Research Summary - 4

Nebulizer use in ruminants: Case review and in vitro evaluation

Date/Time: 9/13/2025    15:30
Author: Elizabeth  Rumfola
Clinic: Texas A&M University
City, State, ZIP: College Station , TX  77843

E.G. Rumfola, DVM, BS 1 ; H.L. Drerup, DVM, BS 1 ; K.M. Wiggins, BS 1 ; A.B. Wethington, DVM 1 ; E.G. Nagy, DVM, MS, PhD, CVC, DACVIM 1 ; R.M. Legere, DVM, MS, PhD, DACVIM 1 ;
1Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843

Introduction:

Treating severe respiratory disease in ruminants is often challenging, especially for judicious antimicrobial stewardship and appropriate treatment duration. Nebulized therapy in ruminants delivers intrapulmonary aerosolized drugs with anecdotally reported success, but efficacy of commonly used therapeutic medications with commercially available veterinary nebulizers is relatively unexplored. Nebulizer performance is characterized by efficiency, to minimize stress and shorten treatment time, and the particle size distribution (PSD) of aerosol droplets, which determine where droplets deposit in the respiratory tract (Cha 2017). Previous investigations of nebulized drug therapy in ruminants focused on devices that are no longer available, drugs that are not legal or commonly used in the U.S., or on clinical outcomes without consideration of the impact of nebulizer device or drug formulation (Spire 1978; Genicot 1992, 1994, 1995, 1996; Sustronck 1995; Yildiz 1997; Joshi 2017; Ok 2020, 2021). Our long-term goal is to develop evidence-based best practices for nebulizer use in ruminants to optimize drug delivery, reduce treatment costs, and ultimately improve patient outcomes. Here, we had 2 specific aims: (1) to perform a retrospective case review at Texas A&M University Large Animal Teaching Hospital to characterize nebulizer drug use and clinical impacts, and (2) to evaluate effects of the nebulizer device and different drug formulations on drug flow rate and clinically relevant PSD parameters correlated with extent of intrapulmonary drug delivery.

Materials and methods:

TAMU LATH clinical case records for all cattle, sheep, and goats seen from January 2020 to June 2025 with complete records and treated with a nebulizer were reviewed for drug(s) used, nebulizer protocol, and clinical parameters including diagnosis, treatment, and case outcomes. All off-label drug use was performed under AMDUCA guidance. The 5 most frequently nebulized drugs were selected for in vitro testing: (1) 0.9% saline, (2) ampicillin sodium, (3) tulathromycin (Draxxin, diluted 1:1 with saline), (4) albuterol sulfate, and (5) dexamethasone (diluted 1:1 with saline. The 2 jet nebulizers used in the clinic (DeVilbiss PulmoAide, Silver Horse Care Down N’ Dirty) and 2 nebulizer cup styles available in the clinic (DeVilbiss VixOne, Hudson MicroMist) were tested in a crossover design, yielding 4 compressor-cup pairs. Drug viscosity was measured by digital rheometer. All 5 drugs were tested in each of the 4 nebulizer compressor-cup pairs for 3 minutes duration, capturing aerosol into a simulated throat with breathing simulator (25 L/min unidirectional flow) and measuring PSD perpendicular to air flow by laser diffraction (Spraytec, Malvern PanAlytical). Flow rate was measured by changes in drug volume in reservoir cup over time of nebulization. All testing was performed in triplicate. Laser diffraction software calculated PSD parameters once per second, and average values over 3 minute test were used in analysis. Data was log-transformed to achieve normality in Graphpad Prism 10 (p < 0.05). Pearson’s correlation and multi-variable analysis was performed to characterize strength of relationship between drug, viscosity, compressor, and cup style on PSD parameters and nebulizer flow rate.

Results:

Inclusion criteria yielded 175 cases, consisting of 52% cattle (91/175), 29.1% goats (151/175), and 10.9% sheep (19/175). Albuterol was the most commonly used drug, given to 90.9% of cases (159/175). Antimicrobials were used in 79.4% of cases (139/175); of these 98.6% also received albuterol concurrently (137/139). Dosing, duration, and nebulizer protocols varied between cases. Clinically important differences for both particle size distribution (i.e., % of particles in size ranges likely to reach the deep lung) & flow rate were observed with the same drug across multiple nebulizer setups (2-way ANOVA; p < 0.0001), different drugs within the same nebulizer setups (2-way ANOVA; p <0.01), and even different reservoir cups for the same drug & air compressor (2-way ANOVA; p < 0.001). Importantly, flow rate was not correlated with extent of inhalable particles, which suggests that visual appearance of aerosol vapors and drug being aerosolized from the device cannot be empirically considered a marker of drug delivery to the lungs.

Significance:

Considerable and clinically relevant differences between nebulization devices and drugs used for treating respiratory disease in ruminants warrant further investigation to optimize treatment efficacy while enhancing patient safety and clinical outcomes. Consistent practices are important to ensure optimal drug delivery, and guidelines should be derived from evidence-based and clinically relevant testing of nebulizer devices and drugs used to treat ruminants in practice today.