Article
Immunology
Emily Fraser, Laura Denney, Agne Antanaviciute, Karl Blirando, Chaitanya Vuppusetty, Yuejuan Zheng, Emmanouela Repapi, Valentina Iotchkova, Stephen Taylor, Neil Ashley, Victoria St Noble, Rachel Benamore, Rachel Hoyles, Colin Clelland, Joseph M. D. Rastrick, Clare S. Hardman, Nasullah K. Alham, Rachel E. Rigby, Alison Simmons, Jan Rehwinkel, Ling-Pei Ho
Summary: Monocytes in idiopathic pulmonary fibrosis (IPF) patients exhibit a distinct immunophenotype from age-matched controls, with an activated type I interferon pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pathology
Laura Sabater, Jean B. Gossart, Inmaculada Hernandez, Daniel Rico, Andy Blanchard, Lee A. Borthwick, Andrew J. Fisher, Joaquim Majo, Kasim Jiwa, Amy Collins, Giuseppe Abbate, Fiona Oakley, Derek A. Mann, Jelena Mann
Summary: miRNAs play a crucial role in regulating gene expression in idiopathic pulmonary fibrosis (IPF). This study compared the expression levels of miRNAs in fibroblastic foci (FF), whole IPF lung tissue, and cultured IPF fibroblasts, and found that FF had a unique and distinct miRNA composition. The differences in miRNA composition between FF and cultured IPF fibroblasts affected multiple signaling pathways, highlighting the importance of characterizing FF biology as a functionally discrete tissue microenvironment.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuang Bai, Rui Ye, Cuihong Wang, Pengbo Sun, Di Wang, Yong Yue, Huiying Wang, Si Wu, Miao Yu, Shuhua Xi, Li Zhao
Summary: This study identified differential protein expression in COPD patients with emphysematous phenotype, indicating that KRT17 and DHRS9 are potentially involved in wound healing and retinol metabolism pathways. GO and KEGG analyses highlighted the importance of these pathways in the molecular mechanism of COPD emphysematous phenotype.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biology
Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy McAlinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A. Zeki, Saeid Ghavami
Summary: The disruption of protein homeostasis in lung cells by stressors leads to activation of the unfolded protein response (UPR) to manage the increased functional demands. Dysregulation of UPR and ER stress are implicated in various human diseases. Compounds targeting the UPR pathway are being considered as potential therapies.
Article
Critical Care Medicine
Anna Duckworth, Michael A. Gibbons, Richard J. Allen, Howard Almond, Robin N. Beaumont, Andrew R. Wood, Katie Lunnon, Mark A. Lindsay, Louise Wain, Jess Tyrrell, Chris J. Scotton
Summary: Using mendelian randomisation, this study found that shorter telomere length is associated with higher odds of IPF but not COPD, suggesting a potential contributory factor in IPF and differing mechanisms in COPD.
LANCET RESPIRATORY MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Kevin Bray, Sandeep Bodduluri, Young-il Kim, Vivek Sthanam, Hrudaya Nath, Surya P. Bhatt
Summary: Previous studies have shown that low forced expiratory volume in one second (FEV1) is associated with coronary artery disease (CAD). This study aimed to investigate if low FEV1 due to airflow obstruction or ventilatory restriction have different associations with CAD.
RESPIRATORY MEDICINE
(2023)
Article
Immunology
Premkumar Siddhuraj, Jimmie Jonsson, Manar Alyamani, Pavan Prabhala, Mattias Magnusson, Sandra Lindstedt, Jonas S. Erjefaelt
Summary: This study investigates the dynamics and spatial distribution of mast cell CPA3 expression in lung diseases, revealing complex and markedly upregulated CPA3 expression profiles in patients with chronic obstructive pulmonary disease (COPD) and idiopathic lung fibrosis (IPF). These alterations are likely to have clinical consequences due to the proposed roles of CPA3 in tissue homeostasis, remodeling, and inflammation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Hongbo Ma, Shengming Liu, Shanrui Li, Yong Xia
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown origin, which currently lacks ideal treatment options. Although some drugs have been approved for the treatment of IPF, they have limitations. Therefore, research on cytokine and growth factor pathways is important for identifying more effective therapeutic targets to improve the prognosis and quality of life for IPF patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Varalakshmi Velagacherla, Chetan Hasmukh Mehta, Yogendra Nayak, Usha Yogendra Nayak
Summary: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with unknown etiological factors. Epigenetic pathways and genetic mutations play important roles in the development of IPF. Environmental factors, such as smoking, also contribute to the progression of the disease. Current and developing drugs for IPF target different epigenetic mechanisms.
Article
Medicine, Research & Experimental
Chia-Yu Yang, Shiao-Wen Li, Chia-Yin Chin, Chia-Wei Hsu, Chi-Ching Lee, Yuan-Ming Yeh, Kuo-An Wu
Summary: The study revealed changes in sputum microbiome in COPD patients with different risks of exacerbation. The bacterial cooperative networks were altered in patients with high risk exacerbations, potentially contributing to disease exacerbation. This suggests that sputum microbiome dysbiosis is associated with different COPD phenotypes and may provide targets for improved therapies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Gabriela Leuschner, Anna Semenova, Christoph H. Mayr, Theodore S. Kapellos, Meshal Ansari, Benjamin Seeliger, Marion Frankenberger, Nikolaus Kneidinger, Rudolf A. Hatz, Anne Hilgendorff, Antje Prasse, Jurgen Behr, Matthias Mann, Herbert B. Schiller
Summary: This study analyzed B cell transcriptomes and developed a proteomic assay to capture antibodies in IPF patients. It found upregulation of specific immunoglobulins and a predictive autoimmune signature linked to reduced survival. Autoantibodies against thrombospondin-1 were associated with decreased survival, suggesting their potential as predictive biomarkers.
Article
Clinical Neurology
Anqi Duan, Zhihua Huang, Meixi Hu, Zhihui Zhao, Qing Zhao, Qi Jin, Lu Yan, Yi Zhang, Xin Li, Chenhong An, Qin Luo, Zhihong Liu
Summary: This study retrospectively analyzed data from 450 patients with pre-capillary pulmonary hypertension and found that the presence and severity of obstructive sleep apnea (OSA) were closely associated with left ventricular function, comorbidity burden, and disease phenotype. OSA was relatively common in pre-capillary pulmonary hypertension patients and was independently associated with various comorbidities and the atypical phenotype, highlighting the importance of OSA as a modifiable factor for optimal treatment in pre-capillary pulmonary hypertension with comorbidities.
Article
Biochemistry & Molecular Biology
Juan Manuel Velazquez-Enriquez, Alma Aurora Ramirez-Hernandez, Luis Manuel Sanchez Navarro, Itayetzi Reyes-Avendano, Karina Gonzalez-Garcia, Cristian Jimenez-Martinez, Luis Castro-Sanchez, Xariss Miryam Sanchez-Chino, Veronica Rocio Vasquez-Garzon, Rafael Baltierrez-Hoyos
Summary: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with unknown causes. This study identified differentially expressed proteins (DEPs) related to IPF pathogenesis by comparing IPF lung fibroblast cell lines with normal lung fibroblast cell lines. The results provide valuable information on the role of DEPs in IPF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Sheiphali Gandhi, Roberto Tonelli, Margaret Murray, Anna Valeria Samarelli, Paolo Spagnolo
Summary: Idiopathic pulmonary fibrosis (IPF) is a common and severe disease that primarily affects middle-aged and elderly males. In addition to aging, occupational and environmental exposures, as well as lifestyle factors such as smoking and diet, have been associated with an increased risk of IPF. Trigger factors may also lead to acute exacerbations and poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Marija Gredic, Isabel Blanco, Gabor Kovacs, Zsuzsanna Helyes, Peter Ferdinandy, Horst Olschewski, Joan Albert Barbera, Norbert Weissmann
Summary: This article summarizes the pathophysiology and treatment options for PH in COPD patients, pointing out that current research still does not fully understand its underlying mechanisms, and some of the treatment methods tested in clinical settings have not been effective. Preclinical studies have proposed some treatment approaches.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amarise Little, Yao Hu, Quan Sun, Deepti Jain, Jai Broome, Ming-Huei Chen, Florian Thibord, Caitlin McHugh, Praveen Surendran, Thomas W. Blackwell, Jennifer A. Brody, Arunoday Bhan, Nathalie Chami, Paul S. de Vries, Lynette Ekunwe, Nancy Heard-Costa, Brian D. Hobbs, Ani Manichaikul, Jee-Young Moon, Michael H. Preuss, Kathleen Ryan, Zhe Wang, Marsha Wheeler, Lisa R. Yanek, Goncalo R. Abecasis, Laura Almasy, Terri H. Beaty, Lewis C. Becker, John Blangero, Eric Boerwinkle, Adam S. Butterworth, Helene Choquet, Adolfo Correa, Joanne E. Curran, Nauder Faraday, Myriam Fornage, David C. Glahn, Lifang Hou, Eric Jorgenson, Charles Kooperberg, Joshua P. Lewis, Donald M. Lloyd-Jones, Ruth J. F. Loos, Yuan- Min, Braxton D. Mitchell, Alanna C. Morrison, Deborah A. Nickerson, Kari E. North, Jeffrey R. O'Connell, Nathan Pankratz, Bruce M. Psaty, Ramachandran S. Vasan, Stephen S. Rich, Jerome Rotter, Albert Smith, Nicholas L. Smith, Hua Tang, Russell P. Tracy, Matthew P. Conomos, Cecelia A. Laurie, Rasika A. Mathias, Yun Li, Paul L. Auer, Timothy Thornton, Alexander P. Reiner, Andrew D. Johnson, Laura M. Raffield
Summary: This study utilized WGS data from TOPMed project to analyze genetic variation contributing to platelet count and volume in a multi-ethnic sample. Secondary signals at MPL and PECAM1 were identified and replicated in African ancestry populations, along with rare variation in Mendelian platelet-related disorder genes influencing platelet traits.
HUMAN MOLECULAR GENETICS
(2022)
Article
Critical Care Medicine
Matthew Moll, Adel Boueiz, Auyon J. Ghosh, Aabida Saferali, Sool Lee, Zhonghui Xu, Jeong H. Yun, Brian D. Hobbs, Craig P. Hersh, Don D. Sin, Ruth Tal-Singer, Edwin K. Silverman, Michael H. Cho, Peter J. Castaldi
Summary: This study aims to evaluate the ability of peripheral blood biomarkers to assess chronic obstructive pulmonary disease (COPD) risk and progression. By developing a transcriptional risk score (TRS) and a polygenic risk score (PRS) model, it was found that TRS can improve the prediction of COPD and lung function decline.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Critical Care Medicine
John S. Kim, Gisli Thor Axelsson, Matthew Moll, Michaela R. Anderson, Elana J. Bernstein, Rachel K. Putman, Tomoyuki Hida, Hiroto Hatabu, Eric A. Hoffman, Ganesh Raghu, Steven M. Kawut, Margaret F. Doyle, Russell Tracy, Lenore J. Launer, Ani Manichaikul, Stephen S. Rich, David J. Lederer, Vilmundur Gudnason, Brian D. Hobbs, Michael H. Cho, Gary M. Hunninghake, Christine Kim Garcia, Gunnar Gudmundsson, R. Graham Barr, Anna J. Podolanczuk
Summary: This study found that higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Critical Care Medicine
Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh
Summary: This study found that carriers of the AAT Z allele (MZ heterozygotes) with COPD had lower lung function and more emphysema compared to MM subjects with COPD. In addition, there were subtle differences in gene expression between the two groups, suggesting that MZ subjects may represent a subtype of COPD.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Critical Care Medicine
Rachel S. Kelly, Kevin M. Mendez, Mengna Huang, Brian D. Hobbs, Clary B. Clish, Robert Gerszten, Michael H. Cho, Craig E. Wheelock, Michael J. McGeachie, Su H. Chu, Juan C. Celedon, Scott T. Weiss, Jessica Lasky-Su
Summary: Current guidelines for asthma classification are not comprehensive enough, necessitating a more detailed molecular approach. This study utilizes metabolomics to validate and explore the underlying biology of asthma endotypes. The findings suggest that metabolomic data can be used to derive clinically meaningful endotypes and investigating their drivers may enhance the understanding of asthma pathophysiology.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Respiratory System
Jingzhou Zhang, Hanfei Xu, Dandi Qiao, Dawn L. DeMeo, Edwin K. Silverman, George T. O'Connor, Brian D. Hobbs, Josee Dupuis, Michael H. Cho, Matthew Moll
Summary: This study found that a polygenic risk score for COPD is associated with earlier age of diagnosis and has predictive value when combined with known early-life risk factors.
EUROPEAN RESPIRATORY JOURNAL
(2022)
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
Critical Care Medicine
Gisli Thor Axelsson, Gunnar Gudmundsson, Katherine A. Pratte, Thor Aspelund, Rachel K. Putman, Jason L. Sanders, Elias F. Gudmundsson, Hiroto Hatabu, Valborg Gudmundsdottir, Alexander Gudjonsson, Takuya Hino, Tomoyuki Hida, Brian D. Hobbs, Michael H. Cho, Edwin K. Silverman, Russell P. Bowler, Lenore J. Launer, Lori L. Jennings, Gary M. Hunninghake, Valur Emilsson, Vilmundur Gudnason
Summary: This study investigates blood proteins associated with interstitial lung abnormalities (ILAs) using large-scale proteomics methods. Several proteins are identified as potential markers of early fibrotic lung disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Editorial Material
Critical Care Medicine
Brian D. Hobbs
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Genetics & Heredity
Fang Chen, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J. Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, Renan Sauteraud, Christine M. Albert, Nicholette D. D. Allred, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, R. Graham Barr, Diane M. Becker, Lawrence F. Bielak, Joshua C. Bis, John Blangero, Meher Preethi Boorgula, Daniel Chasman, Sameer Chavan, Yii-Der Chen, Lee-Ming Chuang, Adolfo Correa, Joanne E. Curran, Sean P. David, Lisa de Las Fuentes, Ranjan Deka, Ravindranath Duggirala, Jessica D. Faul, Melanie E. Garrett, Sina A. Gharib, Xiuqing Guo, Michael E. Hall, Nicola L. Hawley, Jiang He, Brian D. Hobbs, John E. Hokanson, Chao A. Hsiung, Shih-Jen Hwang, Thomas M. Hyde, Marguerite R. Irvin, Andrew E. Jaffe, Eric O. Johnson, Robert Kaplan, Sharon L. R. Kardia, Joel D. Kaufman, Tanika N. Kelly, Joel E. Kleinman, Charles Kooperberg, I-Te Lee, Daniel Levy, Sharon M. Lutz, Ani W. Manichaikul, Lisa W. Martin, Olivia Marx, Stephen T. McGarvey, Ryan L. Minster, Matthew Moll, Karine A. Moussa, Take Naseri, Kari E. North, Elizabeth C. Oelsner, Juan M. Peralta, Patricia A. Peyser, Bruce M. Psaty, Nicholas Rafaels, Laura M. Raffield, Muagututi'a Sefuiva Reupena, Stephen S. Rich, Jerome Rotter, David A. Schwartz, Aladdin H. Shadyab, Wayne H-H Sheu, Mario Sims, Jennifer A. Smith, Xiao Sun, Kent D. Taylor, Marilyn J. Telen, Harold Watson, Daniel E. Weeks, David R. Weir, Lisa R. Yanek, Kendra A. Young, Kristin L. Young, Wei Zhao, Dana B. Hancock, Bibo Jiang, Scott Vrieze, Dajiang J. Liu
Summary: Most TWASs conducted so far have focused on European ancestry and lacked diversity. To address this limitation, researchers aggregated GWAS summary statistics, whole-genome sequences, and eQTL data from diverse ancestries. They developed a new approach called TESLA, which integrates eQTL datasets with multi-ancestry GWAS, improving power and identifying more genes associated with tobacco use phenotypes compared to alternative TWAS methods. The study also suggests potential drug repurposing options for treating nicotine addiction.
Letter
Critical Care Medicine
Auyon J. Ghosh, Matthew Moll, Brian D. Hobbs, Jonathan Cardwell, Aabida Saferali, Peter J. Castaldi, Michael H. Cho, Edwin K. Silverman, Ivana V. Yang, Craig P. Hersh
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Genetics & Heredity
Justin Cosentino, Babak Behsaz, Babak Alipanahi, Zachary R. McCaw, Davin Hill, Tae-Hwi Schwantes-An, Dongbing Lai, Andrew Carroll, Brian D. Hobbs, Michael H. Cho, Cory Y. McLean, Farhad Hormozdiari
Summary: A deep convolutional neural network is utilized to predict COPD case-control status using raw spirograms and noisy medical-record-based labels. The machine-learning-based liability score accurately distinguishes COPD cases and controls, predicts COPD-related hospitalization, and is associated with overall survival and exacerbation events. The genome-wide association study on the liability score replicates known COPD and lung function loci and identifies new loci.
Article
Critical Care Medicine
Daniel D. Fraughen, Auyon J. Ghosh, Brian D. Hobbs, Georg-Christian Funk, Tobias Meischl, Christian F. Clarenbach, Noriane A. Sievi, Karin Schmid-Scherzer, Oliver J. McElvaney, Mark P. Murphy, Adam D. Roche, Louise Clarke, Matthew Strand, Florian Vafai-Tabrizi, Geraldine Kelly, Cedric Gunaratnam, Tomas P. Carroll, Noel G. McElvaney
Summary: This real-world study demonstrates the survival advantage of IV-AAT in severe AATD patients. This improved survival is not related to the decline in lung function FEV1. Patients are divided into two major phenotypes, lung indexes and non-lung indexes, which have implications for clinical trial design, especially when FEV1 is the primary endpoint.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Respiratory System
Lystra P. Hayden, Brian D. Hobbs, Robert Busch, Michael H. Cho, Ming Liu, Camila M. Lopes-Ramos, David A. Lomas, Per Bakke, Amund Gulsvik, Edwin K. Silverman, James D. Crapo, Terri H. Beaty, Nan M. Laird, Christoph Lange, Dawn L. DeMeo
Summary: This study explores the association between genetic variants on the X chromosome and the risk of COPD, as well as the sex differences in COPD manifestations. It identifies loci influencing lung function, COPD, and emphysema and demonstrates the importance of sex differences in complex lung diseases. Comprehensive interrogation of the X chromosome is important in understanding the genetic control of COPD and lung function.
RESPIRATORY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Leonardo Martini, Seung Han Baek, Ian Lo, Benjamin A. Raby, Edwin K. Silverman, Scott T. Weiss, Kimberly Glass, Arda Halu
Summary: The versatility of cellular response arises from the communication and crosstalk of signaling pathways in a complex network. This study presents a network-based statistical approach called MuXTalk that models the unique ways in which signaling and regulatory interactions can interface. Using statistically over-represented multilinks as proxies of crosstalk, crosstalk among 60 signaling pathways is inferred, expanding currently available crosstalk databases significantly.
NUCLEIC ACIDS RESEARCH
(2023)