A New Era of Cystic Fibrosis: Decreased Hospitalizations and Ongoing Challenges

Research study background

Pulmonary exacerbations in children and young adults with cystic fibrosis (CF) are associated with long-term declines in pulmonary function, quality of life and survival. Viral infections are common triggers, and risk factors for severe exacerbations requiring IV antibiotics include aging, lower lung function, prior exacerbations and economic hardship.

In 2019, the U.S. Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ETI) therapy for people with CF with at least one copy of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene. Several studies have demonstrated ETI can improve the function of the CFTR protein leading to profound health improvements.

Five U.S. CF Foundation-accredited centers, including the Mike McMorris Cystic Fibrosis Research and Care Center at Children’s Hospital Colorado, sought to assess demographic and clinical characteristics of people with CF hospitalized and treated with IV antibiotics for pulmonary exacerbations before and after ETI approval. The retrospective study analyzed 2018 and 2022 hospitalization data for qualifying patients up to 25 years old. 

Across the centers, there was a 65% reduction in the number of hospitalizations for pulmonary exacerbations from 2018 to 2022, and the proportion of multiple exacerbations within one year decreased by nearly half. While this decline strongly suggests a clinical benefit of ETI therapy, researchers noted a concerning shift: growing health disparities among minoritized groups with CF. In comparison to 2018, more hospitalized individuals with CF identified as people of color or Hispanic/Latino in 2022, and they were more likely to have two non‐F508del CFTR mutations, which are not responsive to ETI.

Investigators also compared the microbiologic characteristics of respiratory samples collected from the 2018 and 2022 cohorts. They found a lower proportion of methicillin‐resistant Staphylococcus aureus (MRSA) infections during the 2022 hospitalizations. In 2022, children on CFTR modulator therapy (the majority were on ETI), had fewer Pseudomonas aeruginosa and Achromobacter xylosoxidans infections than those that weren’t.

The data show a substantial reduction in hospitalizations and evolving demographic and microbiological profiles of children with CF who require inpatient care for pulmonary exacerbations. These findings support the transformative role of ETI in CF care and also emphasize the need for tailored strategies to address health disparities and expand access to effective therapies for the entire CF population.

Relevance to future research

Future research should include targeted efforts to improve outpatient monitoring of children with CF from minoritized groups who remain at high risk for severe pulmonary exacerbations and are less likely to be eligible for or prescribed CFTR modulators like ETI.

Currently, this multicenter team is focused on developing novel therapies for CF, including investigating bacteriophage (“phage”) therapy for drug-resistant infections. This retrospective review provided preliminary data on bacterial pathogens in hospitalized children with CF which will help researchers estimate the number of participants eligible for proposed clinical trials.