The Utility of Acute-Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia

Viitanen, S.J.; Lappalainen, A.K.; Christensen, M.B.; Sankari, S.; Rajamäki, M.M.

B acterial pneumonia (BP) is an acquired inflammation of the lower airways and lung parenchyma secondary to bacterial infection. 1 The clinical characteristics and microbiological findings in dogs with BP have been well described. [2] [3] [4] [5] However, information concerning the normalization of clinical and radiographic findings during the recovery process and guidelines on assessing the optimal duration of antibiotic treatment in BP still are limited. 1, 6, 7 Acute-phase proteins (APPs) are a group of blood proteins, mainly produced by the liver, which are part of the innate host defense system. 8 The APPs are involved in the protection against infection as well as in the regulation of the immune response and inflammation, especially in the early phases of injury. 9 The major positive APPs in dogs, C-reactive protein (CRP) and serum amyloid A (SAA), have low serum concentrations in healthy dogs. Serum concentrations of CRP and SAA increase markedly within the first hours after inflammatory stimuli and normalize quickly during the recovery period. 9 The APPs have certain advantages in disease monitoring compared to the CBC. The numbers of blood leukocytes are largely affected by extravasation into the pulmonary parenchyma during acute BP, whereas APPs increase consistently with increasing inflammatory stimuli. 9 Minor and moderate positive APPs, such as haptoglobin (Hp), show a more gradual increase and decrease during the acute-phase response (APR). 8 The production of other plasma proteins, socalled negative APPs (such as albumin and transferrin), decreases during the APR. 8 Being nonspecific biomarkers of inflammation, increased serum concentrations of CRP, SAA, and Hp have been observed in dogs with a variety of infectious, immune-mediated and neoplastic diseases. [10] [11] [12] [13] [14] [15] [16] [17] Despite the nonspecific nature of APPs, serum CRP can be useful in discriminating disease processes such as BP from other pulmonary diseases. 18 The APPs have been shown to decrease after initiation of successful treatment. 16, [19] [20] [21] Additionally, the increase in serum CRP during long-term follow-up in dogs with leishmaniasis and immune-mediated polyarthritis predicts the relapse of clinical disease. 14, 21 The utilization of CRP and SAA as possible prognostic biomarkers also has been studied in dogs, and most studies concluded that serum CRP or SAA concentrations at presentation could not predict clinical outcome. [22] [23] [24] [25] [26] However, persistent increases in serum CRP after 48-72 hours of treatment were correlated with poor outcome. [22] [23] [24] Serum CRP has been widely studied in humans with community-acquired pneumonia (CAP), and its use as a diagnostic and follow-up biomarker is recommended by current treatment guidelines. 27, 28 Bacterial pneumonia currently is treated with markedly longer antimicrobial courses than is CAP, and effective means to estimate optimal treatment duration are lacking. 1, 6, 7, 29 Biomarker-guided antimicrobial treatment has been studied in humans with CAP by procalcitonin (PCT), a novel inflammatory biomarker, which indicated that PCT-guided antibiotic use decreased the duration of antimicrobial treatment without increasing the incidence of complications. [30] [31] [32] Similar studies assessing CRP-guided antimicrobial use in humans with CAP are lacking, but serum CRP has been shown to be useful in decreasing the duration of antimicrobial treatment in humans with neonatal