{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:06:04Z","timestamp":1790283964137,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cystic fibrosis is a genetic disease that results in progressive multi-organ manifestations with predominance in the respiratory and gastrointestinal systems. The significant morbidity and mortality seen in the CF population has been the driving force urging the CF research community to further advance treatments to slow disease progression and, in turn, prolong life expectancy. Enormous strides in medical advancements have translated to improvement in quality of life, symptom burden, and survival; however, there is still no cure. This review discusses the most current mainstay treatments and anticipated therapeutics in the CF drug development pipeline within the mechanisms of mucociliary clearance, anti-inflammatory and anti-infective therapies, restoration of the cystic fibrosis transmembrane conductance regulator (CFTR) protein (also known as highly effective modulator therapy (HEMT)), and genetic therapies. Ribonucleic acid (RNA) therapy, gene transfer, and gene editing are being explored in the hopes of developing a treatment and potential cure for people with CF, particularly for those not responsive to HEMT.<\/jats:p>","DOI":"10.3390\/life13091835","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:48:15Z","timestamp":1693388895000},"page":"1835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Advances in the Cystic Fibrosis Drug Development Pipeline"],"prefix":"10.3390","volume":"13","author":[{"given":"Christine","family":"Esposito","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, New Hyde Park, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kamper","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, New Hyde Park, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Trentacoste","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, New Hyde Park, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Galvin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, The Steven and Alexandra Cohen Children\u2019s Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Lake Success, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4573-5671","authenticated-orcid":false,"given":"Halie","family":"Pfister","sequence":"additional","affiliation":[{"name":"Manhasset Office of Clinical Research, The Feinstein Institutes for Medical Research, Lake Success, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, New Hyde Park, New York, NY 11042, USA"},{"name":"Manhasset Office of Clinical Research, The Feinstein Institutes for Medical Research, Lake Success, New York, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Naehrlich, L. (2020). The Changing Face of Cystic Fibrosis and Its Implications for Screening. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6030054"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Frantzen, T., Barsky, S., LaVecchia, G., Marowitz, M., and Wang, J. (2023). Evolving Nutritional Needs in Cystic Fibrosis. Life, 13.","DOI":"10.3390\/life13071431"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcf.2018.05.004","article-title":"CFTR modulator theratyping: Current status, gaps and future directions","volume":"18","author":"Clancy","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jcf.2011.12.005","article-title":"Ivacaftor potentiation of multiple CFTR channels with gating mutations","volume":"11","author":"Yu","year":"2012","journal-title":"J. Cyst. Fibros."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jcf.2014.09.005","article-title":"Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation","volume":"13","author":"Munck","year":"2014","journal-title":"J. Cyst. Fibros."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1136\/thoraxjnl-2015-207369","article-title":"Lumacaftor\/ivacaftor for patients homozygous for Phe508del-CFTR: Should we curb our enthusiasm?","volume":"70","author":"Jones","year":"2015","journal-title":"Thorax"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1056\/NEJMoa1409547","article-title":"Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR","volume":"373","author":"Wainwright","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","article-title":"Tezacaftor\u2013Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del","volume":"377","author":"Munck","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor\u2013Tezacaftor\u2013Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_10","unstructured":"Cystic Fibrosis Foundation (2021). Patient Registry 2021 Annual Data Report, Cystic Fibrosis Foundation."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S2213-2600(22)00504-5","article-title":"Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: Randomised, double-blind, controlled, phase 2 trials","volume":"11","author":"Uluer","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"ref_12","unstructured":"(2023, March 01). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05033080."},{"key":"ref_13","unstructured":"(2023, March 02). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04853368."},{"key":"ref_14","unstructured":"(2023, July 20). Cystic Fibrosis Foundation. Available online: https:\/\/www.cff.org\/press-releases\/2019-10\/cystic-fibrosis-foundation-launches-500-million-path-cure."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-24575-x","article-title":"A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion","volume":"12","author":"Sharma","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jcf.2021.01.009","article-title":"Targeting G542X CFTR nonsense alleles with ELX-02 restores CFTR function in human-derived intestinal organoids","volume":"20","author":"Crawford","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_17","unstructured":"(2023, March 01). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04135495."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rowe, S., Zuckerman, J., Dorgan, D., Lascano, J., McCoy, K., Jain, M., Schechter, M., Lommatzsch, S., Indihar, V., and Lechtzin, N. (2023). Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1\/2 clinical study. J. Cyst. Fibros., 1.","DOI":"10.1016\/j.jcf.2023.04.008"},{"key":"ref_19","unstructured":"(2023, August 07). NACFC 2023 PLENARY 1: Hope for All: Addressing the Needs of Those with Untreated CF Mutations. Available online: https:\/\/www.youtube.com\/watch?v=k-H_hqkhu24."},{"key":"ref_20","unstructured":"(2023, August 07). Available online: https:\/\/pipelinereview.com\/index.php\/2023013182590\/DNA-RNA-and-Cells\/Arcturus-Therapeutics-Announces-Clinical-Trial-Application-for-ARCT-032-Received-Approval-to-Proceed-into-First-in-Human-Studies-to-Treat-Cystic-Fibrosis.html."},{"key":"ref_21","unstructured":"Ishimaru, D., Boudko, D., Meleshkevitch, E.A., Sidhu, M.S., Poniatowski, J.R., Gao, P., Molla, T., Comini, S., Lister, H., and Coquelin, M. (2023, August 07). Functional Rescue of CFTR by Aerosolized Delivery of Optimized CFTR mRNA Using ReCode-LPNs in Primary Human Bronchial Epithelial Cells Derived from Patients with Cystic Fibrosis. Abstrct 507; ATS 2022. Available online: https:\/\/recodetx.com\/wp-content\/uploads\/2022\/10\/ATS-Poster-Daniella-15Apr2022_FINAL-Oct2022.pdf."},{"key":"ref_22","unstructured":"Cystic Fibrosis Foundation (2023, August 07). Drug Development Pipeline. Available online: https:\/\/apps.cff.org\/Trials\/Pipeline\/details\/10204\/VX-522."},{"key":"ref_23","unstructured":"(2023, March 02). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05668741."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.59566\/IJBS.2017.13048","article-title":"Molecular Mechanisms and Biological Functions of siRNA","volume":"13","author":"Dana","year":"2017","journal-title":"Int. J. Biomed. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1136\/thoraxjnl-2017-210670","article-title":"Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung","volume":"73","author":"Tagalakis","year":"2018","journal-title":"Thorax"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7565","DOI":"10.1021\/acsami.1c14975","article-title":"Hybrid Lipid\/Polymer Nanoparticles to Tackle the Cystic Fibrosis Mucus Barrier in siRNA Delivery to the Lungs: Does PEGylation Make the Difference?","volume":"14","author":"Conte","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_27","unstructured":"Patricia, I. First Clinical Trial Begins for RNAbased therapy SPL84 for CF, Cystic Fibrosis News Today, 15 December 2022."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ccm.2022.06.011","article-title":"Non-Modulator Therapies: Developing a Therapy for Every Cystic Fibrosis Patient","volume":"43","author":"Egan","year":"2022","journal-title":"Clin. Chest Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fphar.2019.00121","article-title":"Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine","volume":"10","author":"Pranke","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1164\/rccm.201505-0914OC","article-title":"rAAV-CFTR\u0394R Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice","volume":"193","author":"Carlon","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yan, Z., Feng, Z., Sun, X., Zhang, Y., Zou, W., Wang, Z., Jensen-Cody, C., Liang, B., Park, S.Y., and Qiu, J. (2023, March 02). Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes. 8 May 2017. Available online: https:\/\/europepmc.org\/backend\/ptpmcrender.fcgi?accid=PMC5567599&blobtype=pdf.","DOI":"10.1089\/hum.2017.060"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S2213-2600(15)00245-3","article-title":"Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fi brosis: A randomised, double-blind, placebo-controlled, phase 2b trial","volume":"3","author":"Alton","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.stemcr.2015.02.005","article-title":"Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells","volume":"4","author":"Crane","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bednarski, C., Tomczak, K., H\u00f6vel, B.V., Weber, W.-M., and Cathomen, T. (2016). Targeted Integration of a Super-Exon into the CFTR Locus Leads to Functional Correction of a Cystic Fibrosis Cell Line Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161072"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.stem.2013.11.002","article-title":"Functional Repair of CFTR by CRISPR\/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients","volume":"13","author":"Schwank","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.1038\/ncomms7952","article-title":"Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium","volume":"6","author":"McNeer","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1002\/ppul.25190","article-title":"Bacteriophage therapy for infections in CF","volume":"56","author":"Chan","year":"2021","journal-title":"Pediatr. Pulmonol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1055\/s-0039-1698464","article-title":"Microbiology of Cystic Fibrosis Airway Disease","volume":"40","author":"Blanchard","year":"2019","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_39","unstructured":"Chmiel, J., Rosenfeld, M., and Davis, S.D. (2020). Cystic Fibrosis: A Multi-Organ System Approach, Humana Press Incorporated."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/17425255.2021.1836157","article-title":"The pharmacokinetics of antibiotics in cystic fibrosis","volume":"17","author":"Akkerman","year":"2021","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1513\/AnnalsATS.201404-166OC","article-title":"Cystic Fibrosis Foundation Pulmonary Guideline*. Pharmacologic Approaches to Prevention and Eradication of InitialPseudomonas aeruginosaInfection","volume":"11","author":"Mogayzel","year":"2014","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0207121","DOI":"10.1128\/aac.02071-21","article-title":"Considerations for the Use of Phage Therapy in Clinical Practice","volume":"66","author":"Suh","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1001\/jama.290.13.1749","article-title":"Azithromycin in Patients with Cystic Fibrosis Chronically Infected with Pseudomonas aeruginosa: A randomized controlled trial","volume":"290","author":"Saiman","year":"2003","journal-title":"JAMA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1164\/rccm.202102-0461OC","article-title":"A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment","volume":"204","author":"Goss","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","unstructured":"(2023, May 02). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05548283."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Taccetti, G., Francalanci, M., Pizzamiglio, G., Messore, B., Carnovale, V., Cimino, G., and Cipolli, M. (2021). Cystic Fibrosis: Recent Insights into Inhaled Antibiotic Treatment and Future Perspectives. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030338"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"762","DOI":"10.4187\/respcare.04208","article-title":"Aerosolized Antibiotics","volume":"60","author":"Keyt","year":"2015","journal-title":"Respir. Care"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1517\/14656566.2013.790366","article-title":"Inhaled antibiotics for the treatment of chronic bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis: Systematic review of randomised controlled trials","volume":"14","author":"Olveira","year":"2013","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1513\/AnnalsATS.201812-863OT","article-title":"Developing Inhaled Antibiotics in Cystic Fibrosis: Current Challenges and Opportunities","volume":"16","author":"Nichols","year":"2019","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_50","unstructured":"Cystic Fibrosis Foundation (2023, January 10). Eradication of Initial P. aeruginosa Clinical Care Guidelines. Available online: https:\/\/www.cff.org\/eradication-initial-p-aeruginosa-clinical-care-guidelines."},{"key":"ref_51","unstructured":"NIH (2023, May 02). Clinical Trials.gov, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jcf.2020.12.004","article-title":"Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial","volume":"20","author":"Puvvadi","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1164\/rccm.200712-1804OC","article-title":"Inhaled Aztreonam Lysine for Chronic Airway Pseudomonas aeruginosa in Cystic Fibrosis","volume":"178","author":"McCoy","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.2147\/DDDT.S146111","article-title":"The Use of Amikacin Liposome Inhalation Suspension (Arikayce) in the Treatment of Refractory Nontuberculous Mycobacterial Lung Disease in Adults","volume":"14","author":"Khan","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_55","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?cond=Cystic+Fibrosis&term=amikacin+pseudomonas&cntry=&state=&city=&dist=."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jcf.2019.08.001","article-title":"Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis","volume":"19","author":"Bilton","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1183\/09059180.00001513","article-title":"Systematic review of the dry powder inhalers colistimethate sodium and tobramycin in cystic fibrosis","volume":"22","author":"Uttley","year":"2013","journal-title":"Eur. Respir. Rev."},{"key":"ref_58","unstructured":"Patel, S., Preuss, C.V., and Bernice, F. (2023, August 08). Vancomycin, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK459263\/."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e01776-19","DOI":"10.1128\/AAC.01776-19","article-title":"Phase I, Dose-Escalating Study of the Safety and Pharmacokinetics of Inhaled Dry-Powder Vancomycin (AeroVanc) in Volunteers and Patients with Cystic Fibrosis: A New Approach to Therapy for Methicillin-Resistant Staphylococcus aureus","volume":"64","author":"Waterer","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_60","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03181932?term=aerovanc&draw=2&rank=2."},{"key":"ref_61","unstructured":"Dasenbrook, E.C. (2023, January 15). Nebulized Vancomycin for Eradication of Persistent MRSA in Patients with Cystic Fibrosis. Consult QD. Available online: https:\/\/consultqd.clevelandclinic.org\/nebulized-vancomycin-for-eradication-of-persistent-mrsa-in-patients-with-cystic-fibrosis\/."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/thoraxjnl-2016-208949","article-title":"Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial","volume":"72","author":"Muhlebach","year":"2017","journal-title":"Thorax"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"00190","DOI":"10.1183\/23120541.00190-2022","article-title":"Eradication of early MRSA infection in cystic fibrosis: A novel study design for the STAR-ter trial","volume":"8","author":"Cunningham","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_64","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT03489629."},{"key":"ref_65","unstructured":"Podder, V., and Sadiq, N.M. (2023, August 08). Levofloxacin, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK545180\/."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.jcf.2015.12.004","article-title":"A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients","volume":"15","author":"Flume","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1080\/14787210.2018.1441024","article-title":"Murepavadin: A new antibiotic class in the pipeline","volume":"16","author":"Dale","year":"2018","journal-title":"Expert. Rev. Anti-Infect. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"114066","DOI":"10.1016\/j.addr.2021.114066","article-title":"Advances in the development of antimicrobial peptides and proteins for inhaled therapy","volume":"180","author":"Wang","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_69","unstructured":"(2023, May 02). CysticFibrosisFoundation.org. Available online: https:\/\/apps.cff.org\/Trials\/Pipeline\/details\/10181\/Inhaled-Murepavadin."},{"key":"ref_70","first-page":"1","article-title":"Current knowledge in the use of bacteriophages to combat infections caused by Pseudomonas aeruginosa in cystic fibrosis","volume":"68","year":"2022","journal-title":"Folia Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.jcf.2017.06.012","article-title":"The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways","volume":"16","author":"Trend","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.3389\/fmicb.2019.02537","article-title":"Constructing and Characterizing Bacteriophage Libraries for Phage Therapy of Human Infections","volume":"10","author":"Gibson","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_73","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04596319."},{"key":"ref_74","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05010577."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.medmal.2008.06.023","article-title":"Phage therapy experience at the Eliava Institute","volume":"38","author":"Kutateladze","year":"2008","journal-title":"Med. Mal. Infect."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1111\/j.1751-7915.2011.00259.x","article-title":"Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens","volume":"4","author":"Kvachadze","year":"2011","journal-title":"Microb. Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1111\/ajt.15503","article-title":"Early clinical experience of bacteriophage therapy in 3 lung transplant recipients","volume":"19","author":"Aslam","year":"2019","journal-title":"Am. J. Transpl."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s15010-019-01319-0","article-title":"Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient","volume":"47","author":"Law","year":"2019","journal-title":"Infection"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41591-019-0437-z","article-title":"Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus","volume":"25","author":"Dedrick","year":"2019","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1021\/acsinfecdis.1c00409","article-title":"Variable Susceptibility to Gallium Compounds of Major Cystic Fibrosis Pathogens","volume":"8","author":"Visaggio","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_81","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02354859."},{"key":"ref_82","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03669614."},{"key":"ref_83","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04294043."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"A470","DOI":"10.1016\/j.chest.2022.08.361","article-title":"Home-based treatment of nontuberculous mycobacteria pulmonary disease via a novel nitric oxide generator and delivery system","volume":"162","author":"Thomson","year":"2022","journal-title":"Chest"},{"key":"ref_85","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05101915."},{"key":"ref_86","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04685720."},{"key":"ref_87","unstructured":"(2023, May 02). Beyond air, LungfitTM Go. Available online: https:\/\/www.beyondair.net\/technology\/."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"a025437","DOI":"10.1101\/cshperspect.a025437","article-title":"Fusidic Acid: A Bacterial Elongation Factor Inhibitor for the Oral Treatment of Acute and Chronic Staphylococcal Infections","volume":"6","author":"Fernandes","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_89","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05641298."},{"key":"ref_90","unstructured":"Food and Drug Administration (2023, April 24). Xenelta (Lefamulin) Prescribing Data, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/211672s000,211673s000lbl.pdf."},{"key":"ref_91","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05225805."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"821820","DOI":"10.3389\/fmicb.2022.821820","article-title":"Polycationic Glycopolymer Demonstrates Activity Against Persisters and Biofilms of Non-tuberculosis Mycobacteria Cystic Fibrosis Clinical Isolates in vitro","volume":"13","author":"Narayanaswamy","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_93","unstructured":"National Center for Biotechnology Information (2023, April 26). PubChem Compound Summary for CID 121383526, Opelconazole, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Opelconazole."},{"key":"ref_94","unstructured":"(2023, May 02). Clinicaltrials.gov, Available online: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05037851."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"a009779","DOI":"10.1101\/cshperspect.a009779","article-title":"Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis","volume":"3","author":"Chmiel","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nm.2715","article-title":"Cystic fibrosis: A mucosal immunodeficiency syndrome","volume":"18","author":"Cohen","year":"2012","journal-title":"Nat. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ccm.2007.02.002","article-title":"Inflammation and Anti-Inflammatory Therapies for Cystic Fibrosis","volume":"28","author":"Chmiel","year":"2007","journal-title":"Clin. Chest Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1002\/ppul.24129","article-title":"Inflammation in cystic fibrosis: An update","volume":"53","author":"Roesch","year":"2018","journal-title":"Pediatr. Pulmonol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jcf.2015.03.003","article-title":"Inflmmation in cystic fibrosis ling disease: Pathogensis and therapy","volume":"14","author":"Cantin","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ccm.2022.06.004","article-title":"Update on Innate and Adaptive Immunity in Cystic Fibrosis","volume":"43","author":"Bruscia","year":"2022","journal-title":"Clin. Chest Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"576293","DOI":"10.3389\/fphar.2020.576293","article-title":"Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis","volume":"11","author":"Perrem","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1056\/NEJM199503303321303","article-title":"Effect of High-Dose Ibuprofen in Patients with Cystic Fibrosis","volume":"332","author":"Konstan","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jcf.2015.07.009","article-title":"Inhaled alpha 1 -proteinase inhibitor therapy in patients with cystic fibrosis","volume":"15","author":"Gaggar","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jcf.2020.09.008","article-title":"Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis","volume":"20","author":"Chmiel","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/cts.12428","article-title":"Phase I Studies of Acebilustat: Biomarker Response and Safety in Patients with Cystic Fibrosis","volume":"10","author":"Elborn","year":"2017","journal-title":"Clin. Transl. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1056\/NEJMoa2021713","article-title":"Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis","volume":"383","author":"Chalmers","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jcf.2019.08.020","article-title":"Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis","volume":"19","author":"Barth","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.prrv.2007.02.009","article-title":"Mucolytics in cystic fibrosis","volume":"8","author":"Henke","year":"2007","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1056\/NEJM199409083311003","article-title":"Effect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis","volume":"331","author":"Fuchs","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/j.1875-9114.1996.tb02914.x","article-title":"Dornase alfa: A new option in the management of cystic fibrosis","volume":"16","author":"Witt","year":"1996","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa043891","article-title":"Mucous Clearance and Lung Function in Cystic Fibrosis with Hypertonic Saline","volume":"354","author":"Donaldson","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.jcf.2021.02.011","article-title":"Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study","volume":"20","author":"Flume","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ejphar.2015.06.051","article-title":"Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus","volume":"764","author":"Ermund","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Danahay, H., and Gosling, M. (2020). TMEM16A: An Alternative Approach to Restoring Airway Anion Secretion in Cystic Fibrosis?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072386"},{"key":"ref_115","unstructured":"(2023, April 28). Cystic Fibrosis Foundation, Community Voice. Available online: https:\/\/www.cff.org\/get-involved\/community-voice."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S2213-2600(22)00434-9","article-title":"Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): Results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials","volume":"11","author":"Ratjen","year":"2023","journal-title":"Lancet Respir Med"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.jcf.2019.11.006","article-title":"Integrating the multiple breath washout test into international multicentre trials","volume":"19","author":"Saunders","year":"2020","journal-title":"J. Cyst. Fibros."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/9\/1835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:42:43Z","timestamp":1760128963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/9\/1835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":117,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["life13091835"],"URL":"https:\/\/doi.org\/10.3390\/life13091835","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,30]]}}}