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Novel Therapeutic Strategies for Cystic Fibrosis

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Guest Editor
1. Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1E8, Canada
2. Translational Medicine, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1E8, Canada
Interests: airway inflammation in cystic fibrosis (CF); L-arginine/nitric oxide (NO) metabolism; lung and airways diseases

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Guest Editor Assistant
1. Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1E8, Canada
2. Translational Medicine, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1E8, Canada
Interests: airway inflammation in cystic fibrosis (CF); allergy and asthma; respiratory viral infections

Special Issue Information

Dear Colleagues,

Highly effective modulator therapy has reshaped cystic fibrosis (CF) care—yet important gaps remain. An estimated ~10-15% of people with CF carry CFTR gene variants not eligible for currently approved modulators, and are intolerant or unresponsive to treatment. Even among responders, chronic airway infection and inflammation may persist, and extrapulmonary complications such as CF-related diabetes and liver disease continue to cause morbidity. At the same time, the modulator era raises practical new questions: How do we quantify residual disease activity? Which biomarkers are fit for purpose? And how do we develop effective novel therapies for those who remain without a modulator option?

We invite you to contribute to this Special Issue on emerging therapeutic strategies that extend, complement, or go beyond CFTR modulator therapy. We welcome original research and reviews across the translational spectrum—from target discovery and preclinical development to clinical evaluation and implementation.

Topics of interest include (but are not limited to):

  • Next-generation CFTR rescue strategies (novel modulators, read-through approaches, amplifiers);
  • Gene therapy, gene editing, and mRNA-based therapies;
  • Anti-inflammatory and immunomodulatory strategies in neutrophil-driven airway disease;
  • Novel antimicrobial and anti-biofilm approaches;
  • Mucolytics and airway surface liquid-restoring treatments;
  • Biomarkers for treatment monitoring, risk stratification, and exacerbation prediction;
  • Extracellular vesicles as biomarker sources or therapeutic targets;
  • Therapies addressing extrapulmonary manifestations of CF;
  • Preclinical models enabling therapeutic development;
  • Precision medicine approaches and patient stratification.

We look forward to your contributions.

Prof. Dr. Hartmut Grasemann
Guest Editor

Dr. Dominik Funken
Guest Editor Assistant

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Keywords

  • cystic fibrosis
  • CFTR modulators
  • gene therapy
  • airway inflammation
  • antimicrobial therapy
  • biomarkers
  • mucus
  • extrapulmonary disease
  • clinical trials
  • precision medicine

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Published Papers (1 paper)

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Research

13 pages, 1271 KB  
Article
FT-IR Spectroscopy to Discriminate Old from New Pseudomonas aeruginosa Infections in People with Cystic Fibrosis
by Martina Rossitto, Serena Raimondi, Valeria Fox, Vanessa Tuccio Guarna Assanti, Nour Essa, Maria Stefania Lepanto, Marco Cristiano, Venere Cortazzo, Marilena Agosta, Fabio Majo, Renato Cutrera, Carlo Federico Perno, Paola Bernaschi and Gianluca Vrenna
Int. J. Mol. Sci. 2026, 27(14), 6452; https://doi.org/10.3390/ijms27146452 - 20 Jul 2026
Viewed by 454
Abstract
Chronic Pseudomonas aeruginosa colonisation leads to lung deterioration and poor prognosis in people with cystic fibrosis (pwCF). Early and aggressive therapies can achieve P. aeruginosa eradication, which may recur later. Therefore, determining whether it has resisted therapy or has been newly acquired may [...] Read more.
Chronic Pseudomonas aeruginosa colonisation leads to lung deterioration and poor prognosis in people with cystic fibrosis (pwCF). Early and aggressive therapies can achieve P. aeruginosa eradication, which may recur later. Therefore, determining whether it has resisted therapy or has been newly acquired may guide subsequent treatment(s). This information is crucial also for patients treated with CFTR modulators representing P. aeruginosa after prolonged negativity and to confirm chronic infections. We evaluated the ability of Fourier-transform infrared (FT-IR) spectroscopy to determine intra-patient isoclonality for 103 P. aeruginosa strains isolated from 36 pwCF. Two were chronically and two intermittently colonised; twelve were on modulators with a past P. aeruginosa colonisation; and twenty received eradication therapy, ten of whom were also treated with modulators. FT-IR data were validated by Whole Genome Sequencing (WGS) identification of Sequence Type. FT-IR identified persistence of P. aeruginosa in 24 patients, with a WGS-confirmed positive predictive value of 100% and diagnostic accuracy of 94%. The eradication therapy success rate was 45%, and the time to P. aeruginosa reappearance was similar in both patients with failed eradication treatment and those who initially cleared the infection but later acquired a new strain. Nine patients in modulators showed persistent infections. FT-IR can rapidly determine the clonality of P. aeruginosa isolates, allowing discrimination of recurring versus new infections both in patients with established colonisations and those subjected to eradication therapy representing P. aeruginosa. By overcoming the time-based criteria used to define new infections and by providing the actual success rate of eradication therapies, FT-IR can effectively contribute to the development of efficient therapeutic strategies. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Cystic Fibrosis)
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