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1 Respiratory Dept, Zarzuela Clinic and 2 Hospital Ramón y Cajal, Madrid, Spain. 3 Pulmonary Division, St Thomas Hospital and Vanderbilt University, Nashville, Tennessee, USA
CORRESPONDENCE: D. Jiménez Castro, Emergency Dept Hospital Ramón y Cajal, Madrid, Spain. Fax: 34 949227502. E-mail: djc_69_98@yahoo.com
Keywords: drainage, empyema, loculations, microbiology, parapneumonic effusion, thoracoscopy
Received: October 30, 2002
Accepted January 3, 2003
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Abstract |
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The design of the prospective study involved investigating patients with parapneumonic pleural effusions diagnosed between March 1991 and December 2000 in the respiratory department of Hospital Ramón y Cajal (Madrid, Spain) which is a 1,500 tertiary-care hospital.
The clinical and radiological characteristics and measurements of microbiological and biochemical variables in the pleural fluid taken from the patients were studied. RPT was defined in a posteroanterior chest radiograph as pleural thickening of 
10 mm measured at the lateral chest wall at the level of an imaginary line, tangent to the diaphragmatic dome.
A total of 48 of the 348 patients studied (13.79%) were found to have RPT. Among the factors studied, only presence of pus in the pleural space, Fine classes IV and V, temperature 38°C and delayed resolution of pleural effusions after diagnosis (>15 days) were independently associated with the risk of RPT.
This study showed that significant residual pleural thickening was not a common complication of parapneumonic pleural effusions. There are certain risk factors for the development of residual pleural thickening. However, this complication was not associated with long-term functional repercussions in the series of patients involved in this study.
Despite the advent of potent antibiotics, bacterial pneumonia still results in morbidity and mortality. The annual incidence of bacterial pneumonia is estimated to range from 1.8–8 cases per 1,000, with
20% requiring hospitalisation 1. It has been reported that 57% of hospitalised patients with bacterial pneumonia have an accompanying pleural effusion 2–4. The morbidity and mortality rates in patients with pneumonia and pleural effusions are higher than in patients with pneumonia alone 5. Most pleural effusions associated with pneumonia resolve without any specific therapy directed toward the pleural fluid 2, however 10% require operative intervention for their resolution. Delay in implementing proper therapy for these effusions is responsible for much of the morbidity, which can be substantial. This delay can lead to characteristic changes in the pleural space, including loculations and pleural thickening 6. Previous studies have assessed what features predict pleural thickening in tuberculous pleural effusions 7, 8, however only one study has retrospectively analysed predictive factors for the development of residual pleural thickening (RPT) in parapneumonic pleural effusions (PPE) 9. Moreover, there are no studies addressing if RPT is associated with long-term functional consequences in this group of patients.
The purpose of the present study was to prospectively evaluate the prognostic features of RPT and its functional repercussions in a consecutive series of patients with PPE. The authors therefore hypothesise that RPT is an uncommon complication of PPE and is not associated with long-term functional repercussions.
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Materials and methods |
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The routine study of the pleural fluid included: pH, determined by a blood gas analyser (model 995-Hb; AVL Medical Instruments, Roswell, GA, USA), biochemical testing of pleura/serum (proteins, lactate dehydrogenase (LDH), glucose, cholesterol, triglycerides, albumin and adenosine deaminase), haemogram, cytology and microbiological testing of pleura (Gram stain, Ziehl stain, aerobic, anaerobic and mycobacterial cultures). The following variables were collected through chart review and patient interviews: age, sex, abnormalities on chest radiographs, indication for thoracentesis (diagnostic, therapeutic), number of thoracenteses, pleural effusion volume (as a percentage of the entire hemithorax, subjectively visually assessed), side affected and Fine classes 10 (a five classes prediction rule which accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes; prospectively used from 1997 in the present study). The authors also recorded: antibiotic therapy, pleural drainage (thoracentesis, chest tube, fibrinolytics, thoracoscopy or thoracotomy), length of stay in hospital, complications, in-hospital deaths, 6 month deaths, 6 month re-admissions and RPT at discharge and at 6 months. Pulmonary function tests and Borg scale were performed at discharge and at 6 months to evaluate the functional impact of RPT in this group of patients. Patients were divided into two groups based on the presence or absence of RPT at the 6month radiograph. RPT was measured at the lateral chest wall of a posteroanterior chest radiograph at the level of animaginary line tangent to the diaphragmatic dome. RPT was defined as a pleural thickness of 10 mm because this thickness may have important clinical repercussions.
Statistical analyses were performed using computer software. Results were expressed as mean±sd unless otherwise stated. Variable distributions were compared with a normal distribution using the Kolmogorov-Smirnov test. The characteristics of the patients with and without RPT were compared using the Chi-squared test with Yates correction or Fisher's exact test for noncontinuous variables, the nonparametric Mann-Whitney U-test for continuous variables with non-normal distribution and unpaired t-test for those with normal distribution.
Crude odds ratios (ORs) and their 95% confidence intervals (CI) were used to describe the association between RPT andpotential risk factors. Subsequently, a multiple logistic regression analysis was performed to adjust for the confounding effects of other factors and a logistic regression model was built by a stepwise forward method. Factors were selected from those that were statistically associated with RPT in the univariate analysis and from those that were thought toinfluence the model. Adjusted ORs, in the multivariable logistic regression, were estimated by the method of maximum likelihood and 95% CIs were based on the sd coefficient estimates and normal approximation. Two-tailed p-values of 
0.05 were considered statistically significant.
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Results |
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10 mm 6 months after discharge.
The clinical, radiological and microbiological characteristics of patients with or without RPT are shown in table 1
. The patients with RPT had significantly larger effusions, lower pleural fluid pH and higher pleural fluid LDH and leukocyte levels.
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The results of the univariate analyses are depicted in table 2. Only the results that were statistically significant, or close to significance, are presented. Temperature 38°C, total leukocyte count 104·mm–3 and Fine classes IV and V were associated with RPT. Of the pleural fluid characteristics, presence of pus or pathogens in the pleural space, pleural fluid volume 50%, LDH 1,000 IU·L–1, pH7.20 and leukocyte count 6x103·mm–3 were statistically associated with RPT. Finally, the need for fibrinolisis or thoracoscopy, and a hospital stay >7 days or a resolution of the pleural effusion >15 days were associated with RPT. There was no association between the delay in instituting proper therapy and the development of RPT.
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. The risk indicators for RPT, expressed as estimated ORs, were temperature (13.90 for temperature 38°C versus temperature <38°C), resolution of the pleural effusion (1.22 for resolution >15 days versus resolution 15 days), presence of pus in the pleural space (9.91 for presence of pus versus absence of pus) and Fine classes IV and V (1.08 for classes IV and V versus classes I, II and III).
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). However, the authors did demonstrate a marked reduction in the pleural thickening with regard to time (6.89±5.07 mm at discharge versus 4.55±4.89 mm at 6 months, p<0.01).
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Discussion |
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In cases of tuberculous pleurisy, the prevalence of RPT varies from one study to another. Lee et al. 13 reported 10%, Soler et al. 14 reported 72% and De Pablo et al. 7 and Barbas et al. 8 reported intermediate values of 43% and 52%, respectively. These variations can be attributed to the lack of a uniform concept for RPT. In some instances a pleural thickness of >2 mm is defined as abnormal in other cases a thickness of 10 mm is required to be defined as abnormal. In the present study the authors used an upper limit of 10 mm, because functional disturbances could be found in this group of patients.
The evolution of empyema occurs through three overlapping stages (exudative, fibrinopurulent and organising phases) 15. During these phases, the pleural fluid leukocytes and LDH levels increase with a simultaneous decline in glucose and pH levels. The time required for the progression to the organising stage has been cited as 2–3 weeks 16. The results from the present study, in the univariate analysis, concur with others 17–19 and suggest that patients who eventually developed intense RPT had enhanced inflammatory activity in the pleural space. In patients with RPT 10 mm, the volume of the pleural fluid, pleural leukocyte counts and LDH levels were significantly higher than in those with lower levels of RPT. However, pH levels were significantly lower in patients with RPT measured at 6 months. The authors found that pus and pathogen isolation were more frequent in the group of patients with RPT, as was the need for fibrinolysis and thoracoscopy, these findings support the inflammatory mechanism. Fine's prediction rule identifies patients who are at high risk of death, however this is the first study, to date, that has assessed its value in identifying pleural complications such as RPT. It can be speculated that the severity of illness at presentation predisposes the patient to more severe pleural disease and RPT. The results from the present study cannot confirm a relationship between the delay in initiating proper therapy and a risk for developing pleural thickening. Most patients were treated early in the course of the disease and this could explain the results found from this study.
With multivariable analysis, the present study suggests that fever, delayed resolution of the pleural effusion, presence ofpus in the pleural space and higher Fine scores are independently associated with the risk of developing RPT. To the best of the authors' knowledge, this is the first study in which an association between RPT and clinical conditions (mentioned above) have been demonstrated in a study designed such that confounding risk factors could be eliminated. If this subgroup of patients may benefit from earlier therapeutic interventions or steroid treatment, this has to be addressed in a well-designed, prospective study.
The authors decided to measure FVC at discharge and at 6months, as well as the Borg dyspnoea index, to investigate whether RPT was associated with long-term functional sequelae. The authors could not find differences in these values between patients who developed RPT and those who did not. Patients without RPT experienced significantly higher improvement in FVC between discharge and 6 months when compared with patients who developed RPT. Moreover, the authors could demonstrate a marked reduction in pleural thickening measured at discharge and at 6 months.
In conclusion, in the present study of patients with parapneumonic pleural effusion, 13.79% had residual pleural thickening 10 mm at 6 months. Patients who developed residual pleural thickening 10 mm at 6 months had higher peak temperatures, longer times for resolution of pleural effusion, higher likelihood of the presence of pus in the pleural space and higher Fine scores than the patients without residual pleural thickening. However, patients with residual pleural thickening did not have significantly lower pulmonary functions 6 months postdischarge than those without residual pleural thickening, suggesting that this complication has limited functional impact.
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