Article
Medicine, General & Internal
Teng Moua, Tananchai Petnak, Antonios Charokopos, Misbah Baqir, Jay H. Ryu
Summary: Recent advances in fibrotic hypersensitivity pneumonitis include improved diagnostic guidance, systematic assessments of immunosuppressive therapy, and the recent availability of antifibrotic therapy. Standardized diagnosis may improve future therapeutic protocols and predict disease or treatment response. This review provides a comprehensive overview of diagnostic and treatment challenges, along with supporting evidence and clinical implications.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Xin Zhang, Mengting Shi, Xi Zhao, Ennan Bin, Yucheng Hu, Nan Tang, Huaping Dai, Chen Wang
Summary: This study aimed to investigate the regeneration capacity of AT2 cells with short telomeres. It was found that short telomeres in AT2 cells result in reduced expression level of TPPP3, thereby limiting the differentiation and regeneration capacity of AT2 cells.
CELL PROLIFERATION
(2022)
Article
Medicine, General & Internal
Shuuhei Ohno, Yoshiaki Zaizen, Goushi Matama, Tomonori Chikasue, Saeko Tokisawa, Masaki Okamoto, Kazuhiro Tabata, Masaki Tominaga, Jun Akiba, Kiminori Fujimoto, Junya Fukuoka, Tomoaki Hoshino
Summary: This study investigated the effectiveness of transbronchial lung cryobiopsy (TBLC) in diagnosing hypersensitivity pneumonitis (HP). The results showed that evaluating airway disease with TBLC for the diagnosis of HP is challenging and requires multidisciplinary discussion (MDD). Therefore, understanding the characteristics of TBLC is crucial for accurately diagnosing HP through MDD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Respiratory System
Tracy J. Doyle, Pierre-Antoine Juge, Anna L. Peljto, Seoyeon Lee, Avram D. Walts, Anthony Joseph Esposito, Sergio Poli, Ritu Gill, Hiroto Hatabu, Mizuki Nishino, Paul F. Dellaripa, Michael E. Weinblatt, Nancy A. Shadick, M. Kristen Demoruelle, Jeffrey A. Sparks, Ivan O. Rosas, Benjamin Granger, Kevin D. Deane, Bruno Crestani, Paul J. Wolters, Philippe Dieude, Joyce S. Lee
Summary: This study investigates the association between shortened telomere lengths and interstitial lung disease in individuals with rheumatoid arthritis (RA). The findings suggest that shortened peripheral blood leukocytes-telomere length is associated with ILD in RA patients, and shorter telomere length is also associated with baseline disease severity in RA-ILD.
Article
Radiology, Nuclear Medicine & Medical Imaging
Chi Wan Koo, James M. Williams, Grace Liu, Ananya Panda, Parth P. Patel, Livia Maria M. Frota Lima, Ronald A. Karwoski, Teng Moua, Nicholas B. Larson, Alex Bratt
Summary: QCT features and QCT feature-based ML models successfully differentiate interstitial lung diseases (ILDs). The performance of QCT-ML models outperforms a DL model in ILD classification. Further investigations are needed to determine the superior approach for ILD classification.
EUROPEAN RADIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Georgiana Dinache, Claudiu Costinel Popescu, Corina Mogosan, Luminita Enache, Mihaela Agache, Catalin Codreanu
Summary: This study aimed to assess the clinical characteristics of rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and determine their association with X-ray and high-resolution computed tomography (HR-CT) findings. Results showed that male RA patients had a higher prevalence of nodules, combined fibrosis and nodules, and combined bronchiectasis and nodules on chest X-rays, while rheumatoid factor (RF)-positive patients had a higher prevalence of fibrosis and anti-cyclic citrullinated peptide antibodies (ACPA)-positive patients had a higher prevalence of bronchiectasis. In terms of HR-CT findings, patients on methotrexate treatment had a higher prevalence of nodules, combined fibrosis and nodules, combination of emphysema and nodules, and combination of fibrosis, emphysema, and nodules. ILD was found to develop within approximately 5 years from RA diagnosis, and it was more prevalent in men with RA, among patients with positive RA serology (RF and/or ACPA), and RA patients on methotrexate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Paolo Giannoni, Marco Grosso, Giuseppina Fugazza, Mario Nizzari, Maria Cristina Capra, Rita Bianchi, Roberto Fiocca, Sandra Salvi, Fabrizio Montecucco, Maria Bertolotto, Franco Fais, Mario Salio, Emanuela Barisione, Daniela de Totero
Summary: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of various antigens, while fibrotic HP (fHP) may be associated with idiopathic pulmonary fibrosis and have a worse prognosis. A fibroblastic cell line derived from a patient with fHP was established and characterized, showing features similar to myofibroblasts, and could potentially serve as a tool to model the disease in vitro. Preliminary assessment of pirfenidone demonstrated consistent inhibition of cell growth.
Article
Medicine, General & Internal
Megan A. Koster
Summary: HP is a complex immune-mediated lung disease that can be categorized based on the presence of fibrosis, which has an impact on patient prognosis.
MEDICAL CLINICS OF NORTH AMERICA
(2022)
Review
Medicine, General & Internal
Ahmad Abu Qubo, K. M. Capaccione, Elana J. Bernstein, Maria Padilla, Mary Salvatore
Summary: This article describes the role of radiology in the diagnosis and follow-up of PF-ILD. The manuscript reviews the radiographic diagnosis and unique CT characteristics associated with specific types of fibrosis. Radiology has the potential to make an important contribution to the multidisciplinary discussion for this important diagnosis.
FRONTIERS IN MEDICINE
(2022)
Article
Rheumatology
Brittany L. Adler, Francesco Boin, Paul J. Wolters, Clifton O. Bingham, Ami A. Shah, Carol Greider, Livia Casciola-Rosen, Antony Rosen
Summary: Autoantibodies targeting telomere-associated proteins are found in a subset of patients with systemic sclerosis (SSc), and are associated with short lymphocyte telomere length and lung disease. These autoantibodies are rarely present in rheumatoid arthritis, myositis, and healthy controls, suggesting a specificity for SSc and idiopathic pulmonary fibrosis (IPF).
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Editorial Material
Critical Care Medicine
Onofre Moran-Mendoza, Sharina Aldhaheri, Connor J. A. Black, Marie Clements-Baker, Mohamed Khalil, Alexander Boag
Summary: Hypersensitivity pneumonitis (HP) is an inflammatory and fibrotic lung disease caused by an immune reaction, with unknown antigens in many cases. This study presents two cases of HP associated with mold exposure in foam pillows and mattresses, a previously unrecognized risk factor. Mold in foam bedding may explain a significant number of HP cases, and early identification and avoidance of foam may prevent progression to end-stage pulmonary fibrosis and death.
Review
Medicine, General & Internal
Hui Huang, Ruxuan Chen, Chi Shao, Zuojun Xu, Paul J. Wolters
Summary: Respiratory complications are common in rheumatoid arthritis (RA), with interstitial lung disease being the most common manifestation. Recent progress has been made in understanding the management and progression of RA-associated interstitial lung disease (RA-ILD) and other respiratory diseases in RA. In this review, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA from a chest physicians' perspective.
CHINESE MEDICAL JOURNAL
(2023)
Article
Medicine, General & Internal
Goushi Matama, Masaki Okamoto, Kiminori Fujimoto, Takeshi Johkoh, Masaki Tominaga, Hiroshi Mukae, Noriho Sakamoto, Kosaku Komiya, Kenji Umeki, Masamichi Komatsu, Yasuo Shimizu, Koichiro Takahashi, Saeko Tokisawa, Yoshiaki Zaizen, Norikazu Matsuo, Takashi Nouno, Shinjiro Kaieda, Hiroaki Ida, Kenji Izuhara, Tomoaki Hoshino, Marco Sebastiani
Summary: This study investigated the potential of Periostin as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The results showed that all biomarkers were higher in RA-ILD patients compared to healthy controls and RA patients without ILD. KL-6 accurately detected ILD in RA patients, while SP-D and Periostin moderately detected ILD. Periostin levels were correlated with lung fibrosis but not inflammatory areas. Additionally, Periostin was higher in RA-ILD patients with a typical usual interstitial pneumonia pattern. Immunohistochemical analyses showed that Periostin was expressed in fibroblastic foci. These findings suggest that Periostin can be used as a biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for RA-ILD patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biology
Natalia V. V. Trushenko, Olga A. A. Suvorova, Ekaterina S. S. Pershina, Galina V. V. Nekludova, Svetlana Yu. Chikina, Iuliia A. A. Levina, Andrey L. L. Chernyaev, Maria V. V. Samsonova, Igor E. E. Tyurin, Malika Kh. Mustafina, Andrey I. I. Yaroshetskiy, Nikita B. B. Nadtochiy, Zamira M. M. Merzhoeva, Anna A. A. Proshkina, Sergey N. N. Avdeev
Summary: This study aimed to identify predictors of disease progression and mortality in patients with chronic hypersensitivity pneumonitis (HP) in real clinical practice. The significant predictors of adverse outcomes were a DLco < 50% predicted, an SpO2 at the end of a six-minute walk test (6-MWT) < 85%, and a GAP score >= 4 points. Early detection of these predictors is necessary for timely initiation of antifibrotic therapy in patients with chronic HP.
Article
Physiology
Tsukasa Okamoto, Evgenia Dobrinskikh, Corinne E. Hennessy, Naoko Liu, Marvin I. Schwarz, Christopher M. Evans, Andrew P. Fontenot, Ivana V. Yang, David A. Schwartz
Summary: This study investigates the role of Muc5b in hypersensitivity pneumonitis (HP) using a mouse model. The researchers found that overexpression of Muc5b increases lung inflammation and fibrosis, while Muc5b deficiency reduces inflammation and fibrosis in the HP model. These findings have implications for understanding the development of HP in humans.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Respiratory System
Haruhiko Furusawa, Anna L. Peljto, Avram D. Walts, Jonathan Cardwell, Philip L. Molyneaux, Joyce S. Lee, Evans R. Fernandez Perez, Paul J. Wolters, Ivana Yang, David A. Schwartz
Summary: A study found that a subset of patients with hypersensitivity pneumonitis (HP) develop lung fibrosis that is clinically similar to idiopathic pulmonary fibrosis (IPF). The study also identified certain genetic variants that were significantly associated with fibrotic HP, indicating a shared etiology and pathogenesis between fibrotic HP and IPF.
Article
Critical Care Medicine
Willis S. Bowman, Chad A. Newton, Angela L. Linderholm, Megan L. Neely, Janelle Vu Pugashetti, Bhavika Kaul, Vivian Vo, Gabrielle A. Echt, William Leon, Rupal J. Shah, Yong Huang, Christine Kim Garcia, Paul J. Wolters, Justin M. Oldham
Summary: This study aims to identify plasma biomarkers of progressive fibrosing interstitial lung disease (ILD) and develop a proteomic signature to predict this phenotype. The study identified 17 plasma biomarkers associated with progressive fibrosing ILD and developed a proteomic signature that can differentiate between high-risk and low-risk patients in clinical trials.
LANCET RESPIRATORY MEDICINE
(2022)
Article
Critical Care Medicine
Janet Lee, Emily White, Elizabeth Freiheit, Mary Beth Scholand, Mary E. Strek, Anna J. Podolanczuk, Nina M. Patel
Summary: Cough-specific quality of life assessment can predict disease progression, respiratory hospitalizations, lung transplantation, and death among patients with interstitial lung disease.
Article
Biology
Kuan Zhang, Erica Yao, Biao Chen, Ethan Chuang, Julia Wong, Robert Seed, Stephen L. Nishimura, Paul J. Wolters, Pao-Tien Chuang, Melanie Koenigshoff
Summary: This study revealed the crucial role of mitochondria in the formation of alveoli in mice, affecting cellular functions and key steps of alveologenesis. Mitochondrial regulation enables lung epithelial cells to secrete ligands influencing myofibroblast proliferation and movement, while also impacting myofibroblast contraction and migration.
Letter
Critical Care Medicine
Ryan D. Boente, Emily N. White, Caitlin M. Baxter, Jessica E. Shore, Harold R. Collard, Joyce S. Lee
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Medicine, Research & Experimental
Joyce S. Lee, Adam Martin-Schwarze, Elizabeth Freiheit, Ben Trzaskoma, Cindy Burg
Summary: This study examined the relationship between clinical outcomes and body mass index (BMI) and weight change in patients with idiopathic pulmonary fibrosis (IPF). The results showed that patients with a low BMI or weight loss over 24 months may have worse clinical outcomes, but the causation for these relationships is unknown.
ADVANCES IN THERAPY
(2023)
Article
Critical Care Medicine
Anna L. Peljto, Rachel Z. Blumhagen, Avram D. Walts, Jonathan Cardwell, Julia Powers, Tamera J. Corte, Joanne L. Dickinson, Ian Glaspole, Yuben P. Moodley, Martina Koziar Vasakova, Elisabeth Bendstrup, Jesper R. Davidsen, Raphael Borie, Bruno Crestani, Philippe Dieude, Francesco Bonella, Ulrich Costabel, Gunnar Gudmundsson, Seamas C. Donnelly, Jim Egan, Michael T. Henry, Michael P. Keane, Marcus P. Kennedy, Cormac McCarthy, Aoife N. McElroy, Joshua A. Olaniyi, Katherine M. A. O'Reilly, Luca Richeldi, Paolo M. Leone, Venerino Poletti, Francesco Puppo, Sara Tomassetti, Valentina Luzzi, Nurdan Kokturk, Nesrin Mogulkoc, Christine A. Fiddler, Nikhil Hirani, R. Gisli Jenkins, Toby M. Maher, Philip L. Molyneaux, Helen Parfrey, Rebecca Braybrooke, Timothy S. Blackwell, Peter D. Jackson, Steven D. Nathan, Mary K. Porteous, Kevin K. Brown, Jason D. Christie, Harold R. Collard, Oliver Eickelberg, Elena E. Foster, Kevin F. Gibson, Marilyn Glassberg, Daniel J. Kass, Jonathan A. Kropski, David Lederer, Angela L. Linderholm, Jim Loyd, Susan K. Mathai, Sydney B. Montesi, Imre Noth, Justin M. Oldham, Amy J. Palmisciano, Cristina A. Reichner, Mauricio Rojas, Jesse Roman, Neil Schluger, Barry S. Shea, Jeffrey J. Swigris, Paul J. Wolters, Yingze Zhang, Cecilia M. A. Prele, Juan I. Enghelmayer, Maria Otaola, Christopher J. Ryerson, Mauricio Salinas, Martina Sterclova, Tewodros H. Gebremariam, Marjukka Myllarniemi, Roberto G. Carbone, Haruhiko Furusawa, Masaki Hirose, Yoshikazu Inoue, Yasunari Miyazaki, Ken Ohta, Shin Ohta, Tsukasa Okamoto, Dong Soon Kim, Annie Pardo, Moises Selman, Alvaro U. Aranda, Moo Suk Park, Jong Sun Park, Jin Woo Song, Maria Molina-Molina, Lurdes Planas-Cerezales, Gunilla Westergren-Thorsson, Albert V. Smith, Ani W. Manichaikul, John S. Kim, Stephen S. Rich, Elizabeth C. Oelsner, R. Graham Barr, Jerome I. Rotter, Josee Dupuis, George O'Connor, Ramachandran S. Vasan, Michael H. Cho, Edwin K. Silverman, Marvin I. Schwarz, Mark P. Steele, Joyce S. Lee, Ivana V. Yang, Tasha E. Fingerlin, David A. Schwartz
Summary: This study investigated the role of rare variants, genome-wide, on the risk of idiopathic pulmonary fibrosis (IPF) using whole-genome sequencing. The results showed that rare variants within the TERT and RTEL1 genes were significantly associated with IPF, along with well-established common variants. Therefore, including TERT, RTEL1, common variants, and environmental risk factors in risk profiling and IPF therapy development is likely to have the largest impact on this complex disease.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Letter
Critical Care Medicine
Lauren J. Donoghue, Amy D. Stockwell, Margaret Neighbors, Rebecca X. Sheng, Ramanandan Prabhakaran, Paul J. Wolters, Lisa H. Lancaster, Jonathan A. Kropski, Timothy S. Blackwell, Mark I. McCarthy, Brian L. Yaspan
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Respiratory System
Hsiao-Yen Ma, Jason A. Vander Heiden, Salil Uttarwar, Ying Xi, Elsa-Noah N'Diaye, Ryan LaCanna, Patrick Caplazi, Sarah Gierke, John Moffat, Paul J. Wolters, Ning Ding
Summary: This study found that MRTF signaling is activated in myofibroblasts accumulated in IPF lungs. PFD inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations. These findings suggest that MRTF signaling may be a direct target for PFD and that its anti-fibrotic effects may be due to MRTF inhibition in lung fibroblasts.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Critical Care Medicine
Justin M. Oldham, Richard J. Allen, Jose M. Lorenzo-Salazar, Philip L. Molyneaux, Shwu-Fan Ma, Chitra Joseph, John S. Kim, Beatriz Guillen-Guio, Tamara Hernandez-Beeftink, Jonathan A. Kropski, Yong Huang, Cathryn T. Lee, Ayodeji Adegunsoye, Janelle Vu Pugashetti, Angela L. Linderholm, Vivian Vo, Mary E. Strek, Jonathan Jou, Adrian Munoz-Barrera, Luis A. Rubio-Rodriguez, Richard Hubbard, Nik Hirani, Moira K. B. Whyte, Simon Hart, Andrew G. Nicholson, Lisa Lancaster, Helen Parfrey, Doris Rassl, William Wallace, Eleanor Valenzi, Yingze Zhang, Josyf Mychaleckyj, Amy Stockwell, Naftali Kaminski, Paul J. Wolters, Maria Molina-Molina, Nicholas E. Banovich, William A. Fahy, Fernando J. Martinez, Ian P. Hall, Martin D. Tobin, Toby M. Maher, Timothy S. Blackwell, Brian L. Yaspan, R. Gisli Jenkins, Carlos Flores, Louise V. Wain, Imre Noth
Summary: This study conducted a staged genome-wide association study to identify and validate molecular determinants of survival in idiopathic pulmonary fibrosis (IPF). Four novel variants associated with IPF survival were identified, including one within the PCSK6 gene that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein may play an important role in IPF progression.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Immunology
Chaoqun Wang, Ben Hyams, Nancy C. Allen, Kelly Cautivo, Kiara Monahan, Minqi Zhou, Madelene W. Dahlgren, Carlos O. Lizama, Michael Matthay, Paul Wolters, Ari B. Molofsky, Tien Peng
Summary: Abnormal tissue-immune interactions are characteristic of chronic lung diseases. In emphysema, the expansion of tissue-resident lymphocytes (TRLs) was observed. A stromal niche expressing the disease-variant gene Hhip was identified, and its deletion led to the expansion of TRLs through the hedgehog-IL-7 axis. Expanded TRLs suppressed alveolar stem cell growth through IFNg, and a subset of human alveolar stem cells sensitive to IFNg was lost in emphysema.
Article
Multidisciplinary Sciences
Ayodeji Adegunsoye, Chad A. Newton, Justin M. Oldham, Brett Ley, Cathryn T. Lee, Angela L. Linderholm, Jonathan H. Chung, Nicole Garcia, Da Zhang, Rekha Vij, Robert Guzy, Renea Jablonski, Remzi Bag, Rebecca S. Voogt, Shwu-Fan Ma, Anne I. Sperling, Ganesh Raghu, Fernando J. Martinez, Mary E. Strek, Paul J. Wolters, Christine Kim Garcia, Brandon L. Pierce, Imre Noth
Summary: This study investigated the association between leukocyte telomere length (LTL) and age and mortality in racially diverse patients with pulmonary fibrosis (PF). The study found that LTL shortened with increasing age, and this association was even stronger in PF patients. In all racial groups, LTL below the median predicted worse mortality.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Ayodeji Adegunsoye, Elizabeth Freiheit, Emily N. White, Bhavika Kaul, Chad A. Newton, Justin M. Oldham, Cathryn T. Lee, Jonathan Chung, Nicole Garcia, Sahand Ghodrati, Rekha Vij, Renea Jablonski, Kevin R. Flaherty, Paul J. Wolters, Christine Kim Garcia, Mary E. Strek
Summary: This cohort study examines the age differences and survival patterns in pulmonary fibrosis (PF)-related outcomes among Hispanic, non-Hispanic Black, and non-Hispanic White participants. The study found racial and ethnic disparities, particularly among Black patients, in PF-related outcomes, including earlier onset of death.
Article
Respiratory System
Bhavika Kaul, Laura A. Petersen, Ivan O. Rosas, Joyce S. Lee, Fernando J. Martinez, Venkata D. Bandi, Drew A. Helmer, Paul J. Wolters, Harold R. Collard, Mary A. Whooley
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2023)
Review
Medicine, General & Internal
Hui Huang, Ruxuan Chen, Chi Shao, Zuojun Xu, Paul J. Wolters
Summary: Respiratory complications are common in rheumatoid arthritis (RA), with interstitial lung disease being the most common manifestation. Recent progress has been made in understanding the management and progression of RA-associated interstitial lung disease (RA-ILD) and other respiratory diseases in RA. In this review, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA from a chest physicians' perspective.
CHINESE MEDICAL JOURNAL
(2023)