Chronic rhinosinusitis (CRS) affects about 1 in 7 U.S. adults and is responsible for tens of millions of office visits every year. Despite this, there are still no FDA‑approved drugs specifically for CRS. Most patients cycle through steroids, antibiotics, saline rinses, and often surgery — yet many remain symptomatic. If you can relate to this, a study published in Therapeutics and Clinical Risk Management may change how you think about this condition.
The review by Kern and colleagues challenges the old idea that CRS is mainly a lingering bacterial infection. Instead, it paints a different picture: for many patients, CRS appears to be a chronic inflammatory reaction to fungi, driven by eosinophils, not by classic allergies or simple infection. This model fits well with what you may see every day: a persistent, relapsing inflammatory condition that doesn’t respond predictably to antibiotics.
Normal Fungi, Abnormal Immune Response
Fungi are everywhere. They’re in the air, in the nose, and in the sinuses of healthy people and CRS patients alike. In a key study cited in the review, fungal cultures from sinus mucus were positive in almost all CRS patients and all healthy controls, with similar types of fungi.
So fungi alone aren’t the problem.
The difference is the host response. In most CRS patients, the nasal and sinus lining is infiltrated with eosinophils. These eosinophils move out of the blood vessels into the tissue and then into the mucus. Once there, they degranulate, releasing major basic protein (MBP) and other toxic contents meant to attack large pathogens.
These granule proteins do kill fungal elements. But they also damage the patient’s own epithelial lining and basement membrane. Over time, this leads to chronic inflammation, tissue remodeling, and a weakened barrier that is easier for bacteria to colonize. The pattern looks a lot like what we see in asthma—ongoing eosinophilic inflammation and tissue change—only in the sinuses instead of the bronchi.
An important point from the paper: this eosinophilic pattern shows up even when patients don’t have classic IgE‑mediated allergy. Many will have eosinophilic mucin and high MBP levels, regardless of skin test results or serum IgE. That’s a very different story from simple “allergic sinusitis.”
Diagnosis: Still Clinical, But Think “Chronic Inflammation”
Kern et al. emphasize that CRS is still diagnosed clinically: symptoms for at least 12 weeks plus physical findings. Patients typically have a mix of nasal obstruction, discolored discharge or postnasal drip, facial pressure (especially when paired with other nasal symptoms), and reduced sense of smell.
Anterior rhinoscopy and, ideally, nasal endoscopy help confirm the picture. On endoscopy, you may see swollen, pale or erythematous mucosa, polyps or polypoid tissue, thick or discolored mucus, and crusting.
When the disease is persistent or recurrent, CT imaging is extremely helpful. The CT image on page 7 of the article shows normal sinuses: thin mucosal lining and open drainage pathways. In contrast, the CT on page 8 demonstrates CRS: marked thickening of the maxillary and ethmoid mucosa, plus polyps crowding the middle meatus.
From a practical standpoint, the review supports what many integrative clinicians already suspect: in CRS, you’re often looking at chronic, immune-driven inflammation of the sinonasal mucosa, with bacteria playing a secondary role rather than being the primary driver.
Conventional Treatments: Helpful, But Often Incomplete
Most patients arrive on some version of the standard regimen: intranasal corticosteroids, saline rinses, occasional or frequent antibiotics, antihistamines, and sometimes decongestants. Surgery is reserved for more advanced disease or failure of medical therapy.
The review highlights some key realities:
- Antibiotics may help in acute bacterial flares, but evidence for benefit in stable CRS is weak. Routine long courses can add side effects and resistance without addressing the underlying problem.
- Intranasal corticosteroids can clearly improve congestion and shrink polyps to some degree, but they don’t fully resolve inflammation for many patients.
- Saline irrigation, especially hypertonic saline, has good evidence for symptom relief and is safe and inexpensive—an excellent “baseline” therapy.
- Endoscopic sinus surgery can improve drainage and open access for topical treatments. Outcomes are often good, but surgery doesn’t “cure” CRS. Most patients still need ongoing topical care afterward.
So while these tools are valuable, they don’t fully address the eosinophilic, fungus‑driven model that’s emerging.
Intranasal Amphotericin B: Targeting the Fungal Trigger
This is where topical intranasal Amphotericin B (AmB) comes in.
AmB is an antifungal drug that binds to ergosterol in fungal cell membranes and causes cell death. It’s been used systemically for decades, but at topical doses in the nose, systemic absorption is minimal.
The idea, as presented by Kern et al., is straightforward: if you can lower the fungal load in the sinonasal cavity, you may be able to reduce the stimulus that keeps eosinophils activated and degranulating. Decrease the fungal antigen, and the eosinophilic reaction can settle down. Over time, less MBP means less epithelial injury and a chance for the mucosa to heal.
The review summarizes several studies:
- In a 51‑patient pilot study of intranasal AmB, about three‑quarters of patients improved symptomatically and on endoscopy.
- In another study of 74 patients with persistent nasal polyps despite saline and steroids, adding AmB led to complete disappearance of polyps in 39% of participants.
- A small randomized controlled trial in 30 CRS patients found that, after six months, those using AmB had an average 8.8% reduction in mucosal thickening on CT, while the placebo group actually worsened by 2.3%. Endoscopy scores improved in 70% of AmB patients, and symptom scores improved in most of them as well. Side effects were minimal, with a few patients reporting transient burning.
Not every trial has been positive, and some designs may have excluded exactly the fungal–eosinophilic phenotype that’s most likely to benefit. But taken together, the data suggest that intranasal AmB can be a safe, targeted way to dial down the inflammatory driver in many CRS patients.
A Practical, Integrative Takeaway
Kern and colleagues conclude that topical Amphotericin B is generally well tolerated and should be considered early in the treatment course—even as a first‑line topical therapy—especially before committing to surgery.
This review supports a stepwise approach:
- Think of CRS primarily as chronic mucosal inflammation with a fungal trigger, not just a lingering infection.
- Build a base of saline irrigation, barrier support, and systemic inflammation control.
- Layer on intranasal corticosteroids when appropriate.
- For refractory cases that fit the fungal–eosinophilic pattern, consider topical intranasal Amphotericin B as a way to decrease antigenic load and give the mucosa room to recover.
- Reserve antibiotics for clear bacterial flares, and use surgery judiciously—often as a way to improve access for ongoing topical therapies rather than as a final cure.
For those “frequent flyer” sinus patients you see over and over, this shift — from “chronic infection” to “chronic inflammatory response to fungi” — opens up a more coherent, more targeted, and often more successful way to treat their disease. This review offers a more coherent mechanistic model — and a rational, locally focused therapeutic option in intranasal Amphotericin B that aligns well with integrative principles of targeting root drivers, protecting mucosal integrity, and minimizing systemic burden.
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Reference
Kern EB, Sherris D, Stergiou AM, Katz LM, Rosenblatt LC, Ponikau J. Diagnosis and treatment of chronic rhinosinusitis: focus on intranasal Amphotericin B. Ther Clin Risk Manag. 2007 Jun;3(2):319-25. doi: 10.2147/tcrm.2007.3.2.319. PMID: 18360640; PMCID: PMC1936313.
