Ventilatory response to helium-oxygen breathing during exercise: effect of airway anesthesia.

The substitution of a normoxic helium mixture (HeO2) for room air (Air) during exercise results in a sustained hyperventilation, which is present even in the first breath. We hypothesized that this response is dependent on intact airway afferents; if so, airway anesthesia (Anesthesia) should affect this response. Anesthesia was administered to the upper airways by topical application and to lower central airways by aerosol inhalation and was confirmed to be effective for over 15 min. Subjects performed constant work-rate exercise (CWE) at 69 +/- 2 (SE) % maximal work rate on a cycle ergometer on three separate days: twice after saline inhalation (days 1 and 3) and once after Anesthesia (day 2). CWE commenced after a brief warm-up, with subjects breathing Air for the first 5 min (Air-1), HeO2 for the next 3 min, and Air again until the end of CWE (Air-2). The resistance of the breathing circuit was matched for Air and HeO2. Breathing HeO2 resulted in a small but significant increase in minute ventilation (VI) and decrease in alveolar PCO2 in both the Saline (average of 2 saline tests; not significant) and Anesthesia tests. Although Anesthesia had no effect on the sustained hyperventilatory response to HeO2 breathing, the VI transients within the first six breaths of HeO2 were significantly attenuated with Anesthesia. We conclude that the VI response to HeO2 is not simply due to a reduction in external tubing resistance and that, in humans, airway afferents mediate the transient but not the sustained hyperventilatory response to HeO2 breathing during exercise.

Airway anesthesia and respiratory adaptations to dead space loading and exercise.

In exercising humans, added external dead space (VD) increases minute ventilation (VI) and causes a slower and deeper breathing pattern (J. Appl. Physiol. 1991; 70:55-62). Recent studies suggest that airway receptors sensitive to topical anesthesia influence VI and breathing pattern responses to exercise and to added VD. We tested these hypotheses with a technique of airway anesthesia (Anesthesia) that has been shown to reliably attenuate airway reflexes. Anesthesia was administered by local laryngopharyngeal application and aerosolized lidocaine inhalation, and was confirmed by citric acid aerosol inhalation challenges. Twelve normal males performed maximal incremental cycle ergometer exercise on 4 d (randomized) after Anesthesia with (Anesthesia VD) and without added VD (Anesthesia Control) and after normal saline inhalation (Saline) with (Saline VD) and without added VD (Saline Control). There were no differences in the VI and breathing pattern responses during exercise between the Saline Control and the Anesthesia Control tests. After both Saline and Anesthesia inhalation, added VD resulted in an increase in VI both at rest and during exercise. At matched VI (98 L/min), the differences in tidal volume (VT) between the Saline Control and Saline VD tests (delta = 0.23 +/- 0.24 L, mean +/- SD) and the Anesthesia Control and Anesthesia VD tests (delta = 0.20 +/- 0.28 L) were not significantly different. Our study had a power of greater than 95% to detect significant differences in VI or breathing pattern due to Anesthesia. We conclude that in normal humans, airway receptors do not play a major role in ventilation and breathing pattern control during exercise, and that the respiratory adaptations to added VD during exercise are not mediated by airway afferent reflexes.

Role of hypoxemia and pulmonary mechanics in exercise limitation in interstitial lung disease.

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.

Low-dose nebulized morphine does not improve exercise in interstitial lung disease.

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.

Oxygen improves maximal exercise performance in interstitial lung disease.

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.

Lung volumes and expiratory flow limitation during exercise in interstitial lung disease.

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.