Search

Background: Olfactory dysfunction (OD) is prevalent in people with cystic fibrosis (PwCF) and can negatively impact quality-of-life (QOL). This study evaluated perceptions of OD, investigated how OD impacts QOL, and assessed willingness to participate in OD research among the CF community., Methods: A 21-question survey was distributed through the CF Foundation's Community Voice program in 2023. The survey included questions on olfaction and interest in research. The Brief Questionnaire of Olfactory Disorders (BQOD), a validated person-reported outcome measure to assess QOL, was included., Results: Seventy-six responses were received. Overall, 91% (69/76) reported olfactory problems. Mean BQOD score was 5.0 (standard deviation=4.8), indicating olfactory QOL impairment was present. Ninety-five percent (72/76) reported research on OD is worthwhile and were willing to participate in research., Conclusion: Among PwCF, OD and olfactory-specific QOL impairments are prevalent. There is strong interest and willingness to participate in OD research among the CF community., Competing Interests: Declaration of Competing Interest JEM: none. CML: NIDCD grant related to this work. ETZ: In the last 36 months, she has received grants to her institution from the Cystic Fibrosis Foundation, National Institutes of Health, and Vertex Pharmaceuticals Incorporated; has received fees from the Cystic Fibrosis Foundation and Vertex Pharmaceuticals Incorporated related to consultation, participation on advisory boards, and grant review committees. She served as chair of the CFF Therapeutics Development Network steering committee, reviewed grants for CF Canada, and received travel support from the European CF Society Clinical Trials Network for speaking at their annual meeting. JMW: In the last 36 months, he has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, Vertex Pharmaceuticals Incorporated; has received fees from Polarean LLC related to consultation on clinical and translational research. CHG: In the last 36 months, he has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration; has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. He has stock in Air Therapeutics. JLTC: In the last 36 months, she has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, Vertex Pharmaceuticals Incorporated, Eloxx, and 4DMT; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards and/or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. She served on a DMC for AbbVie. She serves as the adult patient care representative to the CFF Board of Trustees, and on the CF Foundation's Clinical Research Executive Committee, Clinical Research Advisory Board, as immediate past chair of the CF TDN's Sexual Health, Reproduction and Gender Research Working Group, and as Co-Chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily's Entourage, and on the ATS Respiratory Health Awards Working Group and as Chair-Elect of the International Conference Committee. She is an Associate Editor for the Journal of Cystic Fibrosis and a member of the International Advisory Board for the Lancet Respiratory Medicine Journal. She serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health/National Heart. Blood, Lung Institute. DMB: In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the Sue Ann and John L. Weinberg Foundation, honoraria, and consulting fees on medicolegal cases and at Garner Health (equity)., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: Cystic fibrosis (CF) is commonly complicated by chronic rhinosinusitis (CRS). Despite highly effective management options, CRS in people with CF (PwCF+CRS) may be refractory to medical therapy, eventually requiring endoscopic sinus surgery. The impact of sinus surgery on pulmonary, quality of life (QOL), and other outcomes in PwCF+CRS in the expanding era of highly effective modulator therapy has not been fully elucidated. This study aims to determine if endoscopic sinus surgery can offer superior outcomes for PwCF+CRS when compared to continued medical treatment of CRS., Methods and Analysis: This multi-institutional, observational, prospective cohort study will enroll 150 adults with PwCF+CRS across nine US CF Centers who failed initial medical therapy for CRS and elected to pursue either endoscopic sinus surgery or continue medical treatment. To determine if sinus surgery outperforms continued medical therapy in different outcomes, we will assess changes in pulmonary, CF-specific QOL, CRS-specific QOL, sleep quality, depression, headache, cognition, olfaction, productivity loss, and health utility value after treatment. The influence of highly effective modulator therapy on these outcomes will also be evaluated. This study will provide crucial insights into the impact of endoscopic sinus surgery for PwCF+CRS and aid with development of future treatment pathways and guidelines., Ethics and Dissemination: This study has been approved by each institution's internal review board, and study enrollment began August 2019. Results will be disseminated in conferences and peer-reviewed journals., Trial Registration: This study was registered on ClinicalTrials.gov (NCT04469439)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JAA is a consultant for OptiNose and Medtronic; on a speaker panel GSK; on GlycoMira board and is an equity holder. PHH is a consultant for Stryker, Medtronic, Slate Therapeutics; and Equity ownership in Sound Health Systems. AJK is a consultant for Acclarent. ZMS is a consultant for OptiNose, Regeneron, SanofiGenzyme, and Lyra; and on Medical Directory for Healthy Humming. Unrelated to this work, NIC has received grant support from the Burroughs Welcome Fund, American Rhinologic Society, and the National Cancer Institute. In the last 36 months, CHG has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration unrelated to this work. CHG has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. CHG has stock in Air Therapeutics. JLTC reports personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, she have been site Pl on studies for Vertex, 4DMT, and Eloxx; she have done consulting/provided clinical trial design advice for Vertex and 4DMT; she served as Chair of a Data Monitoring Committee for AbbVie. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: she have received grant funding from the CFF and NIH. Professional Memberships include CFF Clinical Research Executive Committee; CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING); ATS International Conference Committee Chair and Respiratory Health Awards Committee Member (Scientific Grant Review and Clinical Problems Programming Committee-complete); National Institutes of Health/National Heart, Blood, Lung Institute Clinical Trials Review Study Section. MTS receives funding from Cystic Fibrosis Foundation unrelated to this work. In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the American Rhinologic Society, honoraria, and consulting fees from Amgen, on medicolegal cases, and at Garner Health (equity). CML, JLF, TEB, NIC, AEG, JCM, TLS have disclosed no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory‐specific quality‐of‐life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. Methods: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution‐based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. Results: Of 129 PwCF included, 65 had QOD scores before and 3–6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was −1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). Conclusion: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner. [ABSTRACT FROM AUTHOR]

Rationale: Elexacaftor, tezacaftor, and ivacaftor (ETI) in triple combination improves pulmonary health for people with cystic fibrosis (PwCF). However, its impact on objective measures of sinus disease and health utility is unestablished. Objectives: To evaluate the impact of ETI on chronic rhinosinusitis (CRS) and general health status incorporating computed tomography (CT), quality-of-life (QOL) and productivity loss. Methods: Adult PwCF+CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. The primary endpoint was change in percent sinus CT opacification (%SO) after 6 months of ETI assessed via deep learning-based methods. Secondary endpoints included changes in sinonasal QOL, health utility value and productivity loss, which were evaluated monthly via validated metrics. Results: 30 PwCF provided baseline data; 25 completed the study. At baseline, the cohort had substantial CRS, with mean 22-question SinoNasal Outcome Test (SNOT-22) score 33.1 and mean sinus CT %SO 63.7%. At 6-month follow-up, %SO improved by mean 22.9% (P < 0.001). %SO improvement trended toward greater magnitude for those naïve to prior modulator therapy (P = 0.09). Mean SNOT-22 scores and health utility improved by 15.3 and 0.068 [6.8%] (all P ⩽ 0.007). Presenteeism, activity impairment and overall productivity loss improved (all P ⩽ 0.049). Improvements in SNOT-22 scores and health utility occurred by one month and remained improved over the study. Conclusions: ETI is associated with substantial improvements in sinus CT opacification and productivity loss, and clinically meaningful improvements in sinonasal QOL and health utility. Most improvements were rapid, robust, and durable over the study. [ABSTRACT FROM AUTHOR]

Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug-drug interactions, are discussed. [ABSTRACT FROM AUTHOR]

Background: Combination treatment with the cystic fibrosis transmembrane conductance regulator (CFTR) modulators tezacaftor (VX-661) and ivacaftor (VX-770) was designed to target the underlying cause of disease in patients with cystic fibrosis.Methods: In this phase 3, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial, we evaluated combination therapy with tezacaftor and ivacaftor in patients 12 years of age or older who had cystic fibrosis and were homozygous for the CFTR Phe508del mutation. Patients were randomly assigned in a 1:1 ratio to receive either 100 mg of tezacaftor once daily and 150 mg of ivacaftor twice daily or matched placebo for 24 weeks. The primary end point was the absolute change in the percentage of the predicted forced expiratory volume in 1 second (FEV1) through week 24 (calculated in percentage points); relative change in the percentage of the predicted FEV1 through week 24 (calculated as a percentage) was a key secondary end point.Results: Of the 510 patients who underwent randomization, 509 received tezacaftor-ivacaftor or placebo, and 475 completed 24 weeks of the trial regimen. The mean FEV1 at baseline was 60.0% of the predicted value. The effects on the absolute and relative changes in the percentage of the predicted FEV1 in favor of tezacaftor-ivacaftor over placebo were 4.0 percentage points and 6.8%, respectively (P<0.001 for both comparisons). The rate of pulmonary exacerbation was 35% lower in the tezacaftor-ivacaftor group than in the placebo group (P=0.005). The incidence of adverse events was similar in the two groups. Most adverse events were of mild severity (in 41.8% of patients overall) or moderate severity (in 40.9% overall), and serious adverse events were less frequent with tezacaftor-ivacaftor (12.4%) than with placebo (18.2%). A total of 2.9% of patients discontinued the assigned regimen owing to adverse events. Fewer patients in the tezacaftor-ivacaftor group than in the placebo group had respiratory adverse events, none of which led to discontinuation.Conclusions: The combination of tezacaftor and ivacaftor was efficacious and safe in patients 12 years of age or older who had cystic fibrosis and were homozygous for the CFTR Phe508del mutation. (Funded by Vertex Pharmaceuticals; EVOLVE ClinicalTrials.gov number, NCT02347657 .). [ABSTRACT FROM AUTHOR]

• HEMT improves multiple measures of sinusitis through 2 years of therapy in adults. • Sinus CT scans analyzed via machine learning methods and sinus symptoms improved. • Health utility increased and productivity loss decreased with 24 months of HEMT. • HEMT initiated in adulthood did not fully resolve chronic rhinosinusitis in adults. [ABSTRACT FROM AUTHOR]

Keywords: computed tomography; cystic fibrosis; modulator; quality of life; sinusitis EN computed tomography cystic fibrosis modulator quality of life sinusitis 1435 1438 4 11/15/22 20221101 NES 221101 INTRODUCTION The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy (HEMT) with elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease and chronic rhinosinusitis (CRS) in people with cystic fibrosis (PwCF).1,2 Adequately managing the sinonasal manifestations of CF is critical for maximizing quality of life (QOL) and optimizing pulmonary status.3 CRS severity can be quantified by patient-reported, radiographic, and endoscopic methods, with patient-reported and objective measures thought to represent different constructs of disease. Computed tomography, cystic fibrosis, quality of life, sinusitis, modulator Objective and patient-based measures of chronic rhinosinusitis in people with cystic fibrosis treated with highly effective modulator therapy. [Extracted from the article]

Keywords: CFTR modulator therapy; computed tomography; cystic fibrosis; olfaction; olfactory cleft; quality of life; smell testing EN CFTR modulator therapy computed tomography cystic fibrosis olfaction olfactory cleft quality of life smell testing 963 966 4 06/21/22 20220701 NES 220701 INTRODUCTION Olfactory dysfunction (OD) is a core component of chronic rhinosinusitis (CRS) and is common in people with cystic fibrosis (PwCF).1,2 However, limited research has investigated factors associated with OD in PwCF. CFTR modulator therapy, computed tomography, cystic fibrosis, olfaction, quality of life, olfactory cleft, smell testing Impact of CFTR therapy on chronic rhinosinusitis and health status: deep learning CT analysis and patient reported outcomes. [Extracted from the article]