# SPIROMICS II: Biological underpinnings of COPD heterogeneity and progression

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $3,976,480

## Abstract

PROJECT SUMMARY
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. No medical
therapies reduce mortality or slow disease progression, in part because COPD is a heterogeneous syndrome,
which hinders the development of targeted therapies. The SPIROMICS study enrolled 2,982 participants into a
3-year longitudinal study of current and former smokers and never-smoking controls, phenotyping them
clinically, radiographically and biologically to identify sources of heterogeneity in COPD. This new project will
extend follow-up of participants enrolled in SPIROMICS, perform a bronchoscopy substudy and perform an
exacerbation substudy to test three specific aims. The overarching premise underlying these aims is that
COPD is a consequence of a heterogeneous group of molecular phenotypes that underlie distinct radiographic
(anatomic) and clinical (physiologic) phenotypes; and that linking molecular phenotypes to specific
radiographic and clinical phenotypes will identify key biological factors associated with disease exacerbation
and progression. The first aim is to define the natural history of “Smokers with symptoms despite preserved
spirometry” and characterize the airway mucus abnormalities underlying this condition. Patients with this newly
recognized condition do not meet current criteria for COPD but nonetheless have symptoms, exacerbation-like
events, activity limitations and airway wall thickening and they may have a precursor condition to bona fide
COPD. The second aim is to determine the radiographic precursor lesion(s) for emphysema, and identify the
molecular phenotypes underlying progression of chronic bronchitis, radiographic airway disease and
emphysema. This aim will leverage several novel radiographic methods for measurement of lung disease and
new approaches to phenotyping based on inflammatory pathways and the lung microbiome that we developed
in SPIROMICS. The third aim is to advance our understanding of the biology of COPD exacerbations through
analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response. This aim
will leverage RNA sequencing methods to simultaneously measure respiratory pathogens and the host
inflammatory response in an exacerbation substudy. Our ultimate goal is to enable targeted approaches to
COPD treatment and disease modification that are based on the heterogeneous biological pathways that
underlie COPD progression and exacerbations.

## Key facts

- **NIH application ID:** 9948706
- **Project number:** 5U01HL137880-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** PRESCOTT G WOODRUFF
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,976,480
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948706

## Citation

> US National Institutes of Health, RePORTER application 9948706, SPIROMICS II: Biological underpinnings of COPD heterogeneity and progression (5U01HL137880-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948706. Licensed CC0.

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