tbuckley/cabot-search huggingface dataset:
Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype
Authors: Maura Massimino, Francesco Barretta, Chiara Dossena, Simone Minasi, Francesca Romana Buttarelli, Veronica Biassoni, Matilde Oriani, Elisabetta Schiavello, Marica Ficorilli, Olga Nigro, Bianca Pollo, Manila Antonelli, Vittoria Donofrio, Marco Maggioni, Marcel Kool, Emilia Pecori, Sabina Vennarini, Felice Giangaspero, Francesca Gianno, Alessandra Erbetta, Luisa Chiapparini, Roberto Luksch, Elena Barzanò, Cristina Meazza, Marta Podda, Filippo Spreafico, Monica Terenziani, Luca Bergamaschi, Andrea Ferrari, Michela Casanova, Stefano Chiaravalli, Giovanna Gattuso, Piergiorgio Modena, Simon Bailey, Loris De Cecco
Journal: Neuro-Oncology (2024)

Abstract Background We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, and MYC/MYCN amplification. Methods Patients over 3 years old received, after surgery, staging and histo-biological analysis, sequential high-dose-methotrexate(HD-MTX), high-dose-etoposide(HD-VP16), high-dose-cyclophosphamide(HD-Cyclo), and high-dose-carboplatin(HD-Carbo). Hyperfractionated-accelerated-radiotherapy–craniospinal(HART-CSI), administered twice daily 1.3 Gy-fractions reached a total dose tailored to the patients’ age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease, 39 Gy in other/older patients. Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy, respectively, but avoided if metastatic nodules were very big or patients were very young. Two courses of high-dose-thiotepa were delivered in case of not CR/PR after the pre-radiotherapy (RT) phase and in all M0 patients either—pre/post-HART. Subgrouping was performed where the tissue was available. Results Eighty-nine patients were enrolled, with a median age of 8.8 years, and a median follow-up of 136 months. Overall survival (OS) and event-free survival (EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively; 5/28 fatal events were not related to relapse(3 developed secondary malignancies). Sex, age less than 10 years, histological subtype, presence of MYC/MYCN amplification, reduction in CSI dose, omission of RT-boosts, implementation of myeloablative therapy, presence–absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P &amp;lt; .001).Subgrouping in 66/89 patients’ samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) versus groups 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. Conclusions This strategy, partly adopted in the ongoing SIOPE protocol, confirmed improved EFS and OS over previously reported outcomes in all high-risk categories; SHH tumors appeared the most aggressive.
Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia
Authors: Marta Santaliestra, Marta Garrote, María Soledad Noya, Manuel Pérez-Encinas, Alicia Senín, Raúl Pérez-López, Francisca Ferrer-Marín, Gonzalo Carreño-Tarragona, Gonzalo Caballero, Elena Magro, Patricia Vélez, Miguel Ángel Cortés Vázquez, Ana Moretó, Anna Angona, Irene Pastor-Galán, José María Guerra, Carmen García Hernández, María Isabel Mata, Ruth Stuckey, María Teresa Gómez-Casares, Laura Fox, Beatriz Cuevas, Valentín García-Gutiérrez, Ana Triguero, Eduardo Arellano-Rodrigo, Juan Carlos Hernández-Boluda, Alberto Alvarez-Larrán
Journal: Leukemia (2024)
VirID: Beyond Virus Discovery - An Integrated Platform for Comprehensive RNA Virus Characterization
Authors: Ziyue Yang, Yongtao Shan, Xue Liu, Guowei Chen, Yuanfei Pan, Qinyu Gou, Jie Zou, Zilong Chang, Qiang Zeng, Chunhui Yang, Jianbin Kong, Yanni Sun, Shaochuan Li, Xu Zhang, Wei-chen Wu, Chunmei Li, Hong Peng, Edward C Holmes, Deyin Guo, Mang Shi
Journal: Molecular Biology and Evolution (2024)

Abstract RNA viruses exhibit vast phylogenetic diversity and can significantly impact public health and agriculture. However, current bioinformatics tools for viral discovery from metagenomic data frequently generate false positive virus results, overestimate viral diversity, and misclassify virus sequences. Additionally, current tools often fail to determine virus–host associations, which hampers investigation of the potential threat posed by a newly detected virus. To address these issues we developed VirID, a software tool specifically designed for the discovery and characterization of RNA viruses from metagenomic data. The basis of VirID is a comprehensive RNA-dependent RNA polymerase database to enhance a workflow that includes RNA virus discovery, phylogenetic analysis, and phylogeny-based virus characterization. Benchmark tests on a simulated data set demonstrated that VirID had high accuracy in profiling viruses and estimating viral richness. In evaluations with real-world samples, VirID was able to identify RNA viruses of all types, but also provided accurate estimations of viral genetic diversity and virus classification, as well as comprehensive insights into virus associations with humans, animals, and plants. VirID therefore offers a robust tool for virus discovery and serves as a valuable resource in basic virological studies, pathogen surveillance, and early warning systems for infectious disease outbreaks.
Twin study identifies early immunological and metabolic dysregulation of CD8 <sup>+</sup> T cells in multiple sclerosis
Authors: Vladyslav Kavaka, Luisa Mutschler, Clara de la Rosa del Val, Klara Eglseer, Ana M. Gómez Martínez, Andrea Flierl-Hecht, Birgit Ertl-Wagner, Daniel Keeser, Martin Mortazavi, Klaus Seelos, Hanna Zimmermann, Jürgen Haas, Brigitte Wildemann, Tania Kümpfel, Klaus Dornmair, Thomas Korn, Reinhard Hohlfeld, Martin Kerschensteiner, Lisa Ann Gerdes, Eduardo Beltrán
Journal: Science Immunology (2024)

Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8 + T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8 + T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8 + T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8 + T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.
HDAC3 integrates TGF-β and microbial cues to program tuft cell biogenesis and diurnal rhythms in mucosal immune surveillance
Authors: Jianglin Zhang, Guoxun Wang, Junjie Ma, Yiran Duan, Samskrathi A. Sharma, Sarah Oladejo, Xianda Ma, Giselle Arellano, Robert C. Orchard, Tiffany A. Reese, Zheng Kuang
Journal: Science Immunology (2024)

The intestinal mucosal surface is directly exposed to daily fluctuations in food and microbes driven by 24-hour light and feeding cycles. Intestinal epithelial tuft cells are key sentinels that surveil the gut luminal environment, but how these cells are diurnally programmed remains unknown. Here, we show that histone deacetylase 3 (HDAC3) controls tuft cell specification and the diurnal rhythm of its biogenesis, which is regulated by the gut microbiota and feeding schedule. Disruption of epithelial HDAC3 decreases tuft cell numbers, impairing antihelminth immunity and norovirus infection. Mechanistically, HDAC3 functions noncanonically to activate transforming growth factor–β (TGF-β) signaling, which promotes rhythmic expression of Pou2f3 , a lineage-defining transcription factor of tuft cells. Our findings reveal an environmental-epigenetic link that controls the diurnal differentiation of tuft cells and promotes rhythmic mucosal surveillance and immune responses in anticipation of exogenous challenges.
Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study
Authors: Ashraf Z Badros, Laahn Foster, Larry D. Anderson, Chakra P. Chaulagain, Erin M Pettijohn, Andrew J Cowan, Caitlin L. Costello, Sarah Larson, Douglas W Sborov, Kenneth H Shain, Rebecca Silbermann, Nina Shah, Alfred Chung, Maria Krevvata, Huiling Pei, Sharmila Patel, Vipin Khare, Annelore Cortoos, Robin Carson, Thomas Lin, Peter M Voorhees
Journal: Blood (2024)
Landscape of biallelic DNMT3A mutant myeloid neoplasms
Authors: Naomi Kawashima, Yasuo Kubota, Carlos Bravo-Perez, Luca Guarnera, Nakisha D Williams, Arda Durmaz, Michaela Witt, Arooj Ahmed, Carmelo Gurnari, Jaroslaw P Maciejewski, Valeria Visconte
Journal: Journal of Hematology & Oncology (2024)
A Flow-based Truncated Denoising Diffusion Model for super-resolution Magnetic Resonance Spectroscopic Imaging
Authors: Siyuan Dong, Zhuotong Cai, Gilbert Hangel, Wolfgang Bogner, Georg Widhalm, Yaqing Huang, Qinghao Liang, Chenyu You, Chathura Kumaragamage, Robert K Fulbright, Amit Mahajan, Amin Karbasi, John A Onofrey, Robin A de Graaf, James S Duncan
Journal: Medical Image Analysis (2024)
Safety and efficacy of CRISPR-mediated genome ablation of VEGFA as a treatment for choroidal neovascularization in nonhuman primate eyes
Authors: Tzu-Ni Sin, Nicole Tng, Jack Dragoli, Sruthi Ramesh Kumar, Carol Villafuerte-Trisolini, Sook Hyun Chung, Lien Tu, Sophie M Le, Jae Ho Shim, Kathryn L Pepple, Resmi Ravindran, Imran H Khan, Ala Moshiri, Sara M Thomasy, Glenn Yiu
Journal: Molecular Therapy (2024)
Anti-amyloid treatment is broadly effective in neuronopathic mucopolysaccharidoses and synergizes with gene therapy in MPS-IIIA
Authors: Giaccio Marianna, Monaco Antonio, Galiano Laura, Parente Andrea, Borzacchiello Luigi, Rubino Riccardo, Klärner Frank-Gerrit, Killa Dennis, Perna Claudia, Piccolo Pasquale, Marotta Marcello, Pan Xuefang, Khijniak Marie, Siddique Ibrar, Schrader Thomas, Alexey V Pshezhetsky, Sorrentino Nicolina Cristina, Bitan Gal, Fraldi Alessandro
Journal: Molecular Therapy (2024)
GTSE1-driven ZEB1 Stabilization Promotes Pulmonary Fibrosis Through the Epithelial-to-mesenchymal Transition
Authors: Hee Jin, So-Yeon Park, Ji Eun Lee, Hangyeol Park, Michaela Jeong, Hyukjin Lee, Jaeho Cho, Yun-Sil Lee
Journal: Molecular Therapy (2024)
A framework for human evaluation of large language models in healthcare derived from literature review
Authors: Thomas Yu Chow Tam, Sonish Sivarajkumar, Sumit Kapoor, Alisa V Stolyar, Katelyn Polanska, Karleigh R McCarthy, Hunter Osterhoudt, Xizhi Wu, Shyam Visweswaran, Sunyang Fu, Piyush Mathur, Giovanni E Cacciamani, Cong Sun, Yifan Peng, Yanshan Wang
Journal: npj Digital Medicine (2024)

Abstract With generative artificial intelligence (GenAI), particularly large language models (LLMs), continuing to make inroads in healthcare, assessing LLMs with human evaluations is essential to assuring safety and effectiveness. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare across various medical specialties and addresses factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Our literature review of 142 studies shows gaps in reliability, generalizability, and applicability of current human evaluation practices. To overcome such significant obstacles to healthcare LLM developments and deployments, we propose QUEST, a comprehensive and practical framework for human evaluation of LLMs covering three phases of workflow: Planning, Implementation and Adjudication, and Scoring and Review. QUEST is designed with five proposed evaluation principles: Quality of Information, Understanding and Reasoning, Expression Style and Persona, Safety and Harm, and Trust and Confidence.
The catalogue of Mycobacterium tuberculosis mutations associated with drug resistance to 12 drugs in China from a nationwide survey: a genomic analysis
Authors: Shaojun Pei, Zexuan Song, Wei Yang, Wencong He, Xichao Ou, Bing Zhao, Ping He, Yang Zhou, Hui Xia, Shengfen Wang, Zhongwei Jia, Timothy M Walker, Yanlin Zhao
Journal: The Lancet Microbe (2024)
Dupilumab in atopic-dermatitis-like eczema associated with inborn errors of immunity: a nationwide study
Authors: Claire Guillemin, Nathalia Bellon, Marie Jachiet, Sébastien Barbarot, Emmanuelle Bourrat, Christine Chiaverini, Pierre Cougoul, Mikaël Ebbo, Mathilde Herber, Thomas Hubiche, Stéphanie Mallet, Marie Tauber, Vivien Béziat, Martin Castelle, Aurélie Du Thanh, Johathan Farhi, Claire Fieschi, Benjamin Fournier, Clément Gourguechon, Tamazoust Guiddir, Dan Lipsker, Nadia Raison-Peyron, Nicolas Garcelon, Morgane Cheminant, Felipe Suarez, Olivier Hermine, Stéphane Blanche, Despina Moshous, Nizar Mahlaoui, Benedicte Neven, Christine Bodemer, Romain Lévy, Laura Polivka
Journal: Journal of the American Academy of Dermatology (2024)
Engineered 3D human neurovascular model of Alzheimer’s disease to study vascular dysfunction
Authors: Georgios Pavlou, Sarah Spitz, Francesca Michela Pramotton, Alice Tsai, Brent M Li, Xun Wang, Olivia M Barr, Eunkyung Clare Ko, Shun Zhang, Savannah J Ashley, Anna Maaser-Hecker, Se Hoon Choi, Mehdi Jorfi, Rudolph E Tanzi, Roger D Kamm
Journal: Biomaterials (2024)
Assessing the built environment through photographs and its association with obesity in 21 countries: the PURE Study
Authors: Daniel J Corsi, Simone Marschner, Scott Lear, Perry Hystad, Annika Rosengren, Rosnah Ismail, Karen Yeates, Sumathi Swaminathan, Thandi Puoane, Chuangshi Wang, Yang Li, Sumathy Rangarajan, Iolanthé M Kruger, Jephat Chifamba, K Vidhu Kumar, Indu Mohan, Kairat Davletov, Galina Artamonov, Lia M Palileo-Villanueva, Nafiza Mat-Nasir, Katarzyna Zatonska, Aytekin Oguz, Ahmad Bahonar, Khalid F Alhabib, Afzalhussein Yusufali, Patricio Lopez-Jaramillo, Fernando Lanas, Agustina Galatte, Álvaro Avezum, Martin Mckee, Salim Yusuf, Clara K Chow
Journal: The Lancet Global Health (2024)
HIV incidence in people receiving government-subsidised pre-exposure prophylaxis in Australia: a whole-of-population retrospective cohort study
Authors: Nicholas A Medland, Hamish McManus, Benjamin R Bavinton, Doug Fraser, Michael W Traeger, Andrew E Grulich, Mark A Stoove, Skye McGregor, Jonathan M King, Dash Heath-Paynter, Rebecca J Guy
Journal: The Lancet HIV (2024)
Trends in avoidable mortality from cardiovascular diseases in the European Union, 1995–2020: a retrospective secondary data analysis
Authors: Avi Cherla, Ilias Kyriopoulos, Pauline Pearcy, Zoi Tsangalidou, Haris Hajrulahovic, Pavlos Theodorakis, Charlotte E Andersson, Mandeep R Mehra, Elias Mossialos
Journal: The Lancet Regional Health - Europe (2024)
Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024
Authors: Peter D Kirwan, Sarah Foulkes, Katie Munro, Dominic Sparkes, Jasleen Singh, Amanda Henry, Angela Dunne, Jean Timeyin, Sophie Russell, Jameel Khawam, Debbie Blick, Ashley D Otter, Nipunadi Hettiarachchi, Michelle D Cairns, Christopher H Jackson, Shaun Seaman, Colin S Brown, Ana Atti, Jasmin Islam, Andre Charlett, Daniela De Angelis, Anne M Presanis, Victoria J Hall, Susan Hopkins
Journal: Journal of Infection (2024)
Smart filtering facepiece respirator with self-adaptive fit and wireless humidity monitoring
Authors: Kangkyu Kwon, Yoon Jae Lee, Yeongju Jung, Ira Soltis, Yewon Na, Lissette Romero, Myung Chul Kim, Nathan Rodeheaver, Hodam Kim, Chaewon Lee, Seung-Hwan Ko, Jinwoo Lee, Woon-Hong Yeo
Journal: Biomaterials (2024)
PDCD4 deficiency in hepatocytes exacerbates nonalcoholic steatohepatitis through enhanced MHC class II transactivator expression
Authors: Kaikai Lu, Lei He, Zizhen Guo, Mengda Li, Xiaona Cheng, Sitong Liu, Tianyun Zhang, Qian Chen, Rong Zhao, Luyun Yang, Xiaodan Wu, Kexin Cheng, Peihai Cao, Litao Wu, Muhammad Shahzad, Minghua Zheng, Lianying Jiao, Yue Wu, Dongmin Li
Journal: Metabolism (2024)
Reductive stress—a common metabolic feature of obesity and cancer
Authors: Man Luo, Xiwen Ma, Jianping Ye
Journal: Acta Pharmaceutica Sinica B (2024)

Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD+ ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepared to address the issue with new insights published recently. NADH is used in production of NADPH, glutathione, ATP and heat in the classical biochemistry. In obesity, elevation of NADH/NAD+ ratio, likely from overproduction due to substrate overloading, has been found in the liver for insulin resistance and gluconeogenesis. New evidence demonstrates that the elevation may induce lipogenesis, purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and NRF2. In cancer cells, NADH/NAD+ elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial respiration. Alternatively, NRF2 overactivation from gene mutation represents another mechanism of NADH/NAD+ elevation from NADH production in the cancer cells. The elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential molecules. It appears that the causes of reductive stress are different between obesity and cancer, while its impact in anabolism is similar in the two conditions.
Maintaining myoprotein and redox homeostasis via an orally recharged nanoparticulate supplement potentiates sarcopenia treatment
Authors: Yang Yu, Xuehan Jiang, Tianhao Yu, Fangman Chen, Runnian Huang, Zhe Xun, Xiaoxun Wang, Xu Liu, Xiaochun Xie, Chen Sun, Yingxi Xu, Xiyan Liu, Huayi Sun, Xiaoyue Yuan, Chunhua Ma, Yibai Li, Xiaoyu Song, Difei Wang, Dan Shao, Xuetao Shi, Liu Cao
Journal: Biomaterials (2024)
Immunogenicity and Safety of SARS-CoV-2 Recombinant Spike Protein Vaccine in South African People Living With and Without HIV-1 Infection: A Phase 2 Randomised Trial
Authors: Chijioke Bennett, Zaheer Hoosain, Anthonet Koen, Umesh Lalloo, Cheryl Louw, Vongane Maluleke, Faeezah Patel, Gabriella Benade, Esme Louise Venter, Shirley Galbiati, Vivek Shinde, Shabir A Madhi
Journal: Journal of Infection (2024)
Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection
Authors: Linda Petrone, Daniela Peruzzu, Anna Maria Gerarda Altera, Andrea Salmi, Valentina Vanini, Gilda Cuzzi, Andrea Coppola, Valeria Mellini, Gina Gualano, Fabrizio Palmieri, Sudhasini Panda, Bjoern Peters, Alessandro Sette, Cecilia Lindestam Arlehamn, Delia Goletti
Journal: Journal of Infection (2024)
Pooled analysis of the MANTICO2 and MONET randomized controlled trials comparing drug efficacy for early treatment of COVID-19 during Omicron waves
Authors: Valentina Mazzotta, Fulvia Mazzaferri, Simone Lanini, Massimo Mirandola, Alessandro Cozzi Lepri, Alessandra Vergori, Alessia Savoldi, Andrea Santoro, Gaia Maccarrone, Ilaria Mastrorosa, Omar Simonetti, Federico De Zottis, Emanuele Nicastri, Giulia Rosini, Laura Rovigo, Lorenzo Tavernaro, Loredana Sarmati, Carlo Tascini, Enrico Girardi, Anna Maria Cattelan, Andrea Antinori, Evelina Tacconelli
Journal: Journal of Infection (2024)
<i>PHF6</i> mutations in chronic myelomonocytic leukemia identify a unique subset of patients with distinct phenotype and superior prognosis
Authors: Ayalew Tefferi, Saubia Fathima, Ali Khalid A. Alsugair, Fnu Aperna, Anuya Natu, Maymona G. Abdelmagid, Clifford M. Csizmar, Mark Gurney, Terra L. Lasho, Christy M. Finke, Abhishek A. Mangaonkar, Aref Al‐Kali, Animesh Pardanani, Kaaren K. Reichard, Rong He, Naseema Gangat, Mrinal M. Patnaik
Journal: American Journal of Hematology (2024)

Abstract The current study was inspired by observations from exploratory analyses of an institutional cohort with chronic myelomonocytic leukemia (CMML; N = 398) that revealed no instances of blast transformation in the seven patients with plant homeodomain finger protein 6 ( PHF6 ) mutation ( PHF6 MUT ). A subsequent Mayo Clinic enterprise‐wide database search identified 28 more cases with PHF6 MUT . Compared with their wild‐type PHF6 counterparts ( PHF6 WT ; N = 391), PHF6 MUT cases ( N = 35) were more likely to co‐express TET2 (89% vs. 45%; p &lt; .01), RUNX1 (29% vs. 14%; p = .03), CBL (14% vs. 2%; p &lt; .01), and U2AF1 (17% vs. 6%; p = .04) and less likely SRSF2 (23% vs. 45%; p &lt; .01) mutation. They were also more likely to display loss of Y chromosome (LoY; 21% vs. 2%; p &lt; .01) and platelets &lt;100 × 10 9 /L (83% vs. 51%; p &lt; .01). Multivariable analysis identified PHF6 MUT (HR 0.28, 95% CI 0.15–0.50) and DNMT3A MUT (HR 5.8, 95% CI 3.3–10.5) as the strongest molecular predictors of overall survival. The same was true for blast transformation‐free survival with corresponding HR (95% CI) of 0.08 (0.01–0.6) and 9.5 (3.8–23.5). At median 20 months follow‐up, blast transformation was documented in none of the 33 patients with PHF6 MUT / DNMT3A WT but in 6 (32%) of 19 with DNMT3A MUT and 74 (20%) of 374 with PHF6 WT / DNMT3A WT ( p &lt; .01). The specific molecular signatures sustained their significant predictive performance in the context of the CMML‐specific molecular prognostic model (CPSS‐mol). PHF6 MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.
Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma
Authors: Nicole Filipow, Stephen Turner, Helen L Petsky, Anne B Chang, Thomas Frischer, Stanley Szefler, Francoise Vermeulen, Sanja Stanojevic
Journal: Thorax (2024)

Aims Spirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the variability of forced expiratory volume in 1 s (FEV 1 ) in children with symptomatically well-controlled asthma by applying three different methods of expressing change in FEV 1 over 3-month intervals. Methods Data from five longitudinal studies of children with asthma which measured FEV 1 at 3-month intervals over 6 or 12 months were used. We analysed paired FEV 1 measurements when asthma symptoms were controlled. The variability of FEV 1 % predicted (FEV 1 %), FEV 1 z-score (FEV 1 z) and conditional z score for change (Zc) in FEV 1 was expressed as limits of agreement. Results A total of 881 children had 3338 FEV 1 measurements on occasions when asthma was controlled; 5184 pairs of FEV 1 measurements made at 3-month intervals were available. Each unit change in FEV 1 z score was equivalent to a Zc 1.45 and an absolute change in FEV 1 % of 11.6%. The limits of agreement for change in FEV 1 % were −20 and +21, absolute change in FEV 1 z were −1.7 and +1.7 and Zc were −2.6 and +2.1. Regression to the mean and increased variability in younger children were present for change in FEV 1 % and FEV 1 z comparisons, but not Zc. Conclusion Given the wide limits of agreement of paired FEV 1 measurements in symptomatically well-controlled children, asthma treatment should primarily be guided by symptoms and not by a change in spirometry.