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Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

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SAGE PUBLICATIONS LTD
DOI: 10.1177/2040622315609251

关键词

ACOS; anti-CRTh2; anti-IL5; anti-IL-13; anti-IL4R; asthma; biomarker; COPD; corticosteroid; eosinophil

资金

  1. Medical Research Council [G0601369] Funding Source: Medline
  2. MRC [G0601369] Funding Source: UKRI
  3. National Institute for Health Research [NF-SI-0512-10018] Funding Source: researchfish

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The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.

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Bartholomew, A. Bataineh, D. Beeby, S. Bell, N. Broughton, C. Buckman, C. Calver, J. Campbell, C. Chabo, M. Chowdhury, K. Cooke, N. Deole, C. Driscoll, A. Elden, H. Eldew, N. Entwistle, F. Farnworth, R. Francis, E. Galloway, M. Garfield, A. Ghosh, G. Gray, P. Greenfield, M. Hadjiandreou, H. Hewer, M. S. Hossain, R. Howard-Griffin, A. Islam, E. Jamieson, Z. Jiao, K. Johannessen, S. Han Lee, R. Lewis, R. Lloyd, L. Andrew Mabelin, D. Morris, S. Nallapareddy, H. C. Ooi, R. Osagie, C. Parkinson, H. Patel, H. Prowse, B. Purewal, P. Ridley, V. Rivers, J. Rosier, S. Sharma, A. Sheik, R. Skelly, R. Smith, R. Sreenivasan, A. Taylor, P. Tovey, A. Turner, K. Turner, K. Vithian, J. Zhixin, E. Potton, N. Jain, A. Khadar, P. Morgan, J. Penny, E. Tatam, S. Abbasi, D. Acharya, A. Acosta, L. Ahmed, S. Ali, M. Alkhusheh, V. Amosun, A. Arter, M. Babi, J. Bacon, K. Bailey, N. Balachandran, S. Bandyopadhyam, L. Banks, J. Barla, T. Batty, S. Bax, A. Belgaumkar, G. Benison-Horner, A. Boles, N. Broomhead, E. Cetti, C. Chan, I. Chaudhry, D. Chudgar, J. Clark, S. Clueit, S. Collins, E. Combes, G. Conway, O. Curtis, M. Das, M. Daschel, S. Davies, E. Potton, S. Abbasi, D. Acharya, A. Acosta, L. Ahmed, S. Ali, M. Alkhusheh, V. Amosun, A. Arter, M. Babi, J. Bacon, K. Bailey, N. Balachandran, S. Bandyopadhyam, L. Banks, J. Barla, T. Batty, S. Bax, A. Belgaumkar, G. Benison-Horner, A. Boles, N. Broomhead, E. Cetti, C. Chan, I. Chaudhry, D. Chudgar, J. Clark, S. Clueit, S. Collins, E. Combes, G. Conway, O. Curtis, M. Das, M. Daschel, S. Davies, A. Day, M. Dhar, K. Diaz-Pratt, C. Dragan, H. Dube, V. Duraiswamy, J. Elias, A. Ellis, T-Y Ellis, J. Emmanuel, A. Engden, Y. Fahmay, B. Field, K. Fishwick, U. Ganesh, C. Gilbert, T. Giokanini-Royal, E. Goudie, S. Griffith, S. Gurung, R. Habibi, C. Halevy, A. Haqiqi, R. Hartley, A. Hayman, J. Hives, M. Horsford, S. Hughes, C. Hui, R. Hussain, C. Iles, L. Jackson, A. James, D. Jayaram, E. Jessup-Dunton, T. Joefield, N. Khan, W. Kieffer, E. Knox, V. Kumar, R. Kumar, V. Kurmars, H. Lafferty, F. Lamb, R. Layug, N. Leitch, W. Lim, U. Limbu, R. Loveless, M. Mackenzie, N. Maghsoodi, S. Maher, M. Maljk, I. Man, N. McCarthy, B. Mearns, C. Mearns, K. Morgan-Jones, G. Mortem, G. Morton, B. Moya, G. Murphy, S. Mutton, A. Myers, T. Nasser, J. Navaratnam, S. Nazir, S. Nepal, K. Nimako, L. Nimako, C. O'Connor, A. Patel, K. Patel, V. Phongsathorn, P. A. Pillai, M. Poole, N. Qureshi, S. Ranjan, A. Rehman, T. Samuels, E. Scott, G. Sekadde, A. Sharma, G. Sharp, S. Shotton, O. Simmons, P. Singh, S. Smith, K. Sri Paranthamen, S. Suresh, K. Thevarajah, L. Thomas, H. Timms, N. Tomasova, S. Tucker, S. Vara, C. Vaz, S. Weller, J. White, M. Wilde, I. Wilkinson, C. Williams, M. Win, D. Woosey, D. Wright, M. Roberts, K. Amsha, G. Cox, N. Downer, D. Hodgson, J. Hutchinson, S. Kalsoom, A. Molyneux, Z. Noor, L. Allsop, T. Brear, P. Buckley, L. Dunn, M. Gill, C. Goodwin, C. Heeley, M. Holmes, R. Holmes, E. Langthorne, C. Moulds, D. Nash, J. Rajeswary, S. Shelton, K. Slack, S. Smith, B. Valeria, I. Wynter, M. Yanney, I. Ynter, J. Azam, K. J. Chandler, M. Abdelfattah, A. Abung, J. Anderson, P. Antill, S. Appleby, P. Armtrong, T. Berriman, D. Bull, O. Clayton, A. Corlett, D. Crocombe, S. Davies, K. Elliott, L. Fahel, J. Ghosh, N. Gott, D. Greenwood, T. Holder, P. Inns, W. Lea, E. Lindsay, K. Mack, N. Marshall, S. McMeekin, T. Momoniat, P. Nikolaos, ,

Summary: Azithromycin has been proposed as a treatment for COVID-19 due to its immunomodulatory actions. However, a study in hospitalized patients with COVID-19 showed that azithromycin did not improve survival or other clinical outcomes. Its use should be restricted to patients with a clear antimicrobial indication.

LANCET (2021)

Article Critical Care Medicine

The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study

P. Jane McDowell, Sarah Diver, Freda Yang, Catherine Borg, John Busby, Vanessa Brown, Rahul Shrimanker, Ciara Cox, Christopher E. Brightling, Rekha Chaudhuri, Ian D. Pavord, Liam G. Heaney

Summary: This study investigated the inflammatory phenotype and physiological characteristics of exacerbation events in patients with severe eosinophilic asthma treated with mepolizumab. The results showed that exacerbations on mepolizumab could be divided into non-eosinophilic events and eosinophilic events, which could be differentiated using FeNO as a marker. This challenges the routine use of oral corticosteroids for all asthma exacerbation events on mepolizumab, and emphasizes the importance of profiling the inflammatory phenotype for better management.

LANCET RESPIRATORY MEDICINE (2021)

Review Pharmacology & Pharmacy

The pharmacology of the prostaglandin D2 receptor 2 (DP2) receptor antagonist, fevipiprant

Chris Brightling, Swarupa Kulkarni, Bart N. Lambrecht, David Sandham, Markus Weiss, Pablo Altman

Summary: Fevipiprant, a DP2 receptor antagonist, regulates allergic and non-allergic asthma inflammatory cascade. Despite demonstrating efficacy in Phase II clinical trials, further clinical development in asthma was not supported in a worldwide Phase III clinical trial program.

PULMONARY PHARMACOLOGY & THERAPEUTICS (2021)

Article Medicine, Research & Experimental

Alterations in T and B cell function persist in convalescent COVID-19 patients

Halima A. Shuwa, Tovah N. Shaw, Sean B. Knight, Kelly Wemyss, Flora A. McClure, Laurence Pearmain, Ian Prise, Christopher Jagger, David J. Morgan, Saba Khan, Oliver Brand, Elizabeth R. Mann, Andrew Ustianowski, Nawar Diar Bakerly, Paul Dark, Christopher E. Brightling, Seema Brij, Timothy Felton, Angela Simpson, John R. Grainger, Tracy Hussell, Joanne E. Konkel, Madhvi Menon

Summary: The study describes the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3-6 months of convalescence. The alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients, while T cells from convalescent patients displayed continued alterations. Different subgroups of convalescent patients were identified based on distinct lymphocyte phenotypes, with one subgroup associated with poorer clinical outcomes.
Article Medicine, General & Internal

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Peter W. Horby, Martin J. Landray

Summary: Tocilizumab improved survival and other clinical outcomes in hospitalized COVID-19 patients with hypoxia and systemic inflammation, regardless of the level of respiratory support, and provided additional benefits on top of systemic corticosteroid therapy.

LANCET (2021)

Article Biochemical Research Methods

Volatile organic compounds in a headspace sampling system and asthmatics sputum samples

Rosa Peltrini, Rebecca L. Cordell, Wadah Ibrahim, Michael J. Wilde, Dahlia Salman, Amisha Singapuri, Beverley Hargadon, Christopher E. Brightling, C. L. Paul Thomas, Paul S. Monks, Salman Siddiqui

Summary: This study characterized the background signal generated from a headspace sampling system in a clinical site, evaluated intra- and inter-day variation of background VOC, and investigated the impact of a sample itself upon commonly reported background VOC using sputum headspace samples from severe asthmatics. The results indicated no significant intra- or inter-day variations in compound levels and underscored the need to consider the background signal derived from the headspace sampling system when developing and validating headspace biomarker signatures using clinical samples.

JOURNAL OF BREATH RESEARCH (2021)

Article Medicine, General & Internal

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

Betty Raman, Mark Philip Cassar, Elizabeth M. Tunnicliffe, Nicola Filippini, Ludovica Griffanti, Fidel Alfaro-Almagro, Thomas Okell, Fintan Sheerin, Cheng Xie, Masliza Mahmod, Ferenc E. Mozes, Adam J. Lewandowski, Eric O. Ohuma, David Holdsworth, Hanan Lamlum, Myles J. Woodman, Catherine Krasopoulos, Rebecca Mills, Flora A. Kennedy McConnell, Chaoyue Wang, Christoph Arthofer, Frederik J. Lange, Jesper Andersson, Mark Jenkinson, Charalambos Antoniades, Keith M. Channon, Mayooran Shanmuganathan, Vanessa M. Ferreira, Stefan K. Piechnik, Paul Klenerman, Christopher Brightling, Nick P. Talbot, Nayia Petousi, Najib M. Rahman, Ling-Pei Ho, Kate Saunders, John R. Geddes, Paul J. Harrison, Kyle Pattinson, Matthew J. Rowland, Brian J. Angus, Fergus Gleeson, Michael Pavlides, Ivan Koychev, Karla L. Miller, Clare Mackay, Peter Jezzard, Stephen M. Smith, Stefan Neubauer

Summary: The study found that COVID-19 patients discharged from the hospital still experience breathlessness, fatigue, cognitive impairment, and mental health issues. MRI revealed abnormalities in multiple organs, which were linked to inflammation and severity of acute illness.

ECLINICALMEDICINE (2021)

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