Evidence map›Paper›PMID 40682114›Full record

Observational studyRespiratory research2025

Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations.

Vickram Tejwani, Nirupama Putcha, Han Woo, Chen Liu, David Lafon, Neil E Alexis, Antoine Azar, R Graham Barr, Igor Barjaktarevic, Russell P Bowler and 20 more

Abstract readObservational StudyLetter
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

30 authors.

Vickram TejwaniDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH, USA. Tejwanv@ccf.org.
Nirupama PutchaDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Han WooDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Chen LiuDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
David LafonDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Neil E AlexisDivision of Allergy, Immunology and Infectious Disease, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Antoine AzarDivision of Allergy and Immunology, Johns Hopkins University, Baltimore, MD, USA.
R Graham BarrDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Igor BarjaktarevicDivision of Pulmonary and Critical Care Medicine, University of California Los Angeles Medical Center, Los Angeles, CA, USA.
Russell P BowlerDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH, USA.
Alejandro ComellasDivision of Pulmonary, Critical Care, and Occupational Medicine, College of Medicine, University of Iowa, Iowa City, IA, USA.
David J CouperDepartment of Biostatistics, Gillings School of Global Public Health, Chapel Hill, NC, USA.
Ashraf FawzyDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
MeiLan K HanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.
Nadia N HanselDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Robert J KanerDepartments of Medicine and Genomic Medicine, Weill-Cornell College of Medicine, New York, NY, USA.
Jerry A KrishnanChicago Center, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois Chicago, Chicago, IL, USA.
Nathaniel MarchettiDepartment of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
Fernando J MartinezDivision of Pulmonary and Critical Care Medicine, University of Massachusetts, Wooster, MA, USA.
Jill OharSection of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University, Winston-Salem, NC, USA.
Wanda O'NealMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Victor E OrtegaDivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Scottsdale, AZ, USA.
Robert Paine IiiDivision of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, USA.
Tess D PottingerDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Martin StämpfliCentre for Gene Therapeutics, CSL Behring, Berne, Switzerland.
Lisa RuvunaDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH, USA.
Prescott G WoodruffDivision of Pulmonary, Critical Care and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Christine M FreemanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.
Yvonne J HuangDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.
Jeffrey L CurtisDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Michigan, USA.

Funding

Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Leukotriene B4 and IL-8 in alpha-1 heterozygotes (PI*MZ genotype)K23HL173570 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Vickram Tejwani · 2024 to 2026
$512k
NHLBI NIH HHS K23 HL173570NHLBI NIH HHS K23HL173570NIEHS NIH HHS P30 ES005605
6 · The paper itself

Abstract

rationaleImmunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined associations of lower respiratory tract bacterial diversity to Ig levels in serum and bronchoalveolar lavage (BAL) and to the memory phenotypes of blood and BAL B cells.

methodsWe analyzed data from phase I of SPIROMICS, an observational cohort study of smoking-related COPD. A subset of participants completed comprehensive research bronchoscopies, including analysis of BAL bacterial microbiota by 16 S rRNA gene (V4 region) sequencing and of blood and BAL B-cells by 12-color flow cytometry. In some participants, we also analyzed serum and BAL Ig levels by ELISA. We constructed linear regression models including either serum or BAL (albumin-corrected) Ig measurements as the independent variable and separate dependent variables, including B-cell subsets, BAL bacterial diversity metrics (Faith phylogenetic diversity, inverse Simpson, and richness indices), and clinical measures (FEV

resultsSerum IgG and IgA (n = 66 participants) were 1,486.1 ± 510.6 mg/dL [mean ± standard deviation (SD)] and 237.7 ± 131.6 mg/dL, respectively. Albumin-corrected BAL IgG and IgA (n = 117) were 0.03 ± 0.02 mg/dL and 0.01 ± 0.01 mg/dL, respectively. B-cells (n = 82) comprised 3.5 ± 3.0% of blood leukocytes. Serum IgA was associated with higher blood switched memory (IgD- CD27+) B-cell percentages (β 6.06, p = 0.01) and inversely associated with blood double-negative (IgD-CD27-) B-cell percentages (β - 9.96, p = 0.02). Available BAL microbiome data (n = 107) showed that reduced lung bacterial diversity associated with lower serum IgG, but not with serum IgA, BAL IgA, or BAL IgG concentrations. Neither BAL IgG nor IgA were associated with lung function or exacerbations.

conclusionsThese results demonstrate an association of low serum IgG with reduced lung bacterial diversity, a feature of dysbiosis that may predispose to exacerbation. Defining the role of Ig in specific anatomic compartments is relevant to designing vaccine strategies.

Indexed as

B-LymphocytesBronchoalveolar Lavage FluidDisease ProgressionImmunologic MemoryLungMemory B CellsMicrobiotaPulmonary Disease, Chronic ObstructiveAgedCohort StudiesFemaleHumansImmunoglobulin AImmunoglobulin GMaleMiddle AgedImmunoglobulin AImmunoglobulin G

Identifiers

PMID40682114
PMCPMC12275290

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Registered trials

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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.