Laude EA, Duffy NC, Baveystock C, Dougill B, Campbell MJ, Lawson R, Jones PW, Calverley PM

Am J Respir Crit Care Med. 2006;173(8):865-870.

Rationale:

Breathing supplemental oxygen reduces breathlessness during exercise in patients with chronic obstructive pulmonary disease (COPD). Replacing nitrogen with helium reduces expiratory flow resistance and may improve lung emptying. Combining these treatments should be independently effective.

Objectives:

To study the effect of changing oxygen or helium concentration in inspired gas during exercise in patients with stable COPD.

Methods:

We measured endurance shuttle walking distance, resting and exercise oxygen saturation, and end-exercise dyspnea (Borg scale) in 82 patients (mean age, 69.7 years; mean FEV1, 42.6% predicted) while they breathed Heliox28 (72% He/28% O₂), Heliox21 (79% He/21% O₂), Oxygen28 (72% N₂/28% O₂), or medical air (79% N₂/21% O₂). Gases were administered using a randomized, blinded, crossover design via a face mask and an inspiratory demand valve.

Results:

Breathing Heliox28 increased walking distance (mean +/- SD; 147 +/- 150 m) and reduced dyspnea (Borg score, -1.28 +/- 1.30) more than any other gas mixture did. Heliox21 significantly increased walking distance (99 +/- 101 m) and reduced dyspnea (Borg score, -0.76 +/- 0.77) compared with medical air. These changes were similar to those in patients breathing Oxygen28. The effects of helium and oxygen in Heliox28 were independent. The increase in walking distance while breathing Heliox28 was inversely related to baseline FEV1 breathing air.

Conclusion:

Reducing inspired gas density can improve exercise performance in COPD as much as increasing inspired oxygen. These effects can be combined as Heliox28 and are most evident in patients with more severe airflow obstruction.

Commentary:

This study addresses another aspect of methods for improving the exercise tolerance of patients with COPD. The use of supplemental oxygen during exercise can improve exercise endurance and facilitate exercise training for patients with COPD (including persons who are normoxic at rest and do not desaturate to SaO₂ <88% during exercise; Emtner. Am J Respir Crit Care Med. 2003;168:1034-1042). The use of supplemental oxygen can reduce ventilatory drive by delaying lactate production and can improve breathing pattern. Heliox, a gas mixture with a lower density than ambient air does, has the potential to reduce airway resistance and, as such, may also facilitate air movement (and in turn reduce dynamic hyperinflation) during exercise for persons with severe airflow obstruction. It has been used previously to assist the breathing of persons with severe airflow obstruction (especially asthma) in the intensive care unit setting. In this study, the investigators hypothesized that oxygen and helium breathing would each improve exercise tolerance of patients with COPD, albeit by different mechanisms, and, as such, proposed that the combination of both (heliox mixture) would be particularly useful, especially for those persons with severe airflow obstruction.

In this randomized, blinded, crossover trial, the investigators compared the endurance shuttle walking distance (performed at the speed that correlated to 85% of baseline VO_2max; note that this is considered a high intensity level of exercise) and postexercise dyspnea scores of 82 patients with stable COPD while breathing medical air (21% O₂/79% N₂), 28% oxygen, Heliox21 (21% O₂/79% He), or Heliox28 (28% O₂/72% He). Enrolled study participants had a mean FEV1 of 1.1 L and resting SaO₂ of 93.9%. The minimum end-exercise SaO₂ of 85% occurred among patients breathing medical air. There was less exercise-induced desaturation when patients breathed either 28% oxygen or the Heliox28 mixture. Breathing Heliox21 improved the endurance shuttle walk distance and reduced dyspnea to a comparable degree as did breathing 25% oxygen compared with medical air. Heliox28 led to significantly greater gains in exercise endurance and dyspnea than either the 28% oxygen or Heliox21 alone, suggesting that there were independent and, at least, additive benefits of breathing oxygen and helium during exercise in this group of patients. Moreover, the patients with the most severe airflow obstruction achieved the greatest gains in exercise endurance from breathing Heliox28. Although there are no data to support the long-term use of helium-oxygen mixtures for patients with COPD during day-to-day life, the use of heliox during supervised pulmonary rehabilitation has the potential to facilitate exercise training. Further studies are needed to determine whether the additive effects of breathing oxygen and helium on exercise endurance relate to additive reductions in dynamic hyperinflation. It would also be of interest in the future to compare the effects of oxygen, helium, or helium-oxygen mixture on endurance walking and dyspnea at a lower level of exercise intensity (eg, closer to that likely to be chosen by the patient during daily walking activities).

CR