Differences in disease severity of F508del homozygotes across European countries

Introduction: Significant phenotypic variation occurs even among patients carrying identical CFTR genotype. This suggests that other factors, such as modifier genes and environmental factors, contribute to the determination of CF severity. The aim of this study is to compare clinical characteristics of patients carrying the common genotype (F508del/F508del) across European countries. Patients: We analysed data from 6663 F508del homozygous patients from 15 countries, included in the European CF Registry in the year 2007. The frequency of F508del homozygotes varies from 70% in Denmark to 11% in Israel. We evaluated differences in clinical characteristics of CF including pulmonary function, anthropometric data, complications, and therapy. Results: Statistically significant (p<0.01) differences were found across countries in median FEV1% (59−91%), proportion of patients with BMI<2 SDS (4−37%), prevalence of chronic Pseudomonas aeruginosa infection (2−56%), meconium ileus (3−19%), liver disease (2−36%), use of inhaled antibiotics (3−95%) and use of inhaled rhDNase (4−85%). Discussion: The differences in disease severity found among patients with the same genotype but living in different countries suggest that environmental and therapeutic factors play an important role in determination of CF disease severity. These could be also due to different therapeutic strategies. Further studies are needed in order to determine if these differences are due to lack of standardization of variable definitions, to missing data points or to true differences in patients care in different countries. Standardization of care according to countries where disease is less severe might be needed.