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Expert Strategies for CRSwNP Management
Expert Strategies for Diagnosing and Treating Patients With CRSwNP

Released: October 17, 2025

Kathleen Buchheit
Kathleen Buchheit, MD
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Key Takeaways
  • Research is ongoing to determine the genetic and environmental factors that predispose patients to CRSwNP and may inform disease phenotyping/endotyping.
  • There is a link between microbial colonization and disease chronicity across all chronic rhinosinusitis endotypes.
  • Biologic therapy should be considered in patients with CRSwNP and uncontrolled symptoms despite adequate medical treatment, contraindications to surgery, or a preference for biologics.

When diagnosing chronic rhinosinusitis with nasal polyps (CRSwNP), it is important to remember that there are genetic and environmental factors that predispose certain patients to this condition. For example, approximately 30% of patients have a family member with CRSwNP, so there is a familial link. However, CRSwNP is not generally a monogenic condition except for cystic fibrosis, which is caused by a single mutation in CFTR gene. Those with cystic fibrosis often present with CRSwNP in childhood, which is unusual and what clued researchers into thinking about this as a genetic condition. Another genetic disorder associated with CRSwNP is primary ciliary dyskinesia. Patients with primary ciliary dyskinesia have defective motile cilia that can impair mucus clearance and predispose them to CRSwNP. 

In thinking more broadly about patients with CRSwNP, especially in the US, these individuals generally have type 2 inflammation. There are several studies looking for specific gene variations or polymorphisms among this population. There certainly are genes that stand out regarding type 2 inflammation, such as polymorphisms in interleukin (IL)-4, IL-13, and IL-33, but these are not nearly so clear.

In addition, epigenetic changes, such as those found in miRNA regulation and DNA methylation, can play a role in CRSwNP. Changes occur that can alter gene expression without changing patients’ DNA sequence. However, in general, our understanding of the genetic factors that predispose certain patients to CRSwNP is constantly evolving, and there is a lot we still do not understand.

In terms of environmental factors, there are some exposures that have an association with CRSwNP. For certain, exposure to secondhand smoke as a child is a known risk factor for chronic rhinosinusitis (CRS). Furthermore, patients who actively smoke also are at increased risk for developing CRS. Many studies are now looking at the role of environmental exposures like air pollution in the development of CRS. This is an area of research with much active interest. 

Microbial Colonization or Biofilms in CRSwNP
Many patients with CRS—with or without nasal polyps—have microbial colonization and develop biofilms. It is not entirely clear if the microbial colonization and biofilms lead to downstream inflammation and the chronicity of CRS or if the abnormal epithelial barrier and dysregulated inflamed tissue is what predisposes them to microbial colonization and biofilms. 

I think that both ideas are true to some extent. In patients with immunodeficiency, whether they have an antibody deficiency or get infected with COVID-19, they are predisposed to developing recurrent respiratory infection. As a result, they can develop chronic inflammation that almost never gets better and CRS. But I also have seen the opposite happen. For example, I have treated patients with aspirin-exacerbated respiratory disease who developed adult-onset CRSwNP and asthma. Their CRSwNP was a sequela of their chronic inflammation and increased risk for respiratory infection. They developed recurrent sinus infections, had evidence of pus on endoscopic nasal examination, or had colonizers, sometimes including unusual organisms, in sinus culture.

How does this impact the chronicity of CRS? Well, biofilms are aggregates of a variety of different microorganisms that are often polymicrobial and are encased in a matrix that can evade the immune system. They cannot be cleared in the same way that our bodies are good at clearing away other infections. As a result, biofilms can lead to persistent inflammation and ongoing epithelial dysfunction. That may impair mucociliary clearance, for example, if the biofilms have an impact on ciliary function, thereby preventing the individual from clearing mucus and other microbes that their body normally would remove. So this is a perpetuating, vicious cycle of inflammation.

Regarding the specific endotypes that are impacted by microbial colonization, we will often bucket patients into type 2 or non–type 2 inflammation (ie, type 1 or 3 inflammation), although some patients may not fit well into either category and have mixed endotypes. Furthermore, microbial association in CRS is more commonly linked with type 1 and 3 endotypes, and patients with the type 3 endotype are more likely to have pus and purulent nasal drainage.

These inflammation types are driven by a variety of cytokines (ie, IL-17, interferon-γ, IL-8, and tumor necrosis factor-α) that are often associated with neutrophil-predominant inflammation. There are a variety of pathogens that influence the inflammatory response in patients with CRS. For example, Staphylococcus aureus drives type 2 inflammation and causes immune dysregulation by stimulating the local production of IgE that further perpetuates type 2 inflammation. So there is evidence that microbial colonization and/or biofilms may perpetuate inflammation across the CRS endotypes, potentially doing so through different mechanisms.

Biomarkers to Predict CRSwNP Severity and Treatment Response
There are some biomarkers that can help predict both disease severity and treatment response in patients with CRSwNP. We typically use these measurements with surgery and/or biologic therapy. There is increased interest in understanding the phenoendotypic markers and how they may help us discuss prognostic factors with patients, including how they may do in general in terms of their disease course and treatment. 

There is evidence showing that increased eosinophil levels in both the tissue and peripheral blood—a marker of type 2 inflammation—may predict response to endoscopic sinus surgery and the likelihood for disease recurrence. In addition, increased eosinophil levels are a useful biomarker when thinking about biologic therapy for CRSwNP. Dupilumab, mepolizumab, and omalizumab all target components of the type 2 inflammatory pathway. It can be helpful to use blood or tissue eosinophilia, to a certain extent, to identify patients with type 2 inflammation and who may benefit from biologic therapy.

Another clinically useful biomarker is serum IgE, which is used to determine the patient’s level of type 2 inflammation. The utility of IgE as a prognostic marker in predicting response to surgery is less well understood. Some research has found that patients with higher IgE levels in nasal tissue are more likely to have rapid CRSwNP recurrence after endoscopic sinus surgery. Therefore, IgE as a biomarker certainly has a role in research and down the line it might help more clinically in terms of providing prognostic information about patients’ expected response to surgery.

Of note, we must use IgE serum to inform the dosing of omalizumab, specifically. So it has a role as a marker of type 2 inflammation and helps put the whole story together when thinking about which patients are good candidates for biologic therapy and, in particular, omalizumab.

Initiating Biologic Therapy in Patients with CRSwNP
I consider starting a biologic therapy in patients with CRSwNP and uncontrolled symptoms despite adequate medical treatment, with or without prior surgery. As an allergist, I receive many referrals from otolaryngologists with patients who have received excellent endoscopic sinus surgery and who continued their postoperative intranasal irrigation and corticosteroid regimen. Despite doing all the right things, they may experience disease recurrence. In these patients, especially considering those who are symptomatic (ie, loss of smell, congestion, and substantial mucus production or postnasal drip that is significantly impairing their quality of life), it is certainly reasonable to consider biologic therapy.

For those who present with CRSwNP and have never had surgery, initiating biologic therapy is a little less clear. I almost always refer these patients to an otolaryngologist because they should receive a good endoscopic nasal examination and have that risk vs benefit discussion about surgery. The final decision should depend on what each patient's wishes and goals are. There are many patients who have endoscopic sinus surgery and do great, and there are others who decide to start biologic therapy without prior surgery. The latter scenario is the exception.

I typically reserve biologic therapy for patients who have tried and failed all first-line therapies, including surgery. An exception to that includes patients with severe, comorbid asthma who need biologic therapy anyway to treat their asthma. In this case, I would choose the biologic therapy that will treat both their upper and lower airway disease. Because their asthma is so severe, they may never go on to have surgery or they may try the biologic for some time and then decide to have endoscopic sinus surgery.

There are other patients with contraindications to surgery—either anesthesia is contraindicated, or they have other medical comorbidities where surgery is not ideal. These patients would be candidates for biologic therapy. Finally, patients may be receiving frequent treatment with systemic corticosteroids for exacerbations of CRS and/or asthma. When I see these patients who are receiving oral corticosteroids several times throughout the year, I will consider biologic therapy as well to try to minimize the cumulative toxicity of steroid exposure.

Future Directions in CRSwNP
In the near term, data from the WAYPOINT trial of tezepelumab vs placebo for treating adults with CRSwNP look promising. Patients saw significant reductions in their nasal-polyp score as well as greater improvements in their congestion and sense of smell with tezepelumab vs placebo. If approved by the FDA, tezepelumab will become an exciting treatment option for patients with CRSwNP. In addition, emerging data for tezepelumab has shown benefit in patients with non–type 2 asthma. But subgroup analyses are needed to understand if there is similar benefit among patients with non–type 2 CRSwNP. 

Another promising therapy is depemokimab, an ultralong-acting IL-5 inhibitor. The reason that this agent is highly anticipated is because it is dosed every 6 months, which may be ideal for many patients. Because some patients find the current CRSwNP treatment options incredibly burdensome, having depemokimab as an option in the future will be incredible.

Beyond tezepelumab and depemokimab, there are other agents in the pipeline—some of which are ultralong-acting therapies. Furthermore, a variety of phase II studies are being done with bispecific antibodies and other agents that, from a mechanistic perspective, will be interesting in terms of how they work differently and if they are more efficacious vs the currently available biologic therapies. So stay tuned! There will be a lot more treatment options to come for CRSwNP down the road.

Your Thoughts
How often are you prescribing biologic therapies for your patients with CRSwNP? You can get involved in the discussion by answering the poll question and posting a comment below.

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