Evidence map›Paper›PMID 41776387›Full record

Observational studyMolecular medicine (Cambridge, Mass.)2026

Metabolic effects following initiation of single-inhaler triple therapy in COPD: a prospective observational study.

Noriane A Sievi, Felix Schmidt, Diego M Baur, Kai Fricke, Jonas Herth, Dora Serényi, Maurice Roeder, Nicole Mosca, Silvan Vesenbeckh, Silvia Ulrich and 2 more

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05458934 (Analysis of Exhaled Breath From Patients With Lung-/Airway Diseases), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

NCT05458934 recruitingnot on this map

Analysis of Exhaled Breath From Patients With Lung-/Airway Diseases (BigExBrESs)

TypeobservationalSponsorUniversity of ZurichRan2021 to 2030Enrolled5,000ConditionsLung-/Airway DiseasesArmsNo intervention
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Noriane A SieviDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland. noriane.sievi@usz.ch.
Felix SchmidtDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Diego M BaurDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Kai FrickeDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Jonas HerthDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Dora SerényiDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Maurice RoederDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Nicole MoscaDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Silvan VesenbeckhDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Silvia UlrichDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Christian F ClarenbachDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Malcolm KohlerDepartment of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, airway inflammation, and oxidative stress. Triple inhaled therapy improves lung function and reduces acute exacerbations, yet its underlying systemic effects remain poorly understood. Exhaled breath analysis offers a non-invasive approach to assessing treatment-related metabolic changes. The objective of this study was to characterize the metabolic changes associated with the initiation of single-inhaler triple therapy in COPD patients through real-time mass spectrometry of exhaled breath.

methodsIn this prospective observational study, patients with COPD were assessed before initiation and after at least 8 weeks of single-inhaler triple therapy. Clinical data, spirometry, symptom scores, and inflammatory markers were collected. Exhaled breath was collected and analyzed by secondary electrospray ionization high-resolution mass spectrometry, and changes in metabolic profiles were evaluated using paired statistics, dimensionality reduction, and pathway enrichment analysis.

resultsTwenty-four patients with COPD (mean (standard deviation) age 65 (7) years, 42% female, median (quartiles) forced expiratory volume in the first second (FEV1) 41 (30, 57) % predicted) completed both visits. Breath analysis revealed significantly altered breath features after initiation of single-inhaler triple therapy, with a total of 40 breath features showing both a relevant effect size (|log2 fold change|≥ 1) and statistical evidence (q < 0.22) for within-subject change. Pathway enrichment analysis suggested predominant changes in lipid peroxidation and β-oxidation associated pathways, consistent with altered lipid catabolism and increased oxidative processes. Additionally, breath signatures strongly correlated with fractional exhaled nitric oxide (r = –0.8) and high-sensitivity C-reactive protein (r = –0.93).

conclusionPredominant molecular changes following initiation of single-inhaler triple therapy were associated with coordinated shifts in breath metabolites consistent with modulation of inflammatory- and oxidative stress-related pathways, suggesting a potential trade-off between anti-inflammatory effects and oxidative processes.

trial registrationClinicalTrials.gov (NCT05458934).

Indexed as

Bronchodilator AgentsPulmonary Disease, Chronic ObstructiveAdministration, InhalationAgedBiomarkersBreath TestsFemaleHumansMaleMiddle AgedOxidative StressProspective StudiesBiomarkersBronchodilator AgentsBreath ResearchCOPDMetabolismSESI-HRMSTriple Inhaled Therapy

Identifiers

PMID41776387
PMCPMC13064315

What OpenQuestion holds

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Registered trials

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.