Analysis of iron status after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis.

BACKGROUND: Iron deficiency is highly prevalent in people with cystic fibrosis (PwCF). While elexacaftor/tezacaftor/ivacaftor (ETI) has shown remarkable improvements in respiratory symptoms in PwCF, the effect of ETI on iron status remains unknown. This study aims to identify the effect of ETI on iron status in PwCF. METHODS: A single-center retrospective cohort study of 127 adult PwCF was conducted to assess the impact of ETI on iron, ferritin, transferrin levels, and percent saturation of transferrin (PSAT). Data were collected from the electronic medical record from January 2017 to September 2022, encompassing 2 years before and after ETI initiation. The primary outcome was serum iron parameters: iron, ferritin, transferrin, and PSAT levels following ETI treatment. Secondary outcomes analyzed iron supplementation. Univariate and multivariate mixed-effects models were used for the analysis of ETI. RESULTS: After adjusting for covariates, following ETI initiation, the mean iron level increased by 20.24 µg/dL (p < .001), ferritin levels were 31.4% (p < .001) higher, PSAT showed a 5.09 percentage point increase (p < .001), and transferrin levels increased by 2.71 mg/dL (p = .439). Patients with and without iron supplementation experienced a significant increase in iron after ETI (p < .001). CONCLUSIONS: ETI is associated with a significant increase in iron, ferritin, and PSAT levels. Patients with and without iron supplementation demonstrated a significant increase in iron. This study shows the benefits of ETI on iron status in PwCF. However, further translational studies are required to understand the impact of ETI on iron absorption and metabolism in PwCF.

Real world study on elexacaftor-tezacaftor-ivacaftor impact on cholesterol levels in adults with cystic fibrosis.

INTRODUCTION: The introduction of the highly effective modulator therapy elexacaftor-tezacaftor-ivacaftor (ETI) has revolutionized the care of persons with cystic fibrosis (PwCF) with major improvements seen in lung function and body mass index. The effects of ETI therapy in real-world cohorts on other parameters such as cholesterol levels are largely unknown. METHODS: A single-center, retrospective chart review study was conducted to assess the change in lipid panels before and after ETI initiation. The study investigated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels using both a univariate and multivariate mixed-effects model to evaluate the change after initiation of ETI in a cohort of PwCF. RESULTS: There were 128 adult PwCF included in the analysis. Statistically significant changes were seen in both univariate and multivariate analyses for TC, LDL-C, and HDL-C. On multivariate analysis, TC increased by an average of 15.0 mg/dL after ETI initiation (p < 0.0001), LDL-C increased by an average of 9.3 mg/dL (p < 0.001), and HDL-C increased by an average of 3.8 mg/dL (p < 0.001) after ETI initiation. CONCLUSION: In this real-world cohort of PwCF, cholesterol parameters increased after initiation with ETI therapy. Further consideration may need to be given for PwCF in regards to screening for cardiometabolic risk factors as PwCF age as well as the potential need for cholesterol-lowering therapies.

Improved recognition of lung function decline as signal of cystic fibrosis pulmonary exacerbation: a Cystic Fibrosis Learning Network Innovation Laboratory quality improvement initiative.

INTRODUCTION: Cystic fibrosis (CF) is a systemic autosomal recessive condition characterised by progressive lung disease. CF pulmonary exacerbations (PEx) are episodes of worsening respiratory status, and frequent PEx are a risk factor for accelerated lung function decline, yet many people with CF (PwCF) go untreated at the time of decline. The goal of this quality improvement (QI) initiative was to improve recognition, treatment and follow-up of PEx in PwCF. METHODS: Using the Model for Improvement, the Cystic Fibrosis Learning Network (CFLN) initiated a QI innovation laboratory (iLab) with a global aim to decrease the rate of lung function decline in PwCF. The iLab standardised definitions for signals of PEx using a threshold for decline in forced expiratory volume in one second (FEV1) and/or changes in symptoms. The FEV1 decline signal was termed FIES (FEV1-indicated exacerbation signal). Processes for screening and recognition of FIES and/or symptom changes, a treatment algorithm and follow-up in the presence of a signal were tested concurrently in multiple settings. SPECIFIC AIMS: The specific aim is to increase the per cent of PwCF assessed for a PEx signal at ambulatory encounters and to increase the per cent of recommendations to follow-up within 6 weeks for PwCF experiencing a PEx signal. RESULTS: FIES recognition increased from 18.6% to 73.4% across all teams during the iLab, and every team showed an improvement. Of PwCF assessed, 15.8% experienced an FIES event (>10% decline in FEV1 per cent predicted (FEV1pp)). Follow-up within 6 weeks was recommended for an average of 70.5% of those assessed for FIES and had an FEV1pp decline greater than 5%. CONCLUSION: The CFLN iLab successfully defined and implemented a process to recognise and follow-up PEx signals. This process has the potential to be spread to the larger CF community. Further studies are needed to assess the impact of these processes on PwCF outcomes.

The Impact of CFTR Modulator Triple Therapy on Type 2 Inflammatory Response in Patients with Cystic Fibrosis.

Background Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF. Methods A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization. Results There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation. Conclusion This study shows reduction in IgE but no change in AEC after ETI therapy initiation. We think that the lack of influence on AEC argues against an impact on previously established T2 inflammation and that the reduction in IgE is likely related to antigen load reduction post ETI. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.

Social determinants of health screening and intervention: A cystic fibrosis quality improvement process.

INTRODUCTION: Lower socioeconomic status is associated with significantly poorer outcomes in weight, lung function, and pulmonary exacerbation rates in people with cystic fibrosis (PwCF). GLOBAL AIM: We aim to reduce health disparities and inequities faced by PwCF by screening for and addressing unmet social needs. SPECIFIC AIMS: We aimed to increase routine social determinants of health (SDoH) screening of eligible PwCF from 0% to 95% and follow-up within 2 weeks for those PwCF who screened positive and requested assistance from 0% to 95% by December 31, 2021. METHODS: The Model for Improvement methodology was used. A process map and a simplified failure mode effects analysis chart were created for the screening and SDoH follow-up process. For those who screened positive for SDoH and requested assistance, follow-up contact was made to offer intervention. INTERVENTION: Adult PwCF who had at least one UVA Clinic encounter in 2021 were screened for SDoH. The SDoH screening tool included eight domains: housing, food, transportation, utilities, health-care access, medication access, income/employment, and education. Follow-up was completed with all PwCF who screened positive for SDoH. RESULTS: A total of 132 of 142 (93.0%) PwCF eligible for screening completed the SDoH screening. Of the PwCF who completed screening, 56 (42.4%) screened positive for SDoH. A follow-up rate of 100% was achieved in June 2021 and maintained through December 2021. CONCLUSION: Implementing screening for SDOH and follow-up to mitigate social difficulties in adult PwCF at UVA was successful and could be reproduced at other CF care centers.

Mental health screening of patients with cystic fibrosis through telehealth during COVID-19: Evaluation of feasibility and process adoption.

INTRODUCTION: Persons with cystic fibrosis (CF) have higher rates of depression and anxiety compared to the general population. The Cystic Fibrosis Foundation guidelines recommend annual screening for depression and anxiety for people with CF. COVID-19 and related social distancing has created challenges for administration of mental health screening by CF centers. The aim of this quality improvement project was to evaluate the feasibility of implementing mental health screening during multidisciplinary telehealth appointments for adult patients with CF during COVID-19, adoption of screening by CF mental health providers, and patient screening results before and after introduction of telehealth. METHOD: Patients were screened via telehealth using the PHQ-9 and GAD-7 between April and October 2020. RESULTS: CF mental health providers implemented a mental health screening process via telehealth and 93.9% of patients seen during that time completed the screening. The screening did not increase clinic visit length and no significant differences were found between rates of depression and anxiety and 2019 clinic rates. DISCUSSION: Implementation of mental health screening during a multidisciplinary telehealth clinic is feasible and can be adopted by providers and patients, even when health systems operations are impacted by COVID-19. It allows CF centers to maintain adherence to mental health screening and treatment guidelines. This method of screening can be applied to other patient populations and systems of care to expand access to mental health services during COVID-19 and beyond. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Real-World Outcomes in Cystic Fibrosis Telemedicine Clinical Care in a Time of a Global Pandemic.

BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes. RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared with in-person clinical care for patients with CF during the COVID-19 pandemic? STUDY DESIGN AND METHODS: Adults with CF were included. The prepandemic year was defined as March 17, 2019, through March 16, 2020, and the pandemic year (PY) was defined as March 17, 2020, through March 16, 2021. Patients were enrolled starting in the PY. Prepandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included previsit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. FEV1 percent predicted, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: One hundred twenty-four patients participated. One hundred ten patients were analyzed (mean age, 35 years; range, 18-69 years). Ninety-five percent had access to telemedicine (n = 105). Telemedicine visits accounted for 64% of encounters (n = 260), hybrid visits with telemedicine support accounted for 28% of encounters (n = 114), and in-person visits accounted for 7% of encounters (n = 30). No difference in lung function or exacerbation rate during the PY was found. BMI increased from 25 to 26 kg/m2 (t100 = -4.72; P < .001). Antibiotic use decreased from 316 to 124 episodes (z = 8.81; P < .0001). INTERPRETATION: This CF care model, which includes IDC-TM, successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests that social mitigation strategies were protective. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04402801; URL: www. CLINICALTRIALS: gov.

Remote monitoring in telehealth care delivery across the U.S. cystic fibrosis care network.

BACKGROUND: Cystic fibrosis (CF) programs and people with CF (PwCF) employed various monitoring methods for virtual care during the COVID-19 pandemic. This paper characterizes experiences with remote monitoring across the U.S. CF community. METHODS: The CF Foundation (CFF) sponsored distribution of home spirometers (April 2020 to May 2021), surveys to PwCF and CF programs (July to September 2020), and a second program survey (April to May 2021). We used mixed methods to explore access, use, and perspectives regarding the use of remote monitoring in future care. RESULTS: By October 2020, 13,345 spirometers had been distributed, and 19,271 spirometers by May 2021. Programs (n=286) estimated proportions of PwCF with home devices increased over seven months: spirometers (30% to 70%), scales (50% to 70%), oximeters (5% to 10%) with higher estimates in adult programs for spirometers and oximeters. PwCF (n=378) had access to scales (89%), followed by oximeters (48%) and spirometers (47%), often using scales and oximeters weekly, and spirometers monthly. Over both surveys, some programs had no method to collect respiratory specimens for cultures associated with telehealth visits (47%, n=132; 41%, n=118). Most programs (81%) had a process for phlebotomy associated with a telehealth visit, primarily through off-site labs. Both PwCF and programs felt future care should advance remote monitoring and recommended improvements for access, training, and data collection systems. CONCLUSIONS: PwCF and programs experienced unprecedented access to remote monitoring and raised its importance for future care. Improvements to current systems may leverage these shared experiences to augment future care models.

Impact of COVID-19 on social determinants of health for adults with cystic fibrosis.

INTRODUCTION: Outcomes in cystic fibrosis are influenced by multiple factors, including social determinants of health. Low socioeconomic status has been shown to be associated with lung function decline, increased exacerbation rates, increased health care utilization, and decreased survival in cystic fibrosis. The COVID-19 pandemic disrupted the US economy, placing people with cystic fibrosis at risk for negative impacts due to changes in social determinants of health. METHODS: To characterize the impact of COVID-19-related changes in social determinants of health in the adult cystic fibrosis population, a social determinants of health questionnaire was designed and distributed to patients as part of a quality improvement project. RESULTS: Of 132 patients contacted, 76 (57.6%) responses were received. Of these responses, 22 (28.9%) answered yes to at least one question that indicated an undesired change in social determinants of health. Patients with stable employment prior to COVID-19 were more likely to endorse undesired change in all domains of the questionnaire, and the undesired changes were most likely to be related to employment, insurance security, and access to medications. Patients receiving disability were more likely to report hardship related to utilities and food security compared with patients previously employed or unemployed. Of patients endorsing risk of socioeconomic hardship, 21 (95.5%) were contacted by a social worker and provided resources. CONCLUSION: Utilizing a social determinants of health questionnaire to screen for social instability in the context of COVID-19 is feasible and beneficial for patients with cystic fibrosis. Identifying social issues early during the pandemic and implementing processes to provide resources may help patients with cystic fibrosis mitigate social hardship and maintain access to health care and medications.

Home spirometry utilisation in telemedicine clinic for cystic fibrosis care during COVID-19 pandemic: a quality improvement process.

IntroductionThe Cystic Fibrosis (CF) Foundation chronic care guidelines recommend monitoring spirometry during quarterly multidisciplinary visits to identify early lung function decline. During the COVID-19 pandemic, the CF adult clinic at University of Virginia (UVA) transitioned from the classic CF care model to a model that included quarterly multidisciplinary telemedicine visits. While using telemedicine, CF care needed to include spirometry monitoring. Only a fraction of adult CF patients at UVA owned and used home spirometers (HS) in March 2020. AIM: The specific aims of this quality improvement (QI) project were to increase the percentage of eligible adult CF patients who owned an HSs from 37% to 85% and to increase the percentage of adult CF patients seen at UVA with available spirometry in telemedicine from 50% to 95% by 31 December 2020. METHODS: Following the Model for Improvement QI methodology, a standardised process was developed for monitoring forced expiratory volume in 1 s with HS during multidisciplinary telemedicine visits during the COVID-19 pandemic. INTERVENTION: (1) HSs were distributed to eligible patients and (2) Home spirometry was monitored in eligible patients with each telemedicine visit and results were used for clinical care decisions. RESULTS: Both specific aims were achieved ahead of expected date. In March 2020, the beginning of the pandemic, 37% (49/131) of patients owned an HS and 50% (9/18) of patients seen via telemedicine performed spirometry at home. By September 2020, 97% (127/131) of adult patients at UVA owned an HS and by October 2020, 96% (24/25) of patients provided spirometry results during their telemedicine encounters. CONCLUSION: Employing QI tools to standardise the process of monitoring spirometry data with home devices via telemedicine is reliable and sustainable and can be replicated across centres that provide care for patients with CF.

Preserving Multidisciplinary Care Model and Patient Safety During Reopening of Ambulatory Cystic Fibrosis Clinic for Nonurgent Care: A Hybrid Telehealth Model.

Introduction: The University of Virginia's (UVA's) adult cystic fibrosis (CF) program implemented a rapid and successful transition to telemedicine care mid-March of 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. In May 2020, the adult UVA CF program redesigned the care model to adjust to the reopening of ambulatory operations and introduced hybrid clinics. The goal remained to minimize person-to-person contacts for patients and care team members (CTMs) while ensuring patient access to quarterly, coproduced, synchronous, multidisciplinary CF care, similar to pre-COVID-19 era regular CF care. Methods: Using quality improvement tools, the UVA adult CF program created a standardized hybrid model of care for in-clinic visits, which included combined components of in-person and synchronous virtual interactions with members of the multidisciplinary team. Results: A total of 16 hybrid visits occurred between May 14 and June 11, 2020. All hybrid visits were multidisciplinary and fulfilled patient requests to see CTMs. All patients seen by hybrid encounter participated in coproduced agenda setting, underwent spirometry, and obtained blood work; 75% provided sputum for surveillance culture. Each hybrid visit type was attended by an average of four CTMs and amounted to 63 separate interactions. Of these interactions, 28 were completed virtually, reducing in-person contacts and personal protection equipment utilization by 44% compared with a fully in-person model of care. Conclusions: Combining in-person and telehealth components in a multidisciplinary CF care model reduces patient and staff interactions and personal protective equipment utilization. The hybrid model of in-person/remote combined care enables reliable access to biological data to support medical decision making while mitigating the risks of person-to-person contact for patients and staff.

A Feasibility Study of Urgent Implementation of Cystic Fibrosis Multidisciplinary Telemedicine Clinic in the Face of COVID-19 Pandemic: Single-Center Experience.

Introduction: The coronavirus 2019 (COVID-19) pandemic has become a major world health problem. All U.S. states have advised their cystic fibrosis (CF) populations to socially isolate. Major health care payors such as Medicare and most private insurance companies have agreed to reimburse health care providers for telemedicine and telephone visits. Methods: The CF adult team at the University of Virginia (UVA) transitioned from face-to-face clinics to multidisciplinary telemedicine clinics by using WebEx® (Cisco Systems, San Jose, CA), a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant platform. Interventions: Patients were contacted before scheduled visits and triaged into: (1) patients eligible for the multidisciplinary telemedicine clinic, (2) patients to be seen in clinic urgently due to acute needs, and (3) stable patients who can be rescheduled at a later time. Ineligible patients for the telemedicine clinic due to lack of access to technology were followed up via telephone. Results: A total of 63 patients were scheduled to be seen in the UVA clinic over 4 weeks, 10 clinic days. Of these patients, 20 (32%) rescheduled their appointment. In addition, 2 patients (3%) were seen in clinic for acute needs and 38 (60%) were seen by the multidisciplinary team through telemedicine. Conclusions: In the context of the COVID-19 pandemic, implementing a telemedicine clinic process that serves the needs of a multidisciplinary care team is paramount to preserving the CF care model. Through a systematic design and test process, a feasible and sustainable program was created that can be utilized by other multidisciplinary programs to adapt to their context.