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
Medical Laboratory Technology
Loris Wauthier, Stephanie Jacques, Joris Delanghe, Julien Favresse
Summary: This study compared two serum protein electrophoresis systems to detect decreased A1AT concentrations, and found that the V8 Nexus alpha(1) band 2 was the best predictor of A1AT deficiency.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
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
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
Multidisciplinary Sciences
Bryce A. Schuler, Lisa Bastarache, Janey Wang, Jing He, Sara L. Van Driest, Joshua C. Denny
Summary: This study compared the risk of liver transplantation associated with hepatitis C infection with alpha-1 antitrypsin deficiency (AATD) heterozygotes and homozygotes. The results showed that liver transplantation was more common in individuals with AATD risk alleles, and there was a gene-environment interaction between AATD and hepatitis C in relation to liver transplantation. SERPINA1 sequencing was found to increase the diagnostic yield for AATD and provide information for stratifying the risk of liver disease and managing individuals with AATD risk alleles and liver disease risk factors.
Article
Cardiac & Cardiovascular Systems
Joanna Chorostowska-Wynimko, A. Rembert Koczulla, Maria Sucena
Summary: There are variations in the management of AATD in different European countries, highlighting the need for education and standardization. Familiarity with and use of ERN-LUNG AATD services vary, indicating a need for increased awareness of these services.
RESPIRATORY MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Shan Guan, Max Darmstaedter, Chuanfei Xu, Joseph Rosenecker
Summary: IVT mRNA has emerged as a potential therapeutic approach for genetic diseases, with nebulized A1AT-mRNA formulations showing promise as a protein replacement therapy for alpha-1-antitrypsin deficiency. Lipoplexes containing A1AT-mRNA can successfully transfect human bronchial epithelial cells without significant toxicity, and increasing the initial number of components can help overcome a reduction in transfection efficiency. The functional A1AT produced from nebulized A1AT-mRNA lipoplexes is capable of inhibiting the enzyme activity of trypsin and elastase, highlighting the potential of aerosolization of A1AT-mRNA therapy for transfecting airway epithelial cells.
Article
Biochemistry & Molecular Biology
Nazli Khodayari, Rejean L. Wang, Regina Oshins, Yuanqing Lu, Michael Millett, Alek M. Aranyos, Sayedamin Mostofizadeh, Yogesh Scindia, Tammy O. Flagg, Mark Brantly
Summary: Alpha-1 antitrypsin deficiency (AATD) is caused by a single mutation in the SERPINA1 gene, leading to the accumulation of misfolded alpha-1 antitrypsin (ZAAT) in hepatocytes, which is associated with mitochondrial dysfunction. Research has shown that ZAAT aggregation in hepatocytes results in abnormal mitochondrial morphology and function, disrupting lipid metabolism balance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Respiratory System
Alessandro N. Franciosi, Tomas P. Carroll, Noel G. McElvaney
Summary: The study showed that individuals with SZ-AATD have a risk of lung disease comparable to MZ-AATD, not ZZ-AATD.
Review
Medicine, Research & Experimental
Mariangela Rondanelli, Clara Gasparri, Claudia Razza, Cinzia Ferraris, Simone Perna, Ilaria Ferrarotti, Angelo Guido Corsico
Summary: Congenital alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by the mutation of the SERPINA1 gene. It can lead to chronic obstructive pulmonary disease (COPD) and liver disease. Nutritional interventions aim to preserve lung and liver function. Dietary advice for different stages of liver disease have been provided.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Respiratory System
Auyon J. Ghosh, Brian D. Hobbs
Summary: This review discusses the gene structure and genetic variation of alpha-1 antitrypsin deficiency, as well as population genetics, genome-wide genetic modifiers, alternative mechanisms of disease, and emerging therapeutics related to lung disease associated with alpha-1 antitrypsin deficiency. The importance of precision medicine in the diagnosis, prognosis, and therapy of this disease is emphasized.
EXPERT REVIEW OF RESPIRATORY MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Leonard Riley, Jorge Lascano
Summary: This study describes the characteristics of patients labeled as AATD in the medical record and finds significant heterogeneity in the labeling of these patients. This heterogeneity exists regardless of the age, gender, PFT measurements, tobacco pack years, or the physician's specialization.
RESPIRATORY MEDICINE
(2022)
Article
Medicine, General & Internal
K. A. Serban, K. A. Pratte, C. Strange, R. A. Sandhaus, A. M. Turner, T. Beiko, D. A. Spittle, L. Maier, N. Hamzeh, E. K. Silverman, B. D. Hobbs, C. P. Hersh, D. L. DeMeo, M. H. Cho, R. P. Bowler
Summary: This study identified unique and shared plasma biomarkers between AATD and COPD subjects, and generated a protein score strongly associated with emphysema. Unique biomarkers associated with DLCO and emphysema were found in PiZZ AATD patients.
Article
Gastroenterology & Hepatology
Sameer Prakash, Arvind R. Murali
Summary: This study investigated whether alpha-1 antitrypsin (A1AT) genotype testing should be the primary screening method for A1AT heterozygous variants. Median and interquartile range of A1AT levels were calculated for different genotypes in 4378 patients with chronic liver disease, and the miss rates of MZ genotype identification at various cutoff levels were determined. There was significant overlap in A1AT levels among Pi*MM, MZ, and MS variants. The miss rates of Pi*MZ were 29%, 18%, 8%, and 4% at cutoff levels <100, <110, <120, and <130, respectively. Therefore, simultaneous measurement of A1AT levels and genotypes is recommended in patients with chronic liver disease.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maria Magallon, Silvia Castillo-Corullon, Lucia Banuls, Daniel Pellicer, Teresa Romero, Carlos Martinez-Ferraro, Maria Mercedes Navarro-Garcia, Alberto Herrejon, Cruz Gonzalez, Francisco Dasi
Summary: This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed.
Article
Cardiac & Cardiovascular Systems
Gillian Murtagh, Luke J. Laffin, Kershaw V. Patel, Amit V. Patel, Catherine A. Bonham, Zoe Yu, Karima Addetia, Nadia El-Hangouche, Francesco Maffesanti, Victor Mor-Avi, D. Kyle Hogarth, Nadera J. Sweiss, John F. Beshai, Roberto M. Lang, Amit R. Patel
ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES
(2016)
Meeting Abstract
Oncology
Scott M. Morris, Anil Vachani, Harvey I. Pass, William N. Rom, Glen J. Weiss, D. Kyle Hogarth, George Runger, Robert J. Penny, Kirk Ryden, Donald Richards, W. Troy Shelton, David W. Mallery
JOURNAL OF THORACIC ONCOLOGY
(2016)
Review
Cardiac & Cardiovascular Systems
Amit K. Mahajan, Diana C. Doeing, Douglas K. Hogarth
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2013)
Article
Oncology
Erik E. Folch, Michael A. Pritchett, Michael A. Nead, Mark R. Bowling, Septimiu D. Murgu, William S. Krimsky, Boris A. Murillo, Gregory P. LeMense, Douglas J. Minnich, Sandeep Bansal, Blesilda Q. Ellis, Amit K. Mahajan, Thomas R. Gildea, Rabih I. Bechara, Eric Sztejman, Javier Flandes, Otis B. Rickman, Sadia Benzaquen, D. Kyle Hogarth, Philip A. Linden, Momen M. Wahidi, Jennifer S. Mattingley, Kristin L. Hood, Haiying Lin, Jennifer J. Wolvers, Sandeep J. Khandhar, Carlos Anciano, Alejandro Aragaki, Douglas Arenberg, Omar Awais, Ricardo Balestra, Sandeep Bansal, Emanuela Barisione, Rabih Bechara, Sadia Benzaquen, Michela Bezzi, Krishnendu Bhadra, Julio Bird, Alessandro Blanco, Mark Bowling, Robert Cerfolio, Merete Christensen, Joseph Cicenia, Antony Courey, John Doty, Kevin Eggleston, Blesilda Ellis, Iker Fernandez, Javier Flandes, Erik Folch, Alexandre Furman, George David Gass, Thomas Gildea, Anil Gogineni, Musija Fikreta Grabcanovic, John David Hinze, David Kyle Hogarth, Raj Karunakara, Jordan Kazakov, Sandeep Khandhar, Sandhya Khurana, William Krimsky, Ganesh Krishna, Roman Krol, Roland Kropfmueller, Bernd Lamprecht, Kelvin Lau, Andrew Lee, Gregory LeMense, Philip Linden, Peter Lutz, Amit Mahajan, Kamran Mahmood, Fabien Maldonado, Rafael Martinez, Jennifer Mattingley, Douglas Minnich, Septimiu Murgu, Boris Murillo, Katie Nason, Michael Nead, Christopher Parks, Kenneth Perret, Peter Porsch, Michael Pritchett, Otis Rickman, Maydee Rosario, Mario Salio, Saiyad Sarkar, Andrew Seevaratnam, Sonali Sethi, Jaspal Singh, Michael Studnicka, Eric Sztejman, Tamejiro Takubo, Catalina Teba, Christopher Towe, Marco Trigiani, JeanRichel Vergnon, Niels-Erik Viby, Momen Wahidi, Ernest Waller, Benjamin Wei, Dragos Zanchi, Michael Zgoda
JOURNAL OF THORACIC ONCOLOGY
(2019)
Article
Allergy
Anukriti Sharma, Bharathi Laxman, Edward T. Naureckas, D. Kyle Hogarth, Anne I. Sperling, Julian Solway, Carole Ober, Jack A. Gilbert, Steven R. White
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2019)
Article
Respiratory System
Muhanned Abu-Hijleh, Kim Styrvoky, Vikram Anand, Fernando Woll, Lonny Yarmus, Michael S. Machuzak, Daniel A. Nader, Timothy W. Mullett, D. Kyle Hogarth, Jennifer W. Toth, Ghazwan Acash, Roberto F. Casal, Stephen Hazelrigg, Douglas E. Wood
Review
Medicine, General & Internal
Ticiana A. Leal, Angela C. Argento, Krish Bhadra, D. Kyle Hogarth, Julia Grigorieva, Rachel M. Hartfield, Robert C. McDonald, Philip D. Bonomi
CURRENT MEDICAL RESEARCH AND OPINION
(2020)
Article
Respiratory System
Kevin M. Magnaye, Katherine A. Naughton, Janel Huffman, D. Kyle Hogarth, Edward T. Naureckas, Steven R. White, Carole Ober
Summary: This study identified reduced A-to-I editing of miR-200b-3p at the 5th position in lower airway cells from moderate-to-severe asthmatics, leading to overexpression of SOCS1 and impaired cytokine signaling. ADAR-mediated editing may contribute to features of moderate-to-severe asthma in adulthood.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Oncology
Daniel V. T. Catenacci, Stephanie Moya, Samantha Lomnicki, Leah M. Chase, Bryan F. Peterson, Natalie Reizine, Lindsay Alpert, Namrata Setia, Shu-Yuan Xiao, John Hart, Uzma D. Siddiqui, D. Kyle Hogarth, Oliver S. Eng, Kiran Turaga, Kevin Roggin, Mitchell C. Posner, Paul Chang, Sunil Narula, Murtuza Rampurwala, Yuan Ji, Theodore Karrison, Chih-Yi Liao, Blase N. Polite, Hedy L. Kindler
Summary: The study aimed to address the challenges of molecular heterogeneity and the rarity of biomarkers in the treatment of advanced gastroesophageal adenocarcinomas, achieving satisfactory treatment outcomes through a personalized treatment strategy.
Article
Medicine, General & Internal
Elliot Ho, Ajay Wagh, Kyle Hogarth, Septimiu Murgu
Summary: Flexible bronchoscopy is critical in managing pulmonary disorders, and single-use flexible bronchoscopes have gained attention due to their sterility and cost-effectiveness, despite some limitations in maneuverability and channel size compared to reusable bronchoscopes.
Article
Multidisciplinary Sciences
Kevin M. Magnaye, Selene M. Clay, Jessie Nicodemus-Johnson, Katherine A. Naughton, Janel Huffman, Matthew C. Altman, Daniel J. Jackson, James E. Gern, Douglas K. Hogarth, Edward T. Naureckas, Steven R. White, Carole Ober
Summary: Maternal asthma is a consistent risk factor for asthma in children, potentially impacting diverse epigenetically mediated pathways leading to distinct subtypes of severe asthma in adults, including hard-to-treat T2-low asthma. Analysis shows differences in DNA methylation patterns between mothers with and without asthma in genes related to impaired T cell signaling and response to pathogens. These findings may have implications for understanding and treating different subtypes of asthma.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Gengjie Jia, Xue Zhong, Hae Kyung Im, Nathan Schoettler, Milton Pividori, D. Kyle Hogarth, Anne Sperling, Steven R. White, Edward T. Naureckas, Christopher S. Lyttle, Chikashi Terao, Yoichiro Kamatani, Masato Akiyama, Koichi Matsuda, Michiaki Kubo, Nancy J. Cox, Carole Ober, Andrey Rzhetsky, Julian Solway
Summary: This study identifies different asthma endotypes based on comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes.
NATURE COMMUNICATIONS
(2022)
Letter
Respiratory System
Elliot Ho, Abhinav Agrawal, Douglas Kyle Hogarth, Septimiu Murgu
JOURNAL OF THORACIC DISEASE
(2021)
Article
Gastroenterology & Hepatology
Huizhen Yang, Huidong Chen, Baoan Gao, Weining Xiong, Xiaoju Zhang, D. Kyle Hogarth, Jiayuan Sun, Mingyao Ke, Felix J. F. Herth
ENDOSCOPIC ULTRASOUND
(2020)
Article
Respiratory System
Amit Kumar Mahajan, Philip Verhoef, Shruti B. Patel, Gordon Carr, Douglas Kyle Hogarth
JOURNAL OF BRONCHOLOGY & INTERVENTIONAL PULMONOLOGY
(2012)