Pulmonary TB is the most common form of disease accounting for 80% of cases in the United States [2]. Extrapulmonary TB is more common among patients who are female, born outside the United States, and with HIV infection [21]. Acute respiratory failure, which occurs in 2% to 13% of hospitalized TB cases, is the most common reason for admission to an ICU [5,6,10,19]. While chronic cough and fevers are usually present, other symptoms suggestive of pulmonary TB include weight loss, dyspnea, and hemoptysis [11]. Of note, dyspnea may be minimal despite fairly extensive lung destruction. Hemoptysis occurs in about 20% of patients and occasionally can be massive [22]. Pulmonary TB may also be asymptomatic, occurring in patients with primarily extrapulmonary disease, or may be a coincidental finding (Fig. 87.1).

Definitively diagnosing pulmonary TB relies on the collection of respiratory samples for smear and culture. Sputum samples should be considered in symptomatic patients at risk for TB even when the chest radiograph appears normal. Positive sputum cultures in the absence of radiographic abnormalities were relatively rare in the pre-AIDS era [23] but appear more commonly among TB cases associated with AIDS [24]. The proportion of hospitalized TB patients who have a positive sputum smear ranges between 35% and 65% [7,9]. A minimum of three sputa or other lower respiratory tract specimens should be collected when pulmonary, pleural, or disseminated TB is suspected. The samples should be collected 8 to 24 hours apart preferably with at least one early morning specimen [25].

Patients who are unable to spontaneously produce sputum should have samples induced using nebulized hypertonic saline [11]. Bronchoscopic specimens are not more sensitive, and should not be considered a replacement for three expectorated or induced sputa [26]. Bronchoscopy is generally helpful if alternative diagnoses are being sought or if a tissue biopsy is needed. For select patients, including young children, who either cannot tolerate the nebulizer or who still do not produce an adequate sputum sample, gastric aspirates should be obtained. When acid-fast bacilli (AFB) smears of respiratory secretions are negative, other specimens that may yield a diagnosis include pleural fluid, pleural biopsy, or transbronchial biopsy [11,27]. More invasive procedures such as transthoracic needle biopsy of the lung or mediastinal lymph nodes or open lung biopsy may be necessary in certain circumstances.

Pleural TB presents in two forms, commonly as tuberculous pleuritis and rarely as tuberculous empyema [11,28]. Tuberculous pleuritis occurs in 6% of HIV-negative and 11% of HIV-positive patients [29], and the incidence increases with declining CD4 cell counts [30]. It results from the rupture of a granuloma into the pleural space and may occur alone or in conjunction with pulmonary disease [28]. Often patients are asymptomatic but some present with acute symptoms of fever and chest pain, suggesting a viral or bacterial cause. The pathogenesis is primarily an immunologic reaction with very few tubercle bacilli actually present in the pleural space. Radiographically, a unilateral effusion covering less than half the hemithorax is typical. Untreated, tuberculous pleuritis often resolves but these patients are at high risk for recurrent pulmonary disease. Tuberculous empyema is much less common and results from the entry of large numbers of bacilli into the pleural space due to the rupture of an adjacent cavity or development of a bronchopleural fistula [31].

Pleural fluid and tissue biopsy are typically needed to definitively diagnose tuberculous pleuritis. Sputum specimens should
also be collected to evaluate for concurrent pulmonary disease. The pleural fluid most often shows a serous exudate with elevated protein and lactate dehydrogenase levels, low-to-normal glucose levels, and a pH range between 7.05 and 7.45 [29,32]. Early in the process, the fluid has a predominance of polymorphonuclear leukocytes that are replaced by lymphocytes within days. Adenosine deaminase (ADA) and other biochemical markers have been studied extensively, alone and in combination, as markers for diagnosing tuberculous pleuritis. Recent studies have supported measuring ADA levels, especially isoenzyme 2, showing additive diagnostic sensitivity and specificity when combined with other tests [33]. Interferon-gamma release assays (IGRA) are also undergoing investigation as diagnostic tools for pleural TB [34]. Both ADA and IGRA tests may be useful in settings that lack the capacity to do cultures, but should not replace a pleural biopsy which provides tissue for culture and pathology review.

AFB smears of pleural fluid and pleural biopsies are rarely positive (10% to 20%). The earliest presumptive diagnosis is provided by pathologic findings of granulomas with or without caseation, which are seen histologically in 60% of specimens [28]. Pleural fluid cultures are positive in only 20% to 30%. The yield increases slightly with multiple samples but usually delays the initiation of TB treatment [35]. Pleural biopsies are culture positive in 55% to 85% of specimens and should be sought whenever TB is considered a likely diagnosis.