Previous studies of exhaled nitric oxide (NO) in patients with primary pulmonary hypertension (PPH) have used varying methodologies and produced conflicting results. We compared exhaled NO using a novel technique that derives three components, in patients with PPH compared with controls. We also repeated these measurements after 3 months of therapy with the endothelin-receptor antagonist, bosentan.
Eleven PPH patients (on no therapy) and 11 controls with similar demographic characteristics were studied. Exhaled NO measurements were obtained with a chemiluminescent analyzer (Seivers 280) using the standardized procedure recommended by the ATS. Fractional concentration of NO (FENO) was obtained at expiratory flow rates of 18, 50, 100 and 250 ml/sec. Using these FENO values, airway wall concentration (Cw), diffusion capacity from airway wall into lumen (Dno) and alveolar concentration (Calv) were calculated using a non-linear regression technique devised by Silkoff et al (Am J Resp Crit Care Med 2000;161:1218). Eight PPH patients had repeat measurements made after 3 months of therapy with bosentan.
PPH patients had a significantly reduced Cw compared with controls (39 +/− 8 ppb vs. 295 +/− 139; P= 0.02), while Dno was considerably higher (26.5 +/− 8 nl/s/ppb x 10−3 vs 10.8 +/− 3; P=0.03). No difference in Calv was noted between the two groups. After 3 months of bosentan, FENO values at 18 and 50 ml/sec increased significantly in the PPH group (P=0.02). The calculated Cw tended to increase (P=0.08) while no significant changes were observed in Dno or Calv.CONCLUSIONS: Airway concentrations of NO are significantly reduced in PPH compared with normal subjects, while diffusing capacity of NO from airway wall into lumen is increased. The reduced Cw tends to increase back towards normal with bosentan therapy.
Reduced airway wall NO concentration may be a useful biomarker of PPH and could play a role in the pathogenesis of this disease. Increased Dno may reflect an attempt to increase the NO releasing surface area of the airways.
R.E. Girgis, Sievers Instruments (NO anaylzer), discussion of product research or unlabeled uses of product; Actelion Pharmaceuticals, Industry.