Assessment of diagnostic accuracy of biomarkers to assess lung consolidation in calves with induced bacterial pneumonia using receiver operating characteristic curves

Abstract

Bovine respiratory disease (BRD) is the most economically significant disease for cattle producers in the U.S. Cattle with advanced lung lesions at harvest have reduced average daily gain, yield grades and carcass quality outcomes. The identification of biomarkers and clinical signs that accurately predict lung lesions could benefit livestock producers in determining a BRD prognosis. Receiver operating characteristic (ROC) curves are graphical plots that illustrate the diagnostic ability of a biomarker or clinical sign. Previously we used the area under the ROC curve (AUC) to identify cortisol, hair cortisol and infrared thermography imaging as having acceptable (AUC > 0.7) diagnostic accuracy for detecting pain in cattle. Herein, we used ROC curves to assess the sensitivity and specificity of biomarkers and clinical signs associated with lung lesions after experimentally induced bovine respiratory disease (BRD). We hypothesized pain biomarkers and clinical signs assessed at specific timepoints after induction of BRD could be used to predict lung consolidation at necropsy. Lung consolidation of >10% was retrospectively assigned at necropsy as a true positive indicator of BRD. Calves with a score of <10% were considered negative for BRD. The biomarkers and clinical signs analyzed were serum cortisol; infrared thermography (IRT); mechanical nociceptive threshold (MNT); substance P; kinematic gait analysis; a visual analog scale (VAS); clinical illness score (CIS); computerized lung score (CLS); average activity levels; prostaglandin E2 metabolite (PGEM); serum amyloid A and rectal temperature. A total of 5,122 biomarkers and clinical signs were collected from 26 calves, eighteen of which were inoculated with M. haemolytica. All statistics were performed using JMP Pro 14.0. Results comparing calves with significant lung lesions to those without yielded the best diagnostic accuracy (AUC > 0.75) for right front stride length at 0 h; gait velocity at 32 h; VAS, CIS, average activity and rumination levels, step count and rectal temperature, all at 48 h; PGEM at 72 h; gait distance at 120 h; cortisol at 168 h; and IRT, right front force and serum amyloid A, all at 192 h. These results show ROC analysis can be a useful indicator of the predictive value of pain biomarkers and clinical signs in cattle with induced bacterial pneumonia. AUC values for VAS score, average activity levels, step count, and rectal temperature seemed to yield good diagnostic accuracy (AUC > 0.75) at multiple timepoints while MNT values, substance P concentrations, and CLS did not (all AUC values < 0.75).

A nationwide survey on producer and veterinarian perceptions of the painfulness of procedures and disease states in dairy and beef cattle

“…The provision of analgesia to mitigate pain associated with painful husbandry procedures and disease states and the associated welfare impacts have been widely discussed in the beef and dairy cattle industries ( 1 , 2 , 4 ). Pain research in cattle has focused on various areas including validating indicators of pain ( 49 – 51 ), evaluating methods of pain mitigation ( 52 – 55 ), and quantifying the frequency of pain mitigation implementation by producers and veterinarians for various procedures ( 19 , 23 , 24 , 25 ). Although many challenges impacting the use of pain mitigation for livestock have been identified by producers and veterinarians ( 18 , 32 ), there has been more limited exploration of how perceptions of pain and demographic factors, considered separately and together, influence the implementation of pain mitigation for some key procedures and conditions relevant to beef and dairy production systems in the United States.…”

Clinical usefulness of infrared thermography to detect sick animals: frequent and current cases

“…Bovine respiratory disease is another pathology that has significant economic repercussions for cattle production units since animals with advanced lung lesions have lower weight gain and poor carcass quality. Martin et al [106] carried out a study to compare and evaluate physiological and behavioral parameters such as rectal temperature, facial thermography (on the medial canthus of the left eye), average activity levels, computerized stethoscope lung scores, blood metabolite levels (cortisol, substance P, prostaglandin E2 metabolite), and lung lesion scores (based on lung consolidation Fig. 9 Importance of IRT on the detection of stressors on farm animals.…”

“…However, it is important to keep in mind that environmental factors and the distance between the IRT camera and the animals can affect thermographic images [108]. For this reason, Martin et al [106] recommend continuing research on biomarkers that predict lung injuries and are specific to pain to improve diagnoses of bovine respiratory disease.…”

Evaluation of a Respiration Rate Sensor for Recording Tidal Volume in Calves under Field Conditions

“…Furthermore, simultaneous recording of RR and Vt would be possible in a larger number of animals due to less personnel and resource requirements. This non-invasive approach of data recording is also an advantage over other methods of lung examination, such as ultrasound [ 13 , 14 , 15 ] and blood sampling [ 11 , 12 ], where a fixation of the calf is mandatory. The IOS was used as the gold standard because (i) it had previously been thoroughly evaluated for pulmonary function testing in calves, and (ii) it is suitable for the assessment of spirometric parameters of spontaneous breathing.…”

“…Therefore, a lot of research has been published on the study of pulmonary diseases in calves and to diagnose them early [ 7 , 8 , 9 , 10 ]. Besides the analysis of biomarkers in the blood [ 11 , 12 ], also ultrasonic methods [ 13 , 14 , 15 ] and different sensors [ 16 , 17 ] have been tested as diagnostic methods.…”