We examined whether arterial hypoxemia impairs incremental exercise performance in subjects with interstitial lung disease (ILD). Seven subjects underwent two incremental exercise tests on a bicycle ergometer in random order; one while breathing room air (RA), and the other while breathing 60% O2. Maximal exercise performance was impaired in all subjects: maximal oxygen uptake (peak VO2) was 56 +/- 4% predicted (+/- SEM); and all subjects demonstrated significant arterial oxygen desaturation during exercise breathing RA (mean 11 +/- 1%). Breathing 60% O2 during exercise resulted in a significant increase in peak VO2 (RA: 1.32 +/- 0.05 L/min; O2: 1.58 +/- 0.08 L/min; p < 0.05), exercise duration (RA: 390 +/- 21 s; O2: 458 +/- 24 s; p < 0.01) and maximal work load (RA: 112 +/- 6 watts; O2: 129 +/- 6 watts; p < 0.005). There was no significant difference in maximal minute ventilation (VI) achieved at the end of both tests. At matched ventilation (90% peak VI from the RA test), respiratory frequency (f) was significantly higher (RA: 33 +/- 2 breaths/min; O2: 35 +/- 2 breaths/min; p < 0.05), and tidal volume (VT) significantly lower (RA: 1.72 +/- 0.15 L; O2: 1.64 +/- 0.12; p < 0.05) when subjects exercised breathing oxygen. We conclude that arterial hypoxemia significantly impairs incremental exercise performance in subjects with ILD, but that mechanisms other than arterial oxygen desaturation are responsible for the rapid, shallow breathing pattern these subjects adopt during exercise.

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.

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