Porth's Essentials of Pathophysiology, 4e

550

Respiratory Function

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and employees in congregate settings (e.g., corrections facilities, homeless shelters, long-term care facilities), and health care workers with high-risk patients. 32,35 The tuberculin test cannot distinguish between active and latent infection, and has several other limitations. Because the hypersensitivity response to the test depends on cell-mediated immunity, false-negative test results can occur in immunocompromised persons; that is, a nega- tive tuberculin test result can mean that the person has a true lack of exposure to tuberculosis or is anergic (unable to mount a normal immune response to the test). False- positive results can also occur; for example, in persons who have nontuberculosis mycobacteria infection or who have received the Bacillus Calmette-Guérin (BCG) vaccine for tuberculosis prevention. Although the BCG vaccine is not used in the United States for tuberculosis prevention, many immigrants will have received it. Recently, two interferon gamma release assays have come on the market. These tests are in vitro assays of CD4 + T-cell-interferon gamma release in response to stimulation by specific M. tuberculosis antigens. Since the antigens are absent from all BCG strains and most nontuberculous mycobacteria, the test is superior to the tuberculin skin test. 16,34 Genotyping can be done to identify different strains of M. tuberculosis in persons who have been diagnosed with active tuberculosis. It can be used to evaluate second episodes of tuberculosis to determine whether the second episode was due to relapse or reinfection. Genotyping also permits the evaluation of isolates with different patterns of drug susceptibility. 35 In addition, it is useful in investigating outbreaks of infection and determining sites and patterns of M. tuberculosis trans- mission in communities. Treatment The goals of therapy are to treat infected individuals by eliminating the tubercle bacilli while preventing the spread of infection and development of drug-resistant forms of the disease. The tubercle bacillus is an aerobic organism that multiplies slowly and remains relatively dormant in oxygen-poor caseous material. However, it undergoes a high rate of mutation and tends to acquire resistance to any one drug. For this reason, multidrug regimens are used for treating persons with active tuber- culosis, and treatment typically continues for 6 months or longer. Treatment duration is prolonged due to the slow- growing nature of the tuberculosis bacteria that impairs the effectiveness of antibiotics that target actively repli- cating organisms. The basic principles of tuberculosis treatment are: (1) to administer multiple drugs to which the organisms are susceptible, (2) to add at least two new drugs when treatment failure is suspected, (3) to provide the safest and most effective therapy in the shortest period of time, and (4) to ensure adherence to therapy. 16 Adherence to treatment can be improved by providing detailed educa- tion about the disease and its treatment in addition to a case manager who supervises all aspects of an indi- vidual’s care. Direct observed therapy (DOT), which

clinical disease. This commonly occurs at the site of the primary lesion or at a distant site as a result of hematog- enous spread. Clinical symptoms, such as pleuritic pain due to extension of the infection to the pleural surfaces between the lung and chest wall are common as the dis- ease progresses. Persons with secondary tuberculosis commonly pres- ent with low-grade fevers, night sweats, easy fatigability, anorexia, and weight loss. 2 A cough initially is dry but later becomes productive with purulent and sometimes blood-tinged sputum. Dyspnea and orthopnea develop as the disease advances. Diagnosis A definitive diagnosis of active pulmonary tuberculosis requires identification of the organism from cultures or DNA amplification techniques. 33,35 Culture remains the gold standard for laboratory confirmation of infec- tion and is required for drug sensitivity testing. Culture specimens may be obtained from early morning spu- tum specimens, gastric aspirations, or bronchial wash- ings obtained during fiber-optic bronchoscopy. Because M. tuberculosis grows slowly, cultures in liquid media require several days, and cultures on solid media require up to 12 weeks. Several nucleic acid amplification [NAA] tests are available. These permit the diagnosis of tuberculosis in as quickly as several hours. 35 However, their applicability is limited by variable sensitivity and high cost. Chest radiographs are used to determine the extent of lung involvement. In patients with secondary tuberculosis, CT scanning may also be performed. The tuberculin skin test, which measures the delayed hypersensitivity response to an intradermal injection of tuberculin, a sterile liquid containing proteins derived from the tubercle bacillus, is used for tuberculosis screen- ing. The test is recommended for high-risk populations, including persons who are in close contact with some- one who has confirmed active tuberculosis, residents FIGURE 22-8. Cavitary tuberculosis in the apex of the left upper lobe of the lung. (From Beasley MB,TravisWD, Rubin E. The respiratory system. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams & Wilkins; 2012:550.)