Mechanisms of Gas-exchange Impairment in Idiopathic Pulmonary Fibrosis

Abstract

To investigate the mechanisms of pulmonary gas-exchange impairment in idiopathic pulmonary fibrosis (IPF) and to evaluate their potential relationship to the CO diffusing capacity (DLCO), we studied 15 patients with IPF (mean DLCO, 52% of predicted) at rest (breathing room air and pure O2) and during exercise. We measured pulmonary hemodynamics and respiratory gas-exchange variables, and we separated the ventilation-perfusion (VAQ) mismatching and O2 diffusion limitation components of arterial hypoxemia using the multiple inert gas elimination technique. At rest VA/Q mismatching was moderate (2 to 4% of cardiac output perfusing poorly or unventilated lung units), and 19% of AaPO2 was due to O2 diffusion limitation. During exercise VA/Q mismatch did not worsen but the diffusion component of arterial hypoxemia increased markedly (40% AaPO2, p less than 0.005). We observed that those patients with higher pulmonary vascular tone (more release of hypoxic pulmonary vasoconstriction) showed less pulmonary hypertension during exercise (p less than 0.05), less VA/Q mismatching [at rest (p less than 0.005) and during exercise (p less than 0.0025)], and higher arterial PO2 during exercise (p = 0.01). We also found that DLCO corrected for alveolar volume (KCO) correlated with the mechanisms of hypoxemia during exercise [VA/Q mismatching (p less than 0.025) and O2 diffusion limitation (p less than 0.05)] and with the increase in pulmonary vascular resistance elicited by exercise (p less than 0.005). In conclusion, we showed that the abnormalities of the pulmonary vasculature are key to modulate gas exchange in IPF, especially during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary exercise testing following hay exposure challenge in farmer's lung

“…There is controversy regarding the relative importance of diffusion limitation in the widened alveolar-arterial gradient [28][29][30][31]. In the present study, we observed a reduced TL,CO in patients with farmer's lung postexposure, but there was no significant difference in TL,CO between the two groups postexposure.…”

“…after induction of an acute alveolitis. Several studies have indicated that ventilation-perfusion mismatch and shunt are responsible for most of the increased D(A-a),O 2 during exercise [28][29][30][31]. As the perfusion rate during exercise increases in the lung units with inflammatory cell infiltrates, O 2 in the gas space can no longer equilibrate with O 2 in the red cell.…”

“…Patients with significant lung fibrosis often display higher levels of V 'E during exercise than normal subjects [28,38]. The observed reduced breathing reserve is one of the criteria often used to establish ventilatory limitation during exercise [10].…”

“…The observed reduced breathing reserve is one of the criteria often used to establish ventilatory limitation during exercise [10]. This is largely due to increased VD/VT, but other factors, such as input from mechanoreceptors, hypoxaemia, exhausted respiratory muscles and mediators of inflammation, may contribute [28,[36][37][38][39][40]. In view of the multiple mechanisms likely to be involved in ventilatory responses observed during exercise in interstitial lung disease, the reasons for this merit additional studies.…”

Imaging alveolar–capillary gas transfer using hyperpolarized 129 Xe MRI

“…Yet certain pulmonary pathologies such as inflammation, fibrosis, and edema may initially have a predominant effect on the gas exchange process but not on ventilation or perfusion. The degree to which such ''diffusion block'' (5) is present or absent is difficult to determine (6). In healthy alveoli, the harmonic mean thickness [as defined by Weibel (7)] of the blood-gas barrier is 0.77 m and oxygen traverses this space in less than 1 ms, saturating the red blood cells (RBCs) in tens of milliseconds.…”