By Wesley Cai, MD, PhD, Garret Choby, MD, and Eric Wang, MD, FACS
For people suffering from chronic rhinosinusitis with nasal polyps (CRSwNP), which affects up to 4% of the population, life can feel like breathing through a fog. With your help, we can revolutionize the treatment paradigm for this condition.
This chronic inflammatory condition has a high individual burden of disease – patients experience nasal obstruction, loss of smell and taste, and thick nasal drainage which can rob them of sleep and energy. Recent studies have shown that the impact on well-being and general quality of life in CRSwNP is profound, even surpassing patients with diseases such as congestive heart failure, chronic obstructive pulmonary disorder, and Parkinson’s disease. The societal burden of chronic rhinosinusitis is also immense, with an economic impact in the U.S. estimated at $12 billion annual productivity cost, and annual healthcare cost for patients of $7 billion.
Although a chronic disease, CRSwNP can be managed with anti-inflammatory nasal steroids and surgery but some patients are unable to achieve disease control. Recently, a new paradigm of treatment was approved for CRSwNP – biologic therapies. Unlike steroids which broadly suppress the immune system, biologics are antibody medications that target specific immune system functions and can achieve durable responses with lower side effects. The downside, however, is cost. Patients treated with a biologic therapy can incur costs of up to $30,000 per year for ongoing treatment. Of course, not all patients respond to biologics. Taken together, patients endure a frustrating cycle of trial and error of different management pathways leading to prolonged symptomatic suffering and financial toxicity.
So why do some patients respond well to surgery, while others require a biologic to gain control of symptoms? Why do some patients relapse quickly while others remain symptom-free for years? There is an unmet need for predictive biomarkers to identify which patients will benefit from what treatment avenue. We believe the answers lie in the biology of the polyps themselves.
Our team will use single-cell RNA sequencing (scRNA-seq)—an advanced genomic tool—to study each individual cell in nasal polyp tissue. By mapping the immune system at single-cell resolution, we aim to identify cellular and molecular signatures that distinguish responders from non-responders to surgery and biologic therapy. Wesley Cai, a resident researcher on the team, has a wealth of experience with tissue sequencing and analyses. Having obtained a PhD in cancer biology prior to pursuing medical school and now otolaryngology residency, he has led impactful projects in cancer bioinformatics producing publications in highly respected scientific journals including Nature and Cell. With this expertise, our primary project goals are to:
- Create a bio-repository of nasal polyp tissue from patients who undergo surgery, steroids and/or biologics treatment
- Apply scRNA-seq on nasal polyp tissue before and after treatment
- Identify gene signatures and immune cell types linked to treatment response
- Develop tools to predict patient responses to specific treatment regimens
This work builds on recent advances showing that CRSwNP is not a single disease, but a collection of endotypes with different immune signatures. Another way to view this is that CRSwNP is the end result of different pro-inflammatory processes, and these differences may explain the different responses to therapy. Studies have shown that scRNA-seq can stratify patients more accurately than clinical symptoms alone. But this research is still in its early stages, and more comprehensive, patient-linked datasets are needed to translate these insights into clinical tools. Right now, there is no reliable biomarker that can predict if surgery or expensive biologics will work. That’s an economic and emotional burden on families, clinicians, and the healthcare system. Your support enables us to:
- Identify biomarkers that predict whether a patient will benefit from surgery, steroids, or biologics
- Develop a precision medicine approach for CRSwNP care
- Discover new therapeutic targets based on the pathways active in non-responders
With your help, we can pave the way to a new era of personalized CRSwNP care, where patients only receive therapies likely to help them—reducing waste, saving time, and giving people their lives back.
