Association between lung consolidation and serum amyloid-A and haptoglobin, and the potential of acute phase proteins to differentiate primary respiratory tract pathogens in calves

Bovine respiratory disease (BRD) remains a leading cause of economic losses, hampered animal welfare and antimicrobial use. The use of acute phase proteins (APPs), such as serum amyloid A (SAA) and haptoglobin (Hp), has been explored for the detection of BRD, as defined by clinical signs. However, whether these APPs are also associated with lung consolidation, as determined by thoracic ultrasonography, and have the potential to differentiate causative pathogens is unknown. Therefore, the primary objective of this study was to explore the association between lung consolidation and SAA and Hp. The second objective was to determine the ability of both SAA and Hp to differentiate pathogen groups (Mycoplasmopsis bovis, viruses and Pasteurellaceae). A cross-sectional study including 170 calves from 25 different herds with a history of Mycoplasmopsis bovis (endemic) or herds (including M. bovis positive herds) that met the inclusion criteria of an outbreak of BRD (i.e., the presence of one or more clinical signs associated with BRD, affecting multiple animals (5 animals; 15% ill animals in the same airspace on a farm within a 48-h period) (epidemic) was conducted between 2020 and 2022 in Belgium. Clinical examination, quick thoracic ultrasonography, blood sampling and non-endoscopic bronchoalveolar lavage were performed on each calf. Linear mixed effect models with a random intercept for herd were fitted, to determine the association between lung consolidation or clinical BRD (and serum SAA and Hp concentrations. Furthermore, multivariable models (linear mixed effect models) were used to evaluate the mutually adjusted associations between pathogen groups and APP concentrations. Test characteristics of APP concentrations to predict the presence of lung consolidation or pathogen groups were assessed, and potential SAA and Hp cutoffs, determined by Youden index, were evaluated. Lung consolidation (≥1 cm) was positively association with higher Hp concentrations in epidemic conditions [regression coefficient (β): 5.3 (95% confidence interval (CI): 1.4–20.3)], while more severe lung consolidation (≥3 cm) was associated with higher Hp concentrations in endemic conditions [β: 3.6 (95% CI: 1.2–11.0)]. No positive association was found between lung consolidation and SAA. Yet, a positive association between M. bovis and SAA was observed [β: 2.3 (95% CI: 1.3–4.3)]. At last, no association was found between M. Bovis and Hp. For Hp, the best cutoff to predict a lung consolidation (≥1 cm) was 2.33 µg/mL (Se: 81.8% and Sp: 66.7%). Moreover, to detect M. bovis among calves with a lung consolidation (≥1 cm), a SAA cutoff of 174.84 µg/mL was determined (Se: 77.8% and Sp: 87.5%). Despite the observed relationships between lung consolidation, pathogen groups, and APPs, the test characteristics in this study suggest that Hp and SAA are currently limited in their (practical) use for the detection of lung consolidation or M. bovis.

呼吸道疾病（BRD）持续成为导致经济损失、动物福利受损以及抗菌素滥用的主要因素。急性期蛋白（APPs），如血清淀粉样蛋白A（SAA）和触珠蛋白（Hp），已被研究用于检测BRD，其定义依据临床体征。然而，这些APPs是否也与肺实变相关联，如通过胸部超声检查所确定的，以及它们是否有能力区分致病病原体，尚不得而知。因此，本研究的主要目标是探讨肺实变与SAA和Hp之间的关联。第二个目标是确定SAA和Hp区分病原体组（牛支原体、病毒和巴氏杆菌科）的能力。一项横断面研究于2020年至2022年在比利时进行，涉及170头来自25个不同牧场的牛犊，这些牛犊有牛支原体（地方性流行）病史或牧场（包括牛支原体阳性牧场）符合BRD爆发（即存在一个或多个与BRD相关的临床体征，影响多个动物（5头动物；48小时内同一牧场的病畜占15%））的纳入标准。对每头牛犊进行了临床检查、快速胸部超声检查、血液采样和非内窥镜式支气管肺泡灌洗。通过拟合具有牧场随机截距的线性混合效应模型，以确定肺实变或临床BRD（以及血清SAA和Hp浓度）之间的关联。此外，使用多变量模型（线性混合效应模型）评估了病原体组与APP浓度之间的相互调整关联。评估了APP浓度测试特征以预测肺实变或病原体组的存在，并通过尤登指数确定了潜在的SAA和Hp截止值。在流行条件下，肺实变（≥1厘米）与较高的Hp浓度呈正相关[回归系数（β）：5.3（95%置信区间（CI）：1.4–20.3）]，而更严重的肺实变（≥3厘米）与地方性流行条件下的较高Hp浓度相关[β：3.6（95% CI：1.2–11.0）]。未发现肺实变与SAA之间的阳性关联。然而，观察到牛支原体与SAA之间的阳性关联[β：2.3（95% CI：1.3–4.3）]。最后，未发现牛支原体与Hp之间的关联。对于Hp，预测肺实变（≥1厘米）的最佳截止值为2.33 µg/mL（Se：81.8%和Sp：66.7%）。此外，为了在肺实变（≥1厘米）的牛犊中检测牛支原体，确定了SAA截止值为174.84 µg/mL（Se：77.8%和Sp：87.5%）。尽管观察到肺实变、病原体组和APPs之间的关系，但本研究中的测试特征表明，目前Hp和SAA在（实际）用于检测肺实变或牛支原体方面仍有限。