Impacts of Elexacaftor/Tezacaftor/Ivacaftor: Comparison of Cystic Fibrosis Healthcare Providers’ Observations in Europe and the United States

Impacts of Elexacaftor/Tezacaftor/Ivacaftor: Comparison of Cystic Fibrosis Healthcare Providers’ Observations in Europe and the United States | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Pediatric Pulmonology This is a preprint and has not been peer reviewed. Data may be preliminary. 26 August 2025 V1 Latest version Share on Impacts of Elexacaftor/Tezacaftor/Ivacaftor: Comparison of Cystic Fibrosis Healthcare Providers’ Observations in Europe and the United States Authors : Sonia Graziano 0000-0002-7478-8414 [email protected] , Eddie Landau 0000-0001-8002-9708 , Horst Mitmansgrubert , Marieke Verkleij 0000-0003-2787-5440 , Anna Georgiopoulos 0000-0002-0924-4031 , Urszula Borawska - Kowalczyk , Beth Smith , Christina Bathgate 0000-0002-7120-2799 , and Alexandra Quittner 0000-0002-4139-6983 Authors Info & Affiliations https://doi.org/10.22541/au.175619006.65159367/v1 302 views 235 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with improvements in physical health and well-being. However, there are growing concerns about side-effects related to sleep, cognition and new or worsening mental health in a subset. This study assessed healthcare providers’ perceptions of the positive and negative impacts of ETI and compared provider ratings in Europe to the United States (US). Methods: The European CF Society’s Mental Health Working Group adapted and distributed the survey developed by the CF Foundation’s Mental Health Advisory Committee. It assessed healthcare providers’ observations of the impacts of ETI in these domains: 1) positive and negative physical and psychological effects, 2) sleep difficulties, 3) cognitive difficulties, 4) worsening mental health, and 5) concerns about the future and finances. Results: Seventy-eight healthcare providers across 21 European (EU) countries responded, endorsing similar percentages of positive physical and psychological effects as US providers. However, in Europe lower percentages of MH side-effects (e.g., increased depression/anxiety, suicidal ideation, body image), and concerns about the future (e.g., copays, food insecurity). Conclusions: Across international providers similar positive results were reported. A substantial proportion of PWCF across EU and US experienced ETI side-effects related to sleep, cognition, and new or worsening mental health. However, EU providers reported significantly fewer side-effects related to mental health, negative body image, planning for the future and finances. MH side-effects led to dosing changes in ETI and in the US, they led to changes in MH medications. These international data document the importance of systematically assessing and managing these side-effects. TITLE PAGE Impacts of Elexacaftor/Tezacaftor/Ivacaftor: Comparison of Cystic Fibrosis Healthcare Providers’ Observations in Europe and the United States Sonia Graziano 1 , Edwina C Landau 2 , Horst Mitmansgrubert 3 , Marieke Verkleij 4 , Anna M Georgiopoulos 5 , Urszula Borawska-Kowalczyk 6 , Beth A. Smith 7 , Christina J. Bathgate 8 , Alexandra L. Quittner 9 1 Psychology Unit, Child & Adolescent Psychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy 2 The Graub CF Center, Pulmonary Institute, Schneider Children’s Medical Center, Petah Tikva, Israel 3 Medical University Innsbruck, Department of Psychiatry II, Innsbruck, Austria 4 Amsterdam UMC location University of Amsterdam, Emma Children’s Hospital, Child and Adolescent Psychiatry & Psychosocial Care, Amsterdam, The Netherlands 5 Department of Child and Adolescent Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA 6 Cystic Fibrosis Department, Institute of Mother and Child, Warsaw, Poland 7 Department of Psychiatry, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA 8 Department of Medicine, National Jewish Health, Denver, Colorado, USA 9 Joe DiMaggio Cystic Fibrosis Pulmonary and Sleep Center, Hollywood, United States Full name, postal address, e-mail, phone and fax numbers of the corresponding author: Sonia Graziano Mail address: Bambino Gesù Children’s Hospital, Piazzale Sant’Onofrio 4 – 00165, Rome, Italy E-mail: [email protected] Phone: 06.68592228 - Fax: 06.68594394 Disclosures and funding information statements This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors declare no conflict of interest. Acknowledgement: The CF Foundation Mental Health Advisory Committee developed this survey. The survey was adapted by the ECFS Mental Health Working Group for European distribution and we would like to thank the European Cystic Fibrosis Society (ECFS) for assisting us with building and distributing the online format of the survey. This work was supported also/by the Italian Ministry of Health with ”Current Research funds” Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with improvements in physical health and well-being. However, there are growing concerns about side-effects related to sleep, cognition and new or worsening mental health in a subset. This study assessed healthcare providers’ perceptions of the positive and negative impacts of ETI and compared provider ratings in Europe to the United States (US). Methods: The European CF Society’s Mental Health Working Group adapted and distributed the survey developed by the CF Foundation’s Mental Health Advisory Committee. It assessed healthcare providers’ observations of the impacts of ETI in these domains: 1) positive and negative physical and psychological effects, 2) sleep difficulties, 3) cognitive difficulties, 4) worsening mental health, and 5) concerns about the future and finances. Results: Seventy-eight healthcare providers across 21 European (EU) countries responded, endorsing similar percentages of positive physical and psychological effects as US providers. However, in Europe lower percentages of MH side-effects (e.g., increased depression/anxiety, suicidal ideation, body image), and concerns about the future (e.g., copays, food insecurity). Conclusions: Across international providers similar positive results were reported. A substantial proportion of PWCF across EU and US experienced ETI side-effects related to sleep, cognition, and new or worsening mental health. However, EU providers reported significantly fewer side-effects related to mental health, negative body image, planning for the future and finances. MH side-effects led to dosing changes in ETI and in the US, they led to changes in MH medications. These international data document the importance of systematically assessing and managing these side-effects. Keywords: elexacaftor/tezacaftor/ivacaftor; cystic fibrosis; depression; anxiety; cognitive difficulties; sleep difficulties; mental health 1. INTRODUCTION Cystic fibrosis (CF) has been transformed by the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) which modulates the primary defect in the CF transmembrane conductance regulator (CFTR). 1-2 For those eligible for ETI, based on genotype, it has led to dramatic improvements in lung function, respiratory symptoms, and health-related quality of life (HRQoL). 1-3 An analysis of the non-respiratory domains of HRQoL from the two pivotal trials of ETI demonstrated substantial improvements of 10-20 points in Physical Functioning, Vitality, Health Perceptions, and Treatment Burden on the Cystic Fibrosis Questionnaire‐Revised. 4 Despite these positive effects, several negative side-effects have also been reported by people with CF (PWCF) who are taking ETI. Several case series, longitudinal studies, and a systematic review, have documented negative side effects of CFTR modulators including insomnia, cognitive fogging, memory and concentration problems, worsening depression and anxiety, and new onset of mental health (MH) concerns. 5-12 A recently published comprehensive review identified behavioral changes with modulator exposure in rodent models of depression, anxiety, and cognition. 13 Longitudinal human studies have suggested that most PWCF show improvement or no change in neuropsychiatric symptoms, however, some experience worsening in these domains. Further, disproportionality analyses of large databases have found elevated odds ratios for psychiatric adverse drug reactions associated with modulators. 14 In one of the first prospective studies, 3 the effects of ETI were systematically measured in a comprehensive, multi-dimensional study of the positive and negative effects of this new medication. Longitudinal assessments included lung function, body mass index (BMI), gastrointestinal symptoms, and HRQoL. Innovative measures of cognitive processing 15-17 and a specific side-effects measure were used to capture insomnia, headache, memory problems, “brain fog” and concentration. Depression improved from baseline to 1 month ( p <.001); however, no changes in anxiety were found. Neuropsychological side-effects occurred in 10-29%, with no reductions over time or differences by age. Significant increases in insomnia were found from baseline to 6 months post-initiation. Moreover, women reported more side-effects than men for insomnia, headache, “brain fog” and concentration over time. Based on the need for national-level data on the prevalence of side-effects, as well as their impacts on daily functioning and implications for clinical management, the CF Foundation’s (CFF) Mental Health Advisory Committee (MHAC) conducted a national survey of healthcare providers’ perceptions of the emerging positive and negative impacts of ETI in the real world. 18 A 26‐item survey was distributed to US multidisciplinary providers assessing their observations of patient‐reported experiences with ETI. Survey responses measured the prevalence of these effects in 5 domains: 1) positive physical and psychological effects (including body image), 2) sleep difficulties, 3) cognitive difficulties, 4) worsening MH, and 5) concerns about the future and finances. Seventy‐five healthcare providers responded from pediatric, adult, and combined centers. Positive physical effects of ETI and increased optimism were reported in the upper quartiles (e.g., observed in 50–100% of PWCF) and were rated as having significant impacts. Sleep and cognitive difficulties were reported in 1-24%, with slight impacts on functioning, and psychological symptoms (e.g., increased stress, depression, anxiety) and new psychiatric medications were reported in 1-24%, with moderate impacts. Concerns about the future and finances were reported in 1-24%, with minimal impacts. 18 The aim of this study was to conduct a similar survey assessing positive and negative effects of ETI in a multidisciplinary cohort of CF providers across Europe, with analyses comparing the results between EU and the US. 2. METHODS The European Cystic Fibrosis Society (ECFS) approved the survey for distribution by the ECFS Mental Health Working Group; the survey was anonymous and all data were de-identified. The survey opened with a statement that “by completing this survey, you have agreed to have your anonymous data analyzed”. We have followed the Ethical Standards adopted by the Declaration of Helsinki and European Medicines Agency Guidelines for Good Clinical Practice. The survey included a statement indicating that by responding to this survey, you agree to have your de-identified data analyzed. The survey was distributed to ECFS members by email from April-June 2023, and via QR codes to attendees at the ECFS Conference in June 2023. 2.1 Study design This was a cross-sectional study the perceptions of positive and negative effects of ETI between providers in EU and US. European respondents included physicians, nurses, pharmacists, psychologists, psychiatrists, social workers, dietitians, respiratory therapists and physical therapists from both Eastern and Western Europe (see Table 1). Seventy-eight participants from 21 countries completed the survey, which took approximately 30 minutes. 2.2 | Measures The US MHAC sought input from US care team members about their patients’ experiences with ETI, based on clinical observations and patient reports. 3-12 Members of the MHAC reviewed published studies, case series, case reports, CF community blogs, and comments from their patients and colleagues to identify common positive and negative physical and MH effects of ETI. The survey went through 5 iterations to improve wording, rating options, and ensure it was not overly burdensome for respondents. The ECFS Mental Health Working Group adapted the 26-item survey using Survey Monkey. Respondents estimated the prevalence and impact of ETI on functioning in the same 5 domains listed above. Healthcare providers were asked to estimate: 1) the proportion of their patients reporting positive and negative experiences in these 5 domains (5 options: 0%, 1-24%, 25-49%, 50-74%, 75-100%); 2) the impact of these effects on daily functioning using a 4-point scale (i.e., no impact, slight impact, moderate impact, significant impact); and 3) the proportion of their patients in whom these experiences led to a change in dosing or discontinuation of ETI (5 options: 0%, 1-24%, 25-49%, 50-74%, 75-100%). Each domain consisted of 3 to 11 items. Respondents also identified their care team role, years of experience working in CF, primary patient population (pediatric, adult, or combined), approximate number of patients seen annually at their CF center, and geographic location. 2.3 | Data analyses Data were downloaded to SPSS Version 20. Data were cleaned and coded to ensure data quality, nonsense values and duplicates were eliminated, and the appropriateness of ranges confirmed. Participants were divided into categories based on their primary patient population: pediatric, adult, or combined. For the purpose of comparing the EU and US data, results are presented for all types of centers and results by type of center are reported in the Supplement. Descriptive statistics were computed for characteristics of the overall sample and stratified by center type. Results for continuous variables were reported as mean ± SD; categorical variables were reported using frequencies and percentages for the domains described above. Values from all US centers were compared to those from all EU centers using chi-square (χ2) tests. The significance level for all analyses was set at 0.05. The false discovery rate was used as a control for the type I error rate due to multiple comparisons. 19 3. RESULTS Seventy-eight respondents from 21 countries, primarily physicians (61.5%), completed the survey representing pediatric (39.7%), adult (35.9%), and combined centers (24.4%) (Table 1). Most EU providers had to 36.3% in the US (see Bathgate et al 2023 for complete demographics of US respondents). 18 3.1 Positive Experiences of ETI and Improved Mental Health There were 11 variables that measured positive experiences of ETI and improved MH (Supplemental Table 1). Providers most commonly reported positive effects of ETI in the highest quartile (75–100% of PWCF) for: reductions in cough/mucus, pulmonary exacerbations, hospitalizations, improved lung function, and increased energy. In the upper quartile (50-74%), providers reported improved BMI and less need for prescribed treatments (Supplemental Table 1). On questions related to improved MH, increased optimism was reported in the highest quartile; however, other effects on MH, such as decreased stress, depression, and anxiety fell primarily in the lower quartiles (0-24% range). Positive physical experiences of ETI (e.g., cough/mucus, improved lung function) were rated as having a significant impact on daily functioning, whereas improved BMI had a moderate impact. Decreased stress, depression and anxiety were rated as having “no impact.” No significant differences in positive changes were observed between the EU and US ( χ2 =ns ). 3.2 Sleep Difficulties Three variables measured sleep disturbances. Providers most commonly (60%) reported difficulty sleeping and insomnia in 1–24% of PWCF, whereas hypnogogic hallucinations were infrequent. Although these hallucinations are rare in the general population, 19% of providers reported these events in 1–24% (Supplemental Table 2). Although 40% of providers reported that difficulty sleeping had a slight impact on daily functioning, an additional 37% rated this as having a moderate to significant impact. Fifty-six percent of providers rated insomnia as having a slight to significant impact. Sleep difficulties, insomnia and hypnogogic hallucinations led to dosing changes in 11-29% of PWCF in the 1 st quartile of the rating scale. Fewer side-effects related to sleep were reported in the EU vs US, however, after using the false discovery rate as a correction for the type 1 error among the 3 variables, no significant differences were observed between EU and the US ( χ2 =ns). 3.3 Cognitive Difficulties Five variables measured cognitive difficulties (Supplemental Table 3). Brain fog and concentration/attention problems were the most frequent cognitive side-effects reported in 1-24%, however, in this rating category, memory, word finding and confusion were also reported in 21-35% of PWCF. Concentration problems had slight impact across pediatric, adult and combined centers, with other cognitive side-effects predominantly falling in the “no impact” category. Concentration problems also led to the highest rating for dosing changes , with 40% of providers reporting dose adjustments to address this side-effect (Supplemental Table 3). No significant differences were found between the EU and US ( χ2= ns ). 3.4 Worsening Mental Health and Body Image Concerns Ten MH symptoms were assessed. Three of the 10 symptoms (increased depression, increased anxiety, mood swings) were reported in the 1-24% range, with the remaining psychological side-effects endorsed in the 0% category (Supplemental Table 4). Importantly, increased stress was endorsed by 44% of respondents and suicidal ideation by 24% of respondents in 1-24% of PWCF. Note that 37% of respondents reported that these symptoms led to starting new psychiatric medications in 1-24% of their patients. Although most providers rated psychological side-effects as having no impact, one-quarter of respondents rated increased depression and stress, mood swings, and survivor’s guilt as having a slight impact. Dose changes in ETI were reported by more than 30% of providers for 1-24% of their patients who experienced depression, anxiety and mood swings. Comparisons of the EU and US data using the false discovery rate 19 to correct for increasing type 1 error rates among the 10 variables indicated that increases in depression [ χ2 (4, N=149) = 20.94, p <.001]; anxiety [χ2 (4, N=149) = 18.60, p <.001]; suicidal ideation [ χ2 (1, N=148) = 7.45, p =.006], and occurrences of survivor’s guilt [ χ2 (4, N=148) = 11.94, p =.018] were reported less frequently in EU vs US (Figure 1). We also assessed 5 potential changes in MH medication management after starting ETI (Supplemental Table 5). The majority of providers endorsed no changes in MH medication management, however, 37% of providers reported starting new MH medications , 31% endorsed changing MH medications , and 19% reported an increase in MH medications in 1-24% of PWCF. These changes were rated as having “no impact” by most, however, 16-19% of providers reported a slight impact for changing and starting new MH medications, respectively (Supplemental Table 5). Comparisons of the EU and US data using the false discovery rate 18 indicated statistically significant differences on all 5 of these MH medication variables: starting MH medications [ χ2 (3, N=146) = 35.95, p <.001]; changing MH medications [ χ2 (4, N=146) = 16.89, p =.002]; increasing current medications [ χ2 (3, N= 45) = 37.01, p <.001]; reducing MH medications [ χ2 (3, N=145) = 10.55, p =.014], and discontinuing all MH medications [ χ2 (3, N=146) = 7.86, p =.049]. Medication changes were reported less frequently by EU vs. US providers (Figure 1). Five body image concerns were assessed (Supplemental Table 6). Providers reported high numbers of PWCF having challenges with body image and weight gain. For negative body image, 47% of providers reported that 1-24% of their patients had concerns, and 30% rated weight gain as an issue for 25-49% of their patients. Acne and rashes were also endorsed in the 1-24% range by 62% and 76% of providers, respectively. Hair loss was the least frequently reported side-effect (32%) rated this as occurring in 1-24% of PWCF). Generally, these body image concerns had a slight impact, with 31-33% of providers endorsing rashes and weight gain as having a moderate impact. Rashes, weight gain and negative body image were associated with changes in dosing for 1-24% of PWCF by one-quarter to nearly one-half of providers. Using the false discovery rate, EU providers differed significantly from US providers on negative body image [ χ2 (4, N=151) = 14.27, p =.006] and weight gain [ χ2 (4, N=152) = 11.79, p =.019] , with EU endorsing these concerns less than the US (Figure 2) . 3.5 Concerns about the Future and Finances Eleven concerns about the future and financial issues were assessed (Supplemental Table 7). Future concerns, such as attending college, job opportunities, marriage and family planning, and copays were endorsed by a majority of providers in the 0% range; however, 30-33% of providers rated job opportunities, marriage and family planning, and loss of identity as a person with CF in the 1-24% range (Supplemental Table 6). Most providers rated these concerns about the future as having no impact, however, job opportunities, marriage and family planning, future retirement, and finances for retirement and savings were rated as having a slight impact. These future concerns did not lead to dosing changes or discontinuation of ETI. Using the false discovery rate, EU providers differed significantly from US providers on copays [ χ2 (4, N=142) = 41.40, p < .001] , food insecurity [ χ2 (4, N=140) = 16.84, p =.002] , and attending college/school [ χ2 (4, N=149) = 12.88, p =.012], which were much less commonly reported in the EU (Figure 3). In sum, similar positive physical and mental health effects were found in EU and the US. Further, no significant differences in side-effects were found for sleep and cognition. In contrast, statistically significant differences were found between EU and the US for worsening mental health and body image, future planning and finances. 4. DISCUSSION This study adapted the US survey of 75 providers to the European context, achieving a similar number of responses across 78 providers in 21 Eastern and Western European countries. 18 The majority of respondents in both surveys were physicians, and in Europe a larger percentage of providers (28%) had more than 20 years of experience working in CF compared to the US (12%). This may reflect the greater stability of work roles in Europe vs the US. A greater percentage of respondents from pediatric centers participated in the EU survey (40%), whereas a larger percentage of adult providers responded in the US (51%). This is likely due to the earlier development of adult CF Centers in the US and a specific focus on transitioning adolescents to adult care. Overall, both EU and US providers reported very similar positive results for PWCF after starting ETI. Positive effects were highly consistent across continents with positive changes reported in the highest quartile for reductions in cough/mucus, pulmonary exacerbations, hospitalizations, improved lung function and BMI. Importantly, in both surveys, providers reported increased energy and optimism, and these improvements were perceived to have significant, positive impacts on daily functioning. Increasing literature in CF indicates that specific psychological strengths, such as resilience and optimism, may mitigate the negative effects of MH conditions and provide key targets for intervention. A 20-year longitudinal study in the UK found that optimism had a beneficial effect on mortality in 116 AWCF. 20 Importantly, despite the prevalence of MH side-effects with modulators, strong results for optimism suggest that PWCF have the resilience to overcome these challenges. Comparisons of the EU and US data indicated that increases in depression, anxiety, suicidal ideation, as well as survivor’s guilt were reported less frequently by EU vs.US providers . EU CF centers have had a longer tradition of including psychologists on the multidisciplinary team, and it is much more common for psychologists in EU to provide psychological support and treatment. Further, access to psychological interventions at CF centers in Europe is typically heavily subsidized (or even free). In contrast, in the US, PWCF and their families typically pay “out of pocket” for psychological services or at a minimum, a copay to receive these services. ETI dose changes were more likely for PWCF reporting increased depression, anxiety or mood swings than other MH symptoms in both surveys; however, these dose changes were made less often by EU vs US providers. The US received approval of ETI two years earlier than EU and thus, there has been more time to evaluate the impact of these side-effects and make dosing changes. It may take more time and experience for EU providers to monitor the impact of these side-effects before considering a dose change. 21 However, cognitive changes led to dosing changes in ETI by over 40% of EU providers vs 30% in the US. After applying the false discovery rate as a correction for type 1 error, EU providers differed significantly from US providers on copays, food insecurity, and attending college/technical school which were much less commonly reported in EU. This may be related to societal differences in the social safety nets between EU and the US. The largest difference we found was the affordability of copays for medication. ETI is very expensive and if covered in the US by private insurance, PWCF have a copay, which is a percentage of the price of the medication. In Europe, medication prices are negotiated with the government, are covered by the healthcare system, and are typically provided to PWCF for free. These differences in the healthcare and social systems are likely responsible for the significant differences in medication costs, food insecurity and ability to attend college/technical schools. In addition, PWCF in the US who qualified for disability payments may be more concerned about losing this funding if their lung function improves above a certain threshold. EU providers differed significantly from those in the US on negative body image and weight gain, with fewer concerns reported in Europe vs the US. This may be explained by differences in the European versus American diet. In Europe, the “mediterranean” diet, which is focused on the consumption of vegetables and healthier fats contrasts with the American diet which commonly includes fast food and less heart-healthy meals. Furthermore, rates of obesity in the US are nearly double those of EU countries. 22-23 There may be additional psychosocial factors accounting for differences in body image, ideal body weight and diet which warrant further study. 27 Future Directions Results of the US and EU surveys point clearly to the need for measures of neuropsychiatric side-effects related to modulators. 3,18 Given that several papers indicate that side-effects are reported in approximately 15-20% of PWCF, this is an important clinical issue that needs to be addressed. 3,21 Systematic assessment of these side-effects would provide an empirical foundation for developing targeted interventions, dosing changes that are evidence-based, and identification of risk factors for side-effects with the initiation of ETI. Several new initiatives are being implemented to address these issues. The General Mental Health Screener (GEM-CF) study, 28 funded by the CF Foundation, led to the first patient-reported outcome measure of modulator side-effects for adults, the GEMS-ModSE. In this study, side-effects of ETI emerged from qualitative interviews with PWCF. A preliminary instrument has been developed, and a national psychometric validation is underway. For younger children with CF, a national epidemiological study was funded in 2024 to collect data at 16 US CF Centers on depression, anxiety, behavior problems and side-effects of modulators (TIDES 2.0) 29 Finally, the mental health arm of RETRIAL ( Restarting Triple Therapy with Robust Monitoring for Adverse Events) , a multi-center observational study recently launched in the US, is prospectively evaluating the impact of starting the new modulator vanzacaftor/tezacaftor/ivacaftor on a population that may be at elevated risk: children and adults with CF who previously discontinued or altered their dose of ETI due to neuropsychiatric side-effects. 13 These are important next steps to increase our understanding of both the positive and negative effects of ETI. This study was limited by the reliance on health care provider’s perceptions and these impacts were not directly assessed from PWCF and their caregivers. However, the strengths of this study include its international scope allowing for comparisons between EU and the US, and inclusion of items assessing a wide range of both positive and negative impacts of ETI. This work cannot substitute for projects eliciting experiences of taking modulators directly from PWCF and caregivers, 24-25 but it does complement these studies by documenting the perceptions of healthcare providers at both pediatric and adult CF centers internationally. As efforts continue to improve worldwide access to high-quality CF care and modulator therapy, 26 MH is increasingly understood as a key aspect of supporting the well-being of PWCF. 24 Our findings suggest that consideration of international differences in culture and healthcare systems will be critical to future work on the positive and negative impacts of modulators for PWCF. Table 1. Demographic characteristics of the European healthcare provider sample (N=78) Mean (Standard Deviation) 202 (124) Range 22 – 700 Types of center N % Pediatric 31 39.7 Adult 28 35.9 Combined 19 24.4 Country of respondents* N % Bulgaria 1 1.3 Macedonia 1 1.3 Portugal 1 1.3 Slovakia 1 1.3 Turkey 1 1.3 Croatia 2 2.6 France 2 2.6 Poland 2 2.6 Romania 2 2.6 Spain 2 2.6 Switzerland 2 2.6 Denmark 2 2.6 Austria 3 3.8 Belgium 3 3.8 Czech Republic 3 3.8 Ireland 3 3.8 Sweden 3 3.8 Netherlands 4 5.1 Italy 8 10.3 Germany 12 15.4 England/United Kingdom 19 24.5 Healthcare role n % Physician 48 61.5 Nurse 14 17.9 Pharmacist 1 1.3 Psychologist 9 11.5 Social worker 2 2.6 Dietitian 0 0 Respiratory therapist 1 1.3 Physical therapist 3 3.8 How long on CF team n % Less than 1 year 2 2.6 1-5 years 17 21.8 5-10 years 18 23.1 10-20 years 19 24.4 More than 20 years 22 28.2 Figure 1 Significant differences between EU and US Mental Health side-effects Figure 2 Significant differences between EU and US on negative body image Figure 3 Significant differences between EU and US on concerns about the future/financial References 1. 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Comparing internalization of appearance ideals and appearance-related pressures among women from the United States, Italy, England, and Australia. Eat Weight Disord. 2019 Oct;24(5):947-951. doi: 10.1007/s40519-018-0544-8. Epub 2018 Jul 17. PMID: 30019258; PMCID: PMC6815512. 28. Quittner AL, Georgiopoulos AM, He J, Chaudhary N, Wei R, Canda ER, Xan Nowakowski AX, Tillman L, Smith BA. Development of the General Mental Health Screener: identification of common mental health comorbidities in a diverse sample of adults with CF (2024). Journal of Cystic Fibrosis 23:S307 DOI:10.1016/S1569-1993(24)01396-1. 29. Quittner A, Georgiopoulos AM, Barker D, Schechter MS, Smith BA. TIDES 2.0: Prevalence and longitudinal course of depression, anxiety, and behavior problems in children with cystic fibrosis (CF) under 12 years of age. 48th European Cystic Fibrosis Conference in Milan 3-7 June 2025. Journal of Cystic Fibrosis [ In press; poster number P369 ]. Supplemental Materials Table 1. Positive experiences/improved Mental Health (MH), and positive impact on daily functioning Positive experiences and improved MH Program Type N 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight impact Moderate impact Significant impact Reductions in cough/ mucus production % Pediatric 31 3.2 3.2 6.5 25.8 61.3 31 0.0 13.3 26.7 60.0 Adult 28 0.0 0.0 3.6 14.3 82.1 28 7.1 3.6 14.3 75.0 Combined 19 0.0 0.0 0.0 15.8 84.2 19 0.0 0.0 10.5 89.5 TOTAL 78 1.3 1.3 3.8 19.2 74.4 78 2.6 6.5 18.2 72.7 Fewer pulmonary exacerbations, % Pediatric 31 3.2 9.7 3.2 38.7 45.2 31 3.3 10.0 36.7 50.0 Adult 28 3.6 10.7 0.0 32.1 53.6 28 7.1 7.1 7.1 78.6 Combined 19 0.0 0.0 5.3 5.3 89.5 19 0.0 0.0 5.3 3.3 TOTAL 78 2.6 3.8 6.4 28.2 59.0 78 3.9 7.8 18.2 70.1 Fewer hospitalizations, % Pediatric 31 3.2 22.6 6.5 22.6 45.2 31 0.0 20.0 36.7 43.3 Adult 28 3.7 7.4 7.4 14.8 66.7 28 7.4 11.1 7.4 74.1 Combined 19 0.0 0.0 0.0 15.8 84.2 19 0.0 10.5 36.3 63.2 TOTAL 78 2.6 11.7 5.2 18.2 62.3 78 2.6 11.8 17.1 68.4 Improved lung function, % Pediatric 31 3.2 3.2 6.5 38.7 48.4 31 3.2 16.1 38.7 41.9 Adult 28 0.0 0.0 3.6 46.4 50.0 28 7.1 3.6 17.9 71.4 Combined 19 0.0 0.0 5.3 26.3 68.4 19 0.0 5.3 21.1 73.6 TOTAL 78 1.3 1.3 5.1 38.5 53.8 78 3.8 9.0 26.9 60.3 Increased optimism, % Pediatric 31 0.0 6.5 19.4 29.0 45.2 31 3.3 30.0 30.0 36.7 Adult 28 0.0 0.0 21.4 46.4 32.1 28 7.1 7.1 39.3 46.4 Combined 19 0.0 0.0 15.8 31.6 52.6 19 0.0 10.5 26.3 63.2 TOTAL 78 0.0 2.6 19.2 35.9 42.3 78 3.9 16.9 32.5 46.8 Increased energy level, % Pediatric 31 6.5 3.2 12.9 29.0 48.4 31 9.7 9.7 29 51.6 Adult 28 0.0 3.6 0.0 42.9 53.6 28 3.6 7.1 17.9 71.4 Combined 19 0.0 0.0 10.5 26.3 63.2 19 0.0 0.0 26.3 73.7 TOTAL 78 2.6 2.6 7.7 33.3 53.8 78 5.1 6.4 24.4 64.1 Improved BMI, % Pediatric 31 6.5 3.2 16.1 38.7 35.5 31 13.3 16.7 53.3 16.7 Adult 28 0.0 3.6 39.3 28.6 28.6 28 7.1 10.7 53.6 28.6 Combined 19 0.0 0.0 15.8 52.6 31.6 19 0.0 15.8 52.6 31.6 TOTAL 78 2.6 2.6 24.4 38.5 32.1 78 7.8 14.3 53.2 24.7 Less need for prescribed treatments, % Pediatric 31 3.2 16.1 25.8 32.3 22.6 31 6.7 16.7 46.7 29.9 Adult 28 3.6 7.1 14.3 60.7 14.3 28 7.1 14.3 32.1 46.4 Combined 19 0.0 10.5 21.1 26.3 42.1 19 0.0 10.5 31.6 57.9 TOTAL 78 2.6 11.5 20.5 41.0 24.4 78 5.2 14.3 37.7 42.9 Decreased stress, % Pediatric 31 32.3 32.3 19.4 9.7 6.5 31 35.5 32.3 16.1 16.1 Adult 28 17.9 25.0 25.0 21.4 10.7 28 25.9 32.1 17.9 25.0 Combined 19 21.1 26.3 10.5 31.6 10.5 19 36.8 15.8 31.6 15.8 TOTAL 78 24.4 28.2 19.2 19.2 9.0 78 32.1 28.2 20.5 19.2 Decreased depression, % Pediatric 31 51.6 32.3 3.2 9.7 3.2 31 51.6 22.6 12.9 12.9 Adult 28 25.0 42.9 10.7 14.3 7.1 28 25.9 33.3 22.22 18.5 Combined 19 31.6 15.8 15.8 15.8 21.1 19 36.8 10.5 26.3 26.3 TOTAL 78 37.2 32.1 9.0 12.8 9.0 78 39.0 23.4 19.5 18.2 Decreased anxiety, % Pediatric 31 38.7 35.5 12.9 6.5 6.5 31 48.4 16.1 22.6 12.9 Adult 28 25.9 40.7 7.4 18.5 7.4 28 29.6 33.3 18.5 18.5 Combined 19 21.1 26.3 15.8 15.8 21.1 19 26.3 21.1 26.3 26.3 TOTAL 78 29.9 35.1 11.7 13.0 10.4 78 36.4 23.4 22.1 18.2 Table 2. Sleep difficulties, impact on daily functioning, and changes in dosing or discontinuation Sleep difficulties Program Type n 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight Impact Moderate impact Significant impact n 0% 1-24% 25-49% 50-74% 75-100% Difficulty sleeping % Pediatric 31 41.9 54.8 0.0 3.2 0.0 31 40.0 33.3 20.0 6.7 31 76.7 20.0 3.3 0.0 0.0 Adult 28 7.4 63.0 14.8 7.4 7.4 28 11.1 48.8 29.6 11.1 28 63.3 33.3 3.7 0.0 0.0 Combined 19 10.5 63.2 15.8 5.3 5.3 19 15.8 36.8 31.6 15.8 19 68.4 31.6 0.0 0.0 0.0 TOTAL 78 22.1 59.7 9.1 5.2 3.9 78 23.7 39.5 26.3 10.5 78 65.8 28.9 3.9 1.3 0.0 Insomnia % Pediatric 31 64.5 29 6.5 0.0 0.0 31 70.0 16.7 10.0 3.3 31 83.3 13.3 3.3 0.0 0.0 Adult 28 17.9 60.7 10.7 7.1 3.6 28 32.1 21.4 32.1 14.3 28 57.1 35.7 0.0 7.1 0.0 Combined 19 36.8 63.2 0.0 0.0 0.0 19 26.3 26.3 26.3 21.1 19 88.9 5.6 0.0 5.6 0.0 TOTAL 78 41.0 48.7 6.4 2.6 1.3 78 45.5 20.8 22.1 11.7 78 70.0 26.0 1.3 2.6 0.0 *Hypnogogic hallucinations % Pediatric 31 80.6 19.4 0.0 0.0 0.0 31 79.3 10.3 0.0 10.3 31 93.1 6.9 0.0 0.0 0.0 Adult 28 82.1 17.9 0.0 0.0 0.0 28 77.8 7.4 7.4 7.4 28 82.1 17.9 0.0 0.0 0.0 Combined 19 79.1 21.1 0.0 0.0 0.0 19 58.8 11.8 11.8 17.6 19 88.9 5.6 0.0 5.6 0.0 TOTAL 78 80.8 19.2 0.0 0.0 0.0 78 74.0 9.6 5.5 11.0 78 88.0 10.7 0.0 1.3 0.0 *Note: Hypnogogic hallucinations include auditory, tactile, and kinetic perceptions, sleep paralysis, hallucinations during sleep Table 3. Cognitive difficulties, impact on daily functioning, and changes in dosing or discontinuation Cognitive difficulties Program Type n 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight impact Moderate impact Significant impact n 0% 1-24% 25.49% 50-74% 75-100% Brain fog % Pediatric 31 61.3 35.5 0.0 3.2 0.0 31 63.3 30.0 6.7 0.0 31 83.3 16.7 0.0 0.0 0.0 Adult 28 32.1 67.9 0.0 0.0 0.0 28 33.3 37.0 14.8 14.8 28 46.4 50.0 0.0 3.6 0.0 Combined 19 21.1 73.7 5.3 0.0 0.0 19 21.1 36.8 15.8 26.3 19 68.4 31.6 0.0 0.0 0.0 TOTAL 78 41.0 56.4 1.3 1.3 0.0 78 42.1 34.2 9.2 14.5 78 66.2 32.5 0.0 1.3 0.0 Concentration/attention problems % Pediatric 31 38.7 58.1 3.2 0.0 0.0 31 41.9 32.3 9.7 16.1 31 71.0 29.0 0.0 0.0 0.0 Adult 28 35.7 64.3 0.0 0.0 0.0 28 40.7 40.7 11.1 7.4 28 51.9 48.1 0.0 0.0 0.0 Combined 19 26.3 57.9 10.5 5.3 0.0 19 22.2 38.9 16.7 22.2 19 52.6 47.4 0.0 0.0 0.0 TOTAL 78 34.6 60.3 3.8 1.3 0.0 78 36.8 36.8 11.8 14.5 78 59.7 40.3 0.0 0.0 0.0 Memory difficulties % Pediatric 31 83.9 16.1 0.0 0.0 0.0 31 83.3 13.3 3.3 0.0 31 90.0 10.0 0.0 0.0 0.0 Adult 28 53.6 39.3 7.1 0.0 0.0 28 55.6 29.6 11.1 3.7 28 60.7 39.3 0.0 0.0 0.0 Combined 19 42.1 57.9 0.0 0.0 0.0 19 33.3 38.9 22.2 5.6 19 77.8 22.2 0.0 0.0 0.0 TOTAL 78 62.8 34.6 2.6 0.0 0.0 78 61.3 25.3 10.7 2.7 78 76.3 23.7 0.0 0.0 0.0 Word finding problems % Pediatric 31 93.5 6.5 0.0 0.0 0.0 31 93.3 3.3 3.3 0.0 31 93.3 6.7 0.0 0.0 0.0 Adult 28 67.9 32.1 0.0 0.0 0.0 28 63.0 25.9 7.4 3.7 28 74.1 25.9 0.0 0.0 0.0 Combined 19 73.7 26.3 0.0 0.0 0.0 19 58.8 17.6 23.5 0.0 19 94.4 5.6 0.0 0.0 0.0 TOTAL 78 79.5 20.5 0.0 0.0 0.0 78 74.3 14.9 9.5 1.4 78 86.7 13.3 0.0 0.0 0.0 Confusion % Pediatric 31 80.6 19.4 0.0 0.0 0.0 31 77.4 12.9 9.7 0.0 31 87.1 12.9 0.0 0.0 0.0 Adult 28 78.6 21.4 0.0 0.0 0.0 28 76.9 15.4 7.7 0.0 28 74.1 25.9 0.0 0.0 0.0 Combined 19 68.4 31.6 0.0 0.0 0.0 19 62.5 18.8 12.5 6.3 19 77.8 22.2 0.0 0.0 0.0 TOTAL 78 76.9 23.1 0.0 0.0 0.0 78 74.0 15.1 5.5 5.5 78 80.3 10.7 0.0 0.0 0.0 Table 4. Worsening mental health (MH), impact on daily functioning, and changes in dosing or discontinuation Worsening in MH Program Type n 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight Impact Moderate impact Significant impact n 0% 1-24% 25-49% 50-74% 75-100% Increased depression % Pediatric 31 51.6 48.4 0.0 0.0 0.0 31 51.6 19.4 9.7 19.4 31 61.3 38.7 0.0 0.0 0.0 Adult 28 46.4 50.0 3.6 0.0 0.0 28 40.7 29.6 14.8 14.8 28 59.3 33.3 3.7 0.0 3.7 Combined 19 42.1 57.9 0.0 0.0 0.0 19 33.3 27.8 11.1 27.8 19 61.1 38.9 0.0 0.0 0.0 TOTAL 78 47.4 51.3 1.3 0.0 0.0 78 43.4 25.0 11.8 19.7 78 60.5 36.8 1.3 0.0 1.3 Increased anxiety % Pediatric 31 51.6 48.4 0.0 0.0 0.0 31 54.8 16.1 9.7 19.4 31 61.3 38.7 0.0 0.0 0.0 Adult 28 35.7 60.7 3.6 0.0 0.0 28 48.1 18.5 14.8 18.5 28 63.0 33.3 0.0 0.0 3.7 Combined 19 36.8 63.2 0.0 0.0 0.0 19 33.3 11.1 38.9 16.7 19 50.0 44.4 5.6 0.0 0.0 TOTAL 78 42.3 56.4 1.3 0.0 0.0 78 47.4 15.8 18.4 78 59.2 38.2 1.3 0.0 1.3 Starting psych medication % Pediatric 31 74.2 25.8 0.0 0.0 0.0 31 80.6 3.2 6.5 9.7 31 87.1 12.9 0.0 0.0 0.0 Adult 28 42.9 53.6 3.6 0.0 0.0 28 46.4 32.1 17.9 3.6 28 64.3 32.1 0.0 3.6 0.0 Combined 19 68.4 31.6 0.0 0.0 0.0 19 68.4 15.8 10.5 5.3 19 89.5 10.5 0.0 0.0 0.0 TOTAL 78 61.5 37.2 1.3 0.0 0.0 78 65.4 16.7 11.5 6.4 78 79.5 19.2 0.0 1.3 0.0 Mood swings % Pediatric 31 38.7 54.8 6.5 0.0 0.0 31 48.4 12.9 19.4 19.4 31 51.6 41.9 3.2 3.2 0.0 Adult 28 39.3 57.1 3.6 0.0 0.0 28 44.4 29.6 18.5 7.4 28 66.7 29.6 0.0 0.0 3.7 Combined 19 31.6 52.6 0.0 0.0 0.0 19 27.8 38.9 27.8 5.6 19 61.1 38.9 0.0 0.0 0.0 TOTAL 78 37.2 55.1 7.7 0.0 0.0 78 42.1 25.0 21.1 11.8 78 59.2 36.8 1.3 0.0 2.6 Increased stress % Pediatric 31 71.0 29.0 0.0 0.0 0.0 31 61.3 19.4 6.5 12.9 31 83.9 16.1 0.0 0.0 0.0 Adult 28 35.7 57.1 7.1 0.0 0.0 28 42.9 32.1 14.3 10.7 28 71.4 21.4 3.6 0.0 3.6 Combined 19 52.6 47.4 0.0 0.0 0.0 19 44.4 22.2 27.8 5.6 19 83.3 11.1 5.6 0.0 0.0 TOTAL 78 53.8 43.6 2.6 0.0 0.0 78 50.6 24.7 14.3 10.4 78 79.2 16.9 2.6 0.0 1.3 Agitation % Pediatric 31 51.6 41.9 0.0 0.0 0.0 31 58.1 22.6 6.5 12.9 31 77.4 19.4 3.2 0.0 0.0 Adult 28 60.7 39.3 0.0 0.0 0.0 28 66.7 14.8 11.1 7.4 28 74.1 22.2 0.0 0.0 3.7 Combined 19 73.7 26.3 0.0 0.0 0.0 19 66.7 27.8 5.6 0.0 19 84.2 15.8 0.0 0.0 0.0 TOTAL 78 60.3 37.2 2.6 0.0 0.0 78 63.2 21.1 7.9 7.9 78 77.9 19.5 0.0 1.3 1.3 Survivor’s Guilt % Pediatric 31 74.2 19.4 3.2 3.2 0.0 31 74.4 12.9 6.5 3.2 31 96.8 3.2 0.0 0.0 0.0 Adult 28 85.7 14.3 0.0 0.0 0.0 28 39.3 42.9 17.9 0.0 28 85.7 14.3 0.0 0.0 0.0 Combined 19 47.4 42.1 10.5 0.0 0.0 19 52.6 21.1 26.3 0.0 19 94.7 0.0 5.3 0.0 0.0 TOTAL 78 53.8 32.1 11.5 1.3 1.3 7878 57.7 25.6 15.4 1.3 78 92.3 6.4 1.3 0.0 0.0 Episodes of mania n % Pediatric 31 93.5 6.5 0.0 0.0 0.0 31 93.5 3.2 3.2 0.0 31 96.8 3.2 0.0 0.0 0.0 Adult 28 71.4 28.6 0.0 0.0 0.0 28 70.4 14.8 3.7 11.1 28 74.1 25.9 0.0 0.0 0.0 Combined 19 84.2 15.8 0.0 0.0 0.0 19 77.8 11.1 5.6 5.6 19 94.4 5.6 0.0 0.0 0.0 TOTAL 78 83.3 16.7 0.0 0.0 0.0 78 81.6 9.2 2.6 6.6 78 88.2 11.8 0.0 0.0 0.0 Suicidal ideation % Pediatric 3167.7 67.7 32.3 0.0 0.0 0.0 31 71.0 6.5 6.5 16.1 31 74.0 25.8 0.0 0.0 0.0 Adult 28 75.0 25.0 0.0 0.0 0.0 28 74.1 7.4 3.7 14.8 28 77.8 18.5 0.0 0.0 3.7 Combined 19 89.5 10.5 0.0 0.0 0.0 19 88.2 5.9 0.0 5.9 19 94.4 5.6 0.0 0.0 0.0 TOTAL 78 75.6 24.4 0.0 0.0 0.0 78 76.0 6.7 4.0 13.3 15.8718.4818.4 80.3 18.4 0.0 0.0 1.3 Psychosis % Pediatric 31 90.3 6.5 3.2 0.0 0.0 31 87.1 3.2 3.2 6.5 31 90.3 6.5 3.2 0.0 0.0 Adult 28 82.1 17.9 0.0 0.0 0.0 28 74.1 11.1 14.8 0.0 28 81.5 18.5 0.0 0.0 0.0 Combined 19 89.5 10.5 0.0 0.0 0.0 19 82.4 5.9 11.8 0.0 19 94.4 5.6 0.0 0.0 0.0 TOTAL 78 87.2 11.5 0.0 0.0 1.3 78 81.3 6.7 4.0 8.0 78 88.2 10.5 0.0 0.0 1.3 Table 5. Need for changes in mental health medications, impact on daily functioning, and changes in dosing or discontinuation Changes in MH medication Program Type n 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight impact Moderate impact Significant impact n 0% 1-24% 25-49% 50-74% 75-100% Change MH medication % Pediatric 31 80.6 19.4 0.0 0.0 0.0 31 87.1 6.5 3.2 3.2 31 90.3 9.7 0.0 0.0 0.0 Adult 28 50.0 50.0 0.0 0.0 0.0 28 51.9 33.3 11.1 3.7 28 70.4 25.9 0.0 3.7 0.0 Combined 19 73.7 21.1 5.3 0.0 0.0 19 73.7 10.5 15.8 0.0 19 89.5 10.5 0.0 0.0 0.0 TOTAL 78 67.9 30.8 1.3 0.0 0.0 78 71.4 16.9 9.1 2.6 78 83.1 15.6 0.0 1.3 0.0 MH medication increase % Pediatric 31 87.1 12.9 0.0 0,0 0.0 31 90.0 3.3 3.3 3.3 31 93.5 0.0 6.5 0.0 0.0 Adult 28 71.4 25.0 0.0 3.6 0.0 28 66.7 18.5 14.8 0.0 28 81.5 18.5 0.0 0.0 0.0 Combined 19 78.9 21.1 0.0 0.0 0.0 19 78.9 10.5 5.3 5.3 19 100 0.0 0.0 0.0 0.0 TOTAL 78 79.5 19.2 0.0 1.3 0.0 78 78.9 10.5 7.9 2.6 78 90.9 9.1 0.0 0.0 0.0 MH medication decrease % Pediatric 31 90.3 6.5 3.2 0.0 0.0 31 93.3 6.7 0.0 0.0 31 93.5 6.5 0.0 0.0 0.0 Adult 28 57.1 35.7 0.0 7.1 0.0 28 59.3 25.9 3.7 11.1 28 85.2 11.1 0.0 3.7 0.0 Combined 19 73.3 10.5 5.3 10.5 0.0 19 68.4 10.5 21.1 0.0 19 94.7 0.0 5.3 0.0 0.0 TOTAL 78 74.4 17.9 2.6 5.1 0.0 78 75.0 14.5 6.6 3.9 78 90.9 6.5 1.3 1.3 0.0 Discontinue MH medication % Pediatric 31 93.5 3.2 3.2 0.0 0.0 31 100 0.0 0.0 0.0 31 100 0.0 0.0 0.0 0.0 Adult 28 82.1 17.9 0.0 0.0 0.0 28 74.1 22.2 0.0 3.7 28 88.9 7.4 0.0 3.7 0.0 Combined 19 94.7 5.3 0.0 0.0 0.0 19 89.5 5.3 5.3 0.0 19 100 0.0 0.0 0.0 0.0 TOTAL 78 89.7 9.0 0.0 0.0 1.3 78 88.0 8.0 1.3 2.7 78 96.0 2.7 0.0 1.3 0.0 Table 6. Body Image-related concerns, impact on daily functioning, and changes in dosing or discontinuation Body image-related Program Type n 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight impact Moderate impact Significant impact n 0% 1-24% 25-49% 50-74% 75-100% Body image % Pediatric 31 45.2 45.2 3.2 6.5 0.0 31 45.2 12.9 32.3 9.7 31 77.4 22.6 0.0 0.0 0.0 Adult 28 32.1 53.6 7.1 7.1 0.0 28 35.7 42.9 10.7 10.7 28 64.3 35.7 0.0 0.0 0.0 Combined 19 47.4 42.1 10.5 0.0 0.0 19 44.4 33.3 16.7 5.6 19 88.2 11.8 0.0 0.0 0.0 TOTAL 78 41.0 47.4 6.4 5.1 0.0 78 41.6 28.6 20.8 9.1 78 75.0 25.0 0.0 0.0 0.0 Weight gain % Pediatric 31 6.5 35.5 16.1 19.4 22.6 31 9.7 32.3 38.7 19.4 31 74.2 25.8 0.0 0.0 0.0 Adult 2828 7.1 7.1 39.3 32.1 14.3 28 14.8 48.1 25.9 11.1 28 53.3 35.7 0.0 10.7 0.0 Combined 19 5.3 26.3 36.8 26.3 5.3 19 10.5 36.8 26.3 26.3 19 83.3 11.1 5.6 0.0 0.0 TOTAL 7878 6.4 23.1 29.5 25.6 15.4 78 11.7 39.0 31.2 18.2 78 68.8 26.0 1.3 3.9 0.0 Rash % Pediatric 31 22.6 77.4 0.0 0.0 0.0 31 35.5 38.7 22.6 3.2 31 61.3 38.7 0.0 0.0 0.0 Adult 28 17.9 64.3 10.7 7.1 0.0 28 37.0 33.3 29.6 0.0 28 39.3 42.9 7.1 7.1 0.0 Combined 19 0.0 89.5 10.5 0.0 0.0 19 5.3 36.8 52.6 5.3 19 47.4 52.6 0.0 0.0 0.0 TOTAL 78 15.4 75.6 6.4 2.6 0.0 78 28.6 36.4 32.5 2.6 78 50.0 43.6 2.6 2.6 1.3 Acne % Pediatric 31 41.9 58.1 0.0 0.0 0.0 31 41.9 32.3 19.4 19.4 31 87.1 12.9 0.0 0.0 0.0 Adult 28 21.4 64.3 10.7 3.6 0.0 28 29.6 51.9 7.4 11.1 28 60.7 32.1 3.6 3.6 0.0 Combined 19 31.6 63.2 5.3 0.0 0.0 19 23.5 47.1 29.4 0.0 19 88.2 11.8 0.0 0.0 0.0 TOTAL 78 32.1 61.5 5.1 1.3 0.0 78 33.3 42.7 17.3 6.7 78 77.6 19.7 1.3 1.3 1.3 Hair loss % Pediatric 31 74.2 25.8 0.0 0.0 0.0 31 80.6 9.7 6.5 3.2 31 96.8 3.2 0.0 0.0 0.0 Adult 28 57.7 34.6 7.7 0.0 0.0 28 56.0 20.0 8.0 16.0 28 69.2 26.9 3.8 0.0 0.0 Combined 19 63.2 36.8 0.0 0.0 0.0 19 56.3 31.3 6.3 6.3 19 94.4 5.6 0.0 0.0 0.0 TOTAL 78 65.8 31.6 2.6 0.0 0.0 78 66.7 18.1 6.9 8.3 78 86.7 12.0 1.3 0.0 0.0 Table 7. Concerns about the future/financial issue and impact on daily functioning Concerns about the future/financial issues Program Type N 0% 1-24% 25-49% 50-74% 75-100% n No impact Slight impact Moderate impact Significant impact Attending college/technical school % Pediatric 31 58.1 29.0 3.2 6.5 3.2 31 58.1 12.9 22.6 6.5 Adult 28 46.4 25.0 17.9 10.7 0.0 28 59.3 14.8 18.5 7.4 Combined 19 31.6 31.6 26.3 5.3 5.3 19 36.8 31.6 21.1 10.5 TOTAL 78 47.4 28.2 14.1 7.7 2.6 78 53.2 18.2 20.8 7.8 Job opportunities % Pediatric 31 64.5 22.6 3.2 6.5 3.2 31 67.7 9.7 16.1 6.5 Adult 28 21.4 35.7 32.1 10.7 0.0 28 30.8 30.8 30.8 7.7 Combined 19 26.3 31.6 26.3 10.5 5.3 19 36.8 31.6 21.1 10.5 TOTAL 78 39.7 29.5 19.2 9.0 2.6 78 47.4 21.1 21.1 10.5 Food insecurity % Pediatric 31 83.9 16.1 0.0 0.0 0.0 31 87.1 6.5 3.2 3.2 Adult 28 53.6 32.1 10.7 3.6 0.0 28 48.1 33.3 14.8 3.7 Combined 19 63.2 26.3 10.5 0.0 0.0 19 63.2 10.5 21.1 5.3 TOTAL 78 67.9 24.4 6.4 1.3 0.0 78 67.5 16.9 11.7 3.9 Copays % Pediatric 31 90.3 6.5 0.0 3.2 0.0 31 90.3 3.2 3.2 3.2 Adult 28 71.4 14.3 7.1 3.6 3.6 28 70.4 18.5 11.1 0.0 Combined 19 68.8 26.3 0.0 5.3 0.0 19 66.7 11.1 22.2 0.0 TOTAL 78 78.2 14.1 2.6 3.8 1.3 78 77.6 10.5 10.5 1.3 Marriage and family planning % Pediatric 31 67.7 22.6 0.0 6.5 3.2 31 67.7 12.9 16.1 3.2 Adult 28 14.3 42.9 28.6 10.7 3.6 28 25.9 33.3 25.9 14.8 Combined 19 26.3 26.3 26.3 15.8 5.3 19 36.8 21.1 26.3 15.8 TOTAL 78 38.5 30.8 16.7 10.3 3.8 78 45.5 22.1 22.1 10.4 Future retirement (general) % Pediatric 31 83.3 10.0 6.7 0.0 0.0 31 86.7 3.3 10.0 0.0 Adult 28 51.9 37.0 3.7 3.7 3.7 28 50.0 38.5 3.8 7.7 Combined 19 52.6 36.8 5.3 5.3 0.0 19 52.6 31.6 15.8 0.0 TOTAL 78 64.9 28.6 5.2 1.3 0.0 78 68.4 25.0 5.3 1.3 Loss of identity as a person with CF, % Pediatric 31 63.3 26.7 10.0 0.0 0.0 31 86.7 10.0 3.3 0.0 Adult 28 35.7 39.3 10.7 14.3 0.0 28 53.8 19.2 15.4 11.5 Combined 19 36.8 31.6 26.3 5.3 0.0 19 36.8 15.8 36.8 10.5 TOTAL 78 46.8 32.5 14.3 6.5 0.0 78 54.7 17.3 18.7 9.3 Savings % Pediatric 31 90.3 6.5 0.0 0.0 3.2 31 90.3 6.5 3.2 0.0 Adult 28 59.3 33.3 7.4 0.0 0.0 28 51.9 37.0 7.4 3.7 Combined 19 47.4 36.8 10.5 0.0 5.3 19 52.6 21.1 21.1 5.3 TOTAL 78 68.8 23.4 5.2 0.0 2.6 78 67.5 20.8 7.8 3.9 Finances for retirement % Pediatric 31 87.1 12.9 0.0 0.0 0.0 31 90.3 9.7 0.0 0.0 Adult 28 48.1 40.7 11.1 0.0 0.0 28 53.8 38.5 3.8 3.8 Combined 19 89.5 10.5 0.0 0.0 0.0 19 50.0 27.8 22.2 0.0 TOTAL 78 61.8 27.7 5.3 3.9 1.3 78 64.9 21.6 10.8 2.7 Purchasing new clothes % Pediatric 31 87.1 9.7 0.0 3.2 0.0 31 93.5 6.5 0.0 0.0 Adult 28 51.9 33.3 11.1 0.0 3.7 28 53.8 34.6 11.5 0.0 Combined 19 47.4 36.8 10.5 5.3 0.0 19 52.6 10.5 36.8 0.0 TOTAL 78 64.9 24.7 6.5 1.3 2.6 78 69.7 17.1 13.2 0.0 Loss of disability payments % Pediatric 31 71.1 16.1 6.5 3.2 3.2 31 74.2 6.5 12.9 6.5 Adult 28 35.7 35.7 14.3 10.7 3.6 28 44.4 25.9 18.5 11.1 Combined 19 78.9 10.5 5.3 5.3 0.0 19 83.3 5.6 11.1 0.0 TOTAL 78 60.3 21.8 9.0 6.4 2.6 78 65.8 13.2 11.8 9.2 Information & Authors Information Version history V1 Version 1 26 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Pediatric Pulmonology Keywords cognitive difficulties cystic fibrosis elexacaftor/tezacaftor/ivacaftor mental health sleep difficulties Authors Affiliations Sonia Graziano 0000-0002-7478-8414 [email protected] Ospedale Pediatrico Bambino Gesu IRCCS View all articles by this author Eddie Landau 0000-0001-8002-9708 Shamir Medical Center Assaf Harofeh Pulmonary Institute View all articles by this author Horst Mitmansgrubert Landeskrankenhaus Innsbruck Universitatsklinik fur Psychiatrie II View all articles by this author Marieke Verkleij 0000-0003-2787-5440 Emma Kinderziekenhuis Amsterdam UMC View all articles by this author Anna Georgiopoulos 0000-0002-0924-4031 Massachusetts General Hospital Division of Child and Adolescent Psychiatry View all articles by this author Urszula Borawska - Kowalczyk Instytut Matki i Dziecka View all articles by this author Beth Smith University at Buffalo Department of Psychiatry View all articles by this author Christina Bathgate 0000-0002-7120-2799 National Jewish Health Department of Medicine View all articles by this author Alexandra Quittner 0000-0002-4139-6983 Pulmonary and Sleep of Tampa Bay Inc View all articles by this author Metrics & Citations Metrics Article Usage 302 views 235 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Sonia Graziano, Eddie Landau, Horst Mitmansgrubert, et al. Impacts of Elexacaftor/Tezacaftor/Ivacaftor: Comparison of Cystic Fibrosis Healthcare Providers’ Observations in Europe and the United States. Authorea . 26 August 2025. DOI: https://doi.org/10.22541/au.175619006.65159367/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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