Pilot study: determining biological effects of low level exposure, developing novel biomarkers and therapies in in vivo animal models of CO toxicity - supplement

There are approximately 4,000 identified cases of accidental carbon monoxide (CO) poisoning in the UK each year requiring medical treatment, according to Department of Health statistics. Each year 200 patients are admitted to hospital with serious brain injuries and around 40 people die, as a result of accidental exposure to CO. It is estimated that CO poisoning costs the UK up to £ 178 M each year. The number of cases of exposure to CO that go undiagnosed and undetected is unknown. Studies indicate that the identified cases of CO toxicity may represent only the tip of a hidden iceberg. A study of 22,831 homes in East London fitted with CO alarms in 2011 – 2012 recorded 106 alarm activations, or an incidence of 0.46%. If this incidence is reflected throughout the UK the number of potentially dangerous CO exposure may be very large.

The figures are particularly concerning given that ownership of CO alarms is low; a survey of 22,000 homes by Merseyside Fire Services found less than 10% of homes had a CO alarm. Another study of 1758 patients at four Accident & Emergency departments in England found that 4.3% of those presenting with non-specific symptoms such as chest pain, headache, seizures or flu-like symptoms had elevated levels of carboxyhaemoglobin. If this figure is representative then the potential numbers of patients currently undiagnosed may represent a silent epidemic of huge proportions, with devastating social and economic costs. The health implications of low level, undiagnosed, CO exposure may be substantial and there is an urgent need for research on the effects of low level CO on the body.

Low level CO toxicity may be much more widespread than even the figures above suggest for the following reasons: (1) it is not known whether there is any safe low level limit for CO exposure, (2) it is unknown whether repeated exposure to CO is additive or cumulative; (3) there are no reliable diagnostic tests or ‘biomarkers’ for low level sub-acute CO exposure; (4) the clinical symptoms of non-lethal CO toxicity are non-specific and easily confused with other medical conditions.

This project will address key gaps in the scientific knowledge with the objective of addressing the issue of low-level CO toxicity and the social its economic cost to the UK. The successful outcome of this pilot study will be a package of preliminary data that will address the question of the extent of low level CO toxicity. This data package will provide results that can be used to leverage funding from other sources (eg Research Councils) to take the work forward to eventual clinical or diagnostic exploitation.

We have generated a large collection of samples, including 30 rat brains and blood and biofluid samples. Further work will involve immunohistology to assess injury in specific brain regions. We need to slice the frozen rat brains and stain them with specific injury-related antibodies. We need to replace a broken tissue cryostat (Leica CM3050) that is unrepairable. In addition we are requesting a part-time technical position in order to complete the slicing and histology.