Background: Modulator therapy restores CFTR function and has led to health benefits for persons with CF (PwCF) including lower rates of pulmonary exacerbations. It is unknown if modulators affect lung function trajectories after inpatient treatment of pulmonary exacerbations (PEx). Methods: We conducted a retrospective review of hospital encounters for PEx for subjects 6-25 years old admitted to a large tertiary care center from 2014-2021 in order to capture hospitalizations of individual PwCF before and after starting modulators. Descriptive analyses were used to characterize the population and lung function findings. Logistic regression analyses were conducted to assess the association between modulators and FEV1pp outcomes. Results: The study sample included 575 encounters representing 149 unique PwCF. Hospital encounters of PwCF taking modulator were associated with higher mean FEV1pp at baseline, midway, discharge, and follow-up assessments. Mean FEV1pp increased during inpatient treatment of APE with loss of lung function at follow-up regardless of modulator use. At follow-up, hospitalizations of PwCF taking modulators were associated with significantly higher probability of sustained improvement in FEV1pp from discharge (average treatment effect (ATE) 0.118, p<0.05). Conclusions: Hospitalizations for PwCF taking modulators were associated with higher lung function at all assessments. Inpatient treatment for PEx was associated with lung function recovery at discharge followed by loss of function at follow-up that was partially ameliorated by taking modulators.

Acute pulmonary exacerbation (APE) in CF is characterized by increased pulmonary symptoms attributed to an increase in inflammation. Antimicrobials, airway clearance and nutritional support remain the mainstay of therapy. However, when patients fail to improve, corticosteroids have been reported as an adjunct therapy. We retrospectively examined the use of rescue steroids in a children’s hospital during CF APE following at least one week of inpatient therapy without expected improvement from 2013 - 2017. 106 encounters, of 53 unique patients: aged 6-20 years; who had FEV1 percent predicted (FEV1pp) data at baseline, admission, midpoint, and discharge; and had admission duration of at least 12 days were studied. Encounters treated with steroids had less improvement at midpoint percent change from admission in FEV1pp (4.9, ±11.3) than admissions not given steroids change in FEV1pp=20.1, ±24.6; p-value<0.001. Failure to improve as expected was documented 98% of the time as the rationale for steroid use. At discharge, there was no difference in mean FEV1pp (p=0.76). Propensity matching was also evaluated and revealed no difference in admission, midpoint, or discharge FEV1pp between groups. Equally, no difference in FEV1pp at follow-up visit or in time until next APE was detected between groups. Moreover, delay in steroid therapy by waiting until the end of the second week increased length of stay. Secondary analysis for associations including gender, genotype, fungal colonization, or inhaled antimicrobials were non-significant. Our data suggest rescue use of corticosteroids during APE does not predictably impact important outcome measures in CF APE.