Uncontrolled oxygen is often administered to breathless patients regardless of whether hypoxaemia is present. In acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) this may result in carbon dioxide (CO2) retention and worsening respiratory failure in some patients. In AECOPD the main mechanism is the release of hypoxic pulmonary vasoconstriction and an increase in the physiological dead space to tidal volume ratio (VD/VT). Acute asthma and pneumonia have features in common with AECOPD, namely significant ventilation – perfusion mismatch; and there is the potential for CO2 retention to occur if uncontrolled high concentration oxygen is given. There have been no randomised controlled trials of oxygen therapy in pneumonia and only one in asthma. The potential mechanisms of any change in arterial CO2 that may occur with oxygen therapy in respiratory disorders other than COPD remain uncertain.

This thesis presents work from three clinical studies. In two randomised controlled trials, high concentration oxygen was compared to titrated oxygen therapy in patients with either acute severe asthma and suspected community acquired pneumonia. Oxygen was administered for one hour in conjunction with standard medical treatment. Transcutaneous CO2 (PtCO2) was continuously monitored and the number of patients with pre-specified increases in PtCO2 were calculated. The proportion of patients with a rise in PtCO2 4 mmHg was significantly higher in the high concentration oxygen groups of both studies. In the pneumonia study 36/72 (50.0%) vs 11/75 (14.7%) met this endpoint, with a relative risk of 3.4 (95% CI 1.9 to 6.2; P <0.001), and in the asthma study 22/50 (44%) vs 10/53 (18.9%) met this endpoint, with a relative risk of 2.3 (95% CI 1.2 to 4.3; P=0.009). Similarly, a rise in PtCO2 8 mmHg was more common with high concentration oxygen. In the pneumonia study 11/72 (15.3%) vs 2/75 (2.7%) of patients met this endpoint, with a relative risk of 5.7 (95% CI 1.3 to 25.0; P=0.007), and 10/50 (20%) vs 3/53 (5.7%) of asthma patients met this endpoint, with a relative risk of 3.6 (95% CI 1.1 to 12.3; P=0.03). A third study measured the physiological response to 20 minutes of 100% oxygen in chronic severe asthma, with comparison to a group of negative controls (normal subjects) and positive controls (COPD patients). There was a significant rise in PtCO2 of similar magnitude in the asthma and COPD groups compared with the normal controls. The mechanism of the PtCO2 rise was similar in asthma and COPD, with an increase in VD/VT but no change in minute ventilation.

These studies demonstrate than uncontrolled high concentration oxygen has the potential to cause CO2 retention in respiratory diseases other than COPD, and that in asthma the mechanism of hypercapnia is similar to that in AECOPD. In acute asthma and community-acquired pneumonia oxygen should be administered only to those patients with evidence of arterial hypoxaemia in a dose that relieves hypoxaemia without causing hyperoxia, thereby achieving the benefits of oxygen therapy while reducing the potential for harm.