An Integrated Approach to Diagnosis

Although the differential diagnosis of lung disease in a person with HIV infection is quite broad, the probabilities of the various diagnoses can be reduced in a given patient by knowing the patient’s symptoms, HIV transmission category, and CD4+ lymphocyte count and further refined by the findings on the chest film.

The first step in the diagnostic evaluation is to define the patient’s symptoms, especially whether or not the patient has cough and/or shortness of breath. If cough is present, it is important to ascertain if it is productive of purulent sputum. It is very uncommon for patients with PCP to have purulent sputum. Moreover, depending on the stain used, the presence of purulent debris in respiratory tract specimens makes it difficult to detect P. carinii in smears of sputum or bronchoalveolar lavage (BAL) fluid. As noted previously, acute bronchitis and bacterial pneumonia are relatively more frequent among persons with higher CD4+ lymphocyte cell counts. Additionally, IDUs have higher rates of bacterial pneumonia and tuberculosis than persons in other HIV transmission categories. Also as noted, the differential diagnosis varies somewhat with the geographic area, with histoplasmosis and coccidioidomycosis being common in their respective endemic areas.

As in all patients with significant respiratory symptoms, radiographic examination of the chest is usually the first test performed. If the chest film shows no abnormalities in a patient with purulent sputum, the likely diagnosis is bronchitis. Patients with a diagnosis of bronchitis should be followed to be certain that the symptoms resolve and, if there is no resolution or worsening, further evaluation should be undertaken. It must be kept in mind that both tuberculosis and PCP may present with normal chest films.

Patients who have normal chest films and a nonproductive cough may also have bronchitis, but if the CD4+ lymphocyte count is < 300 cells per microliter, P. carinii should be considered. In this circumstance, pulmonary function testing with measurement of the diffusing capacity for carbon monoxide (DL CO) should be performed. If the DL CO is < 75% of the predicted normal value, further evaluation directed toward detecting P. carinii should be undertaken. An alternative approach is to replace measurement of the DL CO with thin-section CT scanning, using a limited number of images to reduce cost. This approach has the potential advantage of being able to distinguish among PCP, emphysema and vascular obliteration caused by foreign particle embolization from intravenous drug use.

If the chest film is abnormal, the next step depends on the type of abnormality. Focal infiltration, especially consolidation, in a patient with purulent sputum is most consistent with a diagnosis of bacterial pneumonia or tuberculosis. Sputum should be obtained for Gram stain, acid-fast stain, and cultures for pyogenic organisms and mycobacteria. If there is a poor response or worsening, further evaluation, especially for P. carinii, should be performed.

To this point much of the diagnostic approach is applicable for evaluating respiratory symptoms regardless of the HIV status of the patient. In the group of patients thought likely to have an HIV-related opportunistic infection, however, there is considerable variation both in philosophy and in specific diagnostic tests used. Cogent arguments have been made for empiric treatment with antipneumocystis agents for patients thought highly likely to have PCP, with specific tests for the organism being reserved for patients who fail to respond. With or without an empiric therapeutic trial, when it is decided to seek a specific diagnosis, the approach used varies. In some institutions, as described subsequently, the first step is to examine induced sputum, with bronchoscopy being performed only in those patients with negative sputum examinations. In other institutions, bronchoscopy is the first procedure used to obtain respiratory tract specimens. Also based on experience and preference, there are variations in the bronchoscopic procedure. Usually, BAL is performed with all procedures. Many clinicians also routinely perform a transbronchial biopsy at the time of initial bronchoscopy, whereas others perform biopsies on a case-by-case basis, and others do so only if the BAL does not provide a diagnosis (and perhaps not even then).

If there is diffuse or focal infiltration in a person with a nonproductive cough, generally the evaluation should be directed toward opportunistic organisms. In many institutions the next diagnostic step is to induce sputum by having the patient inhale a hypertonic (3%) saline mist generated by an ultrasonic nebulizer. Careful attention to the details of selecting patients and inducing, processing, and examining the sputum specimens is essential to obtain good results.

Diagnosis of mycobacterial disease and fungal infections can also be established by examining induced sputum. However, in HIV-infected patients, because of the high frequency of oral candidiasis, fungal cultures are frequently overgrown with Candida species.

Because the negative predictive value of a negative examination of induced sputum for P. carinii is in the range of 60%, patients having a negative sputum examination generally should undergo bronchoscopy with BAL unless another diagnosis has been established or the procedure is contraindicated. At San Francisco General Hospital, P. carinii infection, either alone or with another diagnosis, was found in 32% of bronchoscopic examinations in patients who had a negative sputum examination. KS was found in 15%, nontuberculous mycobacteria in 25%, M. tuberculosis in 5%, and fungal pathogens in 4%. In addition, nearly all of the pathogens were found by BAL, and only rarely did transbronchial biopsy provide additional information.

In patients whose chest films show focal or isolated nodular or mass lesions, needle aspiration biopsy, if the lesion is accessible, is an efficient diagnostic approach, and in some instances fluoroscopically guided transbronchial biopsy should be attempted. Enlarged intrathoracic lymph nodes may also be approached via needle aspiration biopsy, either through the bronchoscope (Wang needle) or via a transthoracic approach. The tests that should be performed on the various sorts of specimens described above are listed in

Table 412-5.

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Revision date: June 22, 2011
Last revised: by Sebastian Scheller, MD, ScD