On issues of confidence in determining the time constant for oxygen uptake kinetics.

BACKGROUND: TauVO(2 )at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of tauVO(2) with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application. OBJECTIVES: To design a protocol to determine tauVO(2) reliably but simply. METHODS: On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (VO(2)theta) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. TauVO(2) was determined (a) from the on-transit (on-tauVO(2)) and off-transit (off-tauVO(2)) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-tauVO(2)). RESULTS: Group means (SD) were: VO(2)max 3.84 (0.44) litres/min, VO(2)theta 1.88 (0.23) litres/min, steady state exercise VO(2) 1.67 (0.07) litres/min, on-tauVO(2) 38.0 (5.3) seconds, off-tauVO(2) 39.0 (4.3) seconds, and ramp-tauVO(2) 60.8 (15.4) seconds. On-tauVO(2) correlated with off-tauVO(2) (r = 0.87), VO(2)max (r = -0.73), and VO(2)theta (r = 0.89). The pooled mean tauVO(2) from six superimposed tests agreed with the arithmetic grand mean of the six tests. CONCLUSIONS: The average of on-tauVO(2) and off-tauVO(2) fell within the 95% confidence interval of the pooled mean by the second test. Ramp-tauVO(2) was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of tauVO(2), an approach that reduces the number of transitions necessary for accurate determination of tauVO(2), potentially enhancing its clinical application.

Exercise and interstitial lung disease.

Interstitial lung disease (ILD) limits exercise capacity through a variety of complex and intriguing mechanisms, including ventilatory limitation, diffusion impairment, and ventilation-perfusion derangement. Resting pulmonary function testing seldom explains the symptoms nor defines the specific pathophysiology of the individual patient. Cardiopulmonary exercise testing can elucidate the relative contributions of these mechanisms and guide therapy. A fundamental problem in ILD is one of inadequate time for lung inflation during intense exercise, resulting in dynamic hypoinflation relative to the ventilatory demand. Pulmonary rehabilitation is underused in ILD. Functional CT imaging may provide insight into the relationship between structural and physiologic abnormalities of regional pulmonary function. Recent advances in nitric oxide research will perhaps further our understanding of the basic pathophysiology of ILD and provide specific treatment for the associated pulmonary vascular disease.

Tumor necrosis factor-alpha plays a central role in interleukin-2-induced pulmonary vascular leak and lymphocyte accumulation.

Administration of interleukin-2 (IL-2) leads to pulmonary vascular leak. This form of pulmonary edema has previously been postulated to be due to the in vivo induction of tumor necrosis factor-alpha (TNF-alpha). To determine whether TNF-alpha plays a role in IL-2-induced pulmonary vascular leak, we performed in situ hybridization of lung sections and reverse transcriptase-polymerase chain reaction of bronchoalveolar lavage macrophages from IL-2-challenged mice. The results confirm an in situ upregulation of TNF-alpha mRNA expression in the lungs associated with vascular leak. In addition, a significant increase in TNF-alpha protein production was found in the lung following IL-2 administration, as measured by TNF-alpha-specific ELISA of lung supernatants (P = 0.028). Intravenous administration of a soluble TNF receptor significantly diminished IL-2-induced pulmonary vascular leak (P = 0.006). These findings confirm a central role for TNF-alpha in mediating the pulmonary vascular leak associated with IL-2 toxicity.