Nitric Oxide Diffusing Capacity and Alveolar Microvascular Recruitment in Sarcoidosis

Abstract

We measured diffusing capacities for carbon monoxide (DLCO) and nitric oxide, lung volume, and cardiac output by a rebreathing technique at two alveolar O2 tensions (PAO2) at rest and exercise. Membrane diffusing capacity for CO (DMCO) and VC were estimated from DLCO by the Roughton-Forster (RF) method and also from simultaneous lung diffusing capacity for NO and DLCO measured at one O2 tension (modified RF method). Estimates by these methods agreed closely in normal subjects (Tamhane et al., Chest 2001;120:1850-1856). Using these methods, we studied patients with stages II-III pulmonary sarcoidosis to determine (1) whether the modified RF method accurately estimates DMCO and VC in parenchymal disease and (2) whether sarcoidosis alters recruitment of diffusing capacity with respect to cardiac output. In patients, DMCO and VC estimated by the two methods agreed closely. DMCO was disproportionately reduced relative to VC at any given cardiac output, and the slope of the relationship between DLCO and cardiac output was moderately, though significantly, below normal. We conclude that in sarcoidosis (1) the modified RF method provides comparable estimates of DMCO and VC as the standard RF method and (2) the limitation to diffusive gas transport resides primarily in the membrane barrier, although recruitment of microvascular reserves is also modestly impaired.

TheTL,NO/TL,COratio in pulmonary function test interpretation

“…If all ventilated units were equally involved in the membrane thickening, we would expect KNO and TL,NO, as % pred, to be equally reduced. On exercise [29], recruitment of diffusing capacity (as % of resting values) was similar for normal subjects and patients with sarcoidosis, with a decrease (-15%) in the TL,NO/TL,CO ratio, consistent with capillary dilatation on exercise, which would not be ''seen'' by NO diffusion. In another study of 41 patients with diffuse interstitial lung disease (66% had sarcoidosis) the TL,NO/TL,CO ratio increased [24]; we speculate that these patients may have had more end-stage disease and fibrosis.…”

“…In 25 nonsmoking patients with stage II-III sarcoidosis [29] the TL,NO/TL,CO ratio (,KNO/KCO ratio) determined by a rebreathing technique was reduced (85% predicted) in keeping with the low DM/Vc ratio (79% normal). TL,NO was more reduced than KNO (34% pred normal versus 60%), a similar pattern to TL,CO and KCO, which suggests that loss of alveolar membrane surface area (loss of alveolar units) exceeded membrane thickening.…”

“…Rest to exercise (normals) [22] Voluntary restriction of lung expansion [13] mimicking ''extrapulmonary restriction'' Expansion of capillary volume (per unit VA) increases TL,CO more than TL,NO Decreased Sarcoidosis " [29] Lifelong altitude exposure + [23] Cystic fibrosis [26] Morbid obesity [19] Chronic heart failure [35] (unconfirmed for TL,NO/TL,CO ratio) pulmonary hypertension intervenes in NYHA grades III and IV, the TL,NO/TL,CO ratio might return to normal or increase.…”

“…Table 3 shows that sarcoidosis with end-stage disease and fibrosis [24] had a raised TL,NO/TL,CO ratio, but sarcoidosis without fibrosis [29] had a reduced ratio. An increased ratio suggests that Vc is more compromised than the alveolar-capillary membranes, whereas greater membrane involvement would lead to a reduced TL,NO/TL,CO ratio.…”

A place for TL,NO with TL,CO?

“…Others have taken the pragmatic approach further. In 1957, in a combined group of healthy subjects and patients with sarcoidosis, a was found to be 2.42 [8]. Hence some groups have taken a as 2.42 rather than 1.97.…”