# Identification of immune cell-cell communication networks and inflammatory pulmonary microenvironments associated with the progression of COPD

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $319,844

## Abstract

PROJECT SUMMARY
Chronic obstructive pulmonary disease (COPD) is a fatal lung disease that is the fourth leading cause of death
in the U.S. Despite an estimated $50 billion in yearly healthcare costs, it has no current cure and only palliat-
ive treatments. COPD is clearly characterized by chronic lung inflammation that likely arises from dysregulat-
ion of complex networks of immune factors and cells across multiple tissue compartments. Although multiple
individual genes and proteins have been associated with COPD risk and progression, global mechanistic
understanding of its pathophysiology is lacking, particularly regarding the marked heterogeneity in COPD
phenotypes. The overall objective of our study is to gain systems-level insight into complex inflammatory and
immune mechanisms underlying COPD, by applying data-driven (also called ‘machine learning’) modeling
approaches to clinical samples collected from human pulmonary microenvironments and matched immune cell
networks from peripheral blood. Our central hypothesis is that immune networks will be more predictive of
COPD phenotype, progression, and exacerbation than individual factors. We will test this hypothesis in three
Specific Aims, using matched brochoalveolar lavage (BAL) and blood samples collected in SPIROMICS I and
II clinical trials. Aim 1 will identify changes in immune cell-cell communication networks, by high-throughput
cytokine measurements from stimulated systems of peripheral blood immune cells from smokers with and
without COPD and never-smoking controls (collected from the upcoming SPIROMICS II visit; n=150). Aim 2
will determine systems-level changes that occur in the inflamed lung microenvironment, using high-throughput
cytokine measurements in BAL samples (both archival from SPIROMICS I, n=200, and collected during
upcoming SPIROMICS II bronchoscopies) from smokers with and without COPD and never-smoking controls.
We will identify networks associated with longitudinal clinical progression and exacerbation frequency. Aim 3
will integrate measurements across lung and blood tissue compartments to define key combinatorial
relationships associated with progression and exacerbation events. Overall, this project will provide systems-
level insight into COPD pathogenesis and progression, and create a new paradigm for the study of other
pulmonary conditions involving chronic inflammation, including idiopathic pulmonary fibrosis, asthma, and lung
transplant. Results will aid in the future development of new non-invasive diagnostic assays and will guide
systems-level mechanistic studies that could result in new combinatorial therapies.

## Key facts

- **NIH application ID:** 9888409
- **Project number:** 5R01HL144849-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kelly Arnold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,844
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888409

## Citation

> US National Institutes of Health, RePORTER application 9888409, Identification of immune cell-cell communication networks and inflammatory pulmonary microenvironments associated with the progression of COPD (5R01HL144849-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9888409. Licensed CC0.

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