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Background: Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants., Methods: PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV 1 ) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively., Results: A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV 1 % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators., Conclusions: Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations., Competing Interests: Conflict of interest: E.A. Cromwell reports support for the present study from the Cystic Fibrosis Foundation. J.S. Ostrenga has nothing to disclose. D.B. Sanders reports support for the present study from the Cystic Fibrosis Foundation (CFF), grants from the CFF, consultancy fees from the CFF for roles on the Registry Committee, Data Safety Monitoring Board (DSMB) and Grant Review Committee, and participation on a DSMB or Advisory Board with the CFF. W. Morgan reports support for the present study from the Cystic Fibrosis Foundation (CFF) as a paid consultant for work on the CFF Registry Committee, covering a range of activities including papers, analyses and reviews of protocol/data requests; additionally, grants were received from the NIH/NHLBI for the ORBEX study (Site PI and Executive Committee) and the Tucson Children's Respiratory Study, from Boston Children's Hospital/Harvard for consultancy to the PARK study (NIH/NIAID), and from the CFF for Data Safety Monitoring Board (DSMB) infrastructure; consultancy fees were also received from the CFF for DSMB-related activities; payment for lectures was received from the American College of Chest Physicians for the 2022 Pediatric Pulmonology Board Prep Course; support for attending meetings was provided by the CFF for travel to the CFF DSMB meeting in April 2023; participation on a DSMB or Advisory Board includes serving as Chair of the CFF DSMB, chairing several DSMBs for CF clinical research trials and participation on the NIH/NHLBI PRIMERO Observational Study Monitoring Board. C. Castellani reports participation on a Data Safety Monitoring Board or Advisory Board with Vertex and Chiesi. R. Szczesniak reports payment or honoraria for lectures, presentations, manuscript writing or educational events from the Cystic Fibrosis Foundation (CFF) Patient Registry Committee; additionally, support for attending meetings and/or travel was provided by the CFF Patient Registry Committee. P-R. Burgel reports grants or contracts from GSK and Vertex, and consultancy fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Sanofi, Viatris, Vertex and Zambon., (Copyright ©The authors 2024.)

We conducted a descriptive analysis of people with CF 40 years of age and older using CF Foundation Patient Registry data from 2022 to provide a current estimate of the population size and characteristics. We summarized demographic details including biological sex, race, ethnicity, insurance and employment status. Clinical data including body mass index, lung function, respiratory infections, hospitalization rates, prevalence of CF-related complications and CF therapy prescriptions were collated. A total of 5,243 individuals aged 40 years or older contributed data to the CFFPR: 2,687 (51 %) people aged 40-49 years; 1,410 (27 %) people aged 50-59 years; and 1,146 (22 %) people aged 60 years or older. The ≥60 year old group have unique characteristics compared to younger individuals, with later diagnosis of CF and greater proportion of females (58 %). These results highlight heterogeneity in the older CF adult population and the need to develop and individualize CF care practices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elizabeth Cromwell and Josh Ostrenga report financial support was provided by Cystic Fibrosis Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study aims to characterize the uptake of elexacaftor/tezacaftor/ivacaftor (ETI) following Food and Drug Administration (FDA) approval in October 2019., Methods: People with cystic fibrosis (PwCF) ≥12 years enrolled in the CF Foundation Patient Registry (CFFPR) from 2019-2022 with at least one copy of F508del were included. We calculated summary statistics according to ETI prescription status. We used a Kaplan-Meier estimator to determine median days to ETI prescription to identify differences in prescription uptake by lung function, race, and ethnicity and a Cox proportional hazards model to identify risk factors associated with timing of first ETI prescription., Results: A total of 17,183 people (91 %) were prescribed ETI. The median time to prescription was 121 days (95 % CI: 119, 122), with 75 % prescribed within 311 days (95 % CI: 301, 325). PwCF prescribed ETI were younger, had lower lung function, more pulmonary exacerbations in the prior year, earlier age of diagnosis, and were more likely to have been prescribed another CFTR modulator (if eligible). Public health insurance, ppFEV 1 >90, Black race and Hispanic ethnicity were associated with lower hazards (e.g., later) of ETI prescription whereas prior modulator prescription, pancreatic insufficiency, increased exacerbation frequency and prior infections were associated with a higher hazard (earlier) of prescription., Conclusions: While over 90 % of eligible individuals were prescribed ETI within three years, time of first prescription was associated with demographic factors and disease severity. Further research should investigate the reasons for this delay and approaches to reduce time to initiation for ETI and future therapies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Rationale: Declines in percent predicted forced expiratory volume in 1 second (ppFEV 1 ) are an important marker of clinical progression of cystic fibrosis (CF). Objectives: We examined ppFEV 1 variability in relation to a combined outcome of lung transplant or death. Methods: We estimated the association between ppFEV 1 variability and the combined outcome of lung transplant or death. We included children aged 8 years and older with CF and two prior years of ppFEV 1 data before baseline between 2005 and 2021. We defined ppFEV 1 increased variability as any relative increase or decrease of at least 10% in ppFEV 1 from a 2-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV 1 variability, defined as the cumulative proportion of visits with ppFEV 1 variability at each visit. Kaplan-Meier survival curves were generated on the basis of quartiles of the cumulative distribution of ppFEV 1 variability. Results: We included 9,706 patients with CF in our cohort. The median age at cohort entry was 8.3 (interquartile range, 8.2-8.4) years; 50% of patients were female; 94% were White; and the median baseline ppFEV 1 was 94.4 (interquartile range, 81.6-106.1). The unadjusted hazard ratio for increased ppFEV 1 variability on lung transplant/mortality was 4.13 (95% confidence interval, 3.48-4.90), and the weighted hazard ratio was 1.49 (95% confidence interval, 1.19-1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV 1 variability increased. Conclusions: We found a strong association between ppFEV 1 variability and lung transplant or mortality in a cohort of people with CF in the United States.

Background: The benefit of antibiotic treatment of acute drops in FEV 1 percent predicted (FEV 1 pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant., Methods: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV 1 pp and return to 100% baseline FEV 1 pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category., Results: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV 1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%., Conclusions: A large proportion of acute drops in FEV1 pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV 1 , including those of a magnitude previously believed to be associated with self-recovery., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background and Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR)., Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years., Results: From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life., Conclusions: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy., (© 2024 Wiley Periodicals LLC.)

There is paucity of literature on the health outcomes following liver transplantation (LT) in people with cystic fibrosis (pwCF). We aim to evaluate changes in lung function following LT in pwCF. We performed a retrospective cohort study of pwCF who underwent LT between 1987 and 2019 in the United States and Canada. Simultaneous lung-liver transplants and individuals who had lung transplant prior to LT were excluded. We analyzed pre-LT and post-LT percent predicted forced expiratory volume in 1 second, body mass index, rates of pulmonary exacerbation, and post-LT overall survival. A total of 402 LT recipients were included. The median age of transplant was 14.9 years and 69.7% of the transplants were performed in children less than 18 years old. The rate of decline in percent predicted forced expiratory volume in 1 second was attenuated after LT from -2.2% to -0.7% predicted per year with a difference of 1.5% predicted per year (95% CI, 0.8, 2.2; p < 0.001). Following LT, the rate of decline in body mass index was reduced, and there were fewer pulmonary exacerbations (0.6 pre vs. 0.4 post; rate ratio 0.7, p < 0.01). The median survival time post-transplant was 13.9 years and the overall probability of survival at 5 years was 77.6%. Those with higher lung function pre-LT had a lower risk of death post-LT, and those with genotypes other than F508 deletion had worse survival. LT in pwCF occurs most often in children and adolescents and is associated with a slower rate of decline in lung function and nutritional status, and a reduction in pulmonary exacerbations., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Introduction: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF)., Methods: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years., Results: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%)., Conclusions: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Deaths among those lost to follow-up (LTFU) in the Cystic Fibrosis Foundation Patient Registry (CFFPR) are critically important to the epidemiology of cystic fibrosis (CF). Unreported deaths could impact estimates of survival if LTFU is associated with disease trajectory., Methods: We characterized the LTFU population (1986-2017) from the CFFPR and identified deaths via linkage with the National Death Index (NDI). Median predicted survival age and conditional survival were estimated with and without additional deaths and person-time from the NDI., Results: Of the 10,582 individuals LTFU in the CFFPR, 2,460 (23.2%) matched to an NDI death record. Individuals who died after LTFU with a CF diagnosis were 43% female, 91% White/non-Hispanic, 59% had advanced CF lung disease based on last CFFPR recorded forced expiratory volume in one second (FEV 1 ) %predicted <40 and 18% were post-lung transplant. Median predicted survival age during the most recent period available, 2013-2017, increased from 44.3 years (95% CI: 43.2, 45.7) to 45.8 years (95% CI 44.5, 47.1) with the inclusion of NDI data., Conclusions: Inclusion of deaths and additional person-time among those LTFU changed the point estimate of median predicted survival for most time periods and increased the point estimate from 2009 onwards., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rationale: Studies estimating the rate of lung function decline in cystic fibrosis have been inconsistent regarding the methods used. How the methodology used impacts the validity of the results and comparability between studies is unknown. Objectives: The Cystic Fibrosis Foundation established a work group whose tasks were to examine the impact of differing approaches to estimating the rate of decline in lung function and to provide analysis guidelines. Methods: We used a natural history cohort of 35,252 individuals with cystic fibrosis aged ⩾6 years in the Cystic Fibrosis Foundation Patient Registry (CFFPR), 2003-2016. Modeling strategies using linear and nonlinear forms of marginal and mixed-effects models, which have previously quantified the rate of forced expiratory volume in 1 second (FEV 1 ) decline (percent predicted per year), were evaluated under clinically relevant scenarios of available lung function data. Scenarios varied by sample size (overall CFFPR, medium-sized cohort of 3,000 subjects, and small-sized cohort of 150), data collection/reporting frequency (encounter, quarterly, and annual), inclusion of FEV 1 during pulmonary exacerbation, and follow-up length (<2 yr, 2-5 yr, entire duration). Results: Rate of FEV 1 decline estimates (percent predicted per year) differed between linear marginal and mixed-effects models; overall cohort estimates (95% confidence interval) were 1.26 (1.24-1.29) and 1.40 (1.38-1.42), respectively. Marginal models consistently estimated less rapid lung function decline than mixed-effects models across scenarios, except for short-term follow-up (both were ∼1.4). Rate of decline estimates from nonlinear models diverged by age 30. Among mixed-effects models, nonlinear and stochastic terms fit best, except for short-term follow-up (<2 yr). Overall CFFPR analysis from a joint longitudinal-survival model implied that an increase in rate of decline of 1% predicted per year in FEV 1 was associated with a 1.52-fold (52%) increase in the hazard of death/lung transplant, but the results exhibited immortal cohort bias. Conclusions: Differences were as high as 0.5% predicted per year between rate of decline estimates, but we found estimates were robust to lung function data availability scenarios, except short-term follow-up and older age ranges. Inconsistencies among previous study results may be attributable to inherent differences in study design, inclusion criteria, or covariate adjustment. Results-based decision points reported herein will support researchers in selecting a strategy to model lung function decline most reflective of nuanced, study-specific goals.

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) collects data on individuals with cystic fibrosis (CF) in the United States (US). In 2012, the US CF population was estimated at 33,292 to 34,327 individuals, with 81-84% CFFPR participation., Methods: In this study, we update these estimates via simulation to account for uncertainty in CF incidence by race or Hispanic ethnicity, initiation of CF newborn screening (NBS) programs by state, and updated cumulative survival for CF births 1968-2020. We defined registry participation as the proportion of individuals alive as of 2020 with any prior CFFPR participation as well as the proportion with contributing data in 2019 or 2020; we summarize CFFPR participation for those born prior to 1968., Results: We estimated the 2020 prevalent CF population between 1968-2020 to be 38,804 (95% Uncertainty Interval (UI): 38,532 to 39,065) individuals, with 77% of the prevalent CF population contributing recent data. CFFPR participation differs by age (54% of those born in 1968) and exceeds >90% of the population born in 2009 or later., Conclusions: We demonstrate that the CFFPR remains a valid data source generalizable to the CF population. High participation among younger individuals may reflect the success of newborn screening programs and early referral to CF care. If engagement can be sustained, the percentage of individuals participating in the CFFPR will grow over time and there is an opportunity to identify factors associated with loss to follow up among older individuals to optimize the quality of the CFFPR data., Competing Interests: Conflict of interest statement The authors have no conflict of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rationale: A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results., Objectives: To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences., Methods: We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections ( Pseudomonas aeruginosa , Staphylococcus aureus ) and treatments (rhDnase, hypertonic saline, inhaled antibiotics)., Results: We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK., Conclusions: Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation., Competing Interests: Competing interests: DKS, SC and DT-R were supported by the Strategic Research Centre 'CF-EpiNet: Harnessing data to improve lives' funded by the Cystic Fibrosis Trust. DT-R is funded by the MRC on a Clinician Scientist Fellowship (MR/P008577/1). RS was supported by grants from the Cystic Fibrosis Foundation (SZCZES18AB0) and NIH/NHLBI (R01 HL141286). CHG was supported by grants from the Cystic Fibrosis Foundation, the NIH (UM1 HL119073, P30 DK089507, U01 HL114589, UL1 TR000423) and the FDA (R01 FD003704). RHK is supported by a UKRI Future Leaders Fellowship (MR/S017968/1)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Understanding how health outcomes differ for patients with advanced cystic fibrosis (CF) lung disease living in the United States compared with Canada has health policy implications., Research Question: What are rates of lung transplant (LTx) and rates of death without LTx in the United States and Canada among individuals with FEV 1  < 40% predicted?, Study Design and Methods: This was a retrospective population-based cohort study, 2005 to 2016, using the US CF Foundation, United Network for Organ Sharing, and Canadian CF registries. Individuals with CF and at least two FEV 1 measurements < 40% predicted within a 5-year period, age ≥ 6 years, without prior LTx were included. Multivariable competing risk regression for time to death without LTx (LTx as a competing risk) and time to LTx (death as a competing risk) was performed., Results: There were 5,899 patients (53% male) and 905 patients (54% male) with CF with FEV 1  < 40% predicted living in the United States and Canada, respectively. Multivariable competing risk regression models identified an increased risk of death without LTx (hazard ratio [HR], 1.79; 95% CI, 1.52-2.1) and decreased LTx (HR, 0.66; 95% CI, 0.58-0.74) among individuals in the United States compared with Canada. More pronounced differences were seen in the patients in the United States with Medicaid/Medicare insurance compared with Canadians (multivariable HR for death without LTx, 2.24 [95% CI, 1.89-2.64]; multivariable HR for LTx, 0.54 [95% CI, 0.47-0.61]). Patients of nonwhite race were also disadvantaged (multivariable HR for death without LTx, 1.56 [95% CI, 1.32-1.84]; multivariable HR for LTx, 0.47 [95% CI, 0.36-0.62])., Interpretation: There are lower rates of LTx and an increased risk of death without LTx for US patients with CF with FEV 1  < 40% predicted compared with Canadian patients. Findings are more striking among US patients with CF with Medicaid/Medicare health insurance, and nonwhite patients in both countries, raising concerns about underuse of LTx among vulnerable populations., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Previous literature in cystic fibrosis (CF) has shown a 10-year survival gap between Canada and the United States (US). We hypothesized that differential access to and survival after lung transplantation may contribute to the observed gap. The objectives of this study were to compare CF transplant outcomes between Canada and the US and estimate the potential contribution of transplantation to the survival gap., Methods: Data from the Canadian CF Registry and the US Cystic Fibrosis Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. The probability of surviving after transplantation between 2005 and 2016 was calculated using the Kaplan‒Meier method. Survival by insurance status at the time of transplantation and transplant center volume in the US were compared with those in Canada using Cox proportional hazard models. Simulations were used to estimate the contribution of transplantation to the survival gap., Results: Between 2005 and 2016, there were 2,653 patients in the US and 470 in Canada who underwent lung transplantation for CF. The 1-, 3-, and 5-year survival rates were 88.3%, 71.8%, and 60.3%, respectively, in the US compared with 90.5%, 79.9%, and 69.7%, respectively, in Canada. Patients in the US were also more likely to die on the waitlist (p < 0.01) than patients in Canada. If the proportion of who underwent transplantation and post-transplant survival in the US were to increase to those observed in Canada, we estimate that the survival gap would decrease from 10.8 years to 7.5 years., Conclusions: Differences in waitlist mortality and post-transplant survival can explain up to a third of the survival gap observed between the US and Canada., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The International Depression Epidemiological Study (TIDES) found elevated rates of screen positivity for depression and anxiety among individuals with cystic fibrosis (CF). Depression is associated with worse adherence and health-related quality of life in CF. We investigated the relationship with mortality., Methods: Subjects were untransplanted participants in TIDES 12+ years of age receiving care at one of 45 collaborating US CF care centers who completed the Hospital Anxiety and Depression Scale and/or Center for Epidemiologic Studies Depression Scale during a stable visit between 2006 and 2010. Clinical characteristics and mortality data were obtained from the CF Foundation Patient Registry. The association of a positive screen with 5-year survival was evaluated using Cox Proportional Hazards modeling., Results: Of 1005 eligible patients, 25% screened positive for depression and 34% screened positive for anxiety. Patients who screened positive for depression were more likely to be older, have a residual function mutation, public insurance, and more pulmonary exacerbations in the screening year. There were 96 deaths. The unadjusted 5-year Hazard Ratio (HR) for death among those with depression was 2.0; 95% CI (1.3, 3.0)]. When adjusted for predetermined potential confounders the HR for the entire population was 1.4; 95% CI (0.9, 2.2). The adjusted HR was higher in adults [1.6; 95% CI (1.0, 2.4)] and those screening in the severe range [2.0; 95% CI (1.2, 3.4)]. Anxiety was not associated with mortality., Conclusions: A positive depression screen is associated with increased mortality among adults with CF. Research into the etiology of this relationship is needed., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: Most studies of pulmonary exacerbations (PEx) in cystic fibrosis (CF) focus on intravenous (IV)-treated PEx, though most PEx are treated with oral antibiotics. Our objectives were to describe predictors of antibiotic choice and outcomes for PEx initially identified in clinic., Methods: For each patient in the U.S. CF Foundation Patient Registry, we selected the first PEx recorded at a clinic visit in 2013-14 following a clinic visit without a PEx. We used multivariable logistic regression to determine associations between clinical characteristics and antibiotic treatment choice. We determined outcomes in the 90 days after the first PEx., Results: Among 14,265 patients with a PEx initially identified in clinic, 21.4% received no antibiotics, 61.5% received new oral and/or inhaled antibiotics, and 17.0% had IV antibiotics within 14 days. Compared to IV antibiotics, patients more likely to receive new oral and/or inhaled antibiotics: were male, <13 years old, had BMI >10th percentile or 18.5 kg/m 2 , >90 days between clinic visits, FEV 1  > 70% predicted at the PEx, no prior-year IV-treated PEx, FEV 1 decline <10% predicted, and private insurance. Following the PEx, 30.3% of patients had no clinical encounters within 90 days. Treatment with IV antibiotics within 90 days occurred for 23.7% treated without antibiotics, 22.8% of new oral and/or inhaled antibiotics, and 27.1% of IV antibiotics., Conclusion: Most PEx identified in clinic are treated with new oral and/or inhaled antibiotics. Markers of disease severity are associated with antibiotic treatment choice. Many patients had no follow-up evaluation within 90 days of treatment., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)