BIP: “bronchopneumonia with interstitial pneumonia” as an important cause of death in feedlot cattle

Project Title

Mycoplasma Bovis Pneumonia in Beef Cattle

Researchers

Dr. Jeff Caswell, University of Guelph jcaswell@uoguelph.ca

Kent Fenton, Feedlot Health Management Services Ltd., Okotoks, AB; Jose Perez-Casal, Vaccine and Infectious Disease Organization, Saskatoon, SK; Edouard Timsit, Department of Production Animal Health, University of Calgary Faculty of Veterinary Medicine, Calgary, AB; Ruud Veldhuizen, Lawson Health Research Institute, Departments of Medicine and Physiology and Pharmacology, University of Western Ontario

Scientific Journals

Status Project Code
Completed April, 2021 ANH.13.17

Background

“Bronchopneumonia with interstitial pneumonia” (BIP) is a unique and previously uncharacterized form of respiratory disease in Canadian feedlot cattle. It is usually diagnosed after death and the appearance is unique: simultaneous chronic bacterial pneumonia (BP) of the front (cranioventral) part of the lung and acute interstitial pneumonia (IP) in back (caudodorsal) parts of the lung. Although it is the third leading cause of death from respiratory disease in feedlot cattle, little is known of the cause, nature of the disease, risk factors, or methods to prevent it.

Objectives

Characterize the epidemiologic, clinical and pathologic features of BIP, and identify the role of Mycoplasma bovis infection in causing BIP, including how chronic Mycoplasma bovis pneumonia leads to the acute widespread lung damage that is the cause of death.

What They Did

  • Epidemiologic data on 9909 animals were acquired from 2 years of mortality data from 4 commercial beef feedlots in Western Canada that had a high prevalence of BIP.
  • A case-control-control study was done using cases of BIP (n=15), IP (n=13) and BP (n=23) from Alberta feedlots. The prevalence of key histologic lesions in the lung of BIP cases was evaluated. Lungs from all cases were tested by bacterial and mycoplasma culture and PCR for viruses. Next-generation sequencing was used to detect an unknown or unexpected viral cause.
  • The composition and biophysical properties of lung surfactant (isolated from the caudodorsal lung) were tested on 3 BIP cases, 3 BP cases, 1 IP case, and 6 normal lungs.
  • A preliminary in vitro study investigated how chronic inflammation might worsen toxic lung damage and thereby result in interstitial lung disease. Specifically, this evaluated how inflammatory stimuli affect the expression of enzymes involved in 3-methylindole metabolism, in cultured tracheal cells and macrophages.

What They learned

BIP was diagnosed in 11% of mortalities, confirming BIP as a frequent cause of mortality in the 4 feedlots studied. In BIP cases, the lesions in the cranial part of the lung were older than those in the caudal part of the lung, consistent with clinical observations that these calves have a chronic bacterial bronchopneumonia with a relatively sudden onset of fatal interstitial pneumonia (IP/AIP). Mycoplasma bovis infection was frequently found in calves in this study, from both the cranial and caudal lung, and from both BIP and bronchopneumonia cases, so this infection probably contributes to development of BIP. The histopathology and microbiology findings in the cranial part of the lung of BIP cases resembled that of bronchopneumonia cases (BP). Findings in the caudal part of the lung of BIP cases resembled those of interstitial pneumonia cases (IP/AIP). Thus, the fundamental nature of BIP does not seem to be unique.

However, the epidemiology data on mortalities showed that BIP is a unique disease. BIP occurred with 7.5-times higher frequency than expected by the chance concurrence of bronchopneumonia and acute/chronic interstitial pneumonia. BIP mainly affected steers whereas AIP had a heifer-predominance. Finally, BIP cases were most frequent in winter and to a lesser extent spring, similar to bronchopneumonia, whereas the frequency of AIP cases was relatively constant across the year with a peak in the summer.

In a preliminary in vitro investigation of how chronic inflammation might alter enzymes that metabolize potential toxic substances in the feed, an inflammatory stimulus reduced CYP1A1 gene expression in airway epithelial cells and in macrophages, but increased COX-2 gene expression in macrophages.

What it means

These data are the first characterization of the pathology, microbiology and epidemiology of BIP and directs further investigation into the pathogenesis of this important cause of mortality in Canadian beef feedlots. The findings are of value to inform the possible causes and how the disease arises. Specifically, the findings have led to the hypothesis that inflammation in the lung (chronic bronchopneumonia) changes metabolism of 3-methylindole or other potential toxic substance in feed, and thereby leads to interstitial pneumonia.

The pathology and microbiology data indicate that BIP is similar to its component “parts”, but the epidemiologic findings clearly indicate that BIP is not simply a chance occurrence of bronchopneumonia and AIP. Thus, these data suggest that risk factors for AIP lead to development of the disease AIP in heifers, but these risk factors do not cause development of AIP in steers unless there is concurrent bronchopneumonia. A key question to understanding the development of BIP is to determine how the chronic bronchopneumonia in the cranioventral area of lung triggers the development of interstitial pneumonia in the caudodorsal area of lung. Samples acquired during this study will allow further analysis of this question. Specifically, the preliminary in vitro findings identified a metabolic enzyme that is known to affect 3-methylindole metabolism and is affected by inflammatory stimuli. The next steps will be to refine these in vitro methods, demonstrate effects of inflammation on metabolism of 3-methylindole, and use the samples acquired from this study to confirm the in vitro findings in the in vivo context of cattle affected by this disease.