Current techniques to estimate nitric oxide (NO) production and elimination in the lungs are inherently nonspecific or are cumbersome to perform (multiple-breathing maneuvers). We present a new technique capable of estimating key flow-independent parameters characteristic of NO exchange in the lungs: 1) the steady-state alveolar concentration (C(alv,ss)), 2) the maximum flux of NO from the airways (J(NO,max)), and 3) the diffusing capacity of NO in the airways (D(NO,air)). Importantly, the parameters were estimated from a single experimental single-exhalation maneuver that consisted of a preexpiratory breath hold, followed by an exhalation in which the flow rate progressively decreased. The mean values for J(NO,max), D(NO,air), and C(alv,ss) do not depend on breath-hold time and range from 280-600 pl/s, 3.7-7.1 pl. s(-1). parts per billion (ppb)(-1), and 0.73-2.2 ppb, respectively, in two healthy human subjects. A priori estimates of the parameter confidence intervals demonstrate that a breath hold no longer than 20 s may be adequate and that J(NO,max) can be estimated with the smallest uncertainty and D(NO,air) with the largest, which is consistent with theoretical predictions. We conclude that our new technique can be used to characterize flow-independent NO exchange parameters from a single experimental single-exhalation breathing maneuver.
Endogenous production of nitric oxide (NO) in the human lungs has many important pathophysiological roles and can be detected in the exhaled breath. An understanding of the factors that dictate the shape of the NO exhalation profile is fundamental to our understanding of normal and diseased lung function. We collected single-exhalation profiles of NO and CO2 from normal human subjects after inhalation of ambient air (approximately 15 parts/billion) and examined the effect of a 15-s breath hold and exhalation flow rate (VE) on the following features of the NO profile: 1) series dead space, 2) average concentration in phase III with respect to time and volume, 3) normalized slope of phase III with respect to time and volume, and 4) elimination rate at end exhalation. The dead space is approximately 50% smaller for NO than for CO2 and is substantially reduced after a breath hold. The concentration of exhaled NO is inversely related to VE, but the average NO concentration with respect to time has a stronger inverse relationship than that with respect to volume. The normalized slope of phase III NO with respect to time and that with respect to volume are negative at a constant VE but can be made to change signs if the flow rate continuously decreases during the exhalation. In addition, NO elimination at end exhalation vs. VE produces a nonzero intercept and slope that are subject dependent and can be used to quantitate the relative contribution of the airways and the alveoli to exhaled NO. We conclude that exhaled NO has an airway and an alveolar source.
Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C NO,plat ) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n ϭ 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J NO,max , pl s
While bilateral staple LVRS procedures lead to greater short-term improvement in FEV1, the more rapid rate of FEV1 decline in these patients and the general association between greater short-term incremental improvement and higher rates of deterioration raise questions regarding optimal long-term procedures. Further studies will be needed to answer these important questions.
A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation.
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