Role of Desloratadine in Reducing Inflammation From Occupational Heat Strain

Potential Off-label Use of Desloratadine to Mitigate Inflammation Caused by PPE-induced Heat Stress

The aim of this initial investigational study is to compare the effect of desloratadine on the inflammatory responses to heat stress in firefighters exercising in their personal protective equipment.

Significant heat strain where temperatures approach and exceed 39.0 degrees celsius is known to increase intestinal permeability and induce a graded systemic inflammatory response which includes increases in interleukin-6, tumor necrosis factor alpha, and c-reactive protein. Recent data examining firefighters found fire service instructors possessed greater resting levels of inflammatory markers and that 18-29% of the variation in these markers could be explained by frequency of heat strain. Firefighters themselves are susceptible to core temperatures ranging between 38.5 and 39.0C in as little as 2-3 work cycles. Considering resource limitation in the fire service, such workloads is a realistic possibility when at structural fires, particularly for first alarm apparatus.

Though there is a well-defined role of the inflammatory response in adaptive changes, elevated resting levels begs the question of whether such frequency of exposure and acute inflammatory flux in fire service workers may contribute to chronic elevations of inflammatory markers and altered disease risk. Elevations in c-reactive protein are associated with cardiovascular risk with studies indicating a causative role of monomeric c-reactive protein in platelet activation and thrombus growth.

Cooling methods save for cryotherapy have demonstrated limited to mild effectiveness for mitigating the inflammatory responses to heat strain resulting in no solution to attenuate acute inflammatory responses. The mast-cell stabilizing properties of desloratadine and its safety profile make it an interesting candidate for investigating its use in this context.

This study seeks to determine whether 10mg desloratadine taken before and 24h after exertional heat strain to a core temperature to a core temperature of 39.5 degrees celsius reduces the associated inflammatory response measured over a 72-hour period.

Inclusion Criteria:

• Demonstrated willingness to participate in the study and adhere to procedures by signing a written informed consent
• Biological males aged 19-50
• Successful Physical Activity Readiness Questionnaire (PAR-Q)
• Ability to swallow core temperature capsule
• VO2Max >35 mL/kg/min
• No allergy or current dosage of H1 histamine receptor antagonists
• Participants must be in good health with no 'Category A' diseases/conditions outlined in National Fire Protection Association (NFPA) 1582 (https://www.iafc.org/docs/default-source/1vcos/vws\_rrkit\_nfpa-1582.pdf?sfvrsn=ca9b9f0d\_2)

Exclusion Criteria:

• Biological females
• Males below age of 19, and 51-years or older
• Unsuccessful PAR-Q
• VO2Max below 35 mL/kg/min
• Allergy to H1 histamine receptor antagonists
• Esophageal constriction (inability to swallow core temperature capsule)
• Any condition or disease listed as 'Category A' in NFPA 1582 that would disqualify a person as a firefighter.
• Current use of NSAIDS or steroid drugs (oral or nasal).
• Consumption of caffeine, nicotine, or alcohol in the preceding 12-hours.
• Dehydration (urine specific gravity over 1.030)
• Recent cold/flu (at least 7-days clear of symptom resolution)
• No use of antibiotics in preceding 14-days.
• Dosing of medication that is known to exhibit adverse reactions with desloratadine dosing.