The most appropriate next test in this patient is pleural fluid adenosine deaminase (ADA) measurement. This patient likely has a tuberculous pleural effusion from reactivation tuberculosis. She presented with subacute onset of fever, pleuritic chest pain, and nonproductive cough with a history of tuberculosis, and pleural fluid analysis is consistent with a lymphocyte-predominant exudate. All of these features are consistent with a tuberculous pleural effusion. When clinical suspicion is moderate to high, the most appropriate test is pleural fluid ADA measurement. Pleural fluid ADA has been demonstrated to be highly sensitive and specific when levels are greater than 60 U/L (sensitivity 95%, specificity 96%). A level of less than 40 U/L virtually excludes the diagnosis of tuberculosis effusion. In patients with lymphocytic-predominant effusions and elevated ADA levels, empiric therapy for tuberculosis should be initiated and pleural biopsy should be pursued to confirm the diagnosis. In the absence of treatment, patients have a 65% risk of developing pulmonary or extrapulmonary tuberculosis within 5 years.

Sputum culture is more likely to be positive in a patient with concomitant pulmonary parenchymal disease. In the absence of identifiable parenchymal disease, the sensitivity of sputum culture, if present or induced, ranges from 20% to 50%.

Both pleural fluid stain and culture for acid-fast bacilli lack sensitivity to exclude the diagnosis of tuberculosis. In patients without HIV infection, staining is positive in less than 5% of cases, and pleural fluid cultures are positive in only 20% to 30% of cases.