-5 HZ. Our preliminary data show that with the OVW in healthy or severely constricted lungs we can partition the airway and tissue properties associated with physiological tidal breathing in-situ, i.e., without requiring alveolar capsules. We will first apply the OVW in dogs to separate airway and tissue properties in-situ and in open chest conditions then in-situ during administration of a constrictive agonist. Also the separation will be performed at two PEEP levels. Then airway and tissue properties will be measured in healthy and asthmatic humans before and after a bronchodilator and also at increased lung volumes. These data will allow us to distinguish changes in airway and tissue properties associated with hyperinflation from those associated with agonist induced constriction (in dogs) or human asthma. By use of resident gases with different viscosities and densities we will identify if airway inhomogeneities or turbulence bias the airway-tissue separations and, if so, we propose techniques to remove this bias. The conclusions from this proposal may significantly modify the current view of asthma as exclusively an airways disease. Eventually, our approach can lead to the identification of the primary site of inflammation associated with the so-called late-phase asthmatics who do not respond well to topically administered steroids.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050515-03
Application #
2028940
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1995-01-05
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1998-12-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Boston University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Kaczka, David W; Lutchen, Kenneth R (2004) Servo-controlled pneumatic pressure oscillator for respiratory impedance measurements and high-frequency ventilation. Ann Biomed Eng 32:596-608
Gillis, H L; Lutchen, K R (1999) How heterogeneous bronchoconstriction affects ventilation distribution in human lungs: a morphometric model. Ann Biomed Eng 27:14-22
Lutchen, K R; Sullivan, A; Arbogast, F T et al. (1998) Use of transfer impedance measurements for clinical assessment of lung mechanics. Am J Respir Crit Care Med 157:435-46
Kaczka, D W; Ingenito, E P; Suki, B et al. (1997) Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction. J Appl Physiol 82:1531-41
Suki, B; Petak, F; Adamicza, A et al. (1997) Airway and tissue constrictions are greater in closed than in open-chest conditions. Respir Physiol 108:129-41
Lutchen, K R; Gillis, H (1997) Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance. J Appl Physiol 83:1192-201
Suki, B; Yuan, H; Zhang, Q et al. (1997) Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening. J Appl Physiol 82:1349-59
Lutchen, K R; Greenstein, J L; Suki, B (1996) How inhomogeneities and airway walls affect frequency dependence and separation of airway and tissue properties. J Appl Physiol 80:1696-707
Lutchen, K R; Hantos, Z; Petak, F et al. (1996) Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction. J Appl Physiol 80:1841-9
Christini, D J; Kulkarni, A; Rao, S et al. (1995) Influence of autoregressive model parameter uncertainty on spectral estimates of heart rate dynamics. Ann Biomed Eng 23:127-34

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