Lung volumes were measured at rest and during exercise by an open-circuit N2-washout technique in patients with interstitial lung disease (ILD). Exercise tidal flow-volume (F-V) curves were also compared with maximal F-V curves to investigate whether these patients demonstrated flow limitation. Seven patients underwent 4 min of constant work rate bicycle ergometer exercise at 40, 70, and 90% of their previously determined maximal work rates. End-expiratory lung volume and total lung capacity were measured at rest and near the end of each period of exercise. There was no significant change in end-expiratory lung volume or total lung capacity when resting measurements were compared with measurements at 40, 70, and 90% work rates. During exercise, expiratory flow limitation was evident in four patients who reported stopping exercise because of dyspnea. In the remaining patients who discontinued exercise because of leg fatigue, no flow limitation was evident. In all patients, the mean ratio of maximal minute ventilation to maximal ventilatory capacity (calculated from maximal F-V curves) was 67%. We conclude that lung volumes during exercise do not significantly differ from those at rest in this population and that patients with ILD may demonstrate expiratory flow limitation during exercise. Furthermore, because most patients with ILD are not breathing near their maximal ventilatory capacity at the end of exercise, we suggest that respiratory mechanics are not the primary cause of their exercise limitation.

We have previously shown that respiratory factors (arterial hypoxemia and/or pulmonary mechanics) contribute to limit maximal incremental exercise in interstitial lung disease (ILD). In this study, we tested the hypothesis that arterial hypoxemia, not pulmonary mechanics, primarily limits maximal exercise in subjects with ILD. Seven subjects with ILD underwent two incremental exercise tests in random order. Test 1: breathing room air (RA); Test 2: breathing 60% O2 with added external dead space (O2VD). Added VD was used to prevent the fall in minute ventilation (VI) while breathing O2. All subjects demonstrated impaired exercise performance (maximal oxygen uptake [VO2], 56 +/- 13% predicted) while breathing RA. There was a significant increase in peak VI (RA, 64.9 +/- 22.3 L/min versus O2VD, 71.0 +/- 20.6; p < 0.05), maximal work rate (RA, 99 +/- 12 watts versus O2VD, 109 +/- 15 watts; p < 0.01), exercise duration (RA, 383 +/- 67 s versus O2VD; 426 +/- 72 s; p < 0.0005) and maximal VO2 (RA, 1.25 +/- 0.21 L/min versus O2VD, 1.39 +/- 0.26; p < 0.05) during the O2VD exercise test. There was a significant correlation between the percent increase in exercise duration during the O2VD test and the DLCO (r = -0.813, p < 0.05). At matched levels of ventilation, subjects demonstrated a significantly deeper and slower pattern of breathing during the O2VD test. Because subjects with ILD were able to further improve their exercise and further increase their VI during the O2VD exercise study, we conclude that arterial hypoxemia, and not respiratory mechanics, predominantly limits maximal incremental exercise in subjects with ILD.

Recent reports have suggested that low-dose nebulized morphine may improve exercise tolerance in patients with interstitial lung disease (ILD) by acting on peripheral opioid-sensitive pulmonary receptors. We therefore examined whether the administration of low-dose nebulized morphine would influence dyspnea or the breathing pattern during exercise of subjects with ILD and improve their exercise performance. Each of six subjects with ILD underwent three maximal incremental cycle ergometer tests, each test separated from the last by at least 3 d. Each exercise test was similar except that 30 min before exercise, the subjects received nebulized saline (control), morphine 2.5 mg, or morphine 5.0 mg, respectively, in double-blinded fashion. No significant differences were noted in exercise duration, maximal workload, or sense of dyspnea at the end of exercise in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg. Nor were significant differences noted in resting, submaximal, or end-exercise measurements of oxygen uptake (VO2), carbon dioxide output (VCO2), end-tidal CO2 (PETCO2), oxygen saturation (SaO2), minute ventilation (VI), respiratory frequency (f), tidal volume (VT), or heart rate (HR) in the three tests. Low-dose nebulized morphine did not alter the subjects' breathing pattern or affect the relationship between dyspnea and ventilation during exercise. No significant side effects were noted. The administration of low-dose nebulized morphine to subjects with ILD neither relieves their dyspnea during exercise nor improves their maximal exercise performance.

) and 16 subjects matched for age and BMI without OHS or OSA were studied. Selection criteria included normal arterial blood gas tensions and lung function tests and absence of sleep apnoea on overnight polysomnography. Ventilatory responses to isocapnic hypoxia and to hyperoxic hypercapnia were compared between the two groups. Results-The slope of the ventilatory response to hypercapnia was similar in the relatives (mean 2.33 l/min/mm Hg) and in the control subjects (2.12 l/min/mm Hg), mean diVerence 0.2 l/min/mm Hg, 95% confidence interval (CI) for the diVerence -0.5 to 0.9 l/min/mm Hg, p=0.5. The hypoxic ventilatory response was also similar between the two groups (slope factor A: 379.1 l/min c mm Hg for relatives and 373.4 l/min c mm Hg for controls; mean diVerence 5.7 l/min c mm Hg; 95% CI -282 to 293 l/min c mm Hg, p=0.7; slope of the linear regression line of the fall in oxygen saturation and increase in minute ventilation: 2.01 l/min/% desaturation in relatives, 1.15 l/min/% desaturation in controls; mean diVerence 0.5 l/min/% desaturation; 95% CI -1.7 to 0.7 l/min/% desaturation, p=0.8). Conclusion-There is no evidence of impaired ventilatory chemoresponsiveness in first degree relatives of patients with OHS compared with age and BMI matched control subjects. (Thorax 2000;55:940-945)

with unloading, as did mean Pmus I and pmus E (21 and 44%). 4. The lack of any significant changes in VE, PA,co, or breathing pattern, despite a marked reduction in respiratory muscle load throughout CWHE, indicates that the load on the respiratory muscles has only a minor role in the regulation of ventilation during heavy exercise. 5. The absence of improvement in CWHE duration (control, 11-4 + 1 2 min; unload, 12-6 + 2 1 min, n.s.) with unloading implies that respiratory muscle function does not limit endurance exercise performance during cycling in healthy humans.This study tested the hypothesis that the load on the respiratory muscles is an important determinant of the ventilatory response to heavy exercise in normal humans. We used constant work rate heavy exercise (CWHE) to exhaustion as the ventilatory stimulus and the rationale of the study was as follows. Minute ventilation (VE) and breathing pattern are determined by the intensity and pattern of respiratory muscle contraction (i.e. respiratory muscle output) and the mechanical properties of the respiratory system. The relation between respiratory muscle pressure (Pmus) and VE is illustrated schematically in Fig. 1 (Hussain, Pardy & Dempsey, 1985) previous studies, we have used a linear model to illustrate the Pmus-17E relationsEhip in Fig. 1. A linear model is used to facilitate discussion of concepts raised in this paper but the concepts and questions addressed here do not depend on the linearity (or otherwise) of this relation. The term 'respiratory impedance' will be used in this manuscript as a descriptive term to denote the relation between respiratory muscle pressure generated by the subject (Pmus) and minute ventilation (VE). 'Reducing respiratory impedance' is merely a short-hand way of stating that the 'relation between Pmus and VE was altered such that one gets a higher VE for a given