Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension
1 Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
2 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
3 Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
Respiratory Research 2013, 14:6 doi:10.1186/1465-9921-14-6Published: 22 January 2013
Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange.
We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography.
Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p < 0.01). While DLCO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers.
The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion.