Article
Biochemistry & Molecular Biology
Francesco Amati, Andrea Gramegna, Martina Contarini, Anna Stainer, Cristina Curcio, Stefano Aliberti, Angelo Guido Corsico, Francesco Blasi
Summary: This study investigated the prevalence of AAT deficiency in CF adults and found that AAT deficiency is not common among adults with CF.
Article
Pediatrics
Evi Jaspers, Ine Van Dijck, Ilse Hoffman, Noel Knops, Xavier Stephenne, Peter Witters, Marijke Proesmans
Summary: This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD), two rare inherited diseases that mainly affect the lungs and liver. The diagnosis of CF was confirmed by sweat test and genetic analysis, while the diagnosis of A1ATD was based on clinical suspicion and genetic analysis. The child developed severe liver disease and required an infant liver transplantation.
Article
Medicine, Research & Experimental
Lena Ostermann, Regina Maus, Jennifer Stolper, Lisanne Schutte, Konstantina Katsarou, Srinu Tumpara, Andreas Pich, Christian Mueller, Sabina Janciauskiene, Tobias Welte, Ulrich A. Maus
Summary: The study found that in AAT-deficient mice, NE can degrade lung SP-A and SP-D, affecting lung protective immunity. Treatment with human AAT or the NE-specific inhibitor Sivelestat can protect collectins from degradation and reduce bacterial loads in S. pneumoniae-infected AAT-KO mice.
Article
Respiratory System
Oliver J. McElvaney, Eoin O'Connor, Natalie L. McEvoy, Daniel D. Fraughan, Jennifer Clarke, Oisin F. McElvaney, Cedric Gunaratnam, James O'Rourke, Gerard F. Curley, Noel G. McElvaney
Summary: This study describes the use of alpha-1 antitrypsin (AAT) as a salvage therapy in a critically unwell patient with cystic fibrosis (CF) who developed COVID-19 while awaiting lung transplantation. The results show that AAT can effectively reduce inflammatory markers and improve clinical symptoms, supporting further research on the use of AAT as a treatment for COVID-19.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Pharmacology & Pharmacy
Anna Annunziata, Maurizia Lanza, Antonietta Coppola, Paolo Andreozzi, Sara Spinelli, Giuseppe Fiorentino
Summary: This article describes the experience of using home care intravenous augmentation therapy to manage human alpha-1 antitrypsin deficiency during the emergency of the SARS-CoV2 infection outbreak. The focus is on evaluating the safety of home treatment and the quality of life of patients enrolled in the program.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Dermatology
Alessandro N. Franciosi, James Ralph, Naoimh J. O'Farrell, Colm Buckley, Christian Gulmann, Marina O'Kane, Tomas P. Carroll, Noel G. McElvaney
Summary: The typical features and investigation of AATD-associated panniculitis need further clarification. Dapsone is the most cost-effective therapeutic option, while intravenous AAT augmentation therapy is the most efficacious.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Malin Fromme, Carolin Schneider, Christian Trautwein, Nicola Brunetti-Pierri, Pavel Strnad
Summary: Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the SERPINA1 gene, leading to the retention of AAT in liver cells and resulting in liver injury and lung disease. The Pi*ZZ genotype is responsible for severe AATD cases and can cause liver diseases in both children and adults. This review examines the relationship between genotypes and hepatic phenotypes, discusses the mechanisms of liver disease development, and explores diagnostic and therapeutic approaches for managing this disorder.
JOURNAL OF HEPATOLOGY
(2022)
Article
Medicine, Research & Experimental
Nan He, Xiaoming Liu, Amber R. Vegter, T. Idil A. Evans, Jaimie S. Gray, Junfeng Guo, Shashanna R. Moll, Lydia J. Guo, Meihui Luo, Ningxia Ma, Xingshen Sun, Bo Liang, Ziying Yan, Zehua Feng, Lisi Qi, Arnav S. Joshi, Weam Shahin, Yaling Yi, Katherine N. Gibson-Corley, Eric A. Hoffman, Kai Wang, Christian Mueller, John F. Engelhardt, Bradley H. Rosen
Summary: Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease. This study used ferret models to demonstrate that complete loss of AAT and the most common mutation in AAT result in lung and hepatic diseases similar to those observed in AATD patients, making them a potential platform for preclinical testing of therapeutics including gene therapy.
Article
Medicine, General & Internal
Leonard Riley, Aryaman Sriram, Mark Brantly, Jorge Lascano
Summary: This retrospective cohort study aimed to investigate the testing frequency and disparities for alpha-1 antitrypsin deficiency. The results showed that testing for AAT deficiency continues to have a low uptake in the clinical setting, although it is slowly improving. Individuals of White race and those with concomitant chronic obstructive pulmonary disease and liver disease are more likely to be tested.
AMERICAN JOURNAL OF MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Noor Ahmad Shaik, Najla Bint Saud Al-Saud, Thamer Abdulhamid Aljuhani, Kaiser Jamil, Huda Alnuman, Deema Aljeaid, Nasreen Sultana, Ashraf AbdulRahman El-Harouni, Zuhier Ahmed Awan, Ramu Elango, Babajan Banaganapalli
Summary: This study investigates the impact of SERPINA1 missense variants on the structural and functional characteristics of A1AT protein in Alpha-1 antitrypsin deficiency. The results suggest that these variants alter the structure, stability, and function of A1AT protein, and negatively affect its binding with NE ligand molecule.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Medicine, General & Internal
Victoria Therese Muecke, Janett Fischer, Marcus Maximilian Muecke, Alexander Teumer, Alexander Koch, Johannes Vermehren, Malin Fromme, Stefan Zeuzem, Christian Trautwein, Christoph Sarrazin, Thomas Berg, Biaohuan Zhou, Karim Hamesch
Summary: This study found that the heterozygous Pi*Z allele is not a clinically relevant disease modifier in chronic hepatitis C infection, based on analysis of two cohorts. Further validation in larger cohorts with longitudinal follow-up is needed.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Daniella A. Spittle, Alison Mansfield, Anita Pye, Alice M. Turner, Michael Newnham
Summary: The progression of lung disease in alpha-1 antitrypsin deficiency (AATD) varies and presents differently. Blood biomarkers are a convenient and repeatable method of monitoring diseases. In this study, we compared the levels of seven serum biomarkers between AATD patients with and without COPD. We found that CRP and CCL18 were significantly higher in AATD COPD patients. CC16 was found to be predictive of emphysema progression in AATD COPD.
Article
Immunology
Marilena Pariano, Claudio Costantini, Ilaria Santarelli, Matteo Puccetti, Stefano Giovagnoli, Vincenzo N. Talesa, Luigina Romani, Cinzia Antognelli
Summary: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a decline in respiratory function. Research suggests that GLO1 plays a pathological role in CF and its activity can be restored by blocking interleukin-1 receptor signaling.
Article
Instruments & Instrumentation
Annalisa Bianchera, Viviana Vilardo, Roberta Giaccari, Annalisa Michielon, Gianluca Bazzoli, Francesca Buttini, Marina Aiello, Alfredo Chetta, Stefano Bruno, Ruggero Bettini
Summary: Two nebulizers, a jet and a mesh vibrating system, were compared in terms of performance and effectiveness for delivering alpha-1 antitrypsin (AAT) to the lungs. The mesh nebulizer demonstrated higher efficiency in drug delivery, with preserved protein activity and conformation. Nebulization of AAT is a suitable administration strategy for AATD patients, either as a support therapy or for preventive purposes.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Ting Yang, Jinlong Yu, Tasdiq Ahmed, Katherine Nguyen, Fang Nie, Rui Zan, Zhiwei Li, Pei Han, Hao Shen, Xiaonong Zhang, Shuichi Takayama, Yang Song
Summary: Researchers study the antibacterial activity of synthetic NET-mimetic materials and find that the incorporation of NE into DNA-histone complexes reduces antimicrobial activity, but this effect can be reversed by treatment with AAT. These findings contribute to a better understanding of the complex and sometimes contradictory observations of NETs and AAT in antimicrobial effects.
Article
Radiology, Nuclear Medicine & Medical Imaging
Andrew McCallister, Sang Hun Chung, Michael Antonacci, Margret Z. Powell, Agathe S. Ceppe, Scott H. Donaldson, Yueh Z. Lee, Rosa Tamara Branca, Jennifer L. Goralski
Summary: In CF subjects, ventilation abnormalities can be identified by both (19)F and (HPXe)-Xe-129 imaging, but these abnormalities are not entirely congruent. (19)F and (HPXe)-Xe-129 imaging provide complementary information that allows for differentiation of normally ventilated, slowly ventilated, and non-ventilated regions in the lungs.
MAGNETIC RESONANCE IN MEDICINE
(2021)
Article
Respiratory System
Kelsie Pearson, Nicole Mayer-Hamblett, Christopher H. Goss, George Z. Retsch-Bogart, Jill M. VanDalfsen, Patricia Burks, Daniel Rosenbluth, John Paul Clancy, Amy Hoffman, David P. Nichols
Summary: The global pandemic of SARS-CoV-2 significantly impacted CF clinical research, but over time, research activities gradually recovered and new opportunities for CF research emerged.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Review
Respiratory System
Dave P. Nichols, Scott H. Donaldson, Carla A. Frederick, Steven D. Freedman, Daniel Gelfond, Lucas R. Hoffman, Andrea Kelly, Michael R. Narkewicz, Jessica E. Pittman, Felix Ratjen, Scott D. Sagel, Margaret Rosenfeld, Sarah Jane Schwarzenberg, Pradeep K. Singh, George M. Solomon, Michael S. Stalvey, Shannon Kirby, Jill M. VanDalfsen, John P. Clancy, Steven M. Rowe
Summary: Highly effective CFTR modulator drug therapy is increasingly available for cystic fibrosis patients, with multiple observational research studies underway to better understand its impacts. The PROMISE study focuses on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population, aiming to address important health outcomes, clinical care priorities, and research needs.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Respiratory System
Eden J. VanDevanter, Sonya L. Heltshe, Michelle Skalland, Noah Lechtzin, Dave Nichols, Christopher H. Goss
Summary: The study findings suggest that in this cohort, PO antimicrobial treatment of CF PEx were less effective than IVs at improving ppFEV1 during treatment.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Respiratory System
Amalia S. Magaret, Jack Salerno, Jason F. Deen, Margaret Kloster, Nicole Mayer-Hamblett, Bonnie W. Ramsey, Dave P. Nichols
Summary: The study showed that chronic Azithromycin use in children with CF was not associated with an increased risk of QT prolongation.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Health Care Sciences & Services
Sarah H. Todd, Elizabeth A. Sonntag, Marianne L. Buchanan, Brooke W. Jones, Elisabeth P. Dellon, Scott H. Donaldson, Jennifer L. Goralski
Summary: The University of North Carolina Adult CF Care Team successfully implemented semistructured multidisciplinary outpatient ACP meetings and found that patients' understanding of ACP topics improved following the meetings. The results suggest that establishing ACP before crises is crucial for CF patients.
JOURNAL OF PALLIATIVE MEDICINE
(2021)
Article
Respiratory System
Scott H. Donaldson, Beth L. Laube, Peter Mogayzel, Timothy E. Corcoran, Joseph M. Pilewski, Agathe Ceppe, Jihong Wu, Pradeep G. Bhambhvani, Felix Ratjen, Scott D. Sagel, J. P. Clancy, Steven M. Rowe, William D. Bennett
Summary: This observational study investigated the effect of lumacaftor-ivacaftor on mucociliary and cough clearance in CF patients. The results showed no effect on whole lung mucociliary clearance, but cough-assisted clearance was significantly increased. Sweat chloride improved, indicating a modest restoration of CFTR activity, but there was no demonstrable change in lung function indices. The authors speculate that the modest effect of lumacaftor-ivacaftor on CFTR function was insufficient to improve mucociliary clearance.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Respiratory System
Cecilia Kristensson, Annika Astrand, Scott Donaldson, Ron Goldwater, Raolat Abdulai, Naimish Patel, Philip Gardiner, Ulrika Tehler, Anne-Kristina Mercier, Marita Olsson, Eva Ersdal, Jukka Maenpaa, Tobias Bramer, Anna Malmgren, William Bennett, Christina Keen
Summary: AZD5634 demonstrated favorable pharmacokinetics and safety in both healthy subjects and patients with CF, although proof of mechanism was not achieved in patients with CF.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Pharmacology & Pharmacy
Katherine A. Despotes, Scott H. Donaldson
Summary: Small molecular modulators have transformed the care of cystic fibrosis patients, improving lung function, respiratory symptoms, and nutrition. Efforts are being made to expand these therapies to more pediatric patients. Alternative approaches are needed for those with ineligible mutations.
CURRENT OPINION IN PHARMACOLOGY
(2022)
Article
Respiratory System
Sarah Jane Schwarzenberg, Phuong T. Vu, Michelle Skalland, Lucas R. Hoffman, Christopher Pope, Daniel Gelfond, Michael R. Narkewicz, David P. Nichols, Sonya L. Heltshe, Scott H. Donaldson, Carla A. Frederick, Andrea Kelly, Jessica E. Pittman, Felix Ratjen, Margaret Rosenfeld, Scott D. Sagel, George M. Solomon, Michael S. Stalvey, John P. Clancy, Steven M. Rowe, Steven D. Freedman
Summary: The study aims to investigate the effect of ETI on gastrointestinal symptoms in patients with cystic fibrosis. The results show that there was an overall improvement in gastrointestinal symptoms after 6 months of ETI treatment.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Editorial Material
Respiratory System
Scott H. Donaldson
Summary: Higher concentrations of hypertonic saline provide better protection against pulmonary exacerbation and respiratory symptom improvement in cystic fibrosis patients, and are generally well tolerated when delivered with rapid nebulizer systems.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Respiratory System
Nicole Mayer-Hamblett, David P. Nichols, Katherine Odem-Davis, Kristin A. Riekert, Greg S. Sawicki, Scott H. Donaldson, Felix Ratjen, Michael W. Konstan, Noah Simon, Daniel B. Rosenbluth, George Retsch-Bogart, John P. Clancy, Jill M. VanDalfsen, Rachael Buckingham, Alex H. Gifford
Summary: The study aims to evaluate whether the daily treatment burden can be reduced for individuals with cystic fibrosis receiving new triple-combination therapy, by comparing the effects of discontinuing versus continuing two commonly used chronic therapies.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2021)
Article
Respiratory System
Jonathan D. Cogen, Anna Faino, Frankline Onchiri, Ronald L. Gibson, Lucas R. Hoffman, Matthew P. Kronman, Margaret Rosenfeld, David P. Nichols
Summary: This study aimed to determine whether concomitant use of azithromycin (AZM) with intravenous tobramycin for pulmonary exacerbation (PEx) treatment is associated with worse clinical outcomes. The results suggested that concomitant use of AZM and intravenous tobramycin for in-hospital PEx treatment was associated with poorer clinical outcomes than treatment with intravenous tobramycin without AZM.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2021)
