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.

TITLE: CLINICAL EVIDENCE OF PANCREATIC RECOVERY IN CHILDREN WITH CYSTIC FIBROSIS ON IVACAFTORTo the Editor,Pediatric research has shown that young children with cystic fibrosis (CF) and treated with ivacaftor have seen improvements in pancreatic function. KIWI was a 24-week safety and efficacy trial of ivacaftor in children aged 2-5 years with CF (1). KLIMB was an 84-week open label extension of KIWI (2). Patients enrolled in KIWI revealed an average increase of 99.8 ug/g in fecal elastase (FE). Before beginning ivacaftor, 26 of 27 patients were pancreatic insufficient. After 24 weeks, 25% of these 26 patients had FE results demonstrating pancreatic sufficiency (>200 ug/g) (1). These improvements in FE were maintained during the 84-week KLIMB extension (2).In the ARRIVAL Study, a younger population was studied. Infants aged 12-24 months previously diagnosed with pancreatic insufficiency were assessed (3). After 24 weeks post ivacaftor initiation, six of nine, or 67%, of the infants had repeat FE values of >200 ug/g, consistent with pancreatic sufficiency, as well as evidence of decreased pancreatic inflammation noted with reduction in immunoreactive trypsinogen.Based on this data we instituted a new protocol for repeat FE monitoring in all patients with pancreatic insufficiency who started on ivacaftor by the age of two years. If FE is normal (>200 ug/g), discontinuation of pancreatic enzyme replacement therapy (PERT) is considered along with ongoing monitoring of clinical symptoms and adjustments to vitamin and diet recommendations as indicated.Below is a review of our cohort of pediatric patients who were currently, had been consistently treated with ivacaftor, and were assessed for current pancreatic function by repeat FE testing. All FE values were collected prior to initiation of elexacaftor/tezacaftor/ivacaftor (ETI) in those newly eligible. Nine patients at our CF center who were on PERT have started ivacaftor in the last 6 years with a mean current age of 4.9 years (SD 1.7). The median age of ivacaftor initiation was 1.1 years (range 0.4 - 2). The mean duration of treatment is 3.9 years (SD 1.3).Seven patients had a repeat FE result >200 ug/g. Six of the seven pancreatic insufficient patients presented as newly pancreatic sufficient as evidenced by a FE result of >200 ug/g compared to previous result of <200 ug/g. Patient I was included in this cohort as he was treated with PERT for clinical symptoms of pancreatic insufficiency even though his baseline FE values were above 200 ug/g.The six newly pancreatic sufficient patients started ivacaftor between 0.4 and 1.1 years of age. Our recovery data of 75% is close to the rate seen in the ARRIVAL study. We calculated binomial probability for pancreatic recovery in this small case control series using 0.67 factor based on previous data in ARRIVAL (4). This resulted in a 28% favorability of success.Unsurprisingly, the rate of recovery was higher in the younger age of initiation of ivacaftor than that seen in the older 2–5 year-old cohort in KIWI. A correlation between pancreatic recovery and younger age of initiation was also noted in a recently published multi-center retrospective study of all available CFTR modulators and PE recovery (5). In this study, of the 15 patients with FE results of 200 or greater, 10 had been treated with ivacaftor as their initial modulator therapy. Based on the demographic data, 62.5% of those treated with ivacaftor had pancreatic recovery, which is similar to our cohort data.We urge CF Centers to institute clinical protocols to recheck pancreatic elastase to assess for restoration of pancreatic function in all pediatric patients treated with PERT on ivacaftor. Subsequently, CF Centers should establish processes for discontinuing PERT, monitoring fat soluble vitamins, and adjusting diet as indicated. Resulting medication adjustments will significantly impact the treatment burden and cost for these children and their families. Those with pancreatic restoration should be monitored for symptoms of pancreatic insufficiency as well as growth trends at routine intervals and pursue repeat FE as indicated based on clinical assessment.This study was approved by the Oregon Health and Science University Institutional Review Board (IRB#26442).

Introduction: To help open the clinician dialogue regarding cannabis use in persons with CF in the U.S., we aimed to describe current practices of use assessment and documentation processes related to cannabis. Methods: A cross sectional, anonymous survey study was distributed via email to CF directors and coordinators and to the Cystic Fibrosis Foundation (CFF) listservs of nurse, pharmacist, dietitian, social worker and psychology care team members. The survey tool included multiple choice, scaled and open ended items, which assessed participants’ awareness of current cannabis laws in their state, prescribing practices for medical marijuana, screening and documentation practices, knowledge of and what indications participants believe cannabis and cannabidiol (CBD) could be beneficial. Data was analyzed using descriptive statistics. Results: There were 282 survey participants, with majority as providers (28%) and social workers (29%), representing all U.S. regions. Participants varied in terms of frequency of evaluating cannabis use, with 15.4% “always,” 48.4% “sometimes,” and 41% “rarely” or “never” asking about it. Regarding recreational versus medical cannabis use, 55.4% and 62.5% reported documentation of each type in the medical record, respectively. Participants reported appetite, pain, and nausea as the top three advocated indications for use. About 35% and 72% of participants felt “slightly” or “not at all” prepared to answer patient/family questions about cannabis and CBD, respectively. Conclusions: The approach to cannabis use assessment, documentation, and education across CF care centers is variable. There is a need for care team and patient/caregiver education materials about cannabis/CBD and CF.

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.