DISCUSSION
Disparities in CF survival are the result of a deeply complex interaction between many factors, with SES playing a conspicuous role. Worldwide, median survival in patients with CF varies from country to country; it is estimated between 40 – 50 years, with a lower median survival and worse prognosis in female patients.2, 15, 20 With current treatment strategies, most patients will be able to reach adulthood; however, it remains a life-shortening disease. In addition, new therapies with CFTR modulators and inhaled antibiotics are not widely available in low-middle income countries, such as Mexico, issues that decidedly limit survival in CF patients.
Among factors that influence survival, socioeconomic status plays a major role in CF as in many other chronic diseases.13, 21, 22 The low SES is related to food insecurity, air pollution, reduced access to prompt diagnosis, and specialized treatments due to their high cost and a lack of healthcare coverage.23Patients with low SES and CF have higher mortality,24worse lung function,25 lower body mass index, more pulmonary exacerbations,26 and higher risk of P. aeruginosa infection.27
In addition, chronic infection with P. aeruginosa is a factor closely linked to the SES in Mexico, as many low-income children do not have access to inhaled antibiotics. The only inhaled antibiotic available (tobramycin) costs around $2000 dollars per month and is not supplied by social security institutions that provide care for more than half the patients. As previously reported by our group, Mexican CF patients tend to have their first infection with P. aeruginosaearly in life, 28 while a significant percentage (37%) present chronic infection with this bacterium at 6 years of age.
In the present study, patients with low SES were four times more likely to have shortened survival, compared to their high SES counterparts; median survival for the low SES group was half that observed in the high-income group. Chronic infection with P. aeruginosa and pancreatic insufficiency, along with low SES, were independent predictors of mortality.
Regarding CFTR genotypes and their connection to median survival, no significant difference was observed in the study population. Yet, patients with pancreatic insufficiency, a marker for severe mutations, had significantly lower survival rates than those with sufficiency.
In relation to the CFTR genotype, the risk of meconium ileus (MI) varies between 12.5% to 24.9%, as reported by the United States Patient Registry.29 In our cohort, the frequency of MI was 7.8%. A similar frequency (7.3%) was reported by another group in Mexico.30 This low prevalence rate may be attributed to high heterogeneity in CFTR mutations found in the Mexican population.31
In our study, CF-related diabetes was present in 7.3% of patients, while in the literature the incidence varies according to age, from 2.5% in children and reaching 40 – 50% in adults.10, 12 This relatively low frequency may be due to the cohort being comprised of a young population, as the number of patients who reached adulthood remained low.
As previously mentioned, gender is an additional factor that impacts survival. The cause of this gender gap in CF remains unclear, but some studies suggest that it may be related to reduced activity levels, poor nutritional status, and the effect of estrogens in female patients.32-34 In this cohort, male patients had greater survival, but this difference was statistically insignificant.
In our population, median survival was 21.4 years, with these values ​​below the median reported in high-income countries; for example, Canada has a median survival of 49.7 years.2 These data must be interpreted, while looking at several limitations: the study was conducted in a single center in North Mexico, its retrospective nature, and mutation analysis was not available to all patients. Despite these limitations, our study provides valuable information as its design, based on longitudinal follow-up by the same specialized team, minimized results bias as a consequence of heterogeneity in therapeutic interventions. Moreover, there is scarce information on survival in patients residing in Latin America, especially in Mexico.
In conclusion, socioeconomic status plays a decisive role in CF patient survival, together with P. aeruginosa chronic infection, independent risk factors which are closely linked. To increase patient survival in low-income countries, public health authorities must design policies that fully cover diagnosis and treatment strategies in the CF population.
Acknowledgments: None
Conflict of Interest: The authors have no conflict of interest to declare.