Abstract
Objectives
Pleural effusion is a common presenting cause for feline patients in small animal practice. The objectives of this study were to identify possible correlations between the aetiology of effusion and clinical and laboratory findings.
Methods
In this retrospective study of 306 cats diagnosed with pleural effusion of established aetiology, cats were divided into six major groups: cardiac disease (CD), feline infectious peritonitis (FIP), neoplasia, pyothorax, chylothorax and miscellaneous. Clinical, laboratory and radiographic parameters were compared between groups.
Results
CD was the most common aetiology (35.3%), followed by neoplasia (30.7%), pyothorax (8.8%), FIP (8.5%), chylothorax (4.6%) and miscellaneous diseases (3.7%). In 26 (8.5%) cats, more than one underlying disease was diagnosed as a possible aetiology for pleural effusion. Cats with FIP were significantly younger than those with CD (P <0.001) and neoplasia (P <0.001). Cats with CD were presented with a significantly lower body temperature compared with cats with FIP (P = 0.022). Cats with CD had significantly higher serum alanine aminotransferase activity compared with all other cats (FIP and pyothorax, P <0.001; neoplasia and chylothorax, P = 0.02) and serum alkaline phosphatase activity compared with the pyothorax (P <0.001) and FIP groups (P = 0.04), and significantly lower protein concentrations (FIP, pyothorax and neoplasia, P <0.001; chylothorax, P = 0.04) and nucleated cell counts in the effusion than all other groups (pyothorax and neoplasia, P <0.001; chylothorax, P = 0.02; FIP, P = 0.04). The glucose level in the effusion of cats with pyothorax was significantly lower than glucose levels in patients with CD, neoplasia and chylothorax (P <0.001). Of 249 cats with a follow-up of at least 10 days, 55.8% died or were euthanased during that time.
Conclusions and relevance
CD and neoplasia were the most common causes for feline pleural effusion. Age, liver enzymes, as well as cell count, protein and glucose levels in the effusion can aid in the investigation of underlying aetiologies.
Introduction
Pleural effusion is defined as a pathological accumulation of fluid in the thoracic cavity. A variety of reasons can lead to abnormal fluid accumulation in visceral cavities.1,2 Conditions that increase hydrostatic pressure in the capillaries (eg, congestive heart failure) or reduce oncotic pressure (eg, hypoalbuminaemia) can lead to increased capillary permeability (eg, caused by vasculitis or inflammation), or conditions that cause lymphatic obstruction or dysfunction can lead to abnormal accumulation of fluids in the pleural cavity.3,4 Based on physical examination and diagnostic imaging, as well as biochemical and cytological fluid analysis, the type of effusion can be classified into pure transudate, modified transudate, exudate and special forms such as chylous and haemorrhagic effusions. 5 As pleural effusion per se is not a disease, classification of the effusion is of importance for the identification of the underlying condition. 6 As cats with pleural effusion are often presented in an acute and critical state, it could be of great importance to determine diagnostic parameters that could help in the process of decision-making concerning further diagnostic work-up to identify possible underlying conditions.
To date, there have only been a few studies investigating type and prevalence of underlying diseases including characteristic parameters leading to pleural effusion in cats. In a study that included 82 cats with pleural effusion, neoplasia (23%), pyothorax (18%), feline infectious peritonitits (FIP; 18%) and cardiac disease (CD; 11%) were identified as the most common underlying diseases. 4
The aim of the present study was to identify the most common underlying conditions for pleural effusion in a large number of cats and identify characteristic parameters for different aetiologies that could help to find a diagnosis.
Materials and methods
Study design
The study was performed as a retrospective analysis. Data from 306 cats with pleural effusion, in which a definitive diagnosis regarding the aetiology of the effusion was documented, were included.
Collected information included signalment, parameters of physical examination, thoracic radiographs to differentiate unilateral and bilateral effusions, complete blood count, serum biochemistry and electrolytes, biochemical and cytological analysis of the effusion, and outcome. Based on the aetiology of effusion, feline patients were divided into six major groups, including the most common underlying conditions: CD, FIP, neoplasia, pyothorax and chylothorax. The miscellaneous group was not included in statistical comparison.
The underlying aetiology causing pleural effusion was diagnosed as follows. CD was diagnosed by echocardiography.7,8 The different forms and definitions, as well as the diagnostic criteria of CD included in the study, are listed in Table 1. A diagnosis of FIP was established by immunofluorescent staining of feline coronavirus (FCoV) antigen in macrophages in the effusion, the presence of typical histopathologic changes10,11 or immunohistochemical staining of FCoV antigen in tissue macrophages 12 of biopsy samples or samples obtained during post-mortem examination. Cytological or histopathological examination of tissue, or cytological examination of effusion were used to establish diagnosis of neoplasia. 13 Pyothorax was diagnosed by detection of septic inflammation on cytological preparations of the effusion,14,15 and/or detection of intracellular bacteria on cytology or by a positive bacterial culture.16,17 Chylothorax was diagnosed based upon typical cytological findings in the effusion (predominance of small lymphocytes and non-degenerate neutrophils with background chylomicrons) 5 and an elevation of triglycerides in the fluid sample vs serum or, if no serum analysis was available, a triglyceride concentration >100 mg/dl.18,19
Classification of cardiac disease in 108 cats with pleural effusion
HCM = hypertrophic cardiomyopathy (hypertrophied, non-dilated left ventricle [LV] with no underlying systemic/cardiac disease. HCM was diagnosed when the interventricular septum [IVS] and /or the left ventricular free wall [LVFW] was >6 mm in diastole) 9
DCM = dilated cardiomyopathy (LV enlargement and LV systolic dysfunction leading to abnormal loading conditions of the heart. DCM was diagnosed by a decreased fractional shortening of <26% and an increased end-systolic diameter >11 mm) 9
RCM = restrictive cardiomyopathy (normal ventricular wall thickness, while diastolic and systolic volumes of one or both ventricles might appear normal or reduced. RCM was diagnosed by the appearance of atrial enlargement with normal wall thickness in the echocardiography) 9
ARVC = arrhythmogenic right ventricular cardiomyopathy (characterised by progressive fibrous and fatty replacement of right ventricular myocardium. ARVC was diagnosed by a severely enlarged right ventricle and right atrium in the echocardiogram) 9
UCM = unclassified cardiomyopathy (types of cardiomyopathy with no typical features of the categories above) 9
Heart disease reported with a non-specified cardiomyopathy
TVD = tricuspid valve dysplasia; AV-Block = atrioventricular block; TI = tricuspidal insufficiency; MI = mitral insufficiency; VSD = ventricular septal defect; ASD = atrial septal defect
Methods
Parameters that were evaluated included clinical parameters, laboratory blood parameters, effusion parameters, presence of uni- vs bilateral effusion on radiographs and short-term outcome within 10 days of diagnosis. Collection of pleural effusion was performed by blind or ultrasound-guided thoracentesis. Examination of the effusion included determination of specific gravity using a refractometer (Atago Company), as well as measurement of the total cell count with the Cell-Dyn 3500 System (Abott Laboratories). Biochemical parameters in serum and in effusion were measured using an automatic analyser (Hitachi 717 [2000] and Hitachi 911 [2001–2009]; Roche Deutschland Holding). Haematology was performed using an automatic analyser (Cell-Dyn 3500; Abott Laboratories).
Statistical evaluation
Statistical evaluation was performed with GraphPad Prism 7 for Windows. The D’Agostino and Pearson omnibus normality test was used for verification of normal distribution of the data. Kruskal–Wallis one-way ANOVA was used for evaluation of data not normally distributed. For unpaired data, Pearson’s χ2 test or Fisher’s exact test were used. For all statistical tests the level of significance was set at P <0.05.
Results
Aetiology of effusion
Underlying conditions of effusions in 306 cats are listed in Table 2. In 26 patients (8.5%) two or more conditions were identified as a potential aetiology for the effusion.
Underlying conditions in 306 cats with pleural effusion
Cases with two or three aetiologies included cardiac disease (CD) and feline infectious peritonitis (FIP [n = 1]); CD and neoplasia (n = 8); FIP and pyothorax (n = 2); neoplasia and chylothorax (n = 7); CD, neoplasia and chylothorax (n = 2); CD and chylothorax (n = 5); FIP, chylothorax and trauma (n = 1)
Patients
Signalment, clinical and laboratory parameters for cats of the different groups are listed in Tables 3–5. With a median age of 4.5 years, cats diagnosed with FIP were significantly younger compared with cats with CD (P <0.001) and neoplasia (P <0.001). The most commonly affected breed was domestic shorthair (n = 269; 87.9%). Other breeds included Persian (n = 23; 7.5%), Maine Coon (n = 11; 3.6%), Siamese (n = 11; 3.6%), Chartreux (n = 4; 1.3%), and Burmese, Russian Blue and Oriental Shorthair (n = 2 each; 0.7%), as well as one each of Kanaani, Norwegian Forest Cat, Abyssinian and Birman (each 0.3%). Four cats were documented as mixed breed (1.3%).
Signalment and clinical parameters in cats with different aetiologies for pleural effusion
Data are median (range)
Overall significance tested with ANOVA/Dunn
RI = reference interval; CD = cardiac disease; FIP = feline infectious peritonitis; NA = not applicable (too few observations in this category for statistical analysis)
Complete blood count parameters in cats with different aetiologies for pleural effusion
Data are median (range)
Overall significance tested with ANOVA/Dunn
RI = reference interval; CD = cardiac disease; FIP = feline infectious peritonitis; ALT = alanine aminotransferase; AP = alkaline phosphatase; NA = not applicable (too few observations in this category for analysis)
Effusion parameters in cats with different aetiologies for pleural effusion
Data are median (range)
Overall significance tested with ANOVA/Dunn
CD = cardiac disease; FIP = feline infectious peritonitis; NA = not applicable (too few observations in this category for analysis); LDH = lactate dehydrogenase
Physical examination
Initial body temperature had been recorded in 225 patients. Of these, 29 cats (12.9%) had increased, 107 (47.6%) had normal (37.8–39.2°C) and 89 (39.6%) had decreased body temperature. Cats of the CD group had a significantly lower body temperature (median 37.8°C) than cats diagnosed with FIP (median 38.3°C; P = 0.0022). Comparing the five groups regarding the parameters of heart rate and respiratory rate, no significant differences were detected.
Radiographs
Radiographs were available for 230 cats. Bilateral effusion was diagnosed in 70 (88.6%) and unilateral effusions in 9 (11.4%) patients. Presence of uni- vs bilateral effusion did not differ statistically between groups.
Blood parameters
Compared with cats of all other groups, cats with CD had significantly increased levels of alanine aminotransferase (ALT) (FIP: P = 0.001; neoplasia: P = 0.02; pyothorax: P <0.001); chylothorax: P = 0.02) and alkaline phosphatase (AP) (FIP: P = 0.04; pyothorax: P = 0.001). Cats diagnosed with FIP had significantly lower erythrocyte counts compared with the CD (P = 0.033) and chylothorax (P = 0.011) groups, and a lower haematocrit compared with the CD (P = 0.005) and chylothorax (P = 0.005) groups.
Fluid analysis
While cats with CD had significantly lower total cell counts (P <0.001 [pyothorax and neoplasia]; P = 0.03 [chylothorax]), protein levels (P <0.001 [FIP, neoplasia and pyothorax]; P = 0.004 [chylothorax]) and a lower specific gravity of their effusion compared with the other four groups (P <0.001), cats with pyothorax had significantly higher cell counts compared with all other groups (P <0.001 [CD, FIP and neoplasia]; P = 0.004 [chylothorax]). Feline patients diagnosed with pyothorax had significantly lower glucose levels in effusions compared with cats in the CD, chylothorax (P <0.001) and neoplasia (P = 0.004) groups.
Short-term outcome
Data regarding the length of hospitalisation were available for 222/306 cats. Median duration of hospitalisation for all cats was 2 days (1–32 days). Patients with chylothorax stayed significantly longer in hospital (median 5 days) than cats diagnosed with neoplasia (median 1 day). Of 249 cats with information regarding their discharge status, 8.0% died and 47.8% were euthanased during their hospital stay. The remaining 44.2% were discharged. Cats with CD were significantly more often discharged than cats of the other groups (P <0.001), whereas cats with FIP (P = 0.042) or neoplasia (P <0.001) died or were euthanased significantly more frequently than cats in the other three groups. Long-term outcome was not available for most cases.
Discussion
The present study identified 306 cats with pleural effusion that had a diagnosis regarding the aetiological categorisation of the fluid. This study is the most comprehensive one to date, including a large number of cats with pleural effusion.
The CD group represented the largest group of patients, followed by the FIP and neoplasia groups, which is in contrast to an older study that included 82 cats with pleural effusion. In that study, neoplasia (23%), pyothorax (18%) and FIP (18%) were the most common aetiologies causing effusion; CD comprised only 11% of patients. 4 Reasons for the higher number of cases of CD in the present study might be improved diagnostic modalities and the fact that cases presented to first-opinion practices were also included in the study by Davies and Forrester. 4
The higher number of patients diagnosed with pyothorax in the older study could potentially be explained by geographical differences and the possibility of plant material causing septic pleural effusion in certain areas,14,20–23 and a lower number of outdoor cats with access to plant material or bite wounds in the cat population of the present study (of 251 cats with known housing conditions, 59.7% were strictly indoor cats).
The number of cats with FIP in the present study is surprisingly small, considering the fact that the prevalence of FIP in cats with effusions reached up to 51% in previous studies.24–26 However, the rather small number of cats with FIP can probably be explained by the fact that no cats with ascites only were included. In addition, cats might now more commonly be diagnosed and then euthanased in private practice as a result of improved diagnostic possibilities, such as the availability of specific PCR methods, and not being referred to specialty hospitals for advanced diagnostics and therapeutics. 24
In the present study only cases with chylothorax without any known primary disease (idiopathic chylothorax) were included in the chylothorax group. However, chylous pleural effusion is a result of the leakage of chyle from lymphatics and can also be caused by various underlying conditions (eg, heart failure or neoplasia), as well as being of idiopathic origin. In this study, 14 cats with chylothorax were diagnosed with neoplasia or heart failure, and therefore they could not clearly be assigned to a certain subgroup. For that very reason it is of great importance to rule out a primary underlying disease when chylous effusion is identified in a patient. 27
Several parameters could be identified in the present study that might be helpful in discriminating between different aetiologies of feline pleural effusion. Age seems to be a helpful parameter to make an initial assumption regarding the aetiology of effusion. Cats with FIP were significantly younger than cats diagnosed with other conditions, which was also shown in the study by Davies and Forrester. 4 There are still overlaps with other aetiological groups and age in itself is not sufficient to establish a definitive diagnosis.
Cats with CD displayed a significantly lower body temperature compared with cats of all other groups. Almost 50% of the cats with CD had a temperature below the lower end of the reference interval. This finding can be explained by decreased cardiac output, leading to hypoperfusion. 28 In conjunction with other clinical and diagnostic findings, hypothermia should therefore raise the suspicion of CD as a potential underlying aetiology and initiate for a distinct cardiac work-up. In contrast to body temperature, heart rate and respiratory rate were not helpful to discriminate between different aetiological groups. Most likely, respiratory rate is dependent on the amount of effusion accumulated in the thorax.6,29,30 Fox et al 31 were also not able to detect differences in the average heart rate between normal cats and cats with heart disease on physical examination, but when the heart rate was assessed by Holter monitoring over a certain period of time it was significantly higher in cats with heart failure. 31 The poor diagnostic value of the heart rate in the initial physical examination is most likely due to the susceptibility of cats to stress. 32
Radiographic reports were available for 230 cats, but uni- or bilateral effusion could only be differentiated in 79 cases. In 88.6% of patients with this information available, effusion was bilateral. This is in accordance with the assumption that feline pleural effusion is bilateral in most cases due to communicating pleural cavities,6,30,33 and might be a great argument for blind thoracentesis in cats with suspected effusion if confirmation by radiographs or ultrasound is not possible. Effusion might be found more on one side than the other but usually should be found on both sides.
Similar to other studies, cats with FIP had significantly lower haematocrit and erythrocyte counts compared with cats with CD and chylothorax; however, both parameters were still within the reference interval in the majority of cats and therefore cannot aid in establishing a diagnosis of FIP as the underlying disease.
Surprisingly, most cats with FIP did not show significant alterations in the protein fractions, such as hypoalbuminaemia and hyperglobulinaemia, which have been described as ‘typical’ for FIP.34,35 This finding is consistent with a recent publication that showed that hyperglobulinaemia is not as common in cats with FIP, especially if effusion is present. 36 In accordance with a recent study by Riemer et al, 36 who found that hyperbilirubinaemia was significantly associated with the presence of effusion in cats with FIP, in the present study serum bilirubin in cats with FIP was also significantly elevated compared with cats in the CD, neoplasia and chylothorax groups. Therefore, serum protein levels do not represent good parameters to discriminate between different aetiologies of pleural effusion. However, increased bilirubin levels should lead to a further investigation towards a possible FIP.
Interestingly, cats with pyothorax did not show significantly higher white blood cells compared with other groups, as one would expect.20,23,37 However, this finding can most likely be explained by the small number of cases with pyothorax in this study and should be reassessed in a larger group of cats with this diagnosis.
Compared with cats of all other groups, cats with CD had significantly increased ALT activity, with 46.8% of cats showing concentrations above the reference interval. The CD group also had significantly increased AP levels compared with the FIP and pyothorax groups. Increases in liver enzymes in this group can most likely be explained by hypoperfusion and hypoxia of the liver cells owing to decreased cardiac output as described in previous studies. 38
Pleural effusion in cats with CD was characterised by low total cell count, low protein levels and low specific gravity. Congestive heart failure can induce pleural effusion as a result of increased parietal pleural filtration of fluid into the pleural cavity caused by elevated systemic hydrostatic pressure (right-sided failure) or decreased visceral pleural absorption owing to increased pulmonary hydrostatic pressure (left-sided failure). 3 Therefore, cats with pleural effusion, especially those categorised as transudate, or modified transudate, should further be evaluated for underlying heart disease, as suggested by previous studies. 39 New diagnostic markers such as NTproBNP could additionally help to discriminate between cardiac and non-cardiac pleural effusion in cats.40–42 Measuring NTproBNT in pleural fluid is a highly recommended and reliable test, especially in unstable patients. 42 With a cautious interpretation of the currently published cut-off values the test is useful for considering further specific cardiological work-up.
Pleural effusion in cats with pyothorax in the present study was characterised by increased total cell count and decreased glucose levels compared with effusion of other aetiologies. These findings have previously been described in cats with septic effusion. 39 While increased cell counts can be explained by the septic inflammatory reaction and migration of neutrophils into the thoracic cavity, decreased glucose levels are thought to be caused by utilisation of glucose by bacteria and phagocytic cells and glycolysis in the pleural fluid.43,44 In a previous study investigating potential markers to differentiate between septic and non-septic abdominal effusions in dogs and cats, glucose levels were not significantly altered in cats with septic compared with non-septic abdominal effusion. 45 However, in the present study glucose proved to be a useful indicator for septic pleural effusion.
The present study confirmed that short-term outcome depends on the aetiology of pleural effusion. This is in accordance with results of a previous study, in which thoracic effusion due to FIP or neoplasia in cats also carried a poorer prognosis. 4 Most of the patients with these underlying diseases died or were euthanased shortly after diagnosis. In contrast to the results of the older study, 4 cats with CD were significantly more likely to be discharged from the hospital than other patients with pleural effusion. This finding can most likely be explained by the fact that cats were treated by a specialised cardiologist in the present study, offering advanced treatment options in contrast to the cases mostly seen in first opinion practices in the previous investigation. 4 This underlines the importance of a thorough diagnostic work-up in feline patients with pleural effusion, as prognosis depends on the underlying disease.
The study has some limitations owing to its retrospective character. Full diagnostic work-up was not available for all patients, and radiographic images were not available for a review. Fluid analysis had not been performed in all cats (in almost half of the cats with CD). A further limitation is the fact that the NTproBNP test to differentiate between cardiac and non-cardiac causes of dyspnoea had not been used in most cases. Although a large group of cats with pleural effusion was investigated, the aetiological groups were rather small and thus data might not be representative of all forms of underlying diseases.
Conclusions
The present study was able to show that different clinical and laboratory parameters can aid in establishing a diagnosis in cats with pleural effusion. Age, body temperature and liver enzymes, as well as protein, total cell count and glucose levels in the effusion should be included in the diagnostic work-up in feline patients with pleural effusion.
Footnotes
Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
