Can tuberculous pleural effusions be diagnosed by pleural fluid analysis alone?

OBJECTIVE: To assess whether pleural fluid analysis (PFA) can confidently diagnose tuberculous pleural effusion (TPE). METHODS: PFA of 548 TPEs was performed between January 1991 and December 2011. The control group consisted of patients with malignant PE (MPE), complicated parapneumonic/empyema (infectious) PE (IPE), miscellaneous PE (MisPE) and transudative PE (TrPE). RESULTS: The PFA of 548 histologically or culture-positive consecutive cases of TPE was compared with that of 158 consecutive cases of MPE, 113 cases of IPE, 37 cases of MisPE and 115 cases of TrPE. Statistically significant differences were noted in pleural fluid glucose, pH, cholesterol, triglycerides, adenosine deaminase (ADA), and total percentages of lymphocytes, neutrophils and macrophages when TPEs were compared to all other groups. Of the TPEs, 99.1% were exudates. Pleural fluid protein ≥ 5.0 g/dl, lymphocytes > 80% and ADA > 45 U/l were diagnostic of TPE, with a specificity of 100%, a sensitivity of 34.9% and an area under the curve of 0.975. CONCLUSION: PFA alone was diagnostic in one third of the TPE cases, with a high probability in nearly 60%.

Is the pleural fluid transudate or exudate? A revisit of the diagnostic criteria.

BACKGROUND: Pleural effusions are classified into transudates and exudates based on criteria developed in the 1970s. However, their accuracy has not been evaluated. We compared the performance of the pleural fluid absolute lactic dehydrogenase level (FLDH), fluid to serum ratio of LDH (LDHR), and fluid to serum ratio of total protein (TPR). TPR has been used instead of the absolute value of fluid protein based on the observation that fluid protein is influenced by changes in the serum protein concentration. However, the rationale for using LDHR remains unexplored. METHODS: Of 212 consecutive patients with pleural effusions, four with multiple causes and eight with an uncertain diagnosis were excluded. ROC curves were generated using sensitivity and 1-specificity values for TPR, FLDH, and LDHR and positive likelihood ratios (LR+ve) were computed using the optimum cut off values. The correlation between pleural fluid and serum concentrations of total protein and LDH was also estimated. RESULTS: Of 200 effusions studied, 156 were exudates and 44 were transudates. The optimum cut off levels were: FLDH 163 IU/l, TPR 0.5, LDHR 0.6, and the FLDH-TPR combination 163 and 0.4, respectively. The area under the curve (AUC) with 95% confidence interval (CI) was: 0.89 (0.86 to 0.96) for FLDH, 0.86 (0.80 to 0.91) for TPR, 0.82 (0.77 to 0.89) for LDHR, and 0.90 (0.86 to 95) for FLDH-TPR. A significant correlation was observed between serum and pleural fluid protein levels in transudates and exudates (r=0.5 and 0.6, respectively), but the correlation between serum and pleural fluid LDH levels was insignificant. CONCLUSION: FLDH is the most accurate marker for the diagnostic separation of transudates and exudates and LDHR has no role in this process. Combining TPR with FLDH appears to improve the diagnostic accuracy slightly.

Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement.

OBJECTIVE: Provide explicit expert-based consensus recommendations for the management of adults with primary and secondary spontaneous pneumothoraces in an emergency department and inpatient hospital setting. The use of opinion was made explicit by employing a structured questionnaire, appropriateness scores, and consensus scores with a Delphi technique. The guideline was designed to be relevant to physicians who make management decisions for the care of patients with pneumothorax. OPTIONS: Decisions for observation, chest tube placement, surgical interventions, and radiographic imaging. OUTCOMES: Effectiveness of pneumothorax resolution, duration of and patient tolerance of care, and pneumothorax recurrence. EVIDENCE: Literature review from 1967 to January 1999 and Delphi questionnaire submitted in three iterations to a multidisciplinary physician panel. VALUES: The guideline development group determined by consensus the relevant outcomes to be considered in developing the Delphi questionnaire. BENEFITS, HARMS, AND COSTS: The type and magnitude of benefits, harms, and costs expected for patients from guideline implementation. RECOMMENDATIONS: Management decisions vary between patients with primary or secondary pneumothoraces, with observation of small pneumothoraces being appropriate only for primary pneumothoraces. The level of consensus varies regarding the specific interventions indicated, but agreement exists for the general principles of care. VALIDATION: Recommendations were peer reviewed by physician experts and were reviewed by the American College of Chest Physicians (ACCP) Health and Science Policy Committee. IMPLEMENTATION: The guideline recommendations will be published in printed and electronic form with distribution of synopses for patients and health care providers. Contents of the guideline will be incorporated into continuing medical education programs. SPONSORS: The ACCP.

Malignant pleural effusions.

The estimated annual incidence of malignant pleural effusions in the United States is 150,000 cases. Patients most commonly present with dyspnea, initially on exertion and later at rest. Chemical pleurodesis is the most common modality of therapy for patients with recurrent, symptomatic, malignant pleural effusion. Talc is the most successful pleurodesis agent, and talc poudrage and slurry have equal efficacy. Although a number of cases of acute respiratory failure have been associated with talc pleurodesis, the incidence is < 1% and many of these episodes cannot be clearly attributed to talc alone. Although a low pleural fluid pH is associated with a decreased survival and less successful pleurodesis, pH should not be the sole criterion for recommending or withholding pleurodesis. Other factors that need to be considered before recommending pleurodesis include relief of dyspnea after therapeutic thoracentesis, general health of the patient, performance status, presence of trapped lung, and the primary malignancy. Pleuroperitoneal shunt or chronic indwelling catheter should be considered for patients who fail pleurodesis or who have a trapped lung.

Trapped lung.

Trapped lung is one of the outcomes of fibrinous or granulomatous pleuritis and is a cause of chronic, benign, unilateral pleural effusion. It is characterized by inability of the lung to expand and fill the thoracic cavity due to a restricting fibrous visceral pleural peel. The resulting chronic pleural space is fluid filled, and the persistence of the fluid is solely due to hydrostatic equilibrium. Historically recognized as a complication of therapeutic pneumothorax for treatment of tuberculosis, it is today most commonly a consequence of inadequately treated parapneumonic effusion, but it is also associated with cardiac surgery, chest trauma, and other inflammatory processes involving the pleura. The diagnosis requires documentation of chronicity and stability and the absence of an active inflammatory or malignant pleural process, bronchial obstruction, or severe underlying lung disease. Findings supporting the diagnosis are an initial negative pleural liquid pressure, increased pleural space elastance, and the demonstration of a pleural peel. Confirmation of the diagnosis requires successful surgical decortication, which is the only available therapy. In the asymptomatic patient, decortication is not indicated and observation is warranted.

Management of malignant pleural effusions.

Lung and breast cancer are responsible for the majority of malignant pleural effusions. The diagnosis of a malignant pleural effusion signifies a limited survival for most patients. During their final months, dyspnea is the most common symptom and requires palliation. A decision relating to palliation and the modality of therapy should be based on total assessment of the patient and not a single variable. Local treatment remains the most common and effective palliation. Assessing the response to therapeutic thoracentesis determines the degree of relief of dyspnea and the time-course of recurrence. Lack of a beneficial effect suggests the patient may have a trapped lung, atelectasis, lymphangitic carcinomatosis, or tumor embolism. Short-term chest tube drainage has variable results and is not recommended. Chemical pleurodesis through a standard chest tube or small-bore catheter is a commonly used and effective treatment. Talc slurry consistently produces the highest success rates, followed by the tetracyclines and bleomycin. Although acute respiratory failure has been reported following talc pleurodesis, these episodes represent a very small percentage of the total reported cases of talc poudrage and slurry pleurodesis. Whether acute respiratory failure is directly related to talc in the absence of other risk factors remains unclear. Other possible causes for acute respiratory failure following pleurodesis include re-expansion pulmonary edema, excessive premedication, severe comorbid disease, and sepsis from unsterile talc or poor chest tube technique. Factors that need to be considered before recommending chemical pleurodesis include response to therapeutic thoracentesis, general health of the patient, performance status, pleural space elastance, the primary malignancy, and pleural fluid pH. Chronic indwelling catheters have been shown to be effective alternatives to chemical pleurodesis. Pleuroperitoneal shunting can provide palliation to patients with a trapped lung, a malignant chylothorax, or others who have failed pleurodesis. Parietal pleurectomy should be reserved only for patients who have failed chemical pleurodesis or have a trapped lung with an expected survival > 6 months. To provide the highest quality of life for patients with malignant pleural effusions, the least invasive, morbid and costly therapy should be used. Success of the initial procedure is important, as repeat procedures are associated with additional hospitalization, patient discomfort, and increased expense; therefore, the selection of patients for palliation and the modality utilized is critical to avoiding further hardship to the patient.

Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density in bronchiectasis.

We conducted a placebo-controlled, double-blind, randomized study to evaluate the microbiological efficacy and safety of inhaled tobramycin for treatment of patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or placebo (n = 37), which was self-administered twice daily for 4 wk and followed by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated in 35% of TSI patients but was detected in all placebo patients. Investigators indicated that 62% of TSI patients showed an improved medical condition compared with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1 to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1) percent predicted from Week 0 to Week 4 was similar for the TSI and placebo groups (p = 0.41). More TSI-treated patients than placebo patients reported increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms did not limit therapy. Additional study is warranted to further evaluate TSI in bronchiectasis patients.

Drugs and the pleura.

PURPOSE: To identify the drugs associated with pleural disease and to review the clinical, radiographic, and pleural fluid findings that occur, the natural history of the pleural reaction, and the response to therapy. DATA SOURCES: English-language articles published from January 1966 through April 1998 were identified through searches of the MEDLINE database, selective bibliographies, and personal files. DATA EXTRACTION: Case reports, letters, and review articles were assessed for relevancy. Reports of drug-associated pleural effusion, pleuritis, and/or pleural thickening were analyzed. Drug effect was believed to be causal when exposure induced pleural disease, when the pleural response remitted on discontinuation of the drug, and when the pleural disease recurred with reexposure. Drug association was inferred when the pleural disease occurred following drug exposure and remitted after drug discontinuation. The incidence, clinical presentation, dose and duration of drug therapy, chest radiographic findings, pleural fluid analysis, and response to therapy were recorded. CONCLUSIONS: A relatively small number of drugs were found to induce pleural disease when compared to the number of drugs implicated in causing disease of the lung parenchyma. Treatment of drug-induced pleural disease consists of drug therapy withdrawal and corticosteroids for refractory cases. Knowledge of the potential of drug-induced pleural disease will provide a clinical advantage to the physician and should lead to decreased morbidity and economic burden for the patient by avoidance of further diagnostic testing.

The definitions and epidemiology of pleural space infection.

Infections of the pleural space are caused by a diverse group of clinical conditions that include trauma, post-operative states, and pneumonia. Although pleural effusions accompany bacterial pneumonia in up to 60% of patients, they uncommonly influence management because the effusion in most patients disappears with antibiotic administration. Unfortunately, the large number of patients with pneumonia provide an abundant supply of patients who fail to respond to antibiotic administration alone and subsequently present with pleural fluid loculation, pleural sepsis, or empyema. This article provides an overview of the classification schemes that have been used to characterize pleural space infections and highlight the epidemiology of those patients who present with complicated parapneumonic effusions and empyema.

Tuberculous empyema.

Tuberculous empyema represents a chronic, active infection of the pleural space that contains a large number of tubercle bacilli. It is rare compared with tuberculous pleural effusions that result from an exaggerated inflammatory response to a localized paucibacillary pleural infection with tuberculosis. The inflammatory process may be present for years with a paucity of clinical symptoms. Patients often come to clinical attention at the time of a routine chest radiograph or after the development of bronchopleural fistula or empyema necessitatis. The diagnosis of tuberculous empyema is suspected on computed tomography imaging by finding a thick, calcific pleural rind and rib thickening surrounding loculated pleural fluid. The pleural fluid is grossly purulent and smear positive for acid-fast bacilli. Treatment consists of pleural space drainage and antituberculous chemotherapy. Problematic treatment issues include the inability to re-expand the trapped lung and difficulty in achieving therapeutic drug levels in pleural fluid, which can lead to drug resistance. Surgery, which is often challenging, should be undertaken by experienced thoracic surgeons.

Airway obstruction arising from blood clot: three reports and a review of the literature.

Airway obstruction due to presence of blood clot occurs in a variety of clinical settings; however, it is not always preceded by hemoptysis. The impact on respiratory function may be minimal or result in life-threatening ventilatory impairment. Three illustrative cases and a comprehensive literature review are presented. The presence of endobronchial blood clot is suggested by the clinical and radiographic findings of focal airway obstruction. The diagnosis is established by direct endoscopic evaluation. Initial efforts at removal of the airway clot, if warranted, involve lavage, suctioning, and forceps extraction through a flexible bronchoscope. If unsuccessful, further management options include rigid bronchoscopy, Fogarty catheter dislodgment of the clot, and topical thrombolytic agents.

Malignancy metastatic to the pleura.

Malignancy is one of the most common causes of exudative effusions and increases in incidence in the elderly. Lung cancer is the most common cause of malignant effusion caused by contiguous spread and its propensity to invade the pulmonary vasculature and embolize to the visceral pleura. Lung, breast, ovary, and gastric cancer and lymphomas account for about 80% of all malignant effusions. Dyspnea and cough are the most common symptoms at presentation. Thirty percent of patients have a low pleural fluid pH (> or = 7.30) and glucose (> 60 mg/dL) at presentation, which predicts a decreased survival, an increase yield on diagnostic studies, and a poor response to chemical pleurodesis. Talc by poudrage or slurry is the most successful pleurodesis agent. Pleural peritoneal shunt is an option for patients with an intractable, symptomatic malignant effusion who cannot undergo or who have failed pleurodesis.

Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily in the treatment of acute exacerbations of chronic bronchitis.

In medical practice, antibiotics are generally given empirically for the treatment of acute exacerbations of chronic bronchitis (AECB). To be effective, antibiotic therapy should be broad in spectrum, and it should also cover the common beta-lactamase-producing pathogens. In this multicenter, randomized, investigator-masked study, 469 patients with AECB were randomized (in a ratio of 2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin-clavulanate tablets three times daily for 5 to 15 days. Patients receiving ceftibuten were further divided into those who took the capsule with a meal (fed) and those who took the capsule 1 hour before a meal (fasted). Clinical and microbiologic responses were evaluated after treatment at 0 to 6 days (end of treatment) and 7 to 21 days (follow-up). Overall clinical success was determined by cure/improvement of signs and symptoms of AECB at the end of treatment and at follow-up. Overall microbiologic assessment was graded as eradication, persistence, relapse, reinfection, colonization, superinfection, or unassessable. Tolerability was evaluated by grading observed adverse events. The mean duration of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for patients who received amoxicillin-clavulanate. A total of 252 patients receiving ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for clinical efficacy, and 55 patients were evaluable for microbiologic response. Both treatments improved the signs and symptoms of bronchitis, and overall clinical success rates were equivalent for patients treated with ceftibuten (211 of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin-clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently reported treatment-related adverse events were gastrointestinal disturbances, which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with ceftibuten and amoxicillin-clavulanate, respectively. No significant difference was observed in the ceftibutenfed and ceftibuten-fasted groups in overall clinical assessments of the clinical efficacy population and safety population. In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward fewer gastrointestinal side effects, in the treatment of patients with AECB.