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Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies

Megan L. Crichton, Mike Lonergan, Alan F. Barker, Oriol Sibila, Pieter Goeminne, Amelia Shoemark, James D. Chalmers
European Respiratory Journal 2020 56: 2000608; DOI: 10.1183/13993003.00608-2020
Megan L. Crichton
1Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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Mike Lonergan
1Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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Alan F. Barker
2Division of Pulmonology and Critical Care, Department of Medicine, Oregon Health and Science University, Portland, OR, USA
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Oriol Sibila
3Dept of Respiratory Medicine, Hospital Clinic, Barcelona, Spain
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Pieter Goeminne
4Dept of Respiratory Medicine, AZ Nikolaas, Sint-Niklaas, Belgium
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Amelia Shoemark
1Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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  • ORCID record for Amelia Shoemark
James D. Chalmers
1Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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Abstract

Introduction Inhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment.

Methods Post hoc analysis of the AIR-BX1 studies and two trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis (QOL-B) respiratory symptom scale, were extracted as representing severity of nine distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on-treatment cycle and mixed models were used to evaluate changes across the full 16-week trial.

Results Aztreonam improved cough (difference 0.22, 95% CI 0.08–0.37; p=0.002), sputum production (0.30, 95% CI 0.15–0.44; p<0.0001) and sputum colour (0.29, 95% CI 0.15–0.43; p<0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p<0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82, 95% CI 1.12–8.53; p=0.011 for sputum production and 5.02, 95% CI 1.19–8.86; p=0.01 for sputum colour). In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbation (hazard ratio 1.83, 95% CI 1.02–3.28; p=0.042).

Conclusion Baseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to better identify inhaled antibiotic responders and to evaluate patient response to treatment.

Abstract

Inhaled aztreonam improves cough and sputum production in patients with bronchiectasis but has no impact on other symptoms. More sensitive tools to measure bronchitic symptoms may be useful to enrich for responders and to evaluate patient benefit. https://bit.ly/2UMKM5i

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Support statement: The AIR-BX studies were funded by Gilead Sciences. This work was supported by the Innovative Medicines Initiative (IMI) and EFPIA companies under the European Commission funded project, iABC (grant 115721), the European Respiratory Society through the EMBARC2 consortium. EMBARC2 is supported by project partners Chiesi, Grifols, Insmed, Novartis and Zambon. J.D. Chalmers is supported by the GSK/British Lung Foundation Chair of Respiratory Research. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Conflict of interest: M.L. Crichton has nothing to disclose.

  • Conflict of interest: M. Lonergan has nothing to disclose.

  • Conflict of interest: A.F. Barker has nothing to disclose.

  • Conflict of interest: O. Sibila has nothing to disclose.

  • Conflict of interest: P. Goeminne has nothing to disclose.

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

  • Conflict of interest: J.D. Chalmers reports grants from Gilead, during the conduct of the study; grants and personal fees from AstraZeneca, GlaxoSmithKline, Grifols, Insmed and Boehringer Ingelheim, personal fees from Chiesi, grants from Gilead, outside the submitted work.

  • Received January 31, 2020.
  • Accepted March 31, 2020.
  • Copyright ©ERS 2020
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Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies
Megan L. Crichton, Mike Lonergan, Alan F. Barker, Oriol Sibila, Pieter Goeminne, Amelia Shoemark, James D. Chalmers
European Respiratory Journal Jul 2020, 56 (1) 2000608; DOI: 10.1183/13993003.00608-2020

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Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a post hoc analysis of the AIR-BX studies
Megan L. Crichton, Mike Lonergan, Alan F. Barker, Oriol Sibila, Pieter Goeminne, Amelia Shoemark, James D. Chalmers
European Respiratory Journal Jul 2020, 56 (1) 2000608; DOI: 10.1183/13993003.00608-2020
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