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
Respiratory System
Michelle Casey, Claudie Gabillard-Lefort, Oisin F. McElvaney, Oliver J. McElvaney, Tomas Carroll, Ronan C. Heeney, Cedric Gunaratnam, Emer P. Reeves, Mark P. Murphy, Noel G. McElvaney
Summary: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to improve lung function in people with cystic fibrosis (PWCF). This study investigates the biological effects of ETI on pulmonary and systemic inflammation in PWCF. The results demonstrate that ETI reduces inflammatory markers and normalizes protein levels, suggesting its immunomodulatory effects and potential as a disease modifier.
Article
Biochemistry & Molecular Biology
Madalena C. Pinto, Margarida C. Quaresma, Iris A. L. Silva, Violeta Railean, Sofia S. Ramalho, Margarida D. Amaral
Summary: SLC26A9 is a constitutively active Cl- transporter that contributes to epithelial Cl- secretion and is implicated in respiratory disorders such as CF. Studies have shown that enhancing SLC26A9 expression can increase CFTR function and response to CFTR correctors, suggesting its potential as a therapeutic target for CF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Giulia Gorrieri, Federico Zara, Paolo Scudieri
Summary: SLC26A9, a member of the solute carrier family 26 (SLC26), is involved in ion transport mechanisms. It has emerged as one of the interesting alternative targets for cystic fibrosis (CF) treatment, although there are still controversies regarding its contribution and potential. This review summarizes various studies related to SLC26A9, aiming to reconcile them and highlight the current understanding and knowledge gap regarding its role in human lung physiology and CF treatment.
Review
Medicine, Research & Experimental
Samantha A. Whiteside, John E. McGinniss, Ronald G. Collman
Summary: The healthy lung is not completely sterile, with bacteria entering from the upper respiratory tract through microaspiration. The nature and dynamics of the lung microbiome differ from other ecological niches with self-sustaining microbial communities, and dysbiosis has been demonstrated in many pulmonary diseases.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Biology
Filippo Scialo, Felice Amato, Gustavo Cernera, Monica Gelzo, Federica Zarrilli, Marika Comegna, Lucio Pastore, Andrea Bianco, Giuseppe Castaldo
Summary: The defective mucociliary clearance in CF patients due to CFTR malfunctioning predisposes them to colonization by pathogens, leading to recurrent inflammation and rapid deterioration of lung function, impacting the lung microbiome composition. Understanding of microbial interactions in the lung and how they change during disease progression is still in its early stages, but manipulating the lung microbiome could offer promising prospects for improving therapies for CF patients.
Review
Cell Biology
Elena N. Huang, Henry Quach, Jin-A Lee, Joshua Dierolf, Theo J. Moraes, Amy P. Wong
Summary: Cystic fibrosis is a disease caused by mutations in the CFTR protein, leading to abnormal fluid and ion transport, reduced lung function, and increased mortality rate. Although progress has been made in CF research, clinical outcomes may not be mutation-specific. Research suggests that CFTR protein plays an important role in early lung development and mutant CFTR proteins may impact CF airway disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Health Care Sciences & Services
Mihaela Dediu, Ioana Mihaiela Ciuca, Monica Steluta Marc, Estera Boeriu, Liviu Laurentiu Pop
Summary: This cross-sectional study aimed to identify major factors influencing pulmonary function in CF patients, with results showing significant impact of BMI and age on lung function. The research suggests that better nutritional status and infection prophylaxis should be emphasized in the comprehensive clinical management strategy for pediatric CF patients in Romania.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2021)
Article
Pharmacology & Pharmacy
L. Clara Mok, Antonio Garcia-Uceda, Matthew N. Cooper, Mariette Kemner Van De Corput, Marleen De Bruijne, Nathalie Feyaerts, Tim Rosenow, Kris De Boeck, Stephen Stick, Harm A. W. M. Tiddens
Summary: Newly developed quantitative CT outcomes designed for CF lung disease can assess structural abnormalities. CFTR modulators have the potential to reduce these abnormalities. This study aimed to investigate the effect of CFTR modulators on the progression of structural lung disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Critical Care Medicine
Yi-Hui Zhou, Paul J. Gallins, Rhonda G. Pace, Hong Dang, Melis A. Aksit, Elizabeth E. Blue, Kati J. Buckingham, Joseph M. Collaco, Anna V. Faino, William W. Gordon, Kurt N. Hetrick, Hua Ling, Weifang Liu, Frankline M. Onchiri, Kymberleigh Pagel, Elizabeth W. Pugh, Karen S. Raraigh, Margaret Rosenfeld, Quan Sun, Jia Wen, Yun Li, Harriet Corvol, Lisa J. Strug, Michael J. Bamshad, Scott M. Blackman, Garry R. Cutting, Ronald L. Gibson, Wanda K. O'Neal, Fred A. Wright, Michael R. Knowles
Summary: This study aims to identify genetic modifier loci associated with pulmonary disease severity in patients with cystic fibrosis. The research used whole-genome sequencing data and genetic genotypes to discover two loci associated with lung disease. These findings support mechanistic studies and the development of novel therapeutics for CF lung disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Respiratory System
Meghan R. Pinezich, Manuel A. Tamargo, Sharon Fleischer, Jonathan A. Reimer, Maria R. Hudock, Ahmed E. Hozain, Sarah R. Kaslow, Yuliya Tipograf, Rajesh Kumar Soni, Olimpia P. Gavaudan, Brandon A. Guenthart, Charles C. Marboe, Matthew Bacchetta, John D. O'Neill, N. Valerio Dorrello, Gordana Vunjak-Novakovic
Summary: In this study, the structure and composition of the distal lung extracellular matrix in end-stage cystic fibrosis were comprehensively evaluated. The findings suggest that cystic fibrosis leads to a decrease in matrix protein diversity and alterations in lung tissue structure. Targeting dysregulated matrix pathways may serve as adjunct interventions to support lung recovery.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Review
Biotechnology & Applied Microbiology
Ching-Yee Loo, Wing-Hin Lee
Summary: The physiochemical properties of drugs used in treating inflammation-associated lung diseases are crucial in determining the effectiveness of formulations. The development of drugs and the utilization of nanotechnology show promise in the treatment of inflammatory lung diseases.
Review
Pharmacology & Pharmacy
Lisa Kunzi, Molly Easter, Meghan June Hirsch, Stefanie Krick
Summary: The demographics of the cystic fibrosis (CF) population are changing, with adults now outnumbering children and a median predicted survival of over 40 years. There is a challenge in treating aging CF patients, as previous research primarily focused on pediatric and adolescent patients. Chronic inflammation is a hallmark of CF lung disease and the aging process, but little is known about the effects of accelerated aging in CF lungs.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Lael M. Yonker, Juliana Barrios, Hongmei Mou, Bryan P. Hurley
Summary: Airway inflammation involves recruitment of highly active immune cells, which may cause unintended lung tissue damage. The tissue damage resulting from inflammation is often alleviated by restricting the scope and duration of the inflammatory response.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Lei Xing, Xin Chang, Lijun Shen, Chenglu Zhang, Yatong Fan, Chongsu Cho, Zhiqi Zhang, Hulin Jiang
Summary: Fibrosis is a necessary process in the progression of chronic diseases to cirrhosis or cancer, which is a serious threat to human health. Early treatment of fibrosis has been shown to be a crucial turning point. Significant progress has been made in the development of effective anti-fibrosis drugs and targeted drug delivery, with existing research laying the foundation for breakthrough delivery systems to achieve better anti-fibrosis effects.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Nursing
Lyvonne N. Tume, Bronagh Blackwood, Daniel F. McAuley, Kevin Morris, Mark J. Peters, Joanne Jordan, Timothy Simon Walsh, Lisa McIlmurray
Summary: This paper describes the experience of using the TIDieR checklist in reporting a trial on sedation and ventilation weaning in critically ill children. The checklist provides a structured way to report complex interventions, which aids replication and adoption into practice.
NURSING IN CRITICAL CARE
(2023)
Article
Pharmacology & Pharmacy
Shannice Creane, Mary Joyce, Ronan MacLoughlin, Sinead Weldon, John P. Dalton, Clifford C. Taggart
Summary: This study evaluated the suitability of snake-derived peptides (Sn1b, SnE1 and SnE1-F) for nebulisation using a vibrating mesh nebuliser. The peptides showed similar functions after nebulisation and were respirable during simulated mechanical ventilation. The assessment of droplet distributions demonstrated that each peptide would likely be delivered to the lower airways if administered in vivo, suggesting that nebulisation with a vibrating mesh nebuliser is a viable means of delivering these peptides for the treatment of respiratory infections.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pediatrics
Stefanie Theuring, Mascha Kern, Franziska Hommes, Marcus A. A. Mall, Joachim Seybold, Frank P. P. Mockenhaupt, Toivo Glatz, Tobias Kurth
Summary: During the COVID-19 pandemic, children and adolescents worldwide have been disproportionately affected in their psychological health and wellbeing. A cohort study in Germany found that anxiety symptoms among school children decreased from June to August 2021, but increased again in September 2021. Factors such as gender, school type, household education and income level, and COVID-19 vaccination were significantly associated with reporting anxiety symptoms.
CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH
(2023)
Article
Respiratory System
Patricia Leutz-Schmidt, Daiva-Elzbieta Optazaite, Olaf Sommerburg, Monika Eichinger, Sabine Wege, Eva Steinke, Simon Y. Graeber, Michael U. Puderbach, Jens-Peter Schenk, Abdulsattar Alrajab, Simon M. F. Triphan, Hans-Ulrich Kauczor, Mirjam Stahl, Marcus A. Mall, Mark O. Wielputz
Summary: This study evaluated the occurrence of bronchial artery dilatation (BAD) in patients with cystic fibrosis (CF) and its association with disease severity using magnetic resonance imaging (MRI). The results showed that the onset of BAD was associated with disease severity, lung function, and chronic Pseudomonas aeruginosa infection. This finding is important for assessing the severity of CF.
Article
Pharmacology & Pharmacy
Julian Berges, Simon Y. Graeber, Susanne Haemmerling, Yin Yu, Arne Kruempelmann, Mirjam Stahl, Stephanie Hirtz, Heike Scheuermann, Marcus A. Mall, Olaf Sommerburg
Summary: In this prospective study, the effect of Lumacaftor/ivacaftor on CFTR biomarkers and clinical outcome parameters in CF patients aged 2-11 years was evaluated. The treatment significantly reduced sweat chloride concentration and improved CFTR activity, consistent with previous findings in older CF patients with F508del.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Linus Piehler, Ralf Thalemann, Christine Lehmann, Stephanie Thee, Jobst Roehmel, Zulfiya Syunyaeva, Mirjam Stahl, Marcus A. Mall, Simon Y. Graeber
Summary: Initiation of ETI improves symptoms of depression in adult patients with CF with at least one F508del allele. However, symptoms of anxiety do not change after short-term therapy with ETI.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Critical Care Medicine
Ahmet Z. Uluer, Gordon MacGregor, Pilar Azevedo, Veronica Indihar, Claire Keating, Marcus A. Mall, Edward F. McKone, Bonnie W. Ramsey, Steven M. Rowe, Ronald C. Rubenstein, Jennifer L. Taylor-Cousar, Elizabeth Tullis, Lael M. Yonker, Chenghao Chu, Anna P. Lam, Nitin Nair, Patrick R. Sosnay, Simon Tian, Fredrick Van Goor, Lakshmi Viswanathan, David Waltz, Linda T. Wang, Yingmei Xi, Joanne Billings, Alexander Horsley
Summary: This study demonstrates that once-daily dosing with vanzacaftor-tezacaftor-deutivacaftor is safe and effective in improving lung function and respiratory symptoms in patients with cystic fibrosis, and it enhances CFTR function.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Rebekah A. Eadie, Cathrine A. McKenzie, Daniel J. Hadfield, Nicola J. Kalk, Scott Bolesta, Martin F. Dempster, Daniel F. McAuley, Bronagh Blackwood
Summary: This study investigated the use of opioid, sedative, and preadmission medications in critically ill adults in UK ICUs, and found a high prevalence of medication with potential for iatrogenic withdrawal syndrome. Most ICUs lacked sedation/analgesia policies and did not screen for iatrogenic withdrawal.
INTERNATIONAL JOURNAL OF CLINICAL PHARMACY
(2023)
Article
Critical Care Medicine
Nicole Mayer-Hamblett, John Paul Clancy, Raksha Jain, Scott H. Donaldson, Isabelle Fajac, Christopher H. Goss, Deepika Polineni, Felix Ratjen, Bradley S. Quon, Edith Zemanick, Scott C. Bell, Jane C. Davies, Manu Jain, Michael W. Konstan, Natanya R. Kerper, Tre LaRosa, Marcus A. Mall, Edward McKone, Kelsie Pearson, Joseph M. Pilewski, Lynne Quittell, Jonathan H. Rayment, Steven M. Rowe, Jennifer L. Taylor-Cousar, George Retsch-Bogart, Damian Downey
Summary: The use of modulator therapies for cystic fibrosis has changed clinical trial strategies, dividing the patient population based on eligibility. The development of nucleic acid-based therapies faces challenges due to limited resources and the inability to conduct placebo-controlled trials. Advancing symptomatic therapies is also difficult in a population already receiving modulator treatment.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Cell Biology
Sanja Blaskovic, Pinelopi Anagnostopoulou, Elena Borisova, Dominik Schittny, Yves Donati, David Haberthur, Zhe Zhou-Suckow, Marcus A. Mall, Christian M. Schleputz, Marco Stampanoni, Constance Barazzone-Argiroffo, Johannes C. Schittny
Summary: This study developed a new pipeline for analyzing all airspaces of the entire lung. The results demonstrated irregular widening of parenchymal airspaces in mice with cystic fibrosis-like lung disease and elastase-induced emphysema. The pipeline showed applicability to different imaging modalities and is suitable for studying structural alterations in chronic obstructive lung diseases.
Article
Respiratory System
Mirjam Stahl, Jobst Roehmel, Monika Eichinger, Felix Doellinger, Lutz Naehrlich, Matthias V. Kopp, Anna-Maria Dittrich, Christopher Lee, Olaf Sommerburg, Simon Tian, Tu Xu, Pan Wu, Aniket Joshi, Partha Ray, Margaret E. Duncan, Mark O. Wielputz, Marcus A. Mall
Summary: This study investigated the effects of LUM/IVA treatment on disease progression in children aged 2 to 5 years with CF. Results showed potential early disease modification with LUM/IVA, as indicated by improvements in chest MRI and various clinical markers. LUM/IVA treatment also led to improvements in lung function and growth parameters.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Article
Respiratory System
A. Susanne Dittrich, Markus Dumke, Ferdinand Kapl, Philipp Schneider, Sabine Wege, Simon Graeber, Mirjam Stahl, Felix J. Herth, Lutz Naehrlich, Marcus A. Mall, Olaf Sommburg
Summary: This study aimed to determine updated FEV1 and BMI percentiles for patients with cystic fibrosis (CF) and to study their dependence on mortality attrition. Age- and height-adjusted FEV1 and BMI percentiles were calculated from 4,947 CF patients aged 6-50 years from the German CF Registry for the period 2016-2019. The study found that FEV1 increased throughout childhood and decreased substantially during adulthood. The survival-adjusted percentiles were also estimated.
Article
Respiratory System
Lena Wucherpfennig, Felix Wuennemann, Monika Eichinger, Niclas Schmitt, Angelika Seitz, Ingo Baumann, Mirjam Stahl, Simon Y. Graeber, Jaehi Chung, Jens-Peter Schenk, Abdulsattar Alrajab, Hans-Ulrich Kauczor, Marcus A. Mall, Olaf Sommerburg, Mark O. Wielputz
Summary: This study longitudinally evaluated chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF) using paranasal sinus magnetic resonance imaging (MRI). The results showed that CRS starts early in infancy and progresses in severity until school age. The study also found that lumacaftor/ivacaftor therapy can improve CRS in children with CF.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Article
Respiratory System
Cori L. Daines, Elizabeth Tullis, Stefano Costa, Rachel W. Linnemann, Marcus A. Mall, Edward F. McKone, Deepika Polineni, Bradley S. Quon, Felix C. Ringshausen, Steven M. Rowe, Hiran Selvadurai, Jennifer L. Taylor-Cousar, Nicholas J. Withers, Neil Ahluwalia, Samuel M. Moskowitz, Valentin Prieto-Centurion, Yaoyuan Vincent Tan, Simon Tian, Tanya Weinstock, Fengjuan Xuan, Yaohua Zhang, Bonnie Ramsey, Matthias Griese
Summary: This study assessed the long-term safety and efficacy of ELX/TEZ/IVA in patients with cystic fibrosis (CF) who have at least one F508del allele. The results showed that ELX/TEZ/IVA treatment was generally safe and well tolerated, with sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates, and nutritional status. These findings support the favorable safety profile and durable clinical benefits of ELX/TEZ/IVA.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Respiratory System
Lena Wucherpfennig, Simon M. F. Triphan, Sabine Wege, Hans-Ulrich Kauczor, Claus P. Heussel, Olaf Sommerburg, Mirjam Stahl, Marcus A. Mall, Monika Eichinger, Mark O. Wielpuetz
Summary: This study found that bronchial artery dilatation (BAD) may be partially reversible under elexacaftor/tezacaftor/ivacaftor therapy in adult patients with cystic fibrosis (CF) who have established disease.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
