Predicting Bovine Respiratory Disease Outcome Using Latent Class Analysis

Bovine respiratory disease (BRD) is the most signicant disease affecting feedlot cattle. Indicators of BRD often used in feedlots such as visual signs, rectal temperature, computer-assisted lung auscultation (CALA) score, the number of BRD treatments, presence of viral pathogens, viral seroconversion and lung damage at slaughter vary in their ability to predict an animal’s BRD outcome, and no studies have been published determining how a combination of these BRD indicators may dene the number of BRD disease outcome groups. The objectives of the current study were 1) to identify BRD outcome groups using BRD indicators collected during the feeding phase and at slaughter through latent class analysis, and 2) to determine the importance of these BRD indicators to predict disease outcome. Animals with BRD (n=127) were identied by visual signs and removed from production pens for further examination. Control animals displaying no visual signs of BRD (n=143) were also removed and examined. Blood, nasal swab samples and clinical measurements were collected. Lung and pleural lesions indicative of BRD were scored at slaughter. Latent class analysis was applied to identify possible outcome groups.

Bovine Adenovirus 3; BAdV3). For these samples, 1 × 10 mL EDTA plasma BD vacutainer (BD Vacutainer, Becton, Dickinson and Company, North Ryde, NSW, Australia) for each animal was centrifuged (2,500 x g, 20 min) within 30 minutes of collection. Plasma from the tube was transferred to separate storage vessels and stored at -20 o C until analysis.
Following feedlot induction, animals were designated to four production pens for an average of 114 days on feed, with one pen designated for each week's intake. Animals were fed to allow for ad-libitum feed consumption and were transitioned through three starter rations to a steam-aked barley-based nisher diet over an 18-day period. Detail on ration formulation for the nisher diet has been described previously (7).
Bovine Respiratory Disease monitoring and clinical data collection Animals were checked daily by trained feedlot staff for visual signs of BRD, starting from Day 1 of the study (the day after the rst pen of animals entered the feedlot) until 270 BRD and control animals had been sampled between 2 and 42 days on feed. Animals were scored for visual signs of BRD in the pen by staff using a modi ed version of the Wisconsin calf scoring chart (7). The scoring system included assessment of seven visual signs: lethargy (slow to remove in response to stimulus), head carriage, laboured breathing, cough, nasal discharge, ocular discharge, and rumen ll, with each sign assigned a score ranging from 0 to 3, with 3 being the most severe.
Animals with visual signs of BRD (n = 127; score > 0 for at least one of the visual signs speci c to BRD, nasal or ocular discharge, laboured breathing or cough) and an equivalent number of control animals exhibiting no visual signs of BRD (n = 143; score 0 for all of the seven visual signs) were removed from their pens and taken for blood sampling and clinical data collection using methods described previously (7). Data recorded at rst BRD pull included date, visual identi cation number, electronic identi cation number, pen, live weight, rectal temperature and computer-assisted lung auscultation (CALA) score. The standard treatment protocol at the feedlot for animals diagnosed with BRD based on visual signs, rectal temperature and CALA was applied as follows: For an initial BRD treatment, animals received either Tilmicosin (Micotil, Elanco Animal Health, West Ryde, Australia) at a dosage rate of 10 mg/kg of body weight via subcutaneous injection or Tulathromycin (Draxxin, Zoetis Animal Health, Lincoln, NE, USA) at a dosage rate of 2.5 mg/kg of body weight via subcutaneous injection, depending on the severity of clinical signs. For a second BRD treatment, animals received a two-course treatment of Oxytetracycline (Engemycin, MSD Animal Health, Wellington, New Zealand) at dosage rate of 20 mg/kg of body weight injected intramuscularly two days apart. For a third BRD treatment, animals received a two-course treatment of Florfenicol (Nu or, Merck Animal Health, Madison, NJ, USA) at a dosage rate of 20 mg/kg of body weight injected intramuscularly and Meloxicam (Meloxicam 20, Troy Laboratories, Glendenning, Australia) at a dosage rate of 0.5 mg/kg of body weight injected subcutaneously, two days apart. For a fourth BRD treatment, and for any animals treated for BRD > 60 DOF, Ceftiofur (Excede, Zoetis Animal Health, Lincoln, NE, USA) was administered at a dosage rate of 1.5 mL/45 kg of body weight injected into the base of the ear.
Nasal swabs were obtained from all animals at rst BRD pull for quantitative PCR to test for the BRD associated viruses: BHV1, BVDV, BRSV, BPI3 and BoCV; Bovine Corona Virus. These samples were stored dry at 4 o C in their collection vessel prior to analysis with no media until analysis up to one month after collection. Blood samples were obtained from the tail vein of all animals at rst BRD pull for serology for antibodies to the same BRD associated causative viruses measured at induction (BHV1, BVDV, BRSV, BPI3 and BAdV). Paired sera were identi ed form individual animals at the time of induction to test concurrently with blood samples obtained at the rst BRD pull.
Necropsies of any BRD mortalities were performed by trained feedlot personnel with date and reason of death recorded. These animals were removed from the analysis (n = 16) as they did not have lung and pleural lesion data.

Serological testing
All testing of serum and nasal samples was performed at the Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland. Serum samples at feedlot entry and rst BRD pull were tested using an indirect multiplex ELISA (BIOX K 284 ELISA, Bio-X Diagnostics, Rochefort, Belgium). The assay was carried out according to the protocol described by the manufacturer with the modi cations described in a previously published study (8). Brie y, the test sera are diluted 1:100 using a buffer and incubated on the plate for one hour at 21 o C. The plate was washed and a conjugate in the form of a peroxidase-labelled anti-bovine IgG1 monoclonal antibody added to the wells and the plate is re-incubated at 21 o C for one hour. Following the second incubation, the preparation was washed and the chromogenic substrate added. After 10 min the reaction was stopped and the optical densities at 450 nm read using conventional ELISA plate reader. The test plate was considered valid only if the positive serum yielded a difference in optical density at 10 min that was greater for each valence than BHV1 > 1000; BVDV > 1,100; BRSV > 1,100 and BPI3 > 1000 and the negative serum yielded a difference in optical density that less than 0.300. The raw optical density results for each test plate were exported to a Microsoft Excel spreadsheet and optical densities of the control samples were adjusted for using the formulae speci ed in the test kit algorithm. Each serological result was categorised as 0 ('seronegative', the category with the lowest optical densities), 1, 2, 3, 4, or 5 (where category 5 consisted of the highest optical densities) (8). If an animal was seropositive (> 1 serological result) at either induction or time of rst BRD pull they were considered to be pre-exposed or immune for that particular virus. If an animal was seronegative (0 serological result) at both induction and time of rst BRD pull they were considered to be naïve for that virus.

Detection of virus by Quantitative PCR
The QuantiTect Mutiplex RT-PCR kit (Qiagen, Maryland, USA) was used for real-time, multiplex, one step RT-PCR for analysis of total nucleic acids extracted from nasal swab samples. The assay was conducted using previously described methodology (9). The real-time PCR primers and probes were designed using Primer Express software (Applied Biosystems, Foster City, California, USA). Primers were designed with a T m of 60 o C and probes were designed with a T m of 70 o C. Primers and probes were designed within a narrow annealing temperature range to facilitate optimisation of the multiplex reaction (9). The predicted amplicon size was limited to less than 150 bp for each primer pair. Primers and probes were designed in the most conserved region of the viral genomes. The speci c viral genome regions used for each virus are described in further detail in a previous study (9). Total nucleic acids were extracted from nasal swabs from cattle at rst BRD pull using the DNeasy Blood and Tissue Kit (Qiagen, Maryland, USA) according to the manufacturer's instructions, except for the omission of the RNAse treatment and stored at -80 o C until analysis. The viral species tested for in this study included isolates of BHV1, BVDV, and BPI3. Two additional BRD viruses BRSV and BCoV were also tested according to an in-house method which has not yet been published (Mahony, personal communication). Slaughter and lung scoring All animals were sent to a commercial abattoir located approximately 100 km from the feedlot and slaughtered on the day of arrival or the following morning. All lungs were scored for evidence of pathology by two personnel trained by an experienced veterinarian. Lungs were visually and physically examined for degree of consolidation and pleurisy. Lung consolidation was recorded using a previously described scoring method (10), where the degree of consolidation (lung tissue lled with liquid instead of air) in each lobe was estimated and summed to form a total percentage of lung consolidation. Pleurisy was recorded using a scoring system of 0 to 3 described previously (7). The use of the term pleuritic tags refers to the adhesion of the lung to the rib cage by brous tags where a score of 3 indicates complete adhesion of the lungs to the thoracic cavity. No lung consolidation score was recorded for animals with a pleurisy score of 3 as there was no lung present on the offal table for scoring. These animals were therefore absent from any analysis of percentage of lung consolidation. Grading occurred on all carcasses approximately 24 hours after slaughter using the Meat Standards Australia (MSA) grading system by an accredited inspector (11).

Statistical analysis
Statistical analyses were performed using the software package SAS (SAS version 9.4, SAS Institute, NC, USA). Latent class analysis (LCA) was used to determine the number of latent classes by grouping animals with similar outcomes based on 16 indicators of BRD. All 16 BRD indicators were transformed to a dichotomous outcome (Table 1). Cut-off points used to determine the response category for rectal temperature and CALA score were based on cut-off points used in previous studies and as commonly used in the industry (12)(13)(14). Cut-off points of 10% lung consolidation, pleural lesion score ≤ 2 and number of BRD treatments ≤ 2 were determined based on results from a previously published companion study (7). The LCA was used to determine the number of underlying categorical latent classes with mutually exclusive levels of the variables. Models with two to ve latent classes were obtained and the best model was selected based on t statistics, Akaike's Information Criterion (AIC), Bayesian Information Criterion (BIC) and the likelihood-ratio G 2 statistic (15) as well as the entropy. Lower AIC, BIC, G 2 and entropy values re ect a better model. Model interpretability was also considered when assessing the optimal model to ensure that each latent class was distinguishable from the others on the basis of item response probabilities, no latent class had a near-zero probability of class membership and that a meaningful label could be assigned to each class (15). Two parameters were estimated; the number of animals belonging to each latent class (a priori probability that a selected animal was in each class) and the conditional class membership probabilities which de ne the distribution of the responses to each question within each class. Each animal was allocated to a single latent class with the highest a posteriori probability of membership. The effect of the covariates in-weight, exit weight, days on feed at rst BRD pull, ADG to rst BRD pull and overall ADG (ADG over length of feeding phase) on the probability of class membership in the latent class analysis was assessed using logistic regression. Only statistically signi cant (P < 0.05) covariates remained in the model.
Mixed-effects linear regression models with the MIXED procedure in SAS (SAS Inst. Inc., Cary, NC) were used to estimate differences between the latent classes on animal performance outcomes. Latent class and breed were included as xed effects. Induction weight was included as a covariate for ADG to rst BRD pull and carcass weight. Where breed was found to be non-signi cant (P > 0.05) it was removed from the models. Signi cance was declared at P ≤ 0.05 and means were separated using Bonferroni adjustment for multiple comparisons. Pleural lesions, score 1-3 Score ≤ 2 (n = 221) Score 3 (n = 49) BHV1 serostatus Antibody positive at either induction or rst BRD pull (pre-exposed; n = 110) Seronegative at both induction and rst BRD pull (naïve; n = 134) BVDV serostatus Antibody positive at either induction or rst BRD pull (pre-exposed; n = 168) Seronegative at both induction and rst BRD pull (naïve; n = 77) BRSV serostatus Antibody positive at either induction or rst BRD pull (pre-exposed; n = 240) Seronegative at both induction and rst BRD pull (naïve; n = 6) BPI3 serostatus Antibody positive at either induction or rst BRD pull (pre-exposed; n = 229) Seronegative at both induction and rst BRD pull (naïve; n = 17) BAdV3 serostatus Antibody positive at either induction or rst BRD pull (pre-exposed; n = 223)

Results
Cohort description The performance and clinical characteristics of the cohort are presented in Table 2. The average days on feed an animal was rst pulled for BRD was 21 and animals had an ADG to rst BRD pull of 1.2 kg/day. The majority of these animals (84.4%) received either 0 or 1 treatment for BRD. A large proportion of animals identi ed visually for BRD had a rectal temperature ≥ 40 o C (68.2%) and a high CALA score (62.6%). Only 9.8% of animals had ≥ 10% total lung consolidation at slaughter, whereas 18.2% had severe pleural lesions with lung tissue adhesion to the rib cage. Approximately half of animals showed pre-exposure to BHV1 with the remaining 53.0% of animals being seronegative despite vaccination upon arrival. Approximately two thirds of animals were pre-exposed to BVDV and the vast majority (~ 90%) had been pre-exposed to the other three respiratory viruses. BHV1 was the virus most frequently detected virus by PCR (9.3%) at rst BRD pull and no more than 3% of the animals tested positive for any of the other four viruses. Latent class analysis A model with three latent classes was the optimal baseline model based on the AIC and entropy values, and was intuitively interpretable (Table 3). Just over half (52%) of animals were assigned to latent class one, 'non-BRD', which had a low likelihood of presence of any of the indicators characteristic of BRD such as visual signs, high rectal temperature, lung consolidation or pleural lesions ( Table 4). The non-BRD class also showed lower likelihood of being seronegative to BHV1 compared to the other two classes despite the fact that the seroprevalence of antibodies to BHV1 was 58% (Table 4). Animals in latent classes 2 and 3 corresponded to mild and severe BRD, respectively. Animals in the mild BRD class accounted for 40% of the cohort, which had a greater likelihood of having visual signs of BRD, an elevated CALA score, and being seronegative to BHV1 compared to the non-BRD animals. Animals in this latent class were also less likely to be treated more than once for BRD, have high rectal temperature, lung consolidation ≥ 10% and a score of 3 for pleural lesions compared to class 3 (severe BRD). These animals also had lower probability of being seronegative to BVDV, BPI3 and BAdV compared to those classi ed with severe BRD. Animals classi ed with mild BRD had a higher likelihood for nasal swabs to test positive for BHV1 or BCoV at compared to those classi ed as severe BRD (Table 4). The cohort included 8% of animals classi ed with severe BRD, which was characterised by a high likelihood of being treated for BRD more than once, having a rectal temperature ≥ 40 o C, lung consolidation > 10%, score 3 for pleural lesions and being seronegative for BHV1, BVDV, BPI3 and BAdV. These animals were also more likely to have a positive nasal swab result at rst BRD pull for BRSV, BPI3 and BCoV compared to animals in the mild BRD class.
In the latent class model, the covariates intake weight, exit weight, days on feed at rst BRD pull did not signi cantly affect latent class membership (P > 0.05), however ADG to rst BRD pull and overall ADG were strong predictors of latent classes for BRD (P < 0.001; Table 5). The odds of an animal to belong to the mild or severe BRD group was 1.27 and 1.37 times greater, respectively, for every 1 kg reduction in ADG to rst BRD pull compared to non-BRD animals. The odds of an animal to belong to the mild or severe BRD group were 1.65 and 7.14 times greater, respectively, for every 1 kg reduction in overall ADG compared to the non-BRD animals.  Table 4 Class membership and item response probabilities (± SE) for animals assigned to each of three BRD  Table 5 Parameter estimates (± SE), ß regression coe cients and odds ratios for the covariates average daily gain to rst pull and overall average daily gain associated with Bovine Respiratory Disease outcome group obtained from the latent class analysis. Non-BRD animals is the reference group. Animal performance outcomes associated with each latent class Animals classi ed with mild BRD had reduced production performance compared to non-BRD animals (P < 0.001; Table 6), however production was not as compromised in the mild animals compared to the severe animals. Severe BRD animals had signi cantly reduced performance compared to mild BRD animals for all variables except for initial intake weight (P > 0.05). Animals in the severe BRD class gained 0.6 kg/day less than those in the mild BRD class and 0.9 kg/day less than animals in the non-BRD class (P < 0.001). Exit weight and carcass weight were 71.5 kg and 39.0 kg lower in severe BRD animals compared to mild BRD animals, and 129.9 kg and 71.1 kg lower compared to non-BRD animals (P < 0.001). MSA marble score was 46.5 lower in animals with severe BRD compared to mild BRD (P < 0.001). Within a row, means without a common superscript letter differ (P < 0.05) 1 MSA=Meat Standards Australia

Discussion
The current study aimed to differentiate categories of BRD severity based on 16 indicators of disease using latent class analysis, and then determine which of these BRD indicators were most important in assigning animals to a BRD group. The latent class model showed the best t with 3 latent classes, which differentiated mild BRD and severe BRD, as well as animals that were not impacted by this disease complex. In this cohort, animals with mild BRD were characterised by a high likelihood of visual signs of BRD identi ed by trained pen riders but the infection did not appear to progress, evidenced by minimal lung damage at slaughter. In comparison, severe BRD was characterised by a high likelihood of requiring more than one treatment for BRD and reduced weight gain, with these animals sustaining permanent lung damage at slaughter. Interestingly, rectal temperature and CALA which are commonly used con rmation measures in feedlots, showed much lower importance to de ne BRD outcome group than visual signs, the number of BRD treatments an animal received, and lung consolidation and pleural lesions at slaughter.
Animals with mild BRD exhibited visual signs of BRD, were much less likely to require more than one treatment for BRD and show evidence of lung damage at slaughter. These results suggest that those mild BRD animals responded to an initial BRD treatment which limited disease progression. These results highlight the importance of early recognition and treatment of BRD to increase recovery rates and productivity, and reduce the economic costs that are associated with increasing disease severity (16). Visual signs had the highest in uence on class membership of all BRD indicators. This is interesting considering many studies report the inaccuracy of visual signs to detect BRD when comparing lung damage detected at slaughter (4). Results from the present study may indicate that the lack of agreement between visual signs and lung damage at slaughter is due to the fact animals may recover following early recognition and treatment, and therefor do not sustain permanent lung damage. While these transient BRD infections may still have impacts on production, they don't necessarily cause long term pulmonary pathology recognisable at slaughter. Therefore, it would appear that highly skilled pen riders that can accurately identify signs of the disease early are hugely important in limiting the impacts of severe BRD infections in feedlots. The predictive performance of visual signs in the current study is also likely in part because the surveillance animals were part of a sampling trial and therefore observation of visual signs in these animals may have been more thorough than in a normal non-study situation.
Additionally it is worth noting that the pen riders used in the present study were experienced at identifying BRD animals, all with more than one year's experience pen riding.
Requiring more than one BRD treatment and severe lung damage at slaughter were important indicators that differentiated the severe animals from the mild animals. However, assessment of lung damage at slaughter is only useful as a retrospective indicator of BRD outcome, which limits its use as a predictive tool for BRD ante-mortem. Animals with high rectal temperatures were also more likely to belong to the severe BRD class, although this difference was not as pronounced as some of the other indicators. Rectal temperature is one of the most widely used BRD con rmation tools in feedlots triggering treatment protocols, and these results demonstrate that animals with rectal temperature ≥ 40 o C at rst BRD pull are at a greater risk of not responding to an initial BRD treatment. In agreement with these results, increased rectal temperature was found to be predictive of increased risk of re-treatment and mortality due to BRD in a previous study (17). This suggests that measurement of rectal temperature following initial visual detection is a useful prognostic indicator of disease severity, and may allow these animals to be managed accordingly.
Of interest was the fact that a higher CALA score at rst BRD pull was more likely in animals with mild BRD compared to those with severe BRD. The reasons for this are unknown and appear to be inconsistent with the ndings of a previous study which found that the probability of requiring re-treatment for BRD was 13% lower in animals with normal CALA scores compared to those with more severe scores, and animals with higher CALA scores had a 63% probability of retreatment (17). Additionally, more severe CALA scores were also associated with increased risk of death due to BRD (17). It is worth noting however that the lung auscultation scoring system these authors used differed to that of the present study, with scores ranging from 1 (normal) to 10 (diffuse, severe adventitious lung sounds) which were subjectively scored rather than using the Whisper computer program. The difference in severity de nitions could therefore be the reason for the different ndings between studies.
Sero-negativity indicating naivety to BHV1 and BVDV increased an animal's likelihood of developing BRD of any severity. The relationship between initial BRSV titres and BRD risk have been inconsistent (8,18) but naivety at feedlot entry for BHV1, BVDV and BPI3 appears to increase the risk of developing BRD (8,19). Additionally, it has been found that animals that are naïve or seronegative for more than one virus at feedlot entry are at progressively greater risk of developing BRD (8). This was the case in the current study, where the more severe BRD cases were more likely to be naive to multiple viruses. These results support the use of adequate backgrounding and vaccination programs prior to feedlot entry for protection against more severe infections. Having said this, the fact that 53.0% of animals were still BHV1 naïve despite being vaccinated at feedlot entry may question the effectiveness of a single vaccination at feedlot entry. In a previous study, 39.1% of animals vaccinated with Rhinoguard for BHV1 at induction did not subsequently seroconvert for BHV1 (8). The same study also found that even after vaccination with Rhinoguard, initially seronegative animals were at increased risk of developing BRD in the feedlot. This could be because immunologically stressed animals may be unable to mount an effective immune response early enough following on-arrival vaccination. A study comparing on-arrival vaccination for BHV1 with delayed vaccination (14 days post arrival) found that delayed vaccination improved the acquired immune response (20). Alternatively, intranasal vaccination may not be su cient to trigger an antibody response detectable by the ELISA. These ndings may support the use of delayed vaccination following feedlot arrival or multiple vaccination programs during backgrounding and prior to feedlot entry.
The presence of viral pathogens in nasal swab samples taken at rst BRD pull were generally not a good indicator of disease severity, however this was dependent on the virus. This may have been due to the small proportion of animals with a positive nasal swab result for any BRD virus at the time of rst BRD pull (9.3% for BHV1, 3.0% for BVDV, 3.0% for BRSV, 0.4% for BPI3 and 2.6% for BCoV). This was a limitation of the present study because only one sample was collected from animals at the time when visual signs indicated BRD infection. Most viral infections are thought to resolve at around 14 days, despite a peak in visual signs of BRD occurring at around 21 days post-infection (21). Therefore, animals pulled with visual signs may have already resolved the viral infection by this time and consequently may not have returned a positive nasal swab result. It is also generally accepted that the overt visual signs of BRD are more often associated with secondary bacterial and in ammatory responses compared to the direct viral infection (22,23). Bacterial pathogens were not measured in the current study as the focus was on the initiating pathogens so this relationship could not be explored. Interestingly, animals with mild BRD had greater likelihood of being positive for BHV1 compared to severe BRD animals. A possible explanation for this was that animals in the mild BRD class were pulled earlier in the disease progression timeline and therefore had a higher likelihood of shedding BHV1, however subsequently recovered following treatment. Additionally, there is a possibility animals returned a positive swab result for BHV1 following the modi ed live virus vaccination at feedlot entry (24,25). Animals with severe BRD were more likely to be positive for BRSV and BCoV at rst BRD pull. This appears to be contrary to previous observations that detection of infection with shedding of speci c pathogens does not equate to clinical disease and lung infection requiring treatment (26). These results demonstrate the importance of novel viruses such as BCoV on the aetiology of BRD in feedlot cattle and the need for continuous surveillance of pathogens including new microorganisms that may be involved in the pathogenesis of BRD (27).
The occurrence of BRD and its severity had a large in uence on average daily gain to rst BRD pull and overall ADG in the latent class model. Additionally, production performance outcomes such as ADG to rst BRD pull, overall ADG, exit weight, carcass weight and MSA marbling decreased as disease severity increased. The negative economic outcomes associated with decreased production performance have been demonstrated previously (16,28). However, the strong linear in uence of animal performance on BRD class membership using latent class analysis is novel. Animals suffering from severe, sustained infection were more likely to have reduced weight gain impacting carcass weight at slaughter, as well as reduced carcass quality traits such as marbling, compared to those animals that never suffered from BRD or suffered from a milder infection. This con rms the need to focus both on reducing overall disease incidence affecting production and pro tability, as well as to regularly monitor production parameters such as ADG throughout the feeding phase.

Conclusions
The present study con rms that visual signs are an important indicator to identify animals impacted by BRD provided the pen riders are su ciently trained to identify these signs early. Therefore, emphasis should be placed on training of new pen riders for accurate visual identi cation, as well as in efforts to retain experienced pen riders which seems to be an industry-wide issue. Additionally, early initial treatment for BRD can potentially reduce the progression of infection and limit severity. In contrast, animals that require more than one treatment for BRD appear to be cases of more severe infection resulting in permanent lung damage at slaughter. Lung damage at slaughter was a good predictor of BRD class membership between mild and severe animals, indicating the importance of health feedback information from abattoirs to producers and better technologies to detect lung lesions on live animals in order to manage disease severity. Pre-exposure to BRD viruses reduced the likelihood of both mild and severe BRD, indicating the importance of adequate backgrounding procedures to reduce BRD severity in feedlots. Reductions in animal performance were also seen with increasing BRD severity, translating to signi cant economic losses for feedlots (16). These performance indicators can be easily monitored throughout the feeding phase and used as a simple and practical tool to predict and manage BRD severity and reduce production losses.

Declarations
Ethics approval and consent to participate The study had approval from the Animal Ethics Committee of Research Integrity and Ethics Administration, The University of Sydney (Approval # 1118). All methods were carried out in accordance with the relevant guidelines and regulations.

Consent for publication
Not applicable Availability of data and material