Background Palliative oxygen therapy is widely used for dyspnea in individuals with life-limiting illness ineligible for long-term oxygen therapy. Methods This international double-blind randomized controlled trial evaluatedeffectiveness of oxygen vs. medical (room) air for relieving breathlessness in patients with life-limiting illness, refractory dyspnea, and PaO2>55 mm Hg. Participants were recruited from outpatient clinics at 9 sites (Australia, United States, England). Participants received oxygen or medical air via concentrator through nasal cannulae at 2 liters/minute for 7 days. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice daily. Findings Participants (N=239) were: mean age, 73 (standard deviation [SD] 10); 62% male; mean PaO2, 77 mm Hg (SD 12); mean morning dyspnea, 4.5 on NRS (SD 2.2); chronic obstructive pulmonary disease, 64%; cancer, 16%. Oxygen was not significantly superior to medical air for relief of breathlessness. Over the 7-day period, after provision of medical gas, mean morning and evening dyspnea decreased by -0.8 (95% confidence interval [CI]: -1.1, -0.5) and -0.4 (CI: -0.7, 0.1), respectively (p<0.001), regardless of intervention. Baseline dyspnea predicted improvement with medical gas; participants with moderate (4-6 NRS) and severe (7-10 NRS) baseline dyspnea had average decreases in morning dyspnea of -0.7 (CI: -1.1, -0.4) and -2.4 (CI: -3.0, -1.8), respectively. Interpretation There is no additional symptomatic benefit of oxygen over room air delivered by nasal cannulae for relieving refractory dyspnea related to life-limiting illness in patients with PaO2>55 mm Hg. Dyspnea intensity decreased in both study arms, temporally related to provision of medical gas.

The detailed mechanisms of oxygen-induced hypercapnia were examined in 22 patients during an acute exacerbation of chronic obstructive pulmonary disease. Ventilation, cardiac output, and the distribution of ventilation-perfusion (V A/Q ) ratios were measured using the multiple inert gas elimination technique breathing air and then 100% oxygen through a nose mask. Twelve patients were classified as retainers (R) when Pa(CO(2)) rose by more than 3 mm Hg (8.3 +/- 5.6; mean +/- SD) after breathing 100% oxygen for at least 20 min. The other 10 patients showed a change in Pa(CO(2)) of -1.3 +/- 2.2 mm Hg breathing oxygen and were classified as nonretainers (NR). Ventilation fell significantly from 9.0 +/- 1.5 to 7.2 +/- 1.2 L/min in the R group breathing oxygen (p = 0.007), whereas there was no change in ventilation in the NR group (9.8 +/- 1.8 to 9.9 +/- 1.8 L/min). The dispersion of V A/Q ratios as measured by log SD of blood flow (log SD Q) increased significantly in both R (0.96 +/- 0. 17 to 1.13 +/- 0.17) and NR (0.77 +/- 0.20 to 1.04 +/- 0.23, p < 0.05) groups breathing oxygen, whereas log SD of ventilation (log SD Q ) increased only in the R group (0.97 +/- 0.24 to 1.20 +/- 0.46, p < 0.05). This study suggests that an overall reduction in ventilation characterizes oxygen-induced hypercapnia, as an increased dispersion of blood flow from release of hypoxic vasoconstriction occurred to a significant and similar degree in both groups. The significant increase in wasted ventilation (alveolar dead space) in the R group only may be secondary to the higher carbon dioxide tension, perhaps related to bronchodilatation.

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.