# IMPROVE 2: Inhaled Mometasone to Promote Reduction in Vaso-occlusive Events

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $72,222

## Abstract

With the overall goal of understanding the mechanisms by which inhaled corticosteroids lead to systemic
clinical benefits in individuals with Sickle Cell Disease (SCD) who do not have asthma, we have assembled a
team of experts in hematology, pulmonology, immunology and SCD patient engagement with state-of-the-art
capabilities for phenotyping pulmonary and systemic inflammation, vascular injury, functional status and patient
reported outcomes. In SCD, sickling is caused by de-oxygenation of blood and reversed in the lung. Pulmonary
inflammation interferes with re-oxygenation and potentiates further sickling, hemolysis, inflammation and vaso-
occlusion. Over the last decade, our group and others demonstrated that pulmonary inflammation is present in
SCD mice, that symptoms of episodic cough or wheeze (ECW) occur in half of SCD patients who do not meet
criteria for a diagnosis of asthma and that ECW is a risk factor for increased SCD-related pain and death. In a
pilot trial, inhaled steroids reduced systemic inflammation, hemolysis and daily pain with trends towards
substantial reductions in healthcare utilization. Our global hypothesis is that inhaled steroids improve systemic
inflammation and vascular injury in non-asthmatic SCD patients with ECW. To test this hypothesis, we will
complete the following aims: AIM 1A: Compare pulmonary inflammation profiles in non-asthmatic SCD patients
with and without ECW and, AIM 1B: Determine the effect of inhaled steroids on pulmonary inflammation in
non-asthmatic SCD patients with ECW. AIM 2: Determine the effect of inhaled steroids on peripheral blood
inflammatory and hemolytic signatures in non-asthmatic individuals with SCD and ECW. AIM 3: Establish a
safety protocol for using inhaled steroids in an urban SCD clinical trial setting for 1 year. We will analyze
induced sputum and blood using mass cytometry by time of flight (CyTOF - which has several advantages over
flow cytometry) and multiplex assays, to define patterns of pulmonary and systemic inflammation that underlie
the clinical phenomenon of ECW in SCD and to determine the effects of inhaled steroids on those
inflammatory patterns. Once complete, we will use the knowledge gained to design a phase III trial of inhaled
steroids for non-asthmatic individuals with SCD.

## Key facts

- **NIH application ID:** 10163395
- **Project number:** 3R01HL142671-03S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jeffrey Avins Glassberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,222
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163395

## Citation

> US National Institutes of Health, RePORTER application 10163395, IMPROVE 2: Inhaled Mometasone to Promote Reduction in Vaso-occlusive Events (3R01HL142671-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163395. Licensed CC0.

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