Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

呼出气一氧化氮医学哮喘生物标志物内科学恶化过敏免疫学肺活量测定生物化学化学

作者

Bo Ding,Stephanie Chen,Eleni Rapsomaniki,Anna Quinton,W. James Cook,Helen K. Reddel,Alberto Papi,Ricardo del Olmo,Gary P. Anderson,Helen K. Reddel,Marcelo Fouad Rabahi,Andrew McIvor,Mohsen Sadatsafavi,Ulla Møller Weinreich,Pierre–Régis Burgel,Gilles Devouassoux,Alberto Papi,Hiromasa Inoue,Adrián Rendón,Maarten van den Berge,Richard Beasley,Àlvar Agustí García-Navarro,Rosa Faner,José Olaguibel Rivera,Christer Janson,Magdalena Bilińska-Izydorczyk,Malin Fagerås,Titti Fihn-Wikander,Stefan Franzén,Christina Keen,Kristoffer Ostridge,James D. Chalmers,Timothy Harrison,Ian Pavord,David Price,Adnan Azim,Laura Belton,François-Xavier Blé,Clement Erhard,Kerry Gairy,Rod Hughes,Glenda Lassi,Hana Müllerová,Eleni Rapsomaniki,Ian Scott,Bradley E. Chipps,Stephanie A. Christenson,Barry J. Make,Erin Tomaszewski,Ricardo del Olmo,Gabriel Benhabib,Xavier Bocca Ruiz,Raúl Lisanti,Gustavo Marino,Walter Mattarucco,Juan Nogueira,Maria Parody,Pablo Pascale,Pablo Rodriguez,Damian Silva,Graciela Svetliza,Carlos Victorio,Roxana Willigs Rolon,Anahí Yáñez,Helen K. Reddel,Stuart Baines,Simon Bowler,Peter Bremner,Sheetal Bull,Patrick Carroll,Mariam Chaalan,Claude S. Farah,Gary Hammerschlag,Kerry Hancock,Zinta Harrington,Gregory Katsoulotos,Joshua Kim,David Langton,Donald Lee,Matthew Peters,Lakshman Prassad,Dimitar Sajkov,Francis Santiago,Frederick Graham Simpson,Sze Tai,Paul S. Thomas,Peter Wark,Marcelo Fouad Rabahi,José Eduardo Delfini Cançado,Thúlio Cunha,Marina Andrade Lima,Alexandre Pinto Cardoso,J. Mark FitzGerald,Andrew McIvor,Syed Anees,John Bertley,Alan Bell,Amarjit Cheema,Guy Chouinard,Michael Csanadi,Anil Dhar,Ripple Dhillon,David Kanawaty,Allan Kelly,William Killorn,Daniel Landry,Robert Luton,Piush J. Mandhane,Bonavuth Pek,Robert Petrella,Daniel Stollery,Chen Wang,Meihua Chen,Yan Chen,Wei Gu,Kim Ming Christopher Hui,Manxiang Li,Shiyue Li,Lijun Ma,Guangyue Qin,Weidong Song,Wei Tan,Yijun Tang,Tan Wang,Fuqiang Wen,Feng Wu,PingChao Xiang,Zuke Xiao,Shengdao Xiong,Jinghua Yang,Jingping Yang,Caiqing Zhang,Min Zhang,Ping Zhang,Wei Zhang,Xiaohe Zheng,Dan Zhu,Carlos Matiz Bueno,Fabio Bolívar Grimaldos,Alejandra Cañas,Dora Molina de Salazar,Ulla Møller Weinreich,Elisabeth Bendstrup,Ole Hilberg,Carsten Kjellerup,Pierre–Régis Burgel,Gilles Devouassoux,Chantal Rahérison,Philippe Bonniaud,Olivier Brun,C. Chouaïd,Françis Couturaud,J. de Blic,D. Debieuvre,Dominique Delsart,Axelle Demaegdt,P. Démoly,A. Deschildre,Carole Egron,Lionel Falchero,F. Goupil,Romain Kessler,P. Le Roux,Pascal Mabire,Guillaume Mahay,Stéphanie Martinez,B. Melloni,Laurent Moreau,Emilie Riviere,Pauline Roux-Claudé,Michel Soulier,Guillaume Vignal,Azzedine Yaici,Robert Bals,Sven Philip Aries,Ekkehard Beck,Andreas Deimling,Jan Feimer,Vera Grimm-Sachs,Gesine Groth,Felix J.F. Herth,Gerhard Hoheisel,Frank Kanniess,Thomas Lienert,Silke Mronga,Jörg Reinhardt,Christian Schlenska,Christoph Stolpe,Ishak Teber,Hartmut Timmermann,Thomas Ulrich,Peter Velling,Sabina Wehgartner-Winkler,Juergen Welling,Ernst-Joachim Winkelmann,Alberto Papi,Carlo Barbetta,Fulvio Braido,Vittorio Cardaci,Enrico Clini,Maria Teresa Costantino,Giuseppina Cuttitta,Mario Di Gioacchino,Alessandro G. Fois,Maria Pia Foschino Barbaro,Enrico Gammeri,Riccardo Inchingolo,Federico Lavorini,Antonio Molino,Eleonora Nucera,Vincenzo Patella,Alberto Pesci,Fabio Luigi Massimo Ricciardolo,Paola Rogliani,Riccardo Sarzani,Carlo Vancheri,Rigoletta Vincenti,Hiromasa Inoue,Takeo Endo,Masaki Fujita,Yu Hara,Takahiko Horiguchi,Keita Hosoi,Yumiko Ide,Minehiko Inomata,Koji Inoue,Sumito Inoue,Motokazu Kato,Masayuki Kawasaki,Tomotaka Kawayama,Toshiyuki Kita,Kanako Kobayashi,Hiroshi Koto,Koichi Nishi,Junpei Saito,Yasuo Shimizu,Toshihiro Shirai,Naruhiko Sugihara,Ken-ichi Takahashi,Hiroyuki Tashimo,Keisuke Tomii,Takashi Yamada,Masaru Yanai,Adrián Rendón,Ruth Cerino Javier,Alfredo Domínguez Peregrina,Marco Fernández Corzo,Efraín Montano Gonzalez,Alejandra Ramírez‐Venegas,Maarten van den Berge,Willem Boersma,Remco S. Djamin,Michiel Eijsvogel,Frits Franssen,Martijn Goosens,Lidwien Graat‐Verboom,Johannes in 't Veen,Rob Janssen,Kim Kuppens,Mario van de Ven,Per Bakke,Ole Petter Brunstad,Gunnar Einvik,Kristian Jong Høines,Alamdar Khusrawi,Torbjorn Oien,Ho Joo Yoon,Yoon‐Seok Chang,Young Joo Cho,Yong Il Hwang,Woo Jin Kim,Young‐Il Koh,Byung‐Jae Lee,Kwan-Ho Lee,Sang Pyo Lee,Yong Chul Lee,Seong Yong Lim,Kyung Hun Min,Yeon‐Mok Oh,Choon‐Sik Park,Hae‐Sim Park,Heung‐Woo Park,Chin Kook Rhee,Hyoung-Kyu Yoon,Àlvar Agustí García-Navarro,José Olaguibel Rivera,Rubén Andújar Espinosa,Laura Anoro,María Buendía García,Paloma Campo Mozo,Sergio E. Campos,Francisco Casas Maldonado,Manuel Castilla Martínez,Carolina Cisneros Serrano,Lorena Comeche Casanova,Dolores Corbacho,Félix del Campo,José Echave-Sustaeta,G. Francisco Corral,Pedro Gamboa Setién,Marta García‐Clemente,Ignacio García Núñez,Jose García Robaina,Mercedes García Salmones,José M. Marı́n,Marta Núñez Fernández,Sara Núñez Palomo,Luis Pérez de Llano,Ana Pueyo Bastida,Ana Rañó,José Miguel Rodríguez González-Moro,Albert Roger Reig,José Velasco Garrido,Christer Janson,Dan Curiac,Cornelia Lif-Tiberg,Anders Luts,Lennart Råhlen,Stefan Rustscheff,Timothy Harrison,Frances Adams,Drew Bradman,Emma Broughton,John Cosgrove,Patrick Flood-Page,Elizabeth Fuller,David Hartley,Keith Hattotuwa,Gareth R. Jones,Keir Lewis,Lorcan McGarvey,Alyn H. Morice,Preeti Pandya,Manish Patel,Kay Roy,Ramamurthy Sathyamurthy,S. Thiagarajan,Alice Turner,Jørgen Vestbo,Wisia Wedzicha,Tom Wilkinson,Pete Wilson,Bradley E. Chipps,Lo’Ay Al-Asadi,James D. Anholm,Francis Averill,Sandeep Bansal,Alan P. Baptist,Colin Campbell,Michael Campos,Gretchen Crook,Samuel DeLeon,Alain Eid,Ellen Epstein,Stephen Fritz,Hoadley Harris,Mitzie Hewitt,Fernando Holguín,Golda Hudes,Richard Jackson,Alan Kaufman,David Kaufman,Ari Klapholz,Harshavardhan Krishna,Daria Lee,Robert Y. Lin,Diego Maselli-Caceres,Vinay Mehta,James N. Moy,Ugo Nwokoro,Purvi Parikh,Sudhir Parikh,Frank Perrino,James Ruhlmann,Catherine Sassoon,Russell A. Settipane,Daniel Sousa,Peruvemba Sriram,Richard Wachs

出处

期刊：The Journal of Allergy and Clinical Immunology: In Practice [Elsevier]
日期：2023-12-22 卷期号：12 (4): 970-982

链接

nih.govdoi.org

标识

DOI：10.1016/j.jaip.2023.12.021

摘要

ABSTRACT

BACKGROUND

Many patients with asthma have Type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide (FeNO) levels.

OBJECTIVE

To assess disease burden in relation to Type-2 inflammatory biomarker status (history of allergy, blood EOS count, and FeNO level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329).

METHODS

Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test (ACT) score (uncontrolled <20, controlled ≥20) and/or ≥1 severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and FeNO level), symptom burden (ACT score, modified Medical Research Council [mMRC] dyspnea scale), health status (St George's Respiratory Questionnaire [SGRQ]), exacerbations, and healthcare resource utilization were assessed.

RESULTS

Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among uncontrolled asthma: 196 (44%) had ≥2 positive biomarkers; 187 (42%) had one positive biomarker; 325 (73%) had low blood EOS; and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (ACT score 14.9–16.6), impaired health status (SGRQ total score 46.7–49.4), clinically important breathlessness (mMRC grade ≥2 in 47.3–57.1%), and ≥1 severe exacerbation (70.6–76.2%).

CONCLUSION

Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low Type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed.

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