A Multicentre Study of Environmental Factors on the Severity of Sickle Cell Disease
Authors: Tewari Sanjay , Piel Fred , Brousse Valentine , Inusa Baba PD , Telfer Paul , Menzel Stephan , De Montalembert Mariane , Gardner Kate , Fuller Gary , Thein Swee Lay , Rees David 
Published: October 2019

Abstract
Background:
Sickle cell disease (SCD) is a very variable condition, with some patients being asymptomatic and others admitted frequently to hospital. Genetic factors have been extensively investigated but only explain a small amount of the variability to date. Environmental factors are undoubtedly important, but have not been studied in depth, at least in part because of the difficulty of conducting these studies.
We have analysed the role of climatic, environmental and temporal factors in determining the frequency of hospital admissions in children with SCD to 4 large sickle cell centres in London and Paris.
Participants and Methods:
Clinical data were collected from 1st January 2007 to 31st December 2012. Inclusion criteria were children with SCD (HbSS and HbSC) between the ages of 0 and 17 years, admitted to hospital with acute pain, acute chest syndrome or fever. All children lived within 4 miles radius (London) or 10km (Paris) of the hospital. Data were collected using specific electronic patient records of SCD patients. Data were collected on the reason for admission, date and length of admission. Daily air quality records were collected from sites around Paris and London, including details of black smoke, particulate matter, nitric oxide, carbon monoxide, sulphur dioxide and ozone. Daily meteorological records were obtained from weather stations in London and Paris including wind speed, temperature, rainfall and humidity. Statistical analysis including time series studies were conducted using R software version 3.1.1.
Results: There were a total of 2717 admissions over the six year study period. Overall for the London hospitals there was a mean of 0.39 admissions/patient/year, with 1406 admissions for pain, 153 for acute chest syndrome and 417 for fever. The rate of admission/patient/year by cause for HbSS and HbSC across the London hospitals is shown in table below:
Table 1. Rates of admission/patient/year by cause Sickle genotype/cause of admission All London hospitals Institution A Institution B Institution C HbSS (Pain) 0.31 0.18 0.40 0.43 HbSS (Fever) 0.09 0.03 0.15 0.11 HbSS (acute chest syndrome) 0.04 0.03 0.04 0.04 HbSC (pain) 0.07 0.03 0.08 0.10 HbSC (fever) 0.03 0.01 0.04 0.05 HbSC (acute chest syndrome) 0.004 0.008 0.002 0.002
Overall admission numbers were significantly higher on Mondays and Tuesdays in London but there was no such variation in Paris (Table 2).
Table 2. Mean number of admissions on days of week in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Weekday Monday 0.75** 0.35 Tuesday 0.77** 0.36 Wednesday 0.66 0.36 Thursday 0.64 0.32 Friday 0.60 0.32 Saturday 0.51 0.20 Sunday 0.57 0.27
There was no seasonal variation in admission numbers in London, but significantly higher numbers of patients admitted in Paris during autumn and winter.
Table 3. Mean number of seasonal admissions in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Season Autumn 0.70 0.35** Spring 0.60 0.31 Summer 0.64 0.25 Winter 0.62 0.34**
Conclusion
In London, there is a 2-3 fold variation in admission rates for the same complications between different hospitals. Similarly there is a significant difference on the effects of season and weekday between Paris and London. These results are statistically stronger than many effects which are identified in genetic and therapeutic studies, and show the importance of environmental and cultural factors, which are potentially modifiable. The effect of weather and pollution on hospital admissions is currently being analysed.

Disclosures
No relevant conflicts of interest to declare.