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Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. While cystic fibrosis is a multi-organ disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. Despite the remarkable impact that these therapies have had, there remains a significant proportion of people with cystic fibrosis (estimated at 10-15% of the global cystic fibrosis population) who are genetically ineligible for, or intolerant to, current CFTR-targeting therapies and whose therapeutic needs remain unmet. Inhaled genetic therapies offer the prospect of addressing the unmet pulmonary treatment need in people with cystic fibrosis, with several approaches, including gene addition therapy (the focus of this review), RNA-based therapies, antisense oligonucleotides and gene editing, being explored. Various non-viral and viral vectors have been investigated for cystic fibrosis gene addition therapy for mutation-agnostic restoration of CFTR function in the lungs. Lentiviral vectors offer the prospect of highly efficient and long-lasting gene expression, and the potential to be safely and, in contrast to other commonly used viral vectors, effectively re-dosed. A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of cystic fibrosis. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.

Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF., Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV 1 ) at 24 weeks., Results: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV 1 points with LAU-7b and 1.95 ppFEV 1 with placebo, a 0.77 ppFEV 1 (40 s) difference, p=0.345, and a 0.95 ppFEV 1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV 1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV 1 , in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile., Conclusion: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development., Competing Interests: Declaration of competing interest MW Konstan, LC Lands, D Potvin and D Radzioch report receiving consulting fees from Laurent Pharmaceuticals; JM Houle, R Pislariu, P Colin, I Kianicka are employees of Laurent Pharmaceuticals; D Polineni, J Chmiel, L Bilodeau, PG Middleton, E Matouk, T Kotsimbos, JB Zuckerman, SZ Nasr, TG Liou report no conflict of interest related to this study., (Copyright © 2024. Published by Elsevier B.V.)

Background: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF., Methods: A retrospective cohort study was performed at a CF Foundation accredited institution including adults with CF who received NcTCVCs in interventional radiology from 7/19/2007 to 3/09/2020. Complications analyzed included catheter related deep venous thrombosis (DVT), central line associated blood stream infection (CLABSI), and catheter related central venous stenosis. Complications were considered attributable if they occurred while the catheter was in place or within 30 days of catheter removal., Results: During the study duration, 386 NcTCVCs were placed in 60 unique patients (55 % female) with a mean of 6.4 catheters per patient. Majority of NcTCVCs placed were 4 French (61.4 %). Average duration of indwelling NcTCVC was 16.2 days. No patients demonstrated catheter attributable symptomatic DVT. The incidence of DVT, CLABSI, and central venous stenosis was 0 (0 %), 4 (1 %), and 1 (0.3 %), respectively., Conclusions: Many adults with CF have required insertion of numerous PICCs for the treatment of recurrent pulmonary exacerbations. In those adults that develop PICC-associated peripheral vein stenosis precluding PICC placement, these results indicate NcTCVCs are a safe alternative., Competing Interests: Declaration of Competing Interest J.M. declares Grants or contracts from any entity for Cystic Fibrosis Foundation, Vertex Pharmaceuticals, Armata Pharmaceuticals, Sound Pharmaceuticals, Spirovant Sciences, Calithera Biosciences. Support to attend North American Cystic Fibrosis Conference. A.D., R.T., A.R., K.Y., C.W., L.C., Y.L.: No conflict, (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert's Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert's Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF., (© 2024 Wiley Periodicals LLC.)

Background: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients., Methods: In this phase 3, open-label, single-arm extension study, participants with F508del -minimal function (from a 24-week parent study; n=399) or F508del - F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit., Results: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in forced expiratory volume in 1 s (FEV 1 ) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV 1 % pred was +0.07 (95% CI -0.12-0.26) percentage points among the participants., Conclusions: ELX/TEZ/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA., Competing Interests: Conflicts of interest: All authors received nonfinancial support (assistance with manuscript preparation) from Nucleus Global, which received funding from Vertex Pharmaceuticals Incorporated. C.L. Daines has nothing further to disclose. E. Tullis has received consulting, speaker and travel fees from Vertex Pharmaceuticals. S. Costa serves on an advisory board for Vertex Pharmaceuticals. R.W. Linnemann serves on an advisory board and reports grants paid to her institution and consulting fees from Vertex Pharmaceuticals. M.A. Mall reports patient recruitment fees paid to his institution and advisory fees from Vertex Pharmaceuticals, consulting fees from Antabio, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Santhera, Sterna Biologicals and Vertex Pharmaceuticals, speaker fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim and Vertex Pharmaceuticals, travel fees from Boehringer Ingelheim and Vertex Pharmaceuticals, advisory fees from Antabio, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Santhera and Vertex Pharmaceuticals, and serves on the European Cystic Fibrosis Society (ECFS) board. E.F. McKone reports grants, lecture fees and serving on an advisory board for Vertex Pharmaceuticals, lecture fees from Roche, travel fees from A. Menarini, and serving on advisory boards for Janssen, Insmed and CF Storm. D. Polineni reports grants from Laurent Pharmaceuticals, Parion Sciences, Proteostasis Therapeutics and Vertex Pharmaceuticals, consulting fees from Vertex Pharmaceuticals, nonfinancial support for travel to investigator meeting from Vertex Pharmaceuticals, and serves on an advisory board for Sanofi. B.S. Quon reports payments paid to his institution and speaker fees from Vertex Pharmaceuticals. F.C. Ringshausen reports grants paid to his institution from Basilea Pharmaceutica, German Center for Lung Research (DZL), German Center for Infection Research (DZIF), Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis (iABC)/Innovative Medicines Initiative (IMI), European Federation of Pharmaceutical Industries and Associations (EFPIA), Insmed, Novartis and Polyphor, consulting fees from Grifols, Insmed, Parion, Shionogi and Zambon, speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Grifols, Insmed and Novartis, participation on advisory boards for Grifols, Insmed, Parion, Shionogi and Zambon, unpaid honoraria as co-chair of the German Bronchiectasis Registry (PROGNOSIS), and payments to his institution from AbbVie, AstraZeneca, Boehringer Ingelheim, Corbus, Celtaxsys, Insmed, Novartis, Parion, Polyphor, Vertex and Zambon; and is a steering committee member of the European Bronchiectasis Registry (EMBARC), a steering committee member of the European NTM registry (EMBARC-NTM), a core network lead in ERN-LUNG, a principal investigator for DZL, a chair of the cystic fibrosis working group of the German Respiratory Society (DGP), a steering committee member of the Group of German CF Physicians (AGAM), and co-chair of medical consultants of PCD Patient Advocacy Group (Kartagener Syndrom und Primäre Ciliäre Dyskinesie eV). S.M. Rowe reports grants paid to his institution from AbbVie, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Celtaxsys, Eloxx, Ionis Pharmaceuticals, Novartis, Proteostasis Therapeutics, Synedgen, Synspira Therapeutics, Translate Bio and Vertex Pharmaceuticals, nonfinancial support from AbbVie, Ionis Pharmaceuticals, Proteostasis Therapeutics, Renovion, Synedgen and Synspira Therapeutics, consulting fees from AbbVie, Arrowhead Pharmaceuticals, Bayer, Cystetic Medicines, Ionis Pharmaceuticals, Novartis, Renovion, Synedgen, Synspira Therapeutics and Vertex Pharmaceuticals, and serves as co-chair for the Next Generation Steering Committee on Vertex Pharmaceuticals. H. Selvadurai has nothing further to disclose. J.L. Taylor-Cousar serves on the board of trustees, clinical research executive committee, clinical research advisory board and Women's Health Research-Working Group for the US Cystic Fibrosis Foundation, serves on the scientific advisory board for Emily's Entourage, serves on the respiratory health awards working group, scientific grants review committee and clinical problems assembly programming committee for the American Thoracic Society; reports consulting fees from 4D Molecular Therapeutics, Celtaxsys, Prolarean Imaging, Protalix Biotherapeutics, Proteostasis Therapeutics and Santhera Pharmaceuticals, grants to her institution from Bayer, Celtaxsys, Eloxx Pharmaceuticals, Gilead, N30 and Proteostasis Therapeutics, speaking fees from Celtaxsys and Gilead, serves on advisory board for AbbVie, Genentech, Insmed and Novartis, and is an associate editor for the Journal of Cystic Fibrosis. N.J. Withers reports lecture fees from Vertex Pharmaceuticals and serves on an advisory board for Vertex Pharmaceuticals and Proteostasis Therapeutics. B. Ramsey reports travel fees and grants from, and serves on advisory board for Vertex Pharmaceuticals, and personal fees from Cystetic Medicines. M. Griese reports grants to his institution from Vertex Pharmaceuticals. N. Ahluwalia, S.M. Moskowitz, V. Prieto-Centurion, Y.V. Tan, S. Tian, T. Weinstock, F. Xuan and Y. Zhang are employees of Vertex and may own stock or stock options in Vertex., (Copyright ©The authors 2023.)

Purpose of Review: Advances in cystic fibrosis (CF) therapies over the past decade pivotally changed the morbidity and mortality of CF with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators that rescue dysfunctional CFTR protein in individuals with eligible genotypes. However, a significant proportion of the CF population is in need of alternative treatment strategies to address CFTR variants that are ineligible for therapeutic protein correction and/or potentiation. Current drug development efforts of nucleic-acid based therapies (i.e., DNA and RNA based therapies) in CF are informed by historic challenges of CF gene therapy trials, recent FDA guidance informed by non-CF gene therapy trials, and advances in therapeutic applications related to severe acute respiratory syndrome coronavirus 2 vaccine development. These historic and timely developments are of significant relevance for advancing genetic therapies in CF., Recent Findings: This article reviews the main themes of semi-permanent genetic therapy strategies covering recent literature focused on: adenovirus and adeno-associated virus vector delivery, advances in lentivirus vector use and safety considerations, mRNA delivery and antisense oligonucleotide drug development., Summary: Currently, drug development and clinical trials for genetic therapies in CF are rapidly progressing. This review aims to increase the foundational knowledge of CF genetic therapies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics., Competing Interests: Declaration of interests NM-H reports grants from the Cystic Fibrosis Foundation (CFF), the National Institutes of Health (NIH; P30 DK 089507 and UL1 TR002319), and the Food and Drug Administration (FDA); consulting fees from Enterprise Therapeutics; and data safety monitoring board (DSMB) membership for the NIH. JPC is an employee of CFF. RJ reports grants from CFF; consulting fees from Boehringer Ingelheim and Recode Therapeutics; honoraria from Vertex Pharmaceuticals; and travel support from CFF. SHD reports contracts from Calithera, CFF, NIH (P30 DK065988), Vertex Pharmaceuticals, 4D Molecular Therapeutics, and Chiesi USA; consulting fees from Polarean, 501 Ventures, Enterprise Therapeutics, and Boehringer Ingelheim; fees for participation on advisory boards for Innova Healthcare and Boehringer Ingleheim; travel fees from Enterprise Therapeutics and CFF; and participation on a board for Abbvie. IF reports grants from AbbVie, Bayer, Boehringer Ingelheim, Insmed, GSK, and Vertex Pharmaceuticals; honoraria from Vertex Pharmaceuticals; board participation for AbbVie, Boehringer Ingelheim, Kither Biotech, and Vertex Pharmaceuticals; and support to her institution from the European Cystic Fibrosis Society (ECFS). CHG reports grants and contracts from CFF, NIH (P30 DK 089507 and UL1 TR000423), and FDA; consulting fees from Enterprise Therapeutics; honoraria from Gilead Sciences and Vertex Pharmaceuticals; travel support from Vertex Pharmaceuticals and Enterprise Therapeutics; participation on the board for Novartis; stock options for Air Therapeutics; and leadership roles for the American Thoracic Society (ATS). DP reports grants from CFF (002805121), NIH, and Aclaris Pharmaceuticals; travel support from CFF; and board participation for Vertex Pharmaceuticals and Translate Bio. FR reports grants from Vertex Pharmaceuticals and consulting fees from Vertex Pharmaceuticals and Calithera. BSQ reports grants from CFF, Cystic Fibrosis Canada, Vertex Pharmaceuticals, and Gilead Sciences; honoraria from Vertex Pharmaceuticals; and travel support from CFF. ETZ reports grants from NIH, Vertex Pharmaceuticals, and CFF (002884121); consulting fees from CFF; travel support from CFF, Vertex Pharmaceuticals, and ECFS; and participation on boards for CFF and Vertex Pharmaceuticals. SCB reports grants from the National Health and Medical Research Council Australia (APP1102494), the Medical Research Futures Fund Australia, and CFF (BELL1480 and BELL19A0); and honoraria from Vertex Pharmaceuticals. JCD reports grants from the UK Cystic Fibrosis Trust (as part of their Clinical Trials Accelerator Platform), CFF, Cystic Fibrosis Ireland, the Engineering and Physical Sciences Research Council, and the National Institute for Health and Care Research; and honoraria from Vertex Pharmaceuticals, Boehringer Ingelheim, Eloxx, Algipharma, Abbvie, Arcturus, Enterprise Therapeutics, Recode, LifeArc, Genentech, and Tavanta. JCD serves as Deputy Editor for the Journal of Cystic Fibrosis. MWK reports grants from NIH (P01HL128192 and UL1TR002548) and CFF; consulting fees from AbbVie, AzurRx, Cystetic Medicines, EnBiotix, First Wave Biopharma, Insmed, Laurent Pharmaceuticals, Mylan, and PBM BC Holdings; board participation for AbbVie, CFF, First Wave Biopharma, Insmed, Laurent Pharmaceuticals, Sionna, and Vertex; and committee membership for CFF. MAM reports grants from the German Research Foundation (CRC 1449 project #431232613), the German Ministry for Education and Research (82DZL009B1), the German Innovation Fund, and Vertex Pharmaceuticals; consulting fees from Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Santhera, Splisense, and Vertex Pharmaceuticals; honoraria from Vertex Pharmaceuticals; travel support from Boehringer Ingelheim and Vertex Pharmaceuticals; and participation on boards for Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari, and Vertex Pharmaceuticals. EM reports grants from Vertex Pharmaceuticals; honoraria from Vertex Phamaceuticals; travel support from Menarini; and board participation for the Cystic Fibrosis Storm Clinical Trial, Vertex Pharmaceuticals, Janssen, Abbvie, and Insmed. JHR reports grants from Cystic Fibrosis Canada, CFF, Vertex Phamaceuticals, the Canada Foundation for Innovation, and the Canadian Institutes of Health Research; consulting fees from Sanofi; and travel support from Vertex Pharmaceuticals. SMR reports grant funding from CFF (P30DK072482), NIH (UL1TR003096), Vertex Pharmaceuticals, Galapagos/Abbvie, Eloxx, Synspira, Translate Bio, Arcturus, Astra-Zenica, and Ionis; and consulting fees from Vertex Pharmaceuticals, Synspira (including stock options), Renovion (including stock options), Cystetic Medicines, and Arcturus. SMR's potential competing interests were resolved or ended in 2022 or earlier. JLT-C reports grants and contracts from CFF, Vertex Pharmaceutics, Eloxx, and 4DMT; consulting fees from Vertex Phamaceuticals, Insmed, and 4DMT; participation on a DSMB for Abbvie; and participation on advisory boards for CFF, ATS, Journal of Cystic Fibrosis, The Lancet Respiratory Medicine, and Emily's Entourage. GR-B reports grants and contracts from Vertex Pharmaceuticals and CFF. DGD reports grants from Chiesi Farmaceutici and CFF; consulting fees from Vertex and Insmed; honoraria from Chiesi and Gilead; travel support from ECFS and CFF; board participation for Momab and CSL Behring; and support from ECFS as director of the Clinical Trials Network. MJ, NRK, TL, KP, JMP, and LQ declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The daily treatment regimen for an individual with cystic fibrosis (CF) can take more than 2 h to complete, and chronic treatment adherence rates are low. Developing partnerships between CF clinical researchers and the CF community is essential in developing acceptable, feasible, and effective strategies to improve self-management and adherence., Methods: The Success with Therapies Research Consortium (STRC) was formed as a multi-center US collaborative to conduct rigorous research studies of adherence to CF treatments. A multidisciplinary team of researchers from 15 sites, collaborating with members of the CF community, is charged with developing, implementing, and disseminating real-world, patient-centered interventions for people living with CF., Results: Since 2014, the STRC has conducted 8 studies. The CF community, people with CF (pwCF), and caregivers have come to serve in multiple valuable capacities on the STRC, including as members of the Steering Committee and Co-Principal Investigators. Additionally, while people with CF are irreplaceable participants in STRC studies, their influence, and that of their families and healthcare professionals, extends beyond the traditional research participant role., Conclusions: Engaging broadly with the CF community is the optimal model for developing interventions to support those living with CF in sustaining daily care. Input and direct involvement from people with CF, their families, and their caregivers has enabled the STRC to advance its mission through innovative clinical research approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: A cystic fibrosis (CF)-specific cognitive-behavioral therapy intervention (CF-CBT) was developed in partnership with the CF community to advance preventive mental health care. Multidisciplinary providers across three centers were trained to deliver CF-CBT for this pilot assessing feasibility/acceptability and preliminary effectiveness of an integrated model of care., Methods: The 8-session CF-CBT was delivered to 14 adults with mild depression and/or anxiety symptoms in-person and via audio telehealth. Assessment of attrition, engagement, homework completion, treatment satisfaction, and treatment fidelity informed feasibility/acceptability assessment. Mental health outcomes included depression, anxiety, quality of life (Cystic Fibrosis Questionnaire-Revised [CFQ-R), perceived stress and coping. Preliminary effectiveness was evaluated with Cohen's d metric of effect sizes (ES) of pre-post mean change scores., Results: A total of 108 sessions were conducted; 13 adults completed the intervention; 1 discontinued early. Engagement, homework completion, and treatment acceptability were highly rated (mean = 30; SD = 2, range: 27-32 on a 32-point scale). Fidelity scores ranged from 85.7% to 93.6%. Large ES changes reflected improvements in depressive symptoms (-0.83), CFQ-R (Vitality scale: 1.11), and Relaxation Skills (0.93); moderate ES for CFQ-R Role Functioning (0.63), Awareness of Tension (0.62), Coping Confidence (0.70) and CF-specific Coping (0.55); and small ES for anxiety symptoms (-0.22), perceived stress (-0.25), Behavioral Activation (0.29), and several CFQ-R domains, including Emotional Functioning (0.29). Two CFQ-R subscales decreased (Body Image, Eating Concerns)., Conclusions: Results indicated feasibility and acceptability of CF-CBT and its integration into team-based CF care with promising effectiveness, especially for depression. A multicenter randomized controlled trial of CF-CBT will further examine effectiveness of a CF-specific integrated care model., (© 2022 Wiley Periodicals LLC.)