Review
Cell Biology
Francesca Saluzzo, Luca Riberi, Barbara Messore, Nicola Ivan Lore, Irene Esposito, Elisabetta Bignamini, Virginia De Rose
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to imbalances in the airway microenvironment and increased susceptibility to infections. CFTR modulators have shown promise in improving airway infections, but their long-term effects remain to be fully understood.
Review
Biochemistry & Molecular Biology
Aniello Meoli, Olaf Eickmeier, Giovanna Pisi, Valentina Fainardi, Stefan Zielen, Susanna Esposito
Summary: Cystic fibrosis, a genetically inherited disease caused by mutations in the CFTR gene, is a life-threatening disorder affecting multiple systems. CFTR modulators play a crucial role in influencing and eventually restoring lung phagocyte function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Gastroenterology & Hepatology
Jeremy Dana, Dominique Debray, Aurelie Beaufrere, Sophie Hillaire, Monique Fabre, Caroline Reinhold, Thomas F. Baumert, Laureline Berteloot, Valerie Vilgrain
Summary: Cystic fibrosis-related liver disease (CFLD) is a pathological mechanism caused by the defect in biliary epithelial cells in cystic fibrosis patients. CFLD presents with varying clinical/histological manifestations and severity, with focal biliary fibrosis being the main histological presentation. A minority of cases develop portal hypertension, requiring specific management including liver transplantation. Noncirrhotic portal hypertension, in addition to cirrhotic portal hypertension, is also increasingly prevalent. Accurate classification of CFLD is necessary for evaluating the effect of new therapies on the liver.
JOURNAL OF HEPATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Christelle Bergeron, Andre M. Cantin
Summary: Rare diseases affect 400 million individuals globally, and cystic fibrosis, a genetic disease, has seen advancements in potential therapies that aim to restore CFTR function, showing promise in improving the lives of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pediatrics
I. M. Balfour-Lynn, J. A. King
Summary: CFTR modulators have significantly improved the clinical course of CF, with indirect evidence suggesting potential impact on life expectancy.
PAEDIATRIC RESPIRATORY REVIEWS
(2022)
Review
Medicine, Research & Experimental
Shijing Jia, Jennifer L. Taylor-Cousar
Summary: Cystic fibrosis (CF) is a genetic disease that affects multiple organ systems and can lead to various complications. Traditional treatments focused on managing the symptoms of each affected system. However, the development of modulator therapies targeted at specific genetic mutations has significantly improved the lives and prognosis of CF patients.
ANNUAL REVIEW OF MEDICINE
(2023)
Article
Immunology
Vincent D. Giacalone, Diego Moncada Giraldo, George L. Silva, Justin Hosten, Limin Peng, Lokesh Guglani, Rabindra Tirouvanziam
Summary: This study found that early-life pulmonary exacerbations (PEs) activate airway T cells and shift CF airway immunity towards neutrophil dominance.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Carla M. P. Ribeiro, Matthew G. Higgs, Marianne S. Muhlebach, Matthew C. Wolfgang, Monica Borgatti, Ilaria Lampronti, Giulio Cabrini
Summary: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have provided a significant therapeutic advantage for people with cystic fibrosis (pwCF). However, these modulators face limitations in reducing chronic lung bacterial infection and inflammation, which are the main causes of respiratory damage and insufficiency in pwCF, especially in adults. This article revisits the debated issues of pulmonary bacterial infection and inflammatory processes in pwCF, highlighting the mechanisms favoring bacterial infection, the interplay between Pseudomonas aeruginosa and Staphylococcus aureus, and the cross-talk among bacteria, bronchial epithelial cells, and host immune defenses. The recent findings on the effect of CFTR modulators on bacterial infection and inflammation are also presented to identify potential therapeutic targets for respiratory pathology in pwCF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Article
Critical Care Medicine
Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N. Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L. Metersky, Matthew Vincent, Christopher P. Crum, Richard C. Boucher, Harry Karmouty-Quintana, Howard J. Huang, Ajay Sheshadri, Burton F. Dickey, Kalpaj R. Parekh, John F. Engelhardt, Frank D. McKeon, Wa Xian
Summary: CF patients' lungs harbor proinflammatory stem cell variants that contribute to persistent inflammation and are resistant to CFTR modulator therapy.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Genetics & Heredity
Luka A. Clarke, Vanessa C. C. Luz, Szymon Targowski, Sofia S. Ramalho, Carlos M. Farinha, Margarida D. Amaral
Summary: Recent advances have been made in the development and application of CFTR mutation class-specific modulator therapies, but there are currently no approved modulators for Class I mutations. Different PTC mutations have varying effects on CFTR mRNA abundance, integrity, and stability, and optimizing the rescue of PTC mutations requires consideration of these factors.
Article
Pharmacology & Pharmacy
Zsolt Bene, Zsolt Fejes, Tibor Gabor Szanto, Ferenc Fenyvesi, Judit Varadi, Luka A. Clarke, Gyorgy Panyi, Milan Macek, Margarida D. Amaral, Istvan Balogh, Bela Nagy
Summary: In this study, it was found that decreased HE4 protein levels in CF patients treated with CFTR potentiator therapy were inversely correlated with lung function improvement. Modulation of CFTR function affected HE4 expression in CFBE cells, with activation of NF-kappa B pathway playing a role in regulating HE4 expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Caitlyn Harvey, Sinead Weldon, Stuart Elborn, Damian G. Downey, Clifford Taggart
Summary: The advent of CFTR modulators in cystic fibrosis treatment has transformed the management of the disease, shifting it from being a life-limiting condition to one that can be effectively managed. These genotype-specific therapies have shown significant improvements in various clinical endpoints, but their effects on pathogenic burden and airway infection need further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Deborah M. Cholon, Matthew A. Greenwald, Matthew G. Higgs, Nancy L. Quinney, Susan E. Boyles, Suzanne L. Meinig, John T. Minges, Ashlesha Chaubal, Robert Tarran, Carla M. P. Ribeiro, Matthew C. Wolfgang, Martina Gentzsch
Summary: People with cystic fibrosis (pwCF) often suffer from chronic and recurring bacterial lung infections, even with CFTR modulator therapy. This study established a culture system with persistent Pseudomonas aeruginosa infection to examine the effects of CFTR modulators on CFTR function and bacterial persistence. The presence of P. aeruginosa increased CFTR mRNA, protein, and function, while CFTR modulators decreased bacterial burden. It highlights the importance of considering the effects of infection on CFTR rescue by CFTR modulators in evaluating and optimizing drug therapies for pwCF.
Article
Biochemistry & Molecular Biology
Charles Bengtson, Neerupma Silswal, Nathalie Baumlin, Makoto Yoshida, John Dennis, Sireesha Yerrathota, Michael Kim, Matthias Salathe
Summary: This study explored the effects of the CFTR amplifier nesolicaftor on CFTR function and ciliary beating in an inflammatory environment, demonstrating that nesolicaftor can enhance the response of F508del CFTR to the modulator ETI, and reverse the effects of TGF-beta 1 on CFTR function and cytokine expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Barbara Dhooghe, Charlotte Bouckaert, Arnaud Capron, Pierre Wallemacq, Teresinha Leal, Sabrina Noel
Review
Pharmacology & Pharmacy
Barbara Dhooghe, Jeremy Boris Haaf, Sabrina Noel, Teresinha Leal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2016)
Article
Immunology
Teresinha Leal, Gabriella Bergamini, Francois Huaux, Nadtha Panin, Sabrina Noel, Barbara Dhooghe, Jeremy B. Haaf, Pierluigi Mauri, Sara Motta, Dario Di Silvestre, Paola Melotti, Claudio Sorio
FRONTIERS IN IMMUNOLOGY
(2016)
Article
Pharmacology & Pharmacy
C. Norez, C. Vandebrouck, J. Bertrand, S. Noel, E. Durieu, N. Oumata, H. Galons, F. Antigny, A. Chatelier, P. Bois, L. Meijer, F. Becq
BRITISH JOURNAL OF PHARMACOLOGY
(2014)
Review
Medical Laboratory Technology
Bob Lubamba, Barbara Dhooghe, Sabrina Noel, Teresinha Leal
CLINICAL BIOCHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Darren M. Hutt, David Herman, Ana P. C. Rodrigues, Sabrina Noel, Joseph M. Pilewski, Jeanne Matteson, Ben Hoch, Wendy Kellner, Jeffery W. Kelly, Andre Schmidt, Philip J. Thomas, Yoshihiro Matsumura, William R. Skach, Martina Gentzsch, John R. Riordan, Eric J. Sorscher, Tsukasa Okiyoneda, John R. Yates, Gergely L. Lukacs, Raymond A. Frizzell, Gerard Manning, Joel M. Gottesfeld, William E. Balch
NATURE CHEMICAL BIOLOGY
(2010)
Article
Multidisciplinary Sciences
Francois Huaux, Sabrina Noel, Barbara Dhooghe, Nadtha Panin, Sandra Lo Re, Dominique Lison, Pierre Wallemacq, Etienne Marbaix, Bob J. Scholte, Patrick Lebecque, Teresinha Leal
Article
Multidisciplinary Sciences
Barbara Dhooghe, Sabrina Noel, Caroline Bouzin, Gaetane Behets-Wydemans, Teresinha Leal
Review
Pharmacology & Pharmacy
Sabrina Noel, Barbara Dhooghe, Teresinha Leal
FRONTIERS IN PHARMACOLOGY
(2012)
Article
Medicine, Research & Experimental
Sabrina Noel, Nadtha Panin, Mathilde Beka, Barbara Dhooghe, Francois Huaux, Teresinha Leal
Review
Pharmacology & Pharmacy
BeLa Z. Schmidt, Jeremy B. Haaf, Teresinha Leal, Sabrina Noel
CLINICAL PHARMACOLOGY-ADVANCES AND APPLICATIONS
(2016)
Meeting Abstract
Biochemistry & Molecular Biology
W. Balch, D. Hutt, D. Herman, A. Koulov, P. Lapointe, J. Coppinger, S. Pankow, B. Lu, A. Rodriquez, S. Noel, J. Kelly, M. Gentzsch, J. Riordan, E. Sorscher, R. Frizzell, G. Manning, J. Yates, J. Gottesfeld
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
(2010)
Meeting Abstract
Pediatrics
E. J. Sorscher, J. S. Hong, D. M. Hutt, M. Chalfant, D. M. Roth, W. Balch, S. Noel, R. Frizzell, T. Okiyoneda, G. Veit, G. Lukacs, O. Eidelman, C. Jozwik, H. Caohuy, Y. Eudy, H. Pollard, B. Guggino, M. A. Tessari, D. F. Fischer
PEDIATRIC PULMONOLOGY
(2010)
Meeting Abstract
Pediatrics
B. Z. Schmidt, S. Noel, X. Gong, A. Ahner, R. A. Frizzell
PEDIATRIC PULMONOLOGY
(2010)