Model of Functional Restriction in Chronic Obstructive Pulmonary Disease, Transplantation, and Lung Reduction Surgery

Abstract

Mechanical interactions between lung and chest wall are important determinants of respiratory function. When chest wall expansion during maximal inhalation generates insufficiently negative pleural pressures, the lungs remain functionally underinflated; this may be termed functional restriction. To explore mechanisms and effects of functional restriction in patients with emphysema, and to predict effects of single lung transplantation and lung volume reduction surgery (LVRS), we used a computational model based on standard physiology and measurements from individual patients. The model's lungs, separated by a compliant mediastinum, exhibit flow limitation according to the equal pressure point approach of Mead and coworkers. Pulmonary elastic recoil pressure is characterized by an exponential equation modified to reflect airway closure. Simulated respiratory maneuvers can be specified by variations in flow or pressure at the airway opening or in respiratory muscle activation. Model simulations successfully mimic recordings from individual patients. Input parameter values may then be altered to predict effects of surgical interventions in these same patients. The model simulations show the following. Single lung transplantation in emphysema can cause functional restriction of the normal transplanted lungs, and larger transplanted lungs may perform less well than smaller ones. LVRS improves lung and chest wall function in emphysema, but not in normal states. Surgical reduction of the native emphysematous lung after single lung transplantation can reduce functional restriction of the transplant and thereby improve its function.

Airway dimensions and pulmonary function in chronic obstructive pulmonary disease and bronchial asthma

“…We assumed that the loss of lung parenchyma in patients with asthma plus emphysema would result in a reduction in elastic recoil, although no physiological measurement of elastic recoil was made in this study. A certain point of an airway would partially collapse or inflate at forced expiration according to the dynamic balance of elastic recoil pressure of the lung, pleural pressure, and airway pressure at a certain point 26,27 . Airways in patients with asthma plus emphysema would collapse more easily at forced expiration than in patients with asthma alone.…”

Lung volume reduction surgery and lung transplantation in chronic obstructive pulmonary disease

“…An unchanged chest wall operating on a smaller lung restores the elastic recoil (Loring et al 1999), and expiratory flows at any given lung volume increase on the basis of increased airway traction and delayed airway closure. LVRS translates into reduced thoracic gas compression by improving expiratory flow limitation: FEV 1 is consistently improved, and both total lung capacity (TLC) and residual volume (RV) are reduced.…”

Treatment of chronic respiratory failure: lung volume reduction surgeryversusrehabilitation

“…The hypotheses explaining the improvement include: improved lung mechanics, increased lung elastic recoil [80,81], reduced intrinsic positive inspiratory pressure [82], reduced hyperinflation, increased respiratory muscle strength due to geometric factors [74][75][76][77][78], improved ventilation/perfusion matching, and reduced pulmonary vascular resistance. There is evidence that the major mode of action is resizing of the lungs [83][84][85][86]. This means that, in emphysema, lung mechanics deteriorate because the lung is disproportionately expanded compared to the chest wall.…”