Topical Drug Delivery: The New Trend in Maintenance Therapy for Chronic Rhinosinusitis

By Raj Sindwani, MD, and Troy Woodard, MD

Surgery for chronic rhinosinusitis (CRS) improves quality of life but is not curative, and patients routinely require ongoing postoperative medical therapy. A growing trend in postoperative care is the use of topical drugs delivered directly to the diseased sinus mucosa via nebulization and irrigation. Topical treatments have two primary advantages over oral medications:

• With topical delivery, a higher concentration of drug can be administered directly to the site of the infection or inflammation within the sinuses themselves.
• Patients treated topically are not exposed to the systemic effects and complications of oral medications.

Green Lights, Yellow Flags

The literature in support of the use of topical antimicrobials for CRS and topical steroids for nasal polyps is mounting. The highest levels of evidence exist for studies of culture-directed antibiotic therapy in postsurgical patients, and it appears that both stable and acute exacerbations of CRS may respond to topical therapy. For example, use of adjunctive mupirocin irrigations to treat exacerbations of staphylococcal infections or to help eradicate methicillin-resistant Staphylococcus aureus from the nose is gaining favor. High-dose topical steroids are also now widely used by rhinologists as maintenance therapy for patients with refractory nasal polyps.

Nasal irrigations are easy to perform, they provide mechanical debridement and they can deliver medications into sinuses that have been surgically opened. Among the drugs being used as nasal irrigants are steroids, antibiotics and antifungals. Although the popularity of this type of drug delivery is growing, there is little information in the literature on possible complications or concerns regarding its use. Some recent evidence suggests caveats associated with nasal irrigations of which practitioners need to be aware (see “What to Watch For” sidebar).

A New Type of Sinus Lesion

One such caveat pertains to the emergence of paranasal sinus exostoses (PSE), a new diagnostic entity that was recently characterized by Cleveland Clinic rhinologists. PSE appears to be a complication of cold nasal irrigations affecting postoperative sinus cavities. Once formed, the sinus exostoses appear to be permanent, but they do not progress further after discontinuation of cold irrigations.

On endoscopy, these exostoses characteristically appear as “multiple cysts” (Figure 1), but they are hard to palpation with an instrument. On CT, they appear as multiple small bony growths on the luminal surfaces of the involved sinuses (Figure 2).

Figure 1 (A-B). Endoscopic views show two postoperative sinus cavities with the hard paranasal sinus exostoses.

Figure 2. CT imaging shows paranasal sinus exostoses as bony irregularities on the luminal surfaces of the affected sinuses.

PSE does not require surgical intervention unless the lesions progress to the point of being obstructive. Of note, PSE can mimic Gardner syndrome, an autosomal dominant disease characterized by multiple polyps within the colon, tumors (including skull base osteomas and thyroid cancer), fibromas and a variety of cysts. We suspect that the incidence of PSE will increase, given the rising popularity of nasal irrigations.

Irrigants Are Commonly Cold

Many of the medicated irrigations currently in vogue are compounded by local pharmacists or mixed by patients themselves. Notably, many of these solutions or their components require refrigeration. An analysis found that several standard formulations of medicated nasal solutions took two hours to reach room temperature after being removed from the refrigerator. The rate of passive warming for medicated solutions containing budesonide, mupirocin, amphotericin and tobramycin was not significantly different from the rate for saline. Although the critical temperature associated with PSE formation is unknown, it seems prudent to advise patients to remove irrigation solutions from the refrigerator at least 45 minutes before use to bring them closer to room temperature.

Active warming in a microwave oven or by some other means may compromise the effectiveness of the medication. The good news is that newer methods of formulating medicated solutions by mixing a dry-powder form of the drug (using materials such as Loxasperse®, for example) with room-temperature saline should mitigate some of these concerns.

What to Tell Your Patients

When patients are prescribed a topical nasal therapy for CRS, they should be informed of the planned duration of treatment as well as the risks, benefits and alternatives. Patients should be advised to use a clean irrigation device with clean water and to irrigate with solutions at or close to room temperature.

Dr. Sindwani (sindwar@ccf.org) is Head of the Section of Rhinology, Sinus and Skull Base Surgery in the Head & Neck Institute.

Dr. Woodard (woodart@ccf.org) is a staff physician in the Section of Rhinology, Sinus and Skull Base Surgery.