Article
Immunology
Franziska E. Uhl, Lotte Vanherle, Anja Meissner
Summary: Heart failure (HF) affects 64 million people worldwide. Pulmonary manifestations of HF, including lung inflammation and vascular structure changes, contribute to the poor quality of life for many HF patients. This study investigates the role of cystic fibrosis transmembrane regulator (CFTR) in lung inflammation during HF and suggests that pharmacological correction of CFTR expression could alleviate HF-associated lung inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Qiyu Li, Siyuan Liu, Xuemei Ma, Jiaping Yu
Summary: This meta-analysis evaluated the effectiveness and safety of small molecule therapy in children diagnosed with cystic fibrosis (CF). The results showed that CFTR modulators can improve respiratory function, lung clearance index, sweat chloride concentration, and other aspects of function in children with CF, with comparable adverse events compared to the placebo group.
FRONTIERS IN PEDIATRICS
(2022)
Review
Pharmacology & Pharmacy
Yizi Wang, Bin Ma, Wenya Li, Peiwen Li
Summary: Triple combination therapy for cystic fibrosis patients achieves better clinical results and comparable adverse events compared to the control group.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Lotte Vanherle, Darcy Lidington, Franziska E. Uhl, Saskia Steiner, Stefania Vassallo, Cecilia Skoug, Joao M. N. Duarte, Sangeetha Ramu, Lena Uller, Jean-Francois Desjardins, Kim A. Connelly, Steffen-Sebastian Bolz, Anja Meissner
Summary: Our study investigated the mechanisms that alter hippocampal neurons following myocardial infarction (MI) and explored the therapeutic potential of correcting cystic fibrosis transmembrane regulator (CFTR) as an intervention. We found that MI leads to reduced hippocampal dendrite length and spine density, which is associated with decreased neuronal CFTR expression and inflammatory responses. Blocking CFTR activity down-regulates synaptic regulator PSD-95 expression in neurons, while pharmacologically correcting CFTR expression rescues the down-regulation. Increasing hippocampal neuron CFTR expression improves MI-associated alterations in neuronal structure and memory function. These findings suggest that CFTR therapeutics can attenuate cognitive impairment in heart failure patients.
Review
Biochemistry & Molecular Biology
Laura Carrasco-Hernandez, Esther Quintana-Gallego, Carmen Calero, Rocio Reinoso-Arija, Borja Ruiz-Duque, Jose Luis Lopez-Campos
Summary: The role of CFTR in the pathophysiology of COPD is becoming increasingly important, with its dysfunction leading to thicker and more viscous secretions in the airway, reduced mucociliary clearance, and promotion of airway inflammation. Studying CFTR in the context of COPD pathogenesis is crucial for a comprehensive understanding of COPD's complex pathophysiology and exploring potential therapeutic approaches to address this dysfunction.
Review
Biochemistry & Molecular Biology
Kiera H. Harwood, Rachel M. McQuade, Andrew Jarnicki, Elena K. Schneider-Futschik
Summary: Cystic fibrosis is caused by a defect in the CFTR protein, resulting in respiratory complications and a highly inflammatory environment in the lungs. Neutrophil infiltration plays a critical role in driving inflammation through various pathways. Understanding these mechanisms can lead to the development of new therapeutic targets for CF patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Critical Care Medicine
Pierre-Regis Burgel, Esperie Burnet, Lucile Regard, Clemence Martin
Summary: Cystic fibrosis (CF) is a genetic disease that affects the digestive and respiratory systems. Advances in disease management have significantly improved the prognosis, but there are still disparities in prognosis based on access to specialized care. The article describes the evolution of CF demographics, predicts future trends, and discusses the importance of specialized adult CF care.
Review
Pharmacology & Pharmacy
Alessandro Rimessi, Veronica A. M. Vitto, Simone Patergnani, Paolo Pinton
Summary: Cystic fibrosis is a genetic disorder characterized by airway issues and lung damage. Calcium signaling plays a crucial role in the pathophysiology of CF lung disease, with dysregulated calcium signals leading to impaired cell function and exacerbated inflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Philip R. Tedbury, Candela Manfredi, Frauke Degenhardt, Joseph Conway, Michael C. Horwath, Courtney McCracken, Adam J. Sorscher, Sandy Moreau, Christine Wright, Carolina Edwards, Jo Brewer, Jeannette Guarner, Emmie de Wit, Brandi N. Williamson, Mehul S. Suthar, Yee T. Ong, John D. Roback, David N. Alter, Jan C. Holter, Tom H. Karlsen, Nicoletta Sacchi, Manuel Romero-Gomez, Pietro Invernizzi, Javier Fernandez, Maria Buti, Agustin Albillos, Antonio Julia, Luca Valenti, Rosanna Asselta, Jesus M. Banales, Luis Bujanda, Rafael de Cid, Andre Franke, Stefan G. Sarafianos, Jeong S. Hong, Eric J. Sorscher, Annette Ehrhardt
Summary: Patients with cystic fibrosis (CF) are not highly susceptible to severe COVID-19 despite initial concerns. CFTR carrier status does not affect the severity of COVID-19 clinical outcomes. However, mortality rates are higher in control individuals compared to silent carriers of the common F508del CFTR variant, which requires further investigation. The acidic, viscous, and mucus-obstructed airways in CF patients are unfavorable for coronavirus infection.
Article
Biochemistry & Molecular Biology
Philip R. Tedbury, Candela Manfredi, Frauke Degenhardt, Joseph Conway, Michael C. Horwath, Courtney McCracken, Adam J. Sorscher, Sandy Moreau, Christine Wright, Carolina Edwards, Jo Brewer, Jeannette Guarner, Emmie de Wit, Brandi N. Williamson, Mehul S. Suthar, Yee T. Ong, John D. Roback, David N. Alter, Jan C. Holter, Tom H. Karlsen, Nicoletta Sacchi, Manuel Romero-Gomez, Pietro Invernizzi, Javier Fernandez, Maria Buti, Agustin Albillos, Antonio Julia, Luca Valenti, Rosanna Asselta, Jesus M. Banales, Luis Bujanda, Rafael de Cid, Andre Franke, Stefan G. Sarafianos, Jeong S. Hong, Eric J. Sorscher, Annette Ehrhardt
Summary: Patients with cystic fibrosis (CF) do not have a higher risk of severe COVID-19 due to CFTR carrier status, but control individuals have a higher mortality rate compared to silent carriers. The absence of functional CFTR does not affect the production of SARS-CoV-2 in airway cells, while in vitro experiments suggest that virus proliferation is dependent on features disrupted by absent CFTR in patients with CF. The acidic, viscous, and mucus-obstructed airways in CF patients are unfavorable for coronaviral infection establishment.
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.
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
Biochemistry & Molecular Biology
Chiara Tupini, Adriana Chilin, Alice Rossi, Ida De Fino, Alessandra Bragonzi, Elisabetta D'Aversa, Lucia Carmela Cosenza, Christian Vaccarin, Gianni Sacchetti, Monica Borgatti, Anna Tamanini, Maria Cristina Dechecchi, Francesca Sanvito, Roberto Gambari, Giulio Cabrini, Ilaria Lampronti
Summary: A series of new-generation TMA analogues were synthesized to improve anti-inflammatory activity by inhibiting the NF-kappa B pathway. Among them, GY971a and GY964 showed significant anti-inflammatory effects without evident toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Susannah J. King, Audrey C. Tierney, Deirdre Edgeworth, Dominic Keating, Elyssa Williams, Tom Kotsimbos, Brenda M. Button, John W. Wilson
Summary: Ivacaftor treatment led to initial gains in fat-free mass in the first month, with weight, BMI, and fat mass increases plateauing within the first 6 months and remaining stable over 2.5 years. The long-term metabolic and clinical implications of weight and fat mass gains are still unknown.
Article
Reproductive Biology
Leo Han, Mackenzie Roberts, Addie Luo, Shuhao Wei, Ov D. Slayden, Kelvin D. Macdonald
Summary: This study demonstrates the hormonal regulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression in endocervical cells, both in vitro and in vivo. The researchers also showed that endocervical epithelial cells can be conditionally reprogrammed to study CFTR ion channel function. Furthermore, the study found that estrogen upregulates CFTR expression in the macaque cervix, which is blocked by cotreatment with progesterone.
BIOLOGY OF REPRODUCTION
(2022)
Article
Immunology
Evan Ammerman, Stuart C. Sweet, Gregory A. Storch, Richard S. Buller, Sheila Mason, Carol Conrad, Don Hayes, Albert Faro, Samuel B. Goldfarb, Ernestina Melicoff, Marc Schecter, Gary Visner, Peter S. Heeger, Thalachallour Mohanakumar, Nikki Williams, Lara Danziger-Isakov
TRANSPLANT INFECTIOUS DISEASE
(2020)
Review
Allergy
Brian C. M. Li, Sung Moon Huh, Miguel D. Prieto, Gina Hong, Carsten Schwarz, Richard B. Moss, Bradley S. Quon
Summary: Diagnosing ABPA in CF patients can be challenging, but recent studies have identified promising biomarkers that may aid in diagnosis. Further research is needed to understand their utility better.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Surgery
Sarah Duncan-Park, Claire Dunphy, Jacqueline Becker, Christine D'Urso, Rachel Annunziato, Joshua Blatter, Carol Conrad, Samuel B. Goldfarb, Don Hayes, Ernestina Melicoff, Marc Schecter, Gary Visner, Brian Armstrong, Hyunsook Chin, Karen Kesler, Nikki M. Williams, Jonah N. Odim, Stuart C. Sweet, Lara Danziger-Isakov, Eyal Shemesh
Summary: The study found that remote interventions in pediatric lung transplant recipients can effectively reduce medication level variability, improve blood level stability, and participants successfully completed long-term remote interventions.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Editorial Material
Allergy
Richard B. Moss
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Respiratory System
Gina Hong, Sameer Desai, Richard B. Moss, Patience Eschenhagen, Bradley S. Quon, Carsten Schwarz
Summary: There are significant variations in the diagnosis and management of Aspergillus-related conditions in CF. Future studies are needed to better harmonize the approach to Af-related disease in CF.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Surgery
Stuart C. Sweet, Brian Armstrong, Joshua Blatter, Hyunsook Chin, Carol Conrad, Samuel Goldfarb, Don Hayes, Peter S. Heeger, Victoria Lyou, Ernestina Melicoff-Portillo, Thalachallour Mohanakumar, Jonah Odim, Ranjithkumar Ravichandran, Marc Schecter, Gregory A. Storch, Gary Visner, Nikki M. Williams, Lara Danziger-Isakov
Summary: The study showed that rituximab induction may prevent early DSA development in pediatric lung transplant recipients without adverse effects, but did not significantly differ from the placebo group in terms of the primary endpoint and incidence of adverse events.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Pediatrics
Carol K. Conrad, Haley Hedlin, Hyunsook Chin, Don Hayes, Peter S. Heeger, Albert Faro, Samuel Goldfarb, Ernestina Melicoff-Portillo, Mohanakumar Thalachallour, Jonah Odim, Marc Schecter, Gregory A. Storch, Gary A. Visner, Nikki M. Williams, Karen Kesler, Lara Danziger-Isakov, Stuart C. Sweet
Summary: Cytokine analysis of bronchoalveolar lavage fluid samples from pediatric lung transplant recipients revealed that elevated levels of IL-23 and IL-31 were associated with an increased risk of bronchiolitis obliterans, while lower levels of epithelial growth factor and eotaxin were associated with bronchiolitis obliterans. Furthermore, soluble CD30, pro-inflammatory cytokine IL-23, and sTNFRI levels below cutoff levels were found to be associated with bronchiolitis obliterans-free survival.
PEDIATRIC TRANSPLANTATION
(2022)
Article
Microbiology
Efthymia Iliana Matthaiou, Wayland Chiu, Carol Conrad, Joe Hsu
Summary: Cystic fibrosis lung transplant recipients are at a higher risk of life-threatening invasive aspergillosis. Alkalization of macrophages lacking the CFTR gene is associated with this increased risk, and the presence of iron in the post-transplant microenvironment exacerbates this alkalization. The alkalization impairs the ability of macrophages to clear Aspergillus fumigatus conidia. pH modulation after transplantation may be a therapeutic strategy to reduce the risk of invasive aspergillosis.
Article
Respiratory System
Gregory S. Sawicki, Michael W. Konstan, Edward F. McKone, Richard B. Moss, Barry Lubarsky, Ellison Suthoff, Stefanie J. Millar, David J. Pasta, Nicole Mayer-Hamblett, Christopher H. Goss, Wayne J. Morgan, Margaret E. Duncan, Yoojung Yang
Summary: This study examined the rate of lung function decline in cystic fibrosis patients with F/RF genotypes. The results showed that lung function declines over time in patients of all ages with F/RF genotypes. This finding emphasizes the importance of early intervention and clinical monitoring to preserve lung function in all cystic fibrosis patients.
Article
Microbiology
Richard B. B. Moss
Summary: Allergic asthma has traditionally been treated with inhaled and systemic glucocorticosteroids. A continuum of allergic fungal airways disease associated with Aspergillus fumigatus colonization and/or atopic immune responses that encompasses fungal asthma, severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis is now recognized along a phenotypic severity spectrum of T2-high immune deviation lung disease. Oral triazoles have shown clinical, anti-inflammatory and microbiologic efficacy in this setting; in the future inhaled antifungals may improve the therapeutic index. Humanized monoclonal antibody biologic agents targeting T2-high disease also show efficacy and promise of improved control in difficult cases. Developments in these areas are highlighted in this overview.
Article
Immunology
Joseph E. Levitt, Haley Hedlin, Sophie Duong, Di Lu, Justin Lee, Bryan Bunning, Nadia Elkarra, Benjamin A. Pinsky, Eileen Heffernan, Eric Springman, Richard B. Moss, Hector F. Bonilla, Julie Parsonnet, Roham T. Zamanian, Jamison J. Langguth, Jenna Bollyky, Chaitan Khosla, Mark R. Nicolls, Manisha Desai, Angela J. Rogers
Summary: The study aimed to evaluate the effectiveness of Acebilustat in treating outpatients with COVID-19, and the results showed that the medication did not shorten symptom duration.
CLINICAL INFECTIOUS DISEASES
(2023)
Correction
Microbiology
Richard B. B. Moss
Article
Pediatrics
Rebekah H. Nevel, Gail Deutsch, Daniel Craven, Robin P. Deterding, Martha A. Fishman, Jennifer Wambach, Alicia Casey, Katie R. Krone, Deborah G. Liptzin, Michael O'Connor, Geoffrey B. Kurland, Jane A. Taylor, William S. Gower, James Hagood, Carol B. Conrad, Jade K. Tam-Williams, Elizabeth Fiorino, Samuel C. Goldfarb, Sara M. Sadreameli, Lawrence Nogee, Gregory Montgomery, Aaron A. Hamvas, Theresa Laguna, Manvi Bansal, Cheryl Lew, Maria Santiago, Antonia Popova, Aliva De, Marilynn R. Chan, Michael B. Powers, Maureen Josephson, Devaney Camburn, Laura Voss, Yun R. Li, Lisa Young
Summary: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding these disorders.
PEDIATRIC PULMONOLOGY
(2023)
Article
Respiratory System
Joseph M. Pilewski, Kris De Boeck, Jerry A. Nick, Simon Tian, Cynthia DeSouza, Mark Higgins, Richard B. Moss
Meeting Abstract
Pediatrics
G. Hong, R. B. Moss, P. H. Lomas, B. Marshall, B. Quon, P. Eschenhagen, C. Schwarz
PEDIATRIC PULMONOLOGY
(2020)