Abstract
Background: Atopic eczema, hereinafter referred to as eczema, is a common inflammatory skin condition that predominantly affects children. The cause of eczema is not known; however, is it likely that a combination of genetic and environmental factors leads to its development. In addition, several studies have identified an association between water hardness and eczema, suggesting that this might be an environmental factor of interest in the aetiology of eczema.Objectives: The main objective of this thesis was to evaluate the role of water hardness in the development of eczema and to evaluate whether water hardness is an appropriate target for the prevention of eczema in early life.
Methods: A combination of methods was used to address these objectives: a systematic review and meta-analysis; an epidemiological analysis of an observational cohort, including evaluation of the interaction between water hardness and loss of function mutations in the skin barrier gene filaggrin (FLG); a pilot randomised controlled trial (RCT) to assess the feasibility of an eczema prevention trial using an ion-exchange water softener in the homes of neonates at high risk of eczema
Results: Systematic review: The systematic review identified a positive association between living in a hard water area and eczema in children. There was a lack of longitudinal data on water hardness and eczema risk. Whilst there was evidence that domestic water softeners do not improve objective disease severity in established eczema, studies on the prevention of eczema using domestic water softeners were not identified.
Epidemiological analysis: A longitudinal analysis of data from infants in the Enquiring About Tolerance study found no overall association between exposure to harder (> 257mg L-1 CaCO3) vs softer (≤ 257 mg L-1 CaCO3) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92-1·24. However, there was an increased incidence of eczema in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI2·03-3·66), and statistically significant interactions between hard water plus FLG and both risk of eczema (HR 1·80, 95% CI 1·17-2·78) and transepidermal water loss (0·0081g m-2 h-1 per mg L-1 CaCO3, 95% CI 0·00028-0·016).
Pilot RCT: Of 149 eligible pregnant women, the target number of women, 80 were randomised (54% of those screened). Almost all, 92%, of families in the intervention arm found the study acceptable. By 6 months of age, 27 infants (35%) developed visible eczema, 31% vs 41% in the water softener and hard water groups, respectively. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor diagnosed eczema by 6 months compared to the hard water arm (15% vs 23%).
Conclusions: There may be a role of water hardness in initiating skin inflammation in early life. There is evidence of an interaction between water hardness and FLG skin barrier gene mutations in the development of infantile eczema. The results from the pilot RCT indicate that a definitive RCT of water softeners for the prevention of eczema in high-risk infants is feasible and acceptable.
| Date of Award | 1 Aug 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Carsten Flohr (Supervisor) & Janet Peacock (Supervisor) |