Impaired diffusion at submaximal lung inflation in asthma and copd patients

Dissolved-phase ¹²⁹Xe MRI metrics suggest that gas diffusion may be more compromised at submaximal lung inflation compared to maximal inflation. We hypothesized that this diffusion deficit could be detected by comparing the carbon monoxide transfer coefficient (Kco) at submaximal lung inflation to that measured routinely at total lung capacity (TLC).

Asthma and COPD patients performed carbon monoxide diffusion tests, first at maximal lung inflation for routine Kco and alveolar volume VA and then, at a 30 % reduced inflation (redux; obtaining Kco_redux and VA_redux). At both inflations mixing efficiency was determined as VA/TLC and VA_redux/TLC_redux to examine a potential effect on Kco_redux/Kco behavior.

In normal subjects (n=36), median Kco_redux/Kco amounted to 130 [IQR:122-136]% as expected for normal Kco recruitment response. However, 60 % of asthma patients (49/83) and 80 % of COPD patients (44/55) showed reduced Kco recruitment at submaximal inflation (Kco_redux/Kco<122 %). In the asthma group, with otherwise normal routine Kco, Kco_redux/Kco was significantly correlated with RV/TLC ratio (r=-0.53;P<0.001), but not with VA/TLC. In COPD patients, all with abnormal routine Kco, abnormal Kco_redux/Kco response occurred in those patients with lower FEV₁, higher RV/TLC and lower VA/TLC (P<0.01 for all).

Sizeable portions of COPD and asthma patients showed a lack of normal Kco recruitment at submaximal lung inflation, related to high RV/TLC. In asthma, this was the case despite normal Kco at full lung inflation, suggesting that hyperinflation at lung volumes less than TLC affects the carbon monoxide diffusion rate constant by distorting pulmonary capillaries and alveolar-capillary membranes.