BACKGROUND:Transport-associated pneumonia contributes substantially to morbidity, impaired welfare, and economic loss in high-performance horses and may be associated with alterations in the respiratory microbiota. HYPOTHESIS/OBJECTIVES:Examine the effect of long-distance transport on the respiratory microbiota and correlate changes in microbiota diversity and composition with systemic and airway inflammation. ANIMALS:Seventeen client-owned performance horses transported from New England to Florida under optimized trailering conditions, and 12 non-traveling horses. METHODS:Physical examination, blood testing, nasopharyngeal wash, endoscopy, tracheal aspirates, and thoracic ultrasonography were performed 48 h before, and 24 and 72 h after transport (T1-T3). Upper and lower respiratory microbiota were characterized using high-throughput 16S rRNA sequencing and correlated with clinical variables using constrained ordination. Transport effects were evaluated using repeated measures analysis of variance (ANOVA). RESULTS:Cortisol concentrations decreased post-transport (P = .02), whereas ultrasound scores (P = .01) and serum amyloid A concentrations (P = .03) increased from T1 to T3. Timepoint explained a small but significant portion of microbiota variability (P < .001). Upper and lower airway microbiota differed, with the lower airway showing more β diversity (lower stability; P < .001). Together, timepoint and ultrasound scores explained 19% and 10%, respectively, of nasal and tracheal bacterial microbiota variability. Operational taxonomic units with the highest fit to timepoint and ultrasound were enriched for plant-associated bacterial taxa, mainly Hyphomicrobiales. CONCLUSIONS AND CLINICAL IMPORTANCE:Even under standardized, optimized transport conditions, respiratory microbiota alterations occurred in healthy, athletic horses, correlating with ultrasonographic evidence of pulmonary inflammation. Inclusion of the fungal mycobiome may further improve our understanding of transport-associated respiratory disease.

Aging may modify the pharmacokinetic disposition and excretion of gentamicin, although drug dose adjustments in aged horses are uncommon in clinical practice. Since high-dose, once daily dosing of gentamicin is considered therapeutically most effective, a comparative single-dose study was conducted to evaluate the differences in pharmacokinetics between healthy young-adult (5-10 years) and geriatric (≥ 25 years) horses receiving 6.6 mg/kg gentamicin intravenously. Blood samples were collected at designated time-points following drug administration and frozen at -80°C until assayed by a validated immunoassay. Gentamicin plasma concentrations versus time plots were analyzed by noncompartmental analysis using commercial software (WinNonlin-v8.4). Baseline physical examination and hematological parameters did not differ between age groups, except for a lower mean bodyweight in the geriatric group (477 ± 4 kg vs. 402 ± 6 kg). None of the pharmacokinetic parameters were statistically different between age groups. The oldest geriatric horse (41 years) had a longer half-life and lower clearance of 5.3 h and 22.79 L/h, respectively, compared to a range of 1.39-2.56 h and 26.39-40.59 L/h for the remainder of the geriatric group (25-29 years). Further studies may be indicated in horses > 30 years old to determine if dose reduction is necessary in this population.

BACKGROUND:Corticosteroids are the main pharmacologic treatment for equine asthma (EA) but may have adverse effects in metabolically unstable horses. Recent pilot studies support the use of nebulized lidocaine as an alternative treatment option. HYPOTHESIS/OBJECTIVES:Nebulized lidocaine will improve EA-associated clinical variables and airway inflammation. ANIMALS:Twenty client-owned horses diagnosed with EA. METHODS:Randomized, blinded, in-hospital study comparing 1 mg/kg preservative-free 4% lidocaine (n = 10) nebulized via Flexineb (twice daily for 7 doses) to 0.9% saline control (n = 10). Clinical examination, endoscopy, lung function, bronchoalveolar lavage (BAL) cytology, and inflammatory cytokines in blood and epithelial lining fluid (ELF) were compared between treatment groups using univariate analyses. Global linear models were used to assess covariate impact (P < .05). RESULTS:The effect of treatment on clinical variables (clinical score, lung function, mucus, and BAL cytology) did not differ between saline and lidocaine treated horses. However, the severity of EA as a covariate significantly impacted multiple baseline variables and confounded the effect of treatment type. Saline-treated horses showed significantly larger decreases in ELF tissue necrosis factor alpha (P = .04) and interferon gamma concentrations (P = .03), compared with lidocaine-treated horses, independent of covariates. CONCLUSIONS AND CLINICAL IMPORTANCE:We did not identify a difference in treatment effect of nebulized lidocaine compared to saline on clinical variables in hospitalized asthmatic horses. A longer duration of lidocaine administration or focus on severe EA may be necessary to establish treatment effects. Observed changes in lower airway cytokine concentrations suggest that saline may have more than a placebo effect in treating EA.

OBJECTIVE:To illustrate the use of the ARDSVet (Acute Respiratory Distress Syndromes in Veterinary Medicine) definitions in small and large animal patients using a case-based approach. ETIOLOGY:Acute respiratory distress syndrome (ARDS) in veterinary patients is triggered by a wide range of clinical insults. These include probable risk factors such as systemic inflammation, pancreatitis, and sepsis, as well as possible risk factors such as blood transfusions and ventilator-induced lung injury. These conditions may lead to diffuse alveolar damage and increased pulmonary capillary permeability. DIAGNOSIS:ARDS remains challenging to diagnose, particularly in veterinary patients with variable resources. The updated ARDSVet definitions offer a structured framework based on five criteria: a known or suspected risk factor, onset of respiratory distress within 1 week, exclusion of cardiogenic edema and volume overload, thoracic imaging (including point-of-care ultrasound) demonstrating diffuse pulmonary infiltrates, and impaired oxygenation assessed by PaO2/FiO2 or SpO2/FiO2 ratios. Case vignettes highlight revised oxygenation thresholds, expanded use of point-of-care ultrasound, and the role of advanced respiratory support techniques. THERAPY:ARDS treatment is primarily supportive, focusing on oxygen supplementation, high-flow nasal oxygen, and/or mechanical ventilation, along with management of the underlying cause. While ARDSVet does not offer formal treatment guidelines, case vignettes illustrate how supportive strategies may be adapted across disease stages without endorsing any specific therapeutic interventions. PROGNOSIS:Prognosis in animals with ARDS is influenced by the severity of respiratory compromise, the underlying cause, and the timelines of appropriate interventions. The updated definitions will aid clinicians in early and timely recognition of ARDS, although further studies are needed to assess its impact on clinical outcomes.

BACKGROUND:Sepsis has been defined in humans as the concurrent proven or suspected presence of microbial infection and the systemic inflammatory response syndrome (SIRS). Sepsis is the leading cause of morbidity and mortality in neonatal foals. The clinical utility of using SIRS or its individual components to predict infection and mortality in critically ill foals is currently unknown. OBJECTIVES:Assess the ability of history and signalment, clinical findings, laboratory results, and SIRS-related indices to predict infection and mortality in critically ill foals. ANIMALS:Retrospective, multi-center, cross-sectional study using a convenience sample of 1068 critically ill foals < 3 days of age admitted to 16 veterinary referral hospitals in 4 countries. METHODS:Data were retrieved from medical records. Infection was defined as the presence of bacteremia (positive blood culture) or clinical identification of an infected focus on admission. Univariate non-parametric and categorical methods, multivariate logistic regression, and classification tree methods were used for statistical analysis. RESULTS:Foal age at admission and presence of toxic neutrophils were independent predictors of infection, whereas SIRS-related indices were not predictive of infection. In-hospital mortality was 24%. Independent predictors for mortality were hypokinetic pulses, cold extremities, presence of seizures, blood L-lactate concentration > 6.0 mmol/L, and increased serum potassium and total bilirubin concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE:The presence of infection in critically ill newborn foals was not predicted by SIRS indices. Cardiovascular dysfunction was strongly associated with mortality, suggesting that maintaining adequate perfusion and pulse pressure should be important treatment goals.

OBJECTIVE:To use a systematic, evidence-based consensus process to develop updated definitions for acute respiratory distress syndrome (ARDS) in veterinary medicine to facilitate its recognition and diagnosis. DESIGN:International consensus conference series involving 12 multidisciplinary international content experts from three countries, using consensus conference methodology and implementation science. A systematic review of the literature was carried out for ARDS and acute lung injury in veterinary medicine. Updated definitions of ARDS were generated based on synthesis of human and veterinary literature. Consensus on the definitions was achieved through Delphi-style surveys involving the above subject matter experts. Draft recommendations were made available through industry specialty listservs for feedback, which was incorporated in the final definitions. RESULTS:Updated definitions were developed for Veterinary Acute Respiratory Distress Syndrome (ARDSVet) in small animals (dogs and cats) and large animals (equids). For small animals, 690 publications were identified for dogs and 99 were identified for cats in the initial literature search. Seventeen cats and 103 dogs with ARDS were represented across these publications. For the initial literature search in large animals, there were 83 equid, five camelid, 158 pig, 714 sheep and goat, and 270 cattle publications identified. Additionally, 1084 publications were found across all large animals that addressed interstitial lung disease. Five adult equids and 136 foals with ARDS were represented across these publications. The updated ARDSVet definitions incorporate criteria for risk factors, origin and timing of pulmonary edema, and impaired oxygenation, with severity stratified by oxygenation and definitions for both intubated and nonintubated animals. CONCLUSIONS:The evidence review and consensus process resulted in updated definitions that can be used to improve the recognition of veterinary ARDS as well as facilitate and standardize future research, including the development of an ARDS registry and eventual treatment recommendations.

Glucocorticosteroids remain the most common pharmaceutical approach for the treatment of equine asthma but can be associated with significant side effects, including respiratory microbiome alterations. The goal of the study was to assess the impact of 2% lidocaine nebulization, a projected alternative treatment of equine asthma, on the healthy equine respiratory microbiota. A prospective, randomized, controlled, blinded, 2-way crossover study was performed, to assess the effect of 1 mg/kg 2% lidocaine (7 treatments over 4 days) on the equine respiratory microbiota compared to control horses (saline and no treatment). Clinical assessments and respiratory samples, including nasal wash, endoscopic tracheal aspirate and bronchoalveolar lavage fluid, were obtained at each sample collection timepoint. The profile of the respiratory bacterial microbiota was evaluated using 16S amplicon sequencing, and clinical data compared using related samples analyses, based on data normality. The treatment did not affect the clinical data or alter the tracheal and nasal microbiota in healthy horses. However, time explained 12.6% of microbiota variation among samples. A significant difference in bacterial composition was observed between nasal and tracheal samples, showing the greatest relative abundance of Actinobacteria and Firmicutes, respectively. Bacterial DNA from bronchoalveolar lavage fluid did not amplify with generic primers targeting the V4 variable region of the prokaryotic small subunit ribosomal RNA gene, despite attempting multiple DNA extraction methods and PCR protocols, and after excluding PCR inhibition. This observation indicates that bronchoalveolar lavage fluid of healthy horses has a low bacterial load.

Pulmonary function testing is critical to the diagnosis of equine asthma (EA), an important cause of respiratory disease in the horse, but its clinical use has remained elusive, unfortunately, due to the complexity of reference methods, esophageal balloon/pneumotachography (EBP), and forced oscillatory mechanics (FOM), so we sought a noninvasive, portable method for use in horses through rapid interruption of airflow for equilibration of alveolar pressure with proximal airway pressure, termed flow interruption (FI). Resistance (RINT) was computed as the relationship between the change in pressure at the nose before and immediately after interruption and flow immediately before interruption. A pilot study in five healthy university-owned animals using EBP and FI showed good correspondence between the two methods: RINT (0.33 ± 0.05 cmH2O/L/s) and RL (0.31 ± 0.06 cmH2O/L/s). In two separate populations of client-owned horses, with random assignment of methods to FI versus EBP (n = 8), RINT showed good correlation with RL in horses (rs = 0.995, P = 0.0002) and accords with RL, with no significant difference between RINT and RL. Using FOM (n = 12), RINT (0.67 ± 0.31 cmH2O/L/s) has good correlation with RRS measured with FOM (r = 0.834, P = 0.0001), but is consistently smaller than RRS (0.74 ± 0.33 cmH2O/L/s). Histamine bronchoprovocation (HBP) was performed in a subset of these horses: FI classified one horse in six as less reactive than did EBP, and FI classified one horse in seven as less reactive than did FOM.NEW & NOTEWORTHY We developed and document for the first time the use of flow interruption for the rapid and noninvasive measurement of resistance in equine patients and demonstrated short- and long-term stability and accuracy in comparison with the reference methods.

OBJECTIVE To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (>= >= 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. ANIMALS 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses >= 25 years old). METHODS Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 degrees C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant. RESULTS Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups. CLINICAL RELEVANCE The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses com-- pared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.

OBJECTIVE:This study determined the in vitro efficacy of 6 common anthelmintics (eprinomectin, ivermectin, milbemycin oxime, moxidectin, selamectin, and fenbendazole) on motility (viability) of infectious third-stage larvae (L3) of Crenosoma vulpis, Angiostrongylus vasorum, and Aelurostrongylus abstrusus, which are important causes of canine and feline cardiopulmonary disease.SAMPLES:First-stage larvae (L1) from C vulpis, An vasorum, and Ae abstrusus.PROCEDURES:Naïve Limax maximus slugs were fed 1,000 to 2,000 L1 and held at 16 °C for at least 4 weeks to produce live L3. Approximately 50 to 100 L3/well were subsequently incubated in culture media alone or media containing 6 separate test anthelmintics at 4 concentrations, to bracket expected in vivo drug plasma levels in anthelmintic-treated dogs and cats. Drug effects on L3 motility (viability) were analyzed by multilevel logistic models, generating dose-response relationships. Experiments were completed 1-9/2019.RESULTS:Drug concentration estimates corresponding to a 50% larval mortality rate identified that C vulpis was the most sensitive species to the anthelmintics tested. Ae abstrusus was most susceptible to moxidectin and selamectin, while An vasorum was insusceptible to all anthelmintics tested, except for selamectin at high drug concentrations.CLINICAL RELEVANCE:The in vitro anthelmintic response to antiparasitic agents may guide and improve disease therapy and prevention. Considering the observed lack of efficacy against L3, monthly anthelmintic treatment for protection against An vasorum infection in dogs would primarily rely on the anthelmintic's adulticidal activity. Maximal preventive control for An vasorum would, therefore, require at least 1 treatment administered a minimum of 1 week after the end of the transmission season.

BackgroundHemosiderophages in bronchoalveolar lavage fluid (BALF) are commonly ascribed to exercise-induced pulmonary hemorrhage (EIPH). Little information exists regarding the presence of these cells in horses that perform light or no work and that are referred for respiratory problems. ObjectivesEvaluate the presence of hemosiderophages in BALF of horses suspected of respiratory disease without history of or risk factors for EIPH and determine predictors of hemosiderophages in BALF in this population. MethodsObservational retrospective cross-sectional study using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Bronchoalveolar lavage fluid cytology reports of 353 horses evaluated for respiratory disease between 2012 and 2022 at the Cummings School for Veterinary Medicine were reviewed retrospectively. Horses with a history or likelihood of having performed past strenuous exercise were removed, and the remaining 91 horses were divided into hemosiderin-positive (HSD-POS) and hemosiderin-negative groups based on Perls' Prussian blue staining. Potential predictors for the presence of hemosiderophages in BALF (history, clinical evaluation, baseline lung function, airway reactivity, BALF cytology, and hemosiderin score) were compared between the 2 groups, using univariate and multivariate analyses. ResultsHorses with a diagnosis of severe equine asthma (sEA; odds ratio, 11.1; 95% confidence interval, 3.2-38.5; P < .001) were significantly more likely to be HSD-POS than horses with mild-to-moderate equine asthma. Conclusions and Clinical ImportanceHemosiderophages were found in the BALF cytology in a subset of horses that perform light or no work and presented for respiratory signs; these cells were found more frequently in horses with sEA. The link between hemosiderophages and sEA highlights previously unstudied pathology associated with this common disease.

(1) Background: Equine asthma (EA) is a pervasive and important cause of poor performance and respiratory morbidity in horses. Diagnosis of EA includes an owner complaint, clinical scoring, lung function testing, and cytological analysis of bronchoalveolar lavage (BAL) cytology. There is a paucity of information about the longitudinal course of the disease using these outcome assessments; thus, this study sought to describe and quantify, in horses with more than one visit to a specialty pulmonary clinic in New England, the type and range of clinical presentations with an eventual diagnosis of EA. It also aimed to develop and compare the outcomes of scoring systems for owner complaints and veterinary assessments, document and assess the diagnostic methods used, and evaluate the response of the horses to treatment and time. (2) Methods: This study was a retrospective, cross-sectional, STROBE-compliant observational analysis of equine patients who visited the Tufts Cummings Hospital for Large Animals (HLA) for evaluation of equine asthma (EA) from 1999–2023. The horses were categorized as having mild–moderate (mEA) or severe EA (sEA) using the ACVIM consensus statement guidelines. After excluding those with inadequate documentation or only one visit (n = 936), a total of 76 horses were included in the study. Of the 197 visits, 138 (70.0%) resulted in a diagnosis of mEA and 45 (22.8%) resulted in a diagnosis of sEA. Demographic information, owner complaints, clinical examination and scoring, lung function testing, BAL cytology, and recommendations for environmental remediation and pharmacologic treatment were recorded for all the visits. The data were analyzed for agreement between owner complaints (complaint score, CS) and clinical examination findings (examination score, ES), changes in CS and ES, lung function testing, and BAL cytology over time, with 197 visits recorded. (3) Results: A comparison between the CS and ES showed that the owners were more likely than veterinarians to detect cough, and a decrease in cough was the most common owner observation after treatment. The response to the histamine challenge, used to detect airway hyperreactivity, was significantly improved with treatment or time in the horses with mEA, whereas baseline lung function did not significantly change in mEA or sEA. (4) Conclusions: Owners can be astute observers of clinical signs, especially cough, in EA. Tests of airway hyperreactivity are more successful in detecting changes in mEA than are baseline lung function testing and assessment of BAL cytology.

https://doi.org/10.1093/af/vfac036 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons. org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com © Bedenice, Johnson Feature Article Neurologic conditions in the sport horse

There are limited options for treatment of the common disease, equine asthma. The aim of this study was to estimate the feasibility and potential efficacy of using nebulized lidocaine for treating equine asthma, while at the same time treating a separate cohort of asthmatic horses with inhaled budesonide. Nineteen horses with a history consistent with equine asthma were recruited from our referral population for a double-blind, randomized, controlled pilot clinical trial using Consolidated Standards of Reporting Trials (CONSORT) guidelines. After screening, 16 horses met the inclusion criteria for equine asthma and 13 horses actually completed the study. Horses were treated by their owners at home for 14 d before returning to our hospital for follow-up assessment. Interventions consisted of nebulization q12h for 14 d with 1.0 mg/kg body weight (BW) of lidocaine or corticosteroid treatment (nebulized budesonide 1 μg/kg, q12h). Clinical and tracheal mucus score, pulmonary function testing, and respiratory secretion cytology were assessed after 2 weeks of treatment to determine the outcome. Both lidocaine and budesonide cohorts had significant decreases (P < 0.05) in clinical score; the lidocaine cohort showed a significant decrease in bronchoalveolar lavage (BAL) neutrophil percentage and tracheal mucus score. Neither treatment resulted in significant changes in lung function parameters. No adverse events occurred. Lidocaine may be an effective and safe treatment for equine asthma in horses that cannot tolerate treatment with corticosteroids.

Thromboelastography (TEG) provides a global assessment of hemostasis and fibrinolysis and has broad applications to identify and monitor coagulation dysfunction in veterinary patients. Although alpacas are susceptible to a wide variety of coagulopathies, the assessment of TEG has not been reported in clinically healthy alpacas to date. The purpose of this study was to evaluate the analytical performance of recombinant human tissue factor (rhTF)- and kaolin-activated TEG and to establish reference intervals for TEG parameters (reaction [R] and clotting [K] times, angle [α], maximum amplitude [MA], and shear elastic modulus [G]) in healthy, adult alpacas. Kaolin and rhTF-activated TEG were performed using citrated whole blood samples from 20 clinically healthy, nonpregnant, adult Huacaya alpacas each after 30 min of sample storage at room temperature. Six individuals of a related species, dromedary camels, were also sampled for comparative purposes. All data were presented descriptively, assessed for normality, and compared using either independent-sample t tests or Mann-Whitney U tests, with P ≤ 0.05 considered significant. Reference intervals were calculated using a robust method and Box-Cox-transformed data. Mean TEG values (reference intervals) were determined for rhTF-activated TEG as follows: R 6.99 min (3.41-12.71), K 3.43 min (1.61-6.42), α 48.51° (27.21-67.38), MA 52.05 mm (21.53-65.92), and G 5.71 kdyn/cm2 (1.87-9.60), while mean values (reference intervals) for kaolin-activated TEG included R 7.72 min (4.48-11.43), K 4.24 min (2.03-9.20), α 45.06° (23.66-64.20), MA 52.18 mm (33.49-66.63), and G 5.78 kdyn/cm2 (NR-9.66). None of the measured TEG values differed significantly between activators, suggesting that activator choice may have a limited effect on TEG parameters in healthy alpacas. TEG results in alpacas were comparable to those of dromedary camels. These results will thus provide a useful starting point in the evaluation of hemostasis in adult camelids.

Enteric microbial pathogens, including Escherichia coli , Shigella and Cryptosporidium species, take a particularly heavy toll in low-income countries and are highly associated with infant mortality. We describe here a means to display anti-infective agents on the surface of a probiotic bacterium. Because of their stability and versatility, VHHs, the variable domains of camelid heavy-chain-only antibodies, have potential as components of novel agents to treat or prevent enteric infectious disease. We isolated and characterized VHHs targeting several enteropathogenic E . coli (EPEC) virulence factors: flagellin (Fla), which is required for bacterial motility and promotes colonization; both intimin and the translocated intimin receptor (Tir), which together play key roles in attachment to enterocytes; and E . coli secreted protein A (EspA), an essential component of the type III secretion system (T3SS) that is required for virulence. Several VHHs that recognize Fla, intimin, or Tir blocked function in vitro . The probiotic strain E . coli Nissle 1917 (EcN) produces on the bacterial surface curli fibers, which are the major proteinaceous component of E . coli biofilms. A subset of Fla-, intimin-, or Tir-binding VHHs, as well as VHHs that recognize either a T3SS of another important bacterial pathogen ( Shigella flexneri ), a soluble bacterial toxin (Shiga toxin or Clostridioides difficile toxin TcdA), or a major surface antigen of an important eukaryotic pathogen ( Cryptosporidium parvum ) were fused to CsgA, the major curli fiber subunit. Scanning electron micrographs indicated CsgA-VHH fusions were assembled into curli fibers on the EcN surface, and Congo Red binding indicated that these recombinant curli fibers were produced at high levels. Ectopic production of these VHHs conferred on EcN the cognate binding activity and, in the case of anti-Shiga toxin, was neutralizing. Taken together, these results demonstrate the potential of the curli-based pathogen sequestration strategy described herein and contribute to the development of novel VHH-based gut therapeutics.

Background Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Objective To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability. Animals Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respiratory disease within 6 months. Methods Prospective, descriptive study evaluating the immediate effects of 1 mg/kg 4% preservative-free lidocaine following nebulization with the Flexineb®. Prior to and following nebulization, horses were assessed using upper airway endoscopy, bronchoalveolar lavage, and pulmonary function testing with esophageal balloon/pneumotachography and histamine bronchoprovocation. Additionally, blood and urine were collected at predetermined times following single-dose intravenous and nebulized lidocaine administration for pharmacokinetic analysis. Results Upper airway sensitivity was unchanged following lidocaine nebulization, and no laryngospasm or excessive salivation was noted. Lidocaine nebulization (1 mg/kg) resulted in a mean epithelial lining fluid concentration of 9.63 ± 5.05 μg/mL, and a bioavailability of 29.7 ± 7.76%. Lidocaine concentrations were higher in epithelial lining fluid than in systemic circulation (Cmax 149.23 ± 78.74 μg/L, CELF:Cmaxplasma 64.4, range 26.5–136.8). Serum and urine lidocaine levels remained detectable for 24 and 48 h, respectively, following nebulization of a single dose. Baseline spirometry, lung resistance and dynamic compliance, remained normal following lidocaine nebulization, with resistance decreasing post-nebulization. Compared to the pre-nebulization group, two additional horses were hyperresponsive following lidocaine nebulization. There was a significant increase in mean airway responsiveness post-lidocaine nebulization, based on lung resistance, but not dynamic compliance. One horse had BAL cytology consistent with airway inflammation both before and after lidocaine treatment. Conclusions Nebulized lidocaine was not associated with adverse effects on upper airway sensitivity or BAL cytology. While baseline lung resistance was unchanged, increased airway reactivity to histamine bronchoprovocation in the absence of clinical signs was seen in some horses following nebulization. Further research is necessary to evaluate drug delivery, adverse events, and efficacy in asthmatic horses.

Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM—forced oscillatory mechanics vs. FP—flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3–25 years, 335–650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a randomized cross-over design. AHR was defined by the histamine dose needed to double FOM baseline resistance, or to achieve a 35% increase in FP delta flow. Bronchoalveolar lavage fluid (BALF) was subsequently collected and stained with modified Wright's and toluidine blue stains. Binary statistical tests (related samplesT-test, Mann-WhitneyU, Chi-square analyses) were performed to compare study groups, withP< 0.05 considered significant. Abnormal BALF cytology confirmed EA in 14/19 (73.7%) horses. Both FOM and FP revealed AHR in 7/14 (50%) of these EA horses. An additional 4/19 (21.1%) horses showed AHR based on FP but not FOM, including two horses with normal BALF cytology. A diagnosis of AHR was more often associated with FP than FOM (P= 0.013), although the prevalence of AHR was significantly higher in EA vs. non-EA horses, regardless of testing methodology. The phase angle between thoracic and abdominal components of breathing did not differ between test groups. In conclusion, FP diagnosed AHR more frequently than did FOM, including horses with no other diagnostic evidence of EA. Without further evaluation, these two testing modalities of AHR cannot be used interchangeably.