Evidence map›Paper›PMID 25746630›Full record

ArticleThorax2015

Macrolide therapy suppresses key features of experimental steroid-sensitive and steroid-insensitive asthma.

Ama-Tawiah Essilfie, Jay C Horvat, Richard Y Kim, Jemma R Mayall, James W Pinkerton, Emma L Beckett, Malcolm R Starkey, Jodie L Simpson, Paul S Foster, Peter G Gibson and 1 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Thorax, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.

  1. Macrolides versus placebo for chronic asthma.The Cochrane database of systematic reviews · 2021
    Pooled it
  2. Trial
  3. Article
  4. Review
  5. Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Aerosolization inhalation of non-typeableFrontiers in microbiology · 2023
    Article
  12. Review
  13. Pyroptosis-Induced Inflammation and Tissue Damage.Journal of molecular biology · 2022
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Asthma-COPD overlap: current understanding and the utility of experimental models.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Ama-Tawiah EssilfieCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Jay C HorvatCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Richard Y KimCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Jemma R MayallCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
James W PinkertonCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Emma L BeckettCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Malcolm R StarkeyCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Jodie L SimpsonCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Paul S FosterCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Peter G GibsonCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Philip M HansbroCentre for Asthma and Respiratory Disease and Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
Hunter Medical Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSteroid-insensitive endotypes of asthma are an important clinical problem and effective therapies are required. They are associated with bacterial infection and non-eosinophilic inflammatory responses in the asthmatic lung. Macrolide therapy is effective in steroid-insensitive endotypes, such as non-eosinophilic asthma. However, whether the effects of macrolides are due to antimicrobial or anti-inflammatory mechanisms is not known.

objectiveTo determine and assess the efficacy of macrolide (ie, clarithromycin) and non-macrolide (ie, amoxicillin) antibiotic treatments in experimental models of infection-induced, severe, steroid-insensitive neutrophilic allergic airways disease (SSIAAD), compared with steroid-sensitive AAD and to delineate the antimicrobial and anti-inflammatory effects of macrolide therapy.

methodsWe developed and used novel mouse models of Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment.

resultsClarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor α and interleukin 17 responses that induce SSIAAD.

conclusionsMacrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.

Indexed as

AmoxicillinAnimalsAnti-Bacterial AgentsAsthmaChlamydophila InfectionsChlamydophila pneumoniaeClarithromycinDexamethasoneDisease Models, AnimalFemaleGlucocorticoidsHaemophilus InfectionsHaemophilus influenzaeMiceMice, Inbred BALB CAmoxicillinAnti-Bacterial AgentsClarithromycinDexamethasoneGlucocorticoidsAllergic lung diseaseAsthmaBacterial InfectionRespiratory Infection

Identifiers

PMID25746630
OpenAlexW2141475970

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.