# Diastolic Dysfunction and Pauci-inflammatory Acute Exacerbations of Chronic Obstructive Pulmonary Disease

> **NIH NIH K23** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $142,226

## Abstract

Project Summary/ Abstract
 Acute exacerbations account for the majority of the chronic obstructive pulmonary disease (COPD)-
related morbidity, mortality and costs. Though many exacerbations are triggered by bacterial or viral infections
or exposure to airborne pollutants and result in marked lung inflammation, a significant number occur without a
clear precipitating cause and in the absence of pulmonary or systemic inflammation (pauci-inflammatory),
suggesting an alternative pathophysiology. This may in part explain why current therapies targeting lung
inflammation have only a modest effect on the rate of exacerbations and their outcomes even when used in
combination.
 We and others have shown significant interactions between the lung and the heart in COPD, with
accelerated atherosclerosis, arrhythmias, and a high frequency of diastolic dysfunction which may each cause
or contribute to the development of acute exacerbations. This may be particularly relevant for diastolic
dysfunction which may not only lead to overt pulmonary edema but can also cause subtle pulmonary
congestion leading to bronchial hyper-reactivity. The prevalence, risk factors, mechanisms and consequences
of diastolic dysfunction in this patient population remain unknown. We hypothesize that a subset of pauci-
inflammatory acute exacerbations are due to diastolic dysfunction resulting from cardiac ischemia, cardiac
arrhythmias and/or lung hyperinflation. These “congestive” exacerbations have a different clinical and
inflammatory profile compared with episodes triggered by airway infection or exposure to pollution, and would
therefore be expected to respond to a very different treatment algorithm. It is further hypothesized that that
diastolic dysfunction in acute exacerbations is caused by subclinical coronary ischemia, cardiac arrhythmias,
and/or dynamic lung hyperinflation. We propose a prospective study to answer these high impact questions by
determining the frequency of diastolic dysfunction in acute pauci-inflammatory exacerbations of COPD, its
clinical implications and underlying mechanisms.
 We will prospectively enroll patients hospitalized for acute exacerbations of COPD and test our
hypothesis with the following three specific aims. Aim 1 of this application will be to assess whether diastolic
dysfunction is the primary cause of the pauci-inflammatory phenotype of exacerbations of COPD by evaluation
of diastolic dysfunction and pulmonary and systemic inflammation during acute exacerbation, as well as in
stable phase after recovery. The goal of Aim 2 is to evaluate the clinical implications of diastolic dysfunction by
comparing the length of hospital stay, time to next exacerbation and overall frequency of exacerbations in
patients with and without diastolic dysfunction in the year following their index admission. In Aim 3, we will
evaluate potential mechanisms underlying diastolic dysfunction by assessing coronary ischemia and
surrogates for cardiac arrhythmias, as w...

## Key facts

- **NIH application ID:** 9981812
- **Project number:** 5K23HL133438-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Surya P Bhatt
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $142,226
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981812

## Citation

> US National Institutes of Health, RePORTER application 9981812, Diastolic Dysfunction and Pauci-inflammatory Acute Exacerbations of Chronic Obstructive Pulmonary Disease (5K23HL133438-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981812. Licensed CC0.

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