Topical Intranasal Antifungals

• Fungal colonization is present in >95% of the population.

• The role that colonized sinonasal fungus plays in the pathophysiology of CRS is unknown.

• Topical antifungals, namely amphotericin B, have been trialed to attempt eradication of fungal colonization and reduction of the resulting inflammation.

1. Trials have failed to demonstrate a clinical benefit when utilizing topical amphotericin B.

• Currently, this evidence recommends against the routine use of topical antifungals in the management of CRS

Alternative Topical Therapies

• Many alternative topical therapies have been evaluated such an Manuka honey, surfactants, and xylitol.

• Given the paucity of research on the alternative treatments, it is challenging for guidelines to provide recommendations.

• Alternative topical therapies are often used in patients with recalcitrant CRS.

Surfactants

• Surfactants are amphipathic molecules that act as mucolytics to decrease mucous viscosity; they may have antibacterial or antibiofilm properties.

• There is a high rate of local complications including local irritation, ciliary dysfunction, and olfactory dysfunction.

• Baby shampoo drops placed into isotonic saline irrigation have been studied as a topical surfactant.

• There may be minor improvements in post-nasal drip when using baby shampoo irrigations for CRS.

• The use of topical sinonasal surfactants carries a risk of olfactory injury.

Manuka Honey

• Manuka honey is a naturally occurring honey with natural antibacterial properties against staphylococcus and pseudomonas biofilms.

• In vitro findings (antibiofilm properties) have not been reproduced in clinical trials, however, and data supporting a clinical benefit are limited.

Xylitol

• Xylitol is a naturally occurring sugar alcohol.

• It is often use in patients with xerostomia.

• In addition, it has antimicrobial properties secondary to altering salt properties in sinonasal secretions.

• In vivo, it is associated with decreased bacterial loads, specifically pseudomonas.

• A study examining the efficacy of xylitol irrigations did show improvements in the disease specific QoL in CRS patients.

• Although further study is required, xylitol may be of benefit in selected patients.

Delivery Methods

• A variety of delivery methods for topical medications exist:

1. High volume (>100 ml) irrigations

2. Meter-dose low-volume sprays

3. Atomizer

4. Nebulized solutions

5. Nasal drops

• Evidence suggests that high-volume irrigations (ie, budesonide irrigations) provide the best distribution and penetration of the paranasal sinuses.

• Head position during the topical delivery significantly impacts the distribution to the sinonasal cavity.

1. For high-volume irrigations, the head down forward position provides the best sinonasal penetration and delivery.

2. For low-volume solutions, such as nasal drops, the lying head low and lying head back positions have the best penetration to the olfactory cleft and the nasal cavity.

• The mechanism of action is similar to topical intranasal steroids in decreasing sinonasal inflammation through a variety of pathways including:

1. Reducing circulating leukocytes (neutrophils, eosinophils, and basophils)

2. Decreasing vascular permeability

3. Reducing glycoprotein release from submucosal glands

4. Inhibiting histamine and leukotriene release (from basophils)

5. Inhibiting arachidonic acid metabolites to decrease inflammation

6. Inhibiting neuropeptide induced inflammation but increasing enzymatic degradation

• The use of a short course of systemic corticosteroids have been shown:

1. Reduce polyp size

2. Improve QoL

3. Improve sinonasal symptoms

• The specific dosing for short courses of systemic corticosteroid is variable but often includes prednisone (30 mg to 60 mg, once per day for 10 to 21 days; the taper depends on dose and duration).

• Of note, the improvements from a short course of systemic corticosteroids are not sustained past three months in the absence of continued topical intranasal steroid therapy.

• There are significant potential adverse effects associated with the use of systemic corticosteroids:

1. Skin thinning

2. Purpura

3. Weight gain

4. Cataracts

5. Glaucoma

6. Cardiovascular disease

7. Pancreatitis

8. Hypertension

9. Osteoporosis

10. Acute psychosis

11. Hypothalamic pituitary adrenal axis suppression

12. Adrenal crisis (when steroids stopped)

13. Hyperglycemia

14. Immune system suppression/infection prone

• Use of systemic corticosteroids should be assessed on a case-by-case basis. Clinicians should involve patients in a shared decision-making process in order to balance the benefits with the associated risks.

• As our understanding of the underlying pathophysiology of CRS has increased, the reliance on systemic antibiotics to manage CRS has decreased.

• Systemic antibiotics may be divided into two therapeutic options:

1. Short-term antibiotics (typically <4 weeks)

2. Long-term anti-inflammatory antibiotics (typically 12 weeks or longer)

Short-Term Systemic Antibiotics

• Short-term antibiotics are generally comprised of culture-directed or broad spectrum antibiotics.

• Common short-term antibiotics used include amoxicillin-clavulanate, Trimethoprim-sulfamethoxazole, and moxifloxacin.

• Potential adverse effects of systemic antibiotics include gastrointestinal upset along with risk of C. difficile colitis and antibiotic resistance.