Evidence map›Paper›PMID 39885466›Full record

ArticleRespiratory research2025

NTHi killing activity is reduced in COPD patients and is associated with a differential microbiome.

Vancheswaran Gopalakrishnan, Ben Sparklin, Jung Hwan Kim, Jerome Bouquet, Margaret Kehl, Tara Kenny, Christopher Morehouse, Carolina Caceres, Paul Warrener, Ventzislava A Hristova and 19 more

Abstract read
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Vancheswaran GopalakrishnanBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Ben SparklinBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Jung Hwan KimBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Jerome BouquetBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Margaret KehlBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Tara KennyVirology and Vaccine Discovery, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Christopher MorehouseBioinformatics, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Carolina CaceresTranslational Scientific Management, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Paul WarrenerBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Ventzislava A HristovaDynamic Omics, Centre for Genomics Research (CGR), Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Susan WilsonBiologics Engineering, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Harini ShandilyaBiologics Engineering, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Arnita BarnesBiologics Engineering, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.
Alexey RuzinTranslational Scientific Management, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Junmin WangQuantitative Biology, Data Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Lisa ObergTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Bastian AngermannTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Christopher McCraeTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Adam PlattVP and Head of Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Daniel MuthasTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Sonja HessDynamic Omics, Centre for Genomics Research (CGR), Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Christine TkaczykMicrobial Antibodies and Technologies, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Bret R SellmanBacterial Vaccines, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Kristoffer OstridgeTranslational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Maria G BelvisiSVP and Head of Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Tom M A WilkinsonClinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK.
Karl J StaplesClinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK.
Antonio DiGiandomenicoMicrobial Antibodies and Technologies, Research and Early Development, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. antonio.digiandomenico@astrazeneca.com.
MICA II Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by airway obstruction and inflammation. Non-typeable Haemophilus influenzae (NTHi) lung infections are common in COPD, promoting frequent exacerbations and accelerated lung function decline. The relationship with immune responses and NTHi are poorly understood. Herein, we comprehensively characterized the respiratory microbiome and mycobiome of patients while investigating microbial dynamics and host immune changes attributable to NTHi killing activity. Mild-to-moderate COPD patients encompassing frequent and infrequent exacerbators and healthy volunteers (HV) were enrolled. Microbial composition, proteomics and NTHi killing activity was analyzed using bronchoalveolar lavage fluid (BALF). In addition, antigen-antibody titers in sera to COPD pathogens were determined using a multiplex assay. Differential abundance analysis revealed an enrichment of Actinobacteria and Bacteroidetes in the BALF of COPD and HV subjects respectively. Significant differences in the IgA titer response were observed against NTHi antigens in COPD vs. HV. Notably, there was also significantly greater killing activity against NTHi in BALF from COPD vs. HV subjects (OR = 5.64; 95% CI = 1.75-20.20; p = 0.001). Stratification of COPD patients by NTHi killing activity identified unique microbial and protein signatures wherein Firmicutes, Actinobacteria and haptoglobin were enriched in patients with killing activity. We report that differences in host immune responses and NTHi-killing activity are associated with microbiome changes in mild-to-moderate COPD. This is suggestive of a potential link between the respiratory microbiome and immune activity against NTHi in the context of COPD pathogenesis even at this disease stage.

Indexed as

Haemophilus InfectionsHaemophilus influenzaeMicrobiotaPulmonary Disease, Chronic ObstructiveAgedBronchoalveolar Lavage FluidFemaleHumansMaleMiddle AgedCOPDExacerbationsMicrobiomeNon-typeable Haemophilus influenzae

Identifiers

PMID39885466
PMCPMC11781068

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.