(18) Worlds apart: Comparing cystic fibrosis (CF) registry cohorts in South Africa and Canada

Background: Significant differences in epidemiology and outcomes of CF are expected between low-middle income and high-income countries but comparative data are lacking. Comparing CF outcomes between countries may be helpful for planning targeted interventions and advocacy for improved care where outcomes are less favourable. This study compared South African (SA) and Canadian CF registries’ health outcomes and explored factors that potentially explain differences in outcomes.

Methods: A descriptive cross-sectional study of harmonized SA and Canadian CF registries’ data for period 1 January to 31 December 2018. Demographic, clinical and outcome variables were compared by calculating standardized mean differences (SMD) between countries with SMD > 10 considered clinically important. Genotypes were classified as minimal function (class I-III) or residual function (class IV-VI) CFTR mutations and P.aeruginosa infection status as any in 2018. Outcomes compared were best, stable forced expiratory volume in 1 second percent predicted (FEV1pp) using ethnic-specific Global Lung Initiative references standards; and body mass index (BMI). Poor nutrition was defined as BMI z-score < -1 in children and BMI < 18.5 kg/m² in adults. Multivariable regression modelling was performed to adjust for population differences in pre-selected variables. People on CFTR modulators and lung transplant recipients were excluded from formal analyses.

Results: Data on 4049 Canadian and 446 SA people were analysed after excluding 585 Canadians on CFTR modulators. Compared to Canada, SAs were younger (median age 15.8 years vs. 24.1 years: SMD 52) with fewer males (47.8 % vs 54.2%; SMD 12.5) and Caucasians (70.9 % vs. 93.3%; SMD 61.3). Age of diagnosis was similar in both countries, but more children were diagnosed by newborn screening in Canada compared to SA (n=550 vs. n=1, SMD 54.6). Frequency of class I-III CFTR mutations was similar in SA (n= 384, 86 %) and Canada (n=3426, 85 %) with similar allele frequency of F508del (SA 80% vs. Canada 84 %). In SA, 3120+1G >A (class I) was the second most prevalent mutation (allele frequency 9.9%). P.aeruginosa was isolated more frequently in SA than Canada (SA n= 192, 43.0% vs Canada n= 1458, 36.0%; SMD 26.3). Three hundred and seventy-six (9.3%) Canadians received a lung transplant in 2018 or earlier compared to 11 (2.5 %) in SA . FEV1pp was significantly lower across all ages in SA compared to Canada including children aged 6-12 years (Figure 1), and poor nutrition significantly more prevalent across all age groups in SA compared to Canada, (SA n=91, 22.5% vs Canada 373, 11.0 %: SMD 31.2, including children aged 0-6 years. After adjusting for age, sex, diagnosis age, genotype, and P.aeruginosa infection and nutrition (lung function model), FEV1pp was 11% lower (95% CI -13.35 to -8.21) and poor nutrition 1.8-fold more likely (95% CI 1.37-2.42) in SA compared to Canada.

Conclusions: : Lung function and markers of nutrition are significantly lower in people with CF in SA compared to Canada. Non-biological factors such as lack of newborn screening, early life factors, poor socioeconomic circumstances, different standards of CF care and limited access to CFTR modulators and lung transplantation may be important determinants of CF outcomes in SA. Analysis to explain disparities in CF outcomes between SA and Canada are ongoing.

Acknowledgements: This work is supported by the Cystic Fibrosis Foundation (ZAMPOL19KO), the Harry Crossley Foundation and the Molly McNeil Family Trust.

References: