Targeted therapy for treatment of chronic rhinosinusitis

Abstract

This invention provides an effective, targeted therapy for persons suffering from an endotype of chronic rhinosinusitis which is characterized by elevated levels of LTE4 in urine.

Claims

1. A method for providing targeted antileukotriene therapy to a person suffering from chronic rhinosinusitus (CRS) comprising: a. measuring the LTE4 level in the urine of a person suffering from CRS; b. selecting the person for treatment if the person's LTE4 level is above 104 pg/mg Cr; c. selecting a device that targets the high and deep nasal cavities and paranasal sinuses; and d. treating the selected person with between about 40 micrograms/day and 1 milligram/day of zafirlukast, wherein the zafirlukast is administered topically via the device and is delivered high and deep in the nasal cavities to the regions of the osteomeatal complex and superior turbinate of the person suffering from CRS.

2. The method of claim 1, wherein the zafirlukast is delivered as an aqueous suspension.

3. The method of claim 1, wherein the zafirlukast is delivered as a powder.

4. The method of claim 1, wherein the zafirlukast is delivered via a breath-activated nasal delivery device.

Description

DETAILED DESCRIPTION

[0016] In one aspect of the invention, the LTE4 level in the urine of a person suffering from CRS is measured on 24-hour urine specimens using the LC-MS method developed at Mayo Medical Laboratories. Many commercial diagnostic laboratories are equipped to carry out such measurements. An LTE4 level above about 104 pg/mg Cr is considered to be elevated.

[0017] In one aspect of the claimed invention, the zafirlukast is administered topically. This provides significant advantages over oral delivery of the drug. Oral delivery exposes the drug to the digestive tract, with potential for significant modification of the drug before it reaches the targeted area. Moreover, oral delivery involves systemic exposure, with risk of unwanted side effects. Appropriate delivery devices can deliver higher concentrations of a drug to the targeted tissue (the nasal passages) without systemic exposure, thereby reducing the side-effect profile and improving the efficacy of the drug.

[0018] In one aspect of the claimed invention, the zafirlukast is administered via a spray or aerosol into the nose. In one aspect of the invention, a breath-activated nasal delivery device is used to deliver the spray or aerosol past the anterior portions of the nose and into the nasal passages and cavities, preferably into the regions of the osteomeatal complex and superior turbinate. A suitable example of such a device is currently commercially available from Optinose. The device provides broad, consistent drug delivery high and deep in the nasal passages, leveraging the mucosal surfaces as the target for the treatment of CRS.

[0019] In one aspect of the invention, the zafirlukast that is administered via a breath-activated nasal delivery device is formulated as a powder, with particle size being between 10 and 18 microns. In another aspect, the zafirukast is formulated as an aqueous suspension.