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Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy
  1. Shakti D Shukla1,
  2. Steven L Taylor2,3,
  3. Peter G Gibson1,4,
  4. Daniel Barker1,
  5. John W Upham5,6,
  6. Ian A Yang5,7,
  7. Paul N Reynolds8,9,
  8. Sandra Hodge8,9,
  9. Alan L James10,11,
  10. Geraint B Rogers2,3,
  11. Jodie L Simpson1,4
  1. 1Faculty of Health and Medicine, The University of Newcastle Priority Research Centre for Asthma and Respiratory Disease, Newcastle, New South Wales, Australia
  2. 2Microbiome and Host Health, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  3. 3SAHMRI Microbiome Research Laboratory, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
  4. 4Hunter Medical Research Institute, Newcastle, NSW, Australia
  5. 5Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
  6. 6Translational Research Institute, Brisbane, QLD, Australia
  7. 7Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia
  8. 8Department of Respiratory Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  9. 9School of Medicine, University of Adelaide, Adelaide, SA, Australia
  10. 10Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
  11. 11Medicine School, University of Western Australia, Crawley, WA, Australia
  1. Correspondence to Dr Jodie L Simpson, Respiratory and Sleep Medicine, The University of Newcastle Faculty of Health and Medicine, Callaghan, NSW 2305, Australia; jodie.simpson{at}


Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1β and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced Haemophilus influenzae load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.

  • asthma
  • asthma pharmacology
  • respiratory infection
  • cytokine biology

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  • Contributors Conception and design: JLS, PGG, JWU, IY, PNR, SH and AJ. Data acquisition: JLS, PGG, JWU, IY, PNR, SH, AJ, ST and GBR. Data analysis and interpretation: JLS, DB, SDS, ST and GBR. Drafting manuscript: SDS, JLS, DB, ST and GBR. Revision and approval of final manuscript: All authors.

  • Funding This study was supported by National Health and Medical Research Council (NHMRC) (grant 569246) and NHMRC Centre for Severe Asthma, University of Newcastle.

  • Competing interests JWU reports personal fees from AstraZeneca, personal fees from GSK, personal fees from Novartis, personal fees from Boehringer Ingelheim, personal fees from Sanofi, outside the submitted work. PGG reports personal fees from AstraZeneca, GlaxoSmithKline, Novartis, grants from AstraZeneca, GlaxoSmithKline, outside the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.