Article
Medicine, General & Internal
Mario Castro, Edward Kerwin, David Miller, Andrew Pedinoff, Lawrence Sher, Pamela Cardenas, Barbara Knorr, David Lawrence, Diego Ossa, Wei Wang, Jorge F. Maspero
Summary: The studies did not show significant improvement in lung function or other clinical outcomes with the use of fevipiprant in patients with uncontrolled asthma, suggesting that DP2 receptor inhibition with fevipiprant may not be effective in this patient population.
Article
Medicine, Research & Experimental
Ashley Hernandez-Gutierrez, Sonoor Majid, Adam Eberle, Ashley Choi, Parand Sorkhdini, Dongqin Yang, Alina Xiaoyu Yang, Carmelissa Norbrun, Chuan Hua He, Chun Geun Lee, Jack A. Elias, Yang Zhou
Summary: Exaggerated Type 2 immune responses are crucial in the development of diseases such as asthma, allergy, and pulmonary fibrosis. Recent studies have highlighted the importance of innate type 2 immune responses and innate lymphoid 2 cells (ILC2s) in these disorders. However, the mechanisms controlling the development of pulmonary innate type 2 responses (IT2IR) and the activation of ILC2 cells are unclear. In mouse models, the protein phospholipid scramblase-1 (PLSCR1) was found to play a critical role in regulating IT2IR in the lung. The effects of PLSCR1 on ILC2 activation and IT2IR are mediated through the chemoattractant receptor-homologous molecule (CRTH2). Understanding the role of PLSCR1 provides important insights into the pathogenesis of ILC2 responses and potential targets for controlling chronic diseases such as asthma.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Allergy
Caroline P. E. Price, Amina Guo, Whitney W. Stevens, Leslie Cousens, Thanh-Huyen T. Vu, Lydia A. Suh, Kristin A. Erickson, David Conley, Leslie C. Grammer, Robert C. Kern, Bruce K. Tan, Atsushi Kato, Robert P. Schleimer, Stephanie S. Smith, Kevin C. Welch, Anju T. Peters
Summary: The addition of AZD1981 to intranasal corticosteroids did not improve nasal polyp size, symptoms, or quality of life in adult patients with CRSwNP.
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Pharmacology & Pharmacy
H. Markus Weiss, Thomas Langenickel, Meredith Cain, Swarupa Kulkarni, Bharti Shah, Janardhana Vemula, Gholamreza Rahmanzadeh, Birk Poller
Summary: The study evaluated the impact of probenecid on the pharmacokinetics of fevipiprant, showing that probenecid increased the exposure of fevipiprant and reduced the clearance rates in the body.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Pharmacology & Pharmacy
Xiaojiao Li, Qianqian Li, Tianliang Ji, Hong Zhang, Jingrui Liu, Min Wu, Hong Chen, Jinfeng Lou, Chengjiao Liu, Zhongnan Xu, Yanhua Ding
Summary: This first-in-human study evaluated the pharmacokinetics, safety, and tolerability of TQC3564 in healthy Chinese subjects. The results showed that TQC3564 was safe and well tolerated, without dose-dependent adverse events. The study demonstrated the potential of TQC3564 as a therapeutic option for asthma.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Chemistry, Organic
Mili Litvajova, Emiliano Sorrentino, Brendan Twamley, Stephen J. Connon
Summary: This study demonstrates the application of N-protected oxindole derivatives with unprecedented malleability in enantioselective phase-transfer-catalysed alkylations. By optimizing the structure of the catalyst, high levels of enantioselectivity were achieved. It was found that urea-based catalysts outperformed squaramide derivatives, and that installing a chlorine atom in the quinoline moiety of the catalyst improved reaction selectivity.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yaopeng Zhao, Jixia Wang, Tao Hou, Yancheng Yu, Han Zhou, Yang Han, Junxiang Cheng, Yanfang Liu, Chaoran Wang, Long Chen, Xinmiao Liang
Summary: A series of 2-(2,2-diarylethyl)-cyclamine derivatives were designed and synthesized as M3 mAChR antagonists, showing excellent selectivity and antagonistic activity. These novel compounds have the potential to be candidates for COPD drug development.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yueming Cao, Jahnavi Rudrakshala, River Williams, Shade Rodriguez, Parand Sorkhdini, Alina X. Yang, Miles Mundy, Dongqin Yang, Amy Palmisciano, Thomas Walsh, Cesar Delcompare, Tanis Caine, Luca Tomasi, Barry S. Shea, Yang Zhou
Summary: This study investigated the role of the CHI3L1-CRTH2 pathway in the development of pulmonary fibrosis. The results showed that null mutation or inhibition of CRTH2 prevented the development of pulmonary fibrosis in mice. In addition, monocytes from patients with IPF appeared to be hyperresponsive to CHI3L1 stimulation. The findings support the targeting of the CHI3L1-CRTH2 pathway as a promising therapeutic approach for IPF and suggest that the sensitivity of blood monocytes to CHI3L1-induced profibrotic differentiation may serve as a biomarker for predicting treatment responsiveness.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shengkai Zuo, Bei Wang, Jiao Liu, Deping Kong, Hui Cui, Yaonan Jia, Chenyao Wang, Xin Xu, Guilin Chen, Yuanyang Wang, Linlin Yang, Kai Zhang, Ding Ai, Jie Du, Yujun Shen, Ying Yu
Summary: The study discovered a novel anti-fibrotic function of CRTH2 in the endoplasmic reticulum membrane, where it interacts with LARP6 to promote degradation of collagen mRNA, thereby inhibiting collagen biosynthesis in fibroblasts and reducing organ fibrosis.
Article
Allergy
Teerapol Chantveerawong, Sasipa Sangkangjanavanich, Chirawat Chiewchalermsri, Panitan Pradubpongsa, Wat Mitthamsiri, Sarawut Jindarat, Ming Wang, Mubeccel Akdis, Milena Sokolowska, Cezmi A. Akdis, Atik Sangasapaviliya, Tadech Boonpiyathad
Summary: The frequency of CRTH2(+)Tregs is higher in patients with asthma, especially allergic phenotype, compared to healthy controls, and shows a negative correlation with ACT scores and PEFR. CRTH2(+)Tregs increase during exacerbation and decrease after asthma control. In vitro investigations demonstrate that Tregs of allergic patients with asthma display Th2-biased character.
Article
Biochemistry & Molecular Biology
Ruotian Xie, Bei Wang, Shengkai Zuo, Mei Du, Xiaohong Wang, Ying Yu, Hua Yan
Summary: CRTH2 plays an important role in AMD. Inhibiting CRTH2 can protect RPE from apoptosis, reduce retinal degeneration area, and prevent loss of photoreceptor cells. This suggests that CRTH2 may be a promising therapeutic target for treating AMD.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Misato Kida, Tatsuro Nakamura, Yuki Fujiwara, Masataka Nakamura, Takahisa Murata
Summary: The study revealed that the PGD(2)/CRTH2 signaling pathway plays a defensive role in host response to bee venom injection, promoting the production of BV-specific IgE and facilitating the migration of DCs to regional lymph nodes.
Review
Allergy
Kellen J. Cavagnero, Taylor A. Doherty
Summary: This study synthesizes investigations into the role of lipid-mediated recruitment and activation of ILC2s in AERD, finding higher levels of proinflammatory lipid mediators and type 2 cytokines in tissues from AERD patients, as well as increased ILC2 levels in nasal mucosa. While the literature suggests that lipid-mediated ILC2 activation may occur in AERD, definitive evidence is lacking.
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Toni K. Choueiri, Todd M. Bauer, Kyriakos P. Papadopoulos, Elizabeth R. Plimack, Jaime R. Merchan, David F. McDermott, M. Dror Michaelson, Leonard J. Appleman, Sanjay Thamake, Rodolfo F. Perini, Naseem J. Zojwalla, Eric Jonasch
Summary: The HIF-2 alpha inhibitor belzutifan shows promising clinical activity and a favorable safety profile in heavily pre-treated patients with renal cell carcinoma, suggesting it may offer an effective treatment option. The drug was well tolerated with a confirmed objective response rate of 25% and a median progression-free survival of 14.5 months in patients with ccRCC.
Article
Multidisciplinary Sciences
Heng Liu, R. N. V. Krishna Deepak, Anna Shiriaeva, Cornelius Gati, Alexander Batyuk, Hao Hu, Uwe Weierstall, Wei Liu, Lei Wang, Vadim Cherezov, Hao Fan, Cheng Zhang
Summary: This study elucidated the crystal structure of human CRTH2 bound to a PGD(2) derivative, revealing different binding modes between 15mPGD(2) and PGE(2). The research also highlighted the critical roles of charged residues in lipid recognition by GPCRs, suggesting potential implications for lipid GPCR studies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Rehabilitation
Kathrine Rayce, Lotte Huniche, Kristian Kidholm, Jorgen Vestbo, Claus Duedal Pedersen, Lisbeth Rosenbek Minet
Summary: This study characterized telemediated training for COPD patients and found that training at home through telemediation may compromise patient privacy, leading physiotherapists to be more cautious. Therefore, trade-offs need to be considered and continuous adjustments should be made in the practice of telemediated services.
DISABILITY AND REHABILITATION
(2022)
Article
Respiratory System
Ashley Woodcock, Kai M. Beeh, Hironori Sagara, Simon Aumonier, Emmanuel Addo-Yobo, Javaid Khan, Jorgen Vestbo, Helen Tope
Summary: When selecting inhalers and drugs for respiratory disease, considering the carbon footprint is important. Currently, the most commonly used pMDIs contain potent greenhouse gases, while DPIs and soft mist inhalers have lower carbon footprints. Analyzing the carbon footprint data of inhalers can provide insights for treatment decisions and industry initiatives.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Critical Care Medicine
Yunus Colak, Borge G. Nordestgaard, Peter Lange, Jorgen Vestbo, Shoaib Afzal
Summary: Most patients with chronic obstructive pulmonary disease are not included in major clinical trials, but they experience significant exacerbations and early death.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Critical Care Medicine
Peter M. A. Calverley, Fernando J. Martinez, Jorgen Vestbo, Christine R. Jenkins, Robert Wise, David A. Lipson, Nicholas J. Cowans, Julie Yates, Courtney Crim, Bartolome R. Celli
Summary: Countries participating in COPD trials consistently differ in reporting exacerbations, which may explain why large studies are needed to show differences in exacerbation risk reduction between treatments.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Letter
Respiratory System
Jorgen Vestbo, Grant Waterer, David Leather, Courtney Crim, Nawar Diar Bakerly, Lucy Frith, Loretta Jacques, Catherine Harvey, Imran Satia, Ashley Woodcock
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Yunus Colak, Borge G. Nordestgaard, Jorgen Vestbo, Shoaib Afzal, Peter Lange
Summary: Targeted spirometry in a general population setting can detect undiagnosed cases of COPD. A significant proportion of individuals with undiagnosed COPD also have other treatable conditions, such as smoking, respiratory symptoms, low physical activity, hypertension, hypercholesterolemia, and diabetes.
RESPIRATORY MEDICINE
(2022)
Article
Critical Care Medicine
Tessa M. Kole, Elise Vanden Berghe, Monica Kraft, Judith M. Vonk, Martijn C. Nawijn, Salman Siddiqui, Kai Sun, Leonardo M. Fabbri, Klaus F. Rabe, Kian Fan Chung, Gabriele Nicolini, Alberto Papi, Chris Brightling, Dave Singh, Thys van der Molen, Sven-Erik Dahlen, Alvar Agusti, Rosa Faner, Jadwiga A. Wedzicha, Gavin C. Donaldson, Ian M. Adcock, Lies Lahousse, Huib A. M. Kerstjens, Maarten van den Berge
Summary: This post-hoc analysis investigates the determinants, clinical implications, and outcome of persistent airflow limitation (PAL) in patients with asthma. The study reveals that PAL is not only present in severe asthma, but also in a considerable proportion of patients with milder disease. In patients with mild asthma, PAL is associated with eosinophilic inflammation and a higher risk of exacerbations, suggesting the need for increased treatment intensity.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Respiratory System
Janelle Yorke, Naimat Khan, Adam Garrow, Sarah Tyson, Dave Singh, Jorgen Vestbo, Paul W. Jones
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(2022)
Article
Respiratory System
Efthymia Papadopoulou, Jan Hansel, Zsofia Lazar, Konstantinos Kostikas, Stavros Tryfon, Jurgen Vestbo, Alexander G. Mathioudakis
Summary: This meta-analysis explored the safety and effectiveness of mucolytics as an add-on treatment for COPD exacerbations. The analysis included 24 RCTs involving 2192 patients and showed that mucolytics can increase treatment success rate, improve symptom scores, reduce persistent cough, and facilitate expectoration. There is also some evidence suggesting that mucolytics may reduce future exacerbation risk and improve quality of life.
EUROPEAN RESPIRATORY REVIEW
(2023)
Editorial Material
Respiratory System
Bartolome Celli, Jorgen Vestbo
EUROPEAN RESPIRATORY JOURNAL
(2023)
Letter
Respiratory System
Jorgen Vestbo, Kare Press-Kristensen
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ema Rastoder, Pradeesh Sivapalan, Josefin Ekloef, Imane Achir Alispahic, Alexander Svorre Jordan, Christian B. Laursen, Jorgen Vestbo, Christine Jenkins, Rune Nielsen, Per Bakke, Gustavo Fernandez-Romero, Daniel Modin, Niklas Johansen, Filip Soeskov Davidovski, Tor Biering-Sorensen, Jorn Carlsen, Jens Ulrik Staehr Jensen
Summary: This study compared the efficacy of amlodipine and bendroflumethiazide in treating hypertension in patients with chronic obstructive pulmonary disease (COPD). The results showed that amlodipine use was associated with a reduced risk of death, but had no significant effect on the risk of acute severe exacerbations or hospital admissions.
Article
Biochemistry & Molecular Biology
Peter Kamstrup, Ema Rastoder, Pernille Hogh Hellmann, Pradeesh Sivapalan, Emil List Larsen, Jorgen Vestbo, Charlotte Suppli Ulrik, Jens P. Goetze, Filip Krag Knop, Jens Ulrik Staehr Jensen
Summary: Synthetic corticosteroids are commonly used for their anti-inflammatory and immunosuppressant effects, although their association with venous thromboembolism remains unclear. A trial was conducted to investigate the effects of prednisolone on haemostasis in healthy men. The results showed that prednisolone did not affect clot formation but influenced certain prothrombotic markers and antithrombotic markers.
Article
Respiratory System
Claire Bradley, Panos Alexandris, David R. Baldwin, Richard Booton, Mike Darby, Claire J. Eckert, Rhian Gabe, Neil Hancock, Sam Janes, Martyn Kennedy, Jason Lindop, Richard D. Neal, Suzanne Rogerson, Bethany Shinkins, Irene Simmonds, Sara Upperton, Jorgen Vestbo, Philip A. J. Crosbie, Matthew E. J. Callister
Summary: Spirometry offered alongside LDCT screening can potentially identify cases of undiagnosed and misdiagnosed COPD. Future research should assess the downstream impact of these findings and determine the impact of co-delivering spirometry on other parameters of LDCT screening.
Meeting Abstract
Respiratory System
Y. Colak, B. G. Nordestgaard, P. Lange, J. Vestbo, S. Afzal
EUROPEAN RESPIRATORY JOURNAL
(2022)