Bovine respiratory disease (BRD) continues to be the most significant cause of morbidity, mortality, and economic loss in the U.S. cattle industry [1-3]. Affecting both beef and dairy cattle across all production stages, BRD results in substantial animal welfare concerns and inefficiencies throughout production cycles [1,2]. Stakeholders across the beef, dairy, and allied industries, which includes veterinarians, producers, consultants, and industry partners, continue to identify BRD as a top research and extension priority due to its complex etiology, persistent economic burden, and the continued absence of effective, long-term control strategies [3].

Despite decades of research, BRD remains the leading cause of feedlot morbidity, preweaning calf mortality, and antimicrobial use in cattle [3,4]. Recent industry data also point to emerging challenges associated with respiratory health in evolving production systems, such as beef-on-dairy crossbred calves, which may exhibit unique disease susceptibilities and performance outcomes [3,5]. These production shifts, coupled with changes in management and marketing tactics, highlight the urgent need for renewed collaborative investigation that spans the full range of cattle production systems, from cow-calf and calf ranch operations to stocker, feedlot, and lactating dairy systems.

While the exact amount remains unknown, the annual economic impact of BRD likely exceeds hundreds of millions of dollars (USD) per year in the United States when accounting for mortality, treatment costs, and performance losses [6-8]. However, this figure underestimates the full burden of the disease, as current economic data are outdated, inconsistent, or incomplete across production sectors. Moreover, mortality loss has never been more expensive, yet comprehensive, system-specific economic assessments are scarce. Stakeholders have emphasized the critical need for new economic surveys and data-driven modeling to accurately quantify both direct and indirect impacts of BRD and related cardiopulmonary conditions. These assessments would support producers, consultants, and policymakers in implementing evidence-based, cost-effective strategies that improve animal health and resource efficiency.

Beyond direct financial losses, BRD represents a major constraint to sustainable beef and dairy production, influencing animal welfare, environmental sustainability, and consumer perception of industry practices. Failure to advance our understanding of BRD pathogenesis, epidemiology, and control strategies perpetuate systematic reliance on antimicrobials, increase production inefficiencies, and heighten production system vulnerabilities to emerging or underreported respiratory and cardiopulmonary syndromes. Without the proposed multidisciplinary efforts, the U.S. livestock industry will remain at risk from evolving disease dynamics that continue to influence respiratory disease outcomes.

While BRD remains the central focus, there is growing recognition that respiratory disease exists within a broader cardiopulmonary and systemic context. Emerging evidence links pulmonary disease to gastrointestinal health and systemic inflammation, suggesting that digestive tract integrity and microbial balance can significantly influence respiratory resilience [2,9,10]. Additionally, specific respiratory conditions such as bronchopneumonia, acute interstitial pneumonia, and mixed broncho-interstitial pneumonia contribute substantially to respiratory-related mortality and require refined diagnostic and pathologic characterization for improved prognostic, diagnostic, and therapeutic developments [11]. By broadening the project’s scope to include these cardiopulmonary and interconnected conditions, we would better address the multifactorial nature of respiratory health and expand our capacity to develop integrated diagnostic and management preventive solutions.

Improved surveillance and longitudinal data collection are critical for understanding the changing epidemiology of respiratory disease. There is limited information on disease prevalence and economic impact in the stocker, backgrounding, and beef-on-dairy sectors, in addition to an insufficient approach to standardization in diagnostic reporting across research laboratories. Enhanced surveillance, coupled with advanced data integration and modeling approaches, will facilitate earlier detection of emerging pathogens and quantify how production system attributes contribute to respiratory disease dynamics. This will allow improved identification of critical leverage points where targeted interventions, such as improved vaccination strategies, management changes, or genetic selection, may yield the most significant impact on respiratory disease control and resource efficiency.

The proposed research is built upon the proven capacity and expertise of NC1192 member stations, which collectively possess the infrastructure, datasets, and interdisciplinary expertise required to address BRD and related diseases (e.g., congestive heart failure, endocarditis, liver abscessation, etc.) from molecular to systems-based levels. Advances in genomics, metagenomics, transcriptomics, and systems biology now enable integrated exploration of the host–pathogen–environment relationship and multivariable risk factors that confer respiratory disease resistance or tolerance. Ongoing efforts have identified gene expression markers linked to BRD resistance, characterized virulence mechanisms of key pathogens, and developed improved diagnostic and vaccination tools [12-16]. Moreover, the multistate structure of NC1192 offers unique advantages as it brings together complementary expertise in epidemiology, microbiology, immunology, economics, nutrition, genetics, and animal husbandry while representing the multitude of production environments across the U.S. Coordinated collaboration allows standardized protocols, larger sample sizes, and broader applicability of research findings. Shared access to diagnostic tools, pathogen isolates, and multi-institutional datasets would accelerate discovery, validation, and translation into field-relevant outcomes. Furthermore, active partnerships with national organizations such as the American Association of Bovine Practitioners (AABP), the Academy of Veterinary Consultants (AVC), and industry collaborators ensure that emerging knowledge rapidly reaches stakeholders who can apply it in practice.

Completion of the proposed work will yield measurable scientific, economic, and societal benefits, including:

• Enhanced understanding of respiratory and associated disease etiologies;


• Improved diagnostic, surveillance, and control strategies against respiratory disease;


• Quantified economic impact and system-based solutions for respiratory disease;


• Expanded knowledge transfer and capacity building.

This project directly supports the USDA Research and Development Priorities by utilizing innovative technologies and collaborations within the fields of genomics, data modeling and epidemiology, systems biology, and veterinary medicine to solve a critical problem facing beef cattle production. By developing solutions to mitigate BRD, this work is essential to advancing food and nutrition security and strengthening rural prosperity by ensuring a more resilient, economically viable animal protein supply chain in the United States.