Evidence map›Paper›PMID 40185289›Full record

ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2025

Assessment of ventilation heterogeneity and particle deposition in asthmatics using combined SPECT/CT imaging and computational modeling approaches.

Xuan Zhang, Prathish K Rajaraman, Frank Li, Sanghun Choi, Alejandro P Comellas, Eric A Hoffman, Sean B Fain, David W Kaczka, Benjamin M Smith, Jiwoong Choi and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Asthma endotypes and theratypes.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  3. Article
  4. Article
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

22 authors.

Xuan ZhangIIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; Department of Mechanical Engineering, University of Iowa, Iowa City, IA, USA.
Prathish K RajaramanIIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; Department of Mechanical Engineering, University of Iowa, Iowa City, IA, USA.
Frank LiIIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
Sanghun ChoiSchool of Mechanical Engineering, Kyungpook National University, Daegu, South Korea.
Alejandro P ComellasDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Eric A HoffmanRoy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Department of Radiology, University of Iowa, Iowa City, IA, USA.
Sean B FainRoy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Department of Radiology, University of Iowa, Iowa City, IA, USA; Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA; Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA.
David W KaczkaRoy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Departments of Anesthesia and Radiology, University of Iowa, Iowa City, IA, USA.
Benjamin M SmithDepartment of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Medicine, McGill University Health Centre Research Institute, Montreal, Canada.
Jiwoong ChoiDivision of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
Mario CastroDivision of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
Sally E WenzelDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Nizar N JarjourSchool of Medicine & Public Health, University of Wisconsin, Madison, WI, USA.
Mark L SchieblerSchool of Medicine & Public Health, University of Wisconsin, Madison, WI, USA.
Elliot IsraelBrigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
Bruce D LevyBrigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
John V FahyDepartment of Medicine, University of California-San Francisco, San Francisco, CA, USA.
Serpil C ErzurumCleveland Clinic, Cleveland, OH, USA.
Andrew BabiskinDivision of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Minori KinjoDivision of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Ross WalengaDivision of Therapeutic Performance II, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Ching-Long LinIIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; Department of Mechanical Engineering, University of Iowa, Iowa City, IA, USA; Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Department of Radiology, University of Iowa, Iowa City, IA, USA. Electronic address: ching-long-lin@uiowa.edu.

Funding

Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Brandi Janssen · 1990 to 2026
$40.5M
Chronic obstructive pulmonary disease in non-smokersR01HL130506 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HERBSTMAN, JULIE BETH, SMITH, BENJAMIN M. · 2016 to 2025
$6.3M
Deep Learning and Subtyping of Post-COVID-19 Lung Progression PhenotypesR01HL168116 · NHLBI · UNIVERSITY OF IOWA · PI CHING-LONG LIN · 2023 to 2026
$2.9M
FDA HHS U01 FD005837NHLBI NIH HHS R01 HL130506NHLBI NIH HHS R01 HL168116NIEHS NIH HHS P30 ES005605
6 · The paper itself

Abstract

purposeThis study investigated asthma phenotypes and their associations with ventilation heterogeneity and particle deposition by utilizing Single-Photon Emission Computed Tomography (SPECT) imaging, quantitative Computed Tomography (qCT) imaging-based subgrouping, and a whole-lung computational model. MATERIALS AND

methodsTwo datasets were analyzed: one from a combined SPECT and CT (SPECT/CT) study with six asthmatic subjects, and another from the Severe Asthma Research Program (SARP) with 209 asthmatic subjects. Data from 35 previously acquired healthy subjects served as a control group. Each subject underwent CT scans at full inspiration and expiration, along with pulmonary function testing (PFT). The SPECT/CT study included ventilation SPECT imaging. Key qCT variables such as airway diameter, wall thickness, percentage of air trapping (AirT%), and percentage of small airway disease (fSAD%) were assessed. A subject-specific whole-lung computational fluid and particle dynamics (CFPD) model predicted airway resistance, particle deposition fraction, and the coefficient of variation (CV) for ventilation heterogeneity. Subjects were categorized into four predefined asthma imaging subgroups/clusters with increasing severity (C1-C4). CFPD-predicted CVs were validated against SPECT measurements. We compared PFT, qCT, and CFPD variables across SARP clusters and analyzed particle deposition fractions in large conducting, small conducting, and respiratory airways.

resultsCluster C4 exhibited a significantly distinct ventilation profile compared to other clusters and health controls. This distinction contrasted with the insignificant differences between ventilation profiles in severity subgroups defined by conventional spirometry-based guidelines. Airway resistance varied significantly across the asthma clusters. Although both C3 and C4 clusters represented severe asthma, only C4 showed a significant increase in AirT%, primarily due to fSAD%. Since inflammatory phenotypes differ - C3 with wall thickening in large and small conducting airways, and C4 with elevated fSAD% and Emph% in small conducting and respiratory airways - fine particles (∼5 μm) and extrafine particles (∼1 μm) are more effective at reaching the respective regions in C3 and C4. Given that C2 and C4 have hyper-responsive phenotypes with narrowed conducting airways, fine particles are more effective in reaching these areas. Airway enlargement in targeted segments of the left lower lobe resulted in improved particle deposition.

conclusionOur cluster-informed CFPD-based approach enhances the understanding of ventilation heterogeneity in asthma and holds potential for refining strategies for inhalational therapies.

Indexed as

AsthmaLungAdultComputer SimulationFemaleHumansMaleMiddle AgedPulmonary VentilationRespiratory Function TestsSingle Photon Emission Computed Tomography Computed TomographyTomography, Emission-Computed, Single-PhotonTomography, X-Ray ComputedYoung AdultAsthmaCFPDClustersCTParticle depositionSPECTVentilation heterogeneity

Identifiers

PMID40185289
PMCPMC12145795

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LicenceCC BY-NC-ND
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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.