Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions

New Xpert MTB/XDR: added value and future in the field

Arnold Bainomugisa, Christopher Gilpin, Christopher Coulter, Ben J. Marais
European Respiratory Journal 2020 56: 2003616; DOI: 10.1183/13993003.03616-2020
Arnold Bainomugisa
1Queensland Mycobacterium Reference Laboratory, Pathology Queensland, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Arnold.bainomugisa@health.qld.gov.au
Christopher Gilpin
2International Organization for Migration, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Coulter
1Queensland Mycobacterium Reference Laboratory, Pathology Queensland, Brisbane, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ben J. Marais
3The Marie Bashir Institute for Infectious Diseases and Biosecurity (MBI), University of Sydney, Sydney, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Xpert MTB/XDR is a new rapid molecular test for drug resistant tuberculosis https://bit.ly/3l2t4op

Introduction

The recent launch of the new Xpert MTB/XDR assay (Cepheid Inc., Sunnyvale, CA, USA) by the Foundation for Innovative New Diagnostics [1] was widely welcomed by the tuberculosis (TB) community, given the critical need for new and better diagnostics to guide the treatment of drug resistant tuberculosis (DR-TB). Xpert MTB/XDR detects resistance to isoniazid (target genes: inhA promoter, katG, fabG1, oxyR-aphC intergenic region), ethionamide (inhA promoter), fluoroquinolones (gyrA and gyrB), and second-line injectables (rrs and eis promoter) and is positioned as an add-on or “reflex test” in patients with rifampicin resistance detected by Xpert MTB/RIF or Ultra [2, 3].

The spread of DR-TB strains threatens recent gains in global TB control [4], with evidence that the majority of patients with rifampicin resistant (RR-TB) or multi-drug resistant (MDR-TB) TB acquire their infection through person-to-person transmission. Inadequate diagnostic and treatment options have hampered an effective global response. The use of Xpert MTB/RIF as a rapid and sensitive frontline TB detection test has been shown to improve patient outcomes and is cost effective [5], but data for RR/MDR-TB are lacking; partly hampered by the poor treatment options available in the past. We provide a brief overview of the perceived benefits, limitations and remaining challenges with the new test (table 1).

View this table:
  • View inline
  • View popup
TABLE 1

Overview of perceived benefits and limitations of the new Xpert MTB/XDR assay

Benefits/added value

Existing Xpert MTB/RIF and Ultra assays only detect rifampicin resistance, which prevents RR/MDR-TB differentiation and provides no further treatment guidance. Expanded drug susceptibility testing (DST) is required to guide optimised RR/MDR-TB treatment, which is essential to improve patient outcome, reduce the duration of infectiousness and limit the risk of drug resistance amplification. Drug resistance amplification is a particular concern with the promotion of new bedaquiline containing all-oral short-course regimens [6]. Culture and phenotypic DST is the current gold standard, but is rarely available in TB endemic settings. In the absence of phenotypic DST, molecular techniques such as line probe assays (e.g. MTBDRsl) are recommended. However, these assays have poor sensitivity in sputum smear negative patients and require specialised infrastructure that is not available outside well-equipped central laboratories [7].

A key benefit of the Xpert MTB/XDR assay is that it requires the same sample processing steps as Xpert MTB/RIF and Ultra, which have demonstrated robustness in field conditions. The familiarity, portability and user-friendly format of the Xpert MTB/XDR assay makes it attractive for decentralisation. It also has minimal biosafety requirements, offers rapid turn-around times and can be operated by health personnel with limited training. Results are available in less than 90 min, compared to several weeks with traditional culture-based DST or several days with line probe assays performed at a central laboratory level.

Rapid fluoroquinolone resistance determination is critical, given its pivotal role in RR/MDR-TB treatment and importance in protecting companion second-line drugs like bedaquiline [8, 9]. The 2020 World Health Organization (WHO) recommendations for the treatment of RR/MDR-TB recognise the key contribution of later generation fluoroquinolones in shorter duration all-oral regimens [6]. In initial evaluations, Xpert MTB/XDR was able to identify fluoroquinolone resistance with 91.4% sensitivity and 98.5% specificity compared to phenotypic DST [3]. This is close to WHO targets for diagnostic sensitivity (>95%) and specificity (>98%) of rapid DST [10]. However, the assays' diminished ability to detect mutations (S91P/A90V, D94A) causing low level fluoroquinolone resistance, especially in hetero-resistant strain populations [3], is a concern and highlights the need for further careful monitoring of discrepant geno/phenotypic DST results in different settings.

Limitations/challenges

Apart from cartridge costs, the new assay requires GeneXpert instrument modules with 10 colour multiplex technology, hence the current Xpert instruments will require major refitting and recalibration. This presents a significant challenge, particularly to low- and middle-income countries that may need to shoulder additional shipping and servicing expenses. Although the assay is attractive for decentralisation, its optimal placement in different settings needs to be guided by local diagnostic algorithms, as well as local feasibility and cost-effectiveness. Poor infrastructure, cost and logistical constraints will limit point-of-care placement in most high burden countries [5]. Another imperative to consider is the ability to provide adequate RR/MDR-TB treatment in all settings with diagnostic access [11]. In recent years, MDR-TB programme up-scaling and increased access to high quality second-line TB drugs through the Global Drug Facility successfully narrowed the RR/MDR-TB diagnosis–treatment gap resulting from Xpert MTB/RIF roll-out.

Isoniazid resistance is a key precursor to MDR-TB [12, 13], which indicates the need for improved detection and appropriate treatment of non-MDR isoniazid resistant strains that are not detected by Xpert MTB/RIF or Ultra. Few countries have laboratory capacity to assess isoniazid resistance [14], which the new assay has excellent capacity to detect; sensitivity 98.3% and specificity 95% compared to phenotypic DST [3]. This is important given that WHO recommends a modified treatment regimen for these patients to improve treatment outcomes and to limit MDR-TB generation [6]. However, with placement as a “reflex test” this ability will not be utilised and it would have been of greater value if isoniazid and rifampicin resistance testing was combined in a frontline diagnostic. It should be noted that isoniazid resistance (including high-level resistance) can be conferred by mutations in genes not targeted by the Xpert MTB/XDR, such as aphC, ndh, mshA and mymA. These mutations are uncommon, but their geographic distribution has not been assessed. Furthermore, their frequency may increase with diagnostic selection, a phenomena observed in Swaziland where rifampicin resistance mediated by mutation outside the resistance hotspot has become common [15].

Ethionamide has chemical similarity to isoniazid and shares a final common pathway targeting mycolic acid biosynthesis. Ethionamide resistance is evaluated through identification of mutations in the inhA promoter region known to confer co-resistance to isoniazid (low level) and ethionamide (high level) [16, 17]. However, there are additional genes (ethA, ethR, ndh and mshA) and unknown mechanisms that also confer resistance [18]. Since phenotypic ethionamide DST is lacking in most settings [19], genotypic approaches are valuable for identification of ethionamide resistance. Although new WHO guidelines classify ethionamide as a group C drug that is only considered when newer/re-purposed agents are not available [6], it remains a potent agent to consider and knowledge of inhA promoter mutations also guide potential use of high dose isoniazid [20].

Given evidence for improved treatment outcomes and reduced adverse effects, new RR/MDR-TB treatment guidelines prioritise the use of oral agents (e.g. bedaquiline, linezolid, clofazimine, cycloserine) [6, 21]. Therefore, the detection of resistance to injectable agents has become less relevant. However, knowledge of susceptibility to injectable drugs remains useful in instances where an effective all-oral treatment regimen cannot be assembled and if adequate measures to monitor adverse effects are in place [22]. With positioning as a “reflex test”, minimum sample volume to permit follow-on testing and conditions for sample storage will have to be critically evaluated to streamline logistics and maintain good performance.

Future in the field

As with the implementation of Xpert MTB/RIF and Ultra, future studies should assess the performance of Xpert MTB/XDR in different geographical settings and with different clinical specimens. This is particularly important in people living with HIV and in children, in whom extra-pulmonary and paucibacillary disease are more common [23, 24]. Samples such as fine needle aspiration biopsies may deliver excellent yields, as for Xpert MTB/RIF [25], while reduced sensitivity is expected in cerebrospinal fluid, although a positive test will have major clinical significance [26]. The new assay demonstrated comparable sensitivity to Xpert MTB/RIF in pulmonary samples, but its performance using extra-pulmonary samples has not been evaluated [3, 27]. The limit of detection for Mycobacterium tuberculosis by Xpert MTB/XDR (71.9 CFU·mL−1) is comparable to MTB/RIF (86.9 CFU·mL−1), but not as low as Ultra (15.6 CFU·mL−1). How to deal with Xpert Ultra “trace” calls will have to be discussed by an independent WHO-convened guideline development group, who will consider different scenarios for incorporating the new assay into existing diagnostic algorithms.

As WHO looks to expand the capacity for detection of DR-TB, new rapid molecular diagnostic technologies are critical to improve TB control and progress towards ultimate TB elimination [28]. The new assay will improve rapid diagnosis of patients with second-line drug resistance, enabling early initiation of appropriate treatment and optimal person-centred care. However, the assay only targets a limited number of resistance variants recognised as “hot spots” in particular target genes, which may lead to variable sensitivity in different settings. The detection of isoniazid resistance should ideally be included with a front-line TB detection test, not as an add-on after rifampicin resistance has been detected. The main value of the assay is the rapid detection of fluoroquinolone resistance to guide all-oral MDR-TB treatment, but a caveat is the fact that it does not detect resistance against newer/re-purposed drugs included in the regimen. Routine whole genome sequencing (WGS) overcomes this shortcoming by interrogating the entire genetic repertoire, but this is currently only feasible in high resource settings and a full understanding of the genetic determinants of resistance against newer/re-purposed drugs is lacking. Moreover, in most instances WGS still requires initial culture of the specimen, which introduces potential strain biases and critical delays in patient management.

A key benefit of the Xpert MTB/XDR assay is the robustness of the Xpert platform, its minimal biosafety requirements and the fact that TB programmes are already familiar with its use. Its launch is timely, given the urgent need for rapid fluoroquinolone resistance determination to guide the use of new all-oral short-course RR/MDR-TB regimens, and especially to protect bedaquiline against the rapid emergence of drug resistance. However, strategies that integrate the new assay into existing algorithms require careful consideration of how to extract optimal value and establish appropriate monitoring processes in a variety of settings. While molecular targets chosen by the manufacturers several years prior may no longer be as contemporary as desired, this new assay successfully demonstrates rapid multiplex technology suitable for near patient testing that is potentially amenable to inclusion of alternate target mutations.

Shareable PDF

Supplementary Material

This one-page PDF can be shared freely online.

Shareable PDF ERJ-03616-2020.Shareable

Footnotes

  • Conflict of interest: A. Bainomugisa has nothing to disclose.

  • Conflict of interest: C. Gilpin has nothing to disclose.

  • Conflict of interest: C. Coulter has nothing to disclose.

  • Conflict of interest: B.J. Marais has nothing to disclose.

  • Received August 31, 2020.
  • Accepted September 26, 2020.
  • Copyright ©ERS 2020
https://www.ersjournals.com/user-licence

References

  1. ↵
    FIND. New Rapid Molecular Test for Tuberculosis can Simultaneously Detect Resistance to First- and Second-line Drugs. www.finddx.org/newsroom/pr-16jul20/ Date last updated: 16 July 2020. Date last accessed: 16 July 2020.
  2. ↵
    1. Chakravorty S,
    2. Roh SS,
    3. Glass J, et al.
    Detection of isoniazid-, fluoroquinolone-, amikacin-, and kanamycin-resistant tuberculosis in an automated, multiplexed 10-color assay suitable for point-of-care use. J Clin Microbiol 2016; 55: 183–198. doi:10.1128/JCM.01771-16
    OpenUrl
  3. ↵
    1. Cao Y,
    2. Parmarl H,
    3. Gaur R, et al.
    Xpert MTB/XDR: a ten-color reflex assay suitable for point of care settings to detect isoniazid, fluoroquinolone, and second line injectable drug-resistance directly from Mycobacterium tuberculosis positive sputum. BioRxiv 2020; preprint [https://doi.org/10.1101/2020.09.08.288787]. doi:10.1101/2020.09.08.288787
  4. ↵
    1. Abubakar I,
    2. Zignol M,
    3. Falzon D, et al.
    Drug-resistant tuberculosis: time for visionary political leadership. Lancet Infect Dis 2013; 13: 529–539. doi:10.1016/S1473-3099(13)70030-6
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    1. Pooran A,
    2. Theron G,
    3. Zijenah L, et al.
    Point of care Xpert MTB/RIF versus smear microscopy for tuberculosis diagnosis in southern African primary care clinics: a multicentre economic evaluation. Lancet Glob Health 2019; 7: e798–e807. doi:10.1016/S2214-109X(19)30164-0
    OpenUrl
  6. ↵
    World Health Organization. WHO Consolidated Guidelines on Drug-resistant Tuberculosis Treatment. www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/ Last updated: December 2019. Date last accessed: 28 June 2020.
  7. ↵
    1. Tomasicchio M,
    2. Theron G,
    3. Pietersen E, et al.
    The diagnostic accuracy of the MTBDRplus and MTBDRsl assays for drug-resistant TB detection when performed on sputum and culture isolates. Sci Rep 2016; 6: 17850. doi:10.1038/srep17850
    OpenUrlCrossRef
  8. ↵
    1. Migliori GB,
    2. Lange C,
    3. Girardi E, et al.
    Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis? Eur Respir J 2008; 31: 904–905. doi:10.1183/09031936.00159807
    OpenUrlFREE Full Text
  9. ↵
    1. Tweed CD,
    2. Dawson R,
    3. Burger DA, et al.
    Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: a multicentre, open-label, partially randomised, phase 2b trial. Lancet Respir Med 2019; 7: 1048–1058. doi:10.1016/S2213-2600(19)30366-2
    OpenUrl
  10. ↵
    World Health Organization. High-priority Target Product Profiles for New Tuberculosis Diagnostics: Report of a Consensus Meeting. www.who.int/tb/publications/tpp_report/en/ Last updated: December 2014. Date last accessed: 4 Jan 2020.
  11. ↵
    1. Heidi A,
    2. Ruvandhi RN,
    3. Chris I, et al.
    Development, roll-out and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how can we do better? Eur Respir J 2016; 48: 516–525. doi:10.1183/13993003.00543-2016
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Cohen KA,
    2. Abeel T,
    3. Manson MA, et al.
    Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal. PLoS Med 2015; 12: e1001880. doi:10.1371/journal.pmed.1001880
    OpenUrlCrossRefPubMed
  13. ↵
    1. Bainomugisa A,
    2. Lavu E,
    3. Hiashiri S, et al.
    Multi-clonal evolution of multi-drug-resistant/extensively drug-resistant Mycobacterium tuberculosis in a high-prevalence setting of Papua New Guinea for over three decades. Microb Genom 2018; 4: e000147. doi:10.1099/mgen.0.000147
    OpenUrl
  14. ↵
    1. Stagg HR,
    2. Lipman MC,
    3. McHugh TD, et al.
    Isoniazid-resistant tuberculosis: a cause for concern? Int J Tuberc Lung Dis 2017; 21: 129–139. doi:10.5588/ijtld.16.0716
    OpenUrlCrossRef
  15. ↵
    1. Sanchez-Padilla E,
    2. Merker M,
    3. Beckert P, et al.
    Detection of drug-resistant tuberculosis by xpert MTB/RIF in Swaziland. N Engl J Med 2015; 372: 1181–1182. doi:10.1056/NEJMc1413930
    OpenUrlCrossRefPubMed
  16. ↵
    1. Miotto P,
    2. Tessema B,
    3. Tagliani E, et al.
    A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis. Eur Respir J 2017; 50: 1701354. doi:10.1183/13993003.01354-2017
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Sandgren A,
    2. Strong M,
    3. Muthukrishnan P, et al.
    Tuberculosis drug resistance mutation database. PLoS Med 2009; 6: e2. doi:10.1371/journal.pmed.1000002
    OpenUrlCrossRefPubMed
  18. ↵
    1. Brossier F,
    2. Veziris N,
    3. Truffot-Pernot C, et al.
    Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2011; 55: 355–360. doi:10.1128/AAC.01030-10
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Van Ingen J,
    2. Simons S,
    3. De Zwaan R, et al.
    Comparative study on genotypic and phenotypic second-line drug resistance testing of Mycobacterium tuberculosis complex isolates. J Clin Microbiol 2010; 48: 2749–2753. doi:10.1128/JCM.00652-10
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Dooley KE,
    2. Miyahara S,
    3. von Groote-Bidlingmaier F, et al.
    Early bactericidal activity of different isoniazid doses for drug-resistant tuberculosis (INHindsight): a randomized, open-label clinical trial. Am J Respir Crit Care Med 2020; 201: 1416–1424. doi:10.1164/rccm.201910-1960OC
    OpenUrl
  21. ↵
    1. Gandhi NR,
    2. Brust JM,
    3. Sarita SN
    . A new era for treatment of drug-resistant tuberculosis. Eur Respir J 2018; 52: 1801350. doi:10.1183/13993003.01350-2018
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Nahid P,
    2. Mase SR,
    3. Migliori GB, et al.
    Treatment of drug-resistant tuberculosis an official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019; 200: 93–142. doi:10.1164/rccm.201909-1874ST
    OpenUrl
  23. ↵
    1. Dorman SE,
    2. Schumacher SG,
    3. Alland D, et al.
    Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis 2018; 18: 76–84. doi:10.1016/S1473-3099(17)30691-6
    OpenUrlCrossRefPubMed
  24. ↵
    1. Nicol MP,
    2. Workman L,
    3. Prins M, et al.
    Accuracy of Xpert Mtb/Rif Ultra for the diagnosis of pulmonary tuberculosis in children. Pediatr Infect Dis J 2018; 37: 261–263. doi:10.1097/INF.0000000000001960
    OpenUrl
  25. ↵
    1. Ligthelm LJ,
    2. Nicol MP,
    3. Hoek KG, et al.
    Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle-aspiration biopsy specimens. J Clin Microbiol 2011; 49: 3967–3970. doi:10.1128/JCM.01310-11
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Denkinger CM,
    2. Schumacher SG,
    3. Boehme CC, et al.
    Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. Eur Respir J 2014; 44: 435–446. doi:10.1183/09031936.00007814
    OpenUrlAbstract/FREE Full Text
  27. ↵
    1. Xie YL,
    2. Chakravorty S,
    3. Armstrong DT, et al.
    Evaluation of a rapid molecular drug-susceptibility test for tuberculosis. N Engl J Med 2017; 377: 1043–1054. doi:10.1056/NEJMoa1614915
    OpenUrlCrossRefPubMed
  28. ↵
    1. Lönnroth K,
    2. Migliori GB,
    3. Abubakar I, et al.
    Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J 2015; 45: 928–952. doi:10.1183/09031936.00214014
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top
View this article with LENS
Vol 56 Issue 5 Table of Contents
European Respiratory Journal: 56 (5)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
New Xpert MTB/XDR: added value and future in the field
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
New Xpert MTB/XDR: added value and future in the field
Arnold Bainomugisa, Christopher Gilpin, Christopher Coulter, Ben J. Marais
European Respiratory Journal Nov 2020, 56 (5) 2003616; DOI: 10.1183/13993003.03616-2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
New Xpert MTB/XDR: added value and future in the field
Arnold Bainomugisa, Christopher Gilpin, Christopher Coulter, Ben J. Marais
European Respiratory Journal Nov 2020, 56 (5) 2003616; DOI: 10.1183/13993003.03616-2020
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Introduction
    • Benefits/added value
    • Limitations/challenges
    • Future in the field
    • Shareable PDF
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Towards a better mucolytic
  • Relationship between gastroesophageal reflux and pulmonary fibrosis
  • The right ventricle tamed
Show more Editorials

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society