OBJECTIVE To evaluate the effectiveness and safety of dipyrone to control pyrexia in horses with naturally occurring disease under field conditions. ANIMALS 138 horses with pyrexia and various infections evaluated at 14 veterinary sites in 12 states. PROCEDURES In the first (effectiveness) phase of this 2-phase study, horses were randomly assigned 3:1 to receive 1 dose of dipyrone (30 mg/kg [13.6 mg/lb], IV) or an equivalent amount of placebo. Effectiveness was defined as a decrease in rectal temperature ≥ 1.1°C (2°F), compared with the pretreatment value, or a rectal temperature of ≤ 38.3°C (101.0°F) 6 hours after treatment administration. Horses deemed to have an appropriate reduction in rectal temperature (regardless of treatment group) by 6 hours were immediately entered into the safety phase of the study, in which dipyrone was administered IV at 30 mg/kg between 0 and 8 times up to every 8 hours on an as-needed basis, as determined by the clinical investigators. Horses were monitored throughout for adverse events. RESULTS A significantly greater proportion of dipyrone-treated horses (76/99 [77%]) had an effective treatment response than did placebo-treated horses (6/31 [19%]). Posttreatment adverse events were mild and transient. No differences in types or prevalence of gastrointestinal adverse events were evident between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE Dipyrone was effective in controlling pyrexia by 6 hours after IV administration of a single 30-mg/kg dose in a large proportion of treated horses. Adverse effects were minimal.

Severe equine asthma (SEA) is a chronic inflammation of airways affecting ~14–20% of adult horses in the Northern Hemisphere. SEA is characterized by a mixed phenotype of T helper cell responses with marked neutrophilia in the bronchoalveolar lavage fluid (BALF) of affected horses. Human studies have demonstrated the impact of gut microbiota in many diseases, including asthma susceptibility and severity. However, the potential role of the gut–lung axis in the development and persistence of SEA remains to be determined. This study aimed to identify key bacterial, archaeal, and fungal microbiota alterations in the feces of horses with severe neutrophilic asthma (n = 4) compared to healthy horses (n = 8). Archaea alpha diversity was lower in the feces of SEA-affected horses, but with high abundance of archaea genus Candidatus Nitrosocosmicus, which impacts hydrogen metabolism in horses with SEA. Other key bacterial and fungi species differences lower in SEA included Blautia and Alternaria, respectively. Blautia is associated with positive metabolic health due to its fibrolytic capabilities. Overall, our findings indicate that horses experiencing severe neutrophilic asthma have an imbalance in the intestinal microbiota that may exacerbate systemic inflammatory responses through the gut–lung axis.