(25) Impact of repeated non-treatment on long-term lung function

Background: Previous findings from the Epidemiologic Study of Cystic Fibrosis (ESCF) indicated that more consistent treatment of declines in FEV₁ ≥10% from baseline in people with CF (PWCF) was associated with better pulmonary outcomes, yet, over a third of declines were not treated. However, data are lacking from a more recent cohort and regarding the impact of repeated untreated declines. Our objective was to determine the prevalence of untreated lung function declines in a pediatric cohort and evaluate the impact of repeated non-treated declines on the probability of FEV₁ percent predicted (FEV₁pp) recovery to 100% of baseline.

Methods: We included PWCF aged 6 to ≤17 years followed in the CF Foundation Patient Registry between 2016-19. Baseline FEV₁pp was the average of the highest three FEV₁pp recorded during a period of stability spanning 30-365 days. We assessed relative decreases in FEV₁pp from baseline between 2017 and 2018. PWCF must have ≥3 relative declines of at least 5% within a 12-month window and have a follow-up FEV₁pp in 2019 to determine if individuals returned to baseline. Treatment within 28 days of decline was categorized as any (IV antibiotics, oral or inhaled antibiotics (non-IV antibiotics)) versus no antibiotic treatment. We defined our exposure of repeated non-treatment as 50% or more decline events not treated by any antibiotic therapy. Alternate definitions of repeated non-treatment were tested in sensitivity analyses.

Results: A total of 4,088 children were reported to have at least 3 declines of >5% in a 12-month window between 2017-2018. We identified 2,826 (69.1%) individuals who experienced repeated non-treatment and 1,262 (30.9%) children with >50% of their decline events having received any antibiotic therapy within 28 days. Children who experienced repeated non-treatment had a median (IQR) baseline age of 11.6 years (9.2, 14.7) and baseline FEV₁pp of 96.7% (85.4, 106.0). The group for whom at least half of their declines were treated had a median age (IQR) of 13.5 years (10.1, 15.8) and baseline FEV₁pp of 85.9% (72.7, 96.8). Among the group who experienced repeated non-treatment, 35.5% returned to 100% or more of their baseline compared to 59.7% of the group which received more frequent antibiotic treatment.

Conclusions: We found a substantial proportion of pediatric PWCF with multiple declines of at least 5% are not being treated with antibiotic therapy, especially in those with high baseline FEV₁pp. Children who experienced repeated non-treatment were younger and had over 10% higher baseline FEV₁pp compared to children more frequently treated with antibiotic therapy, and two-thirds did not return to baseline by the end of 2019. Next steps include modeling FEV₁pp to evaluate whether repeated non-treatment is associated with an accelerated decline in lung function.

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