Stomach acidity is an important host defence against ingested pathogens, and it provides protection against infections. Treatments that reduce the amount of acid in the stomach, such as proton pump inhibitors, have been shown to increase the risk of pneumonia and Clostridium difficile diarrhoea. If acid suppression is the true cause of pneumonia and Clostridium difficile infection in patients receiving these forms of medication, then the highest risk of infection should be seen with achlorhydia (no acid production), a state associated with pernicious anaemia. This study, therefore, will determine whether people with pernicious anaemia are more likely to develop pneumonia or diarrhoea due to Clostridium difficile infection than those who do not have pernicious anaemia. If an association between the achlorhydic state and these infections is found, then very low stomach acid levels is probably also the mechanism of the increased risk of pneumonia and Clostridium difficile infection in people who have received acid suppression medication.
The aim of this study is to determine the risk of pneumonia and Clostridium difficile diarrhoea in patients with pernicious anaemia. This is a retrospective cohort study conducted in CPRD and utilising linked HES data where available. The exposed group will be patients who have a diagnosis of pernicious anaemia and who have been treated with vitamin B12 therapy. Exposed patients will be matched with ten non-pernicious anaemia patients in terms of age, gender, and general practice. Pneumonia and Clostridium difficile are the primary outcomes in this study. Cox regression analysis will be used to determine the hazard ratio for the associated outcome with pernicious anaemia. Potential confounders will be controlled in the Cox regression analysis.
Timothy Card - Chief Investigator - University of Nottingham
Fatmah Othman - Corresponding Applicant - University of Nottingham
Colin Crooks - Collaborator - University of Nottingham
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation