Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus-infected persons. The Pulmonary Complications of HIV Infection Study Group.

Human immunodeficiency virus (HIV)-associated respiratory infections, most notably Pneumocystis carinii pneumonia (PCP), but also bacterial pneumonia (BP), result in reductions in lung function that have been studied mainly during the course of acute infection. Whether HIV-associated pneumonias also cause permanent changes in pulmonary function is unknown. In this study we investigated the long-term effects of PCP and BP on pulmonary function in a cohort of HIV-infected persons. One thousand, one hundred forty-nine HIV-infected persons were followed in a prospective, observational cohort study at six centers in the United States. Study participants had pulmonary function testing performed at regular preset intervals. PCP and BP diagnoses were verified with defined criteria. Longitudinal multivariate analysis was used to model pulmonary function in terms of demographic data and occurrence of PCP or BP. We found that PCP or BP was associated with permanent decreases in FEV(1), FVC, FEV(1)/FVC, and the diffusing capacity of carbon monoxide. Neither infection resulted in statistically significant changes in TLC. We conclude that PCP and BP result in expiratory airflow reductions that persist after the acute infection resolves. The clinical implications of these changes are unknown, but they may contribute to prolonged respiratory complaints in HIV-infected patients who have had pneumonia.

Pharmacokinetics of trimetrexate and dapsone in AIDS patients with Pneumocystis carinii pneumonia.

The objective of this study was to determine the pharmacokinetics of trimetrexate and dapsone in AIDS patients with moderate to severe pneumocystis pneumonia. Trimetrexate, leucovorin, and dapsone were administered for 21 +/- 3 days in the following doses: trimetrexate glucuronate, 45 mg/m2; leucovorin, 20 mg/m2; and dapsone, 100 mg daily. The pharmacokinetics of trimetrexate, dapsone, and dapsone's metabolite, monoacetyldapsone, were determined at three separate periods over the course of treatment. Serial blood samples were obtained over 24 hours after dosing and analyzed for trimetrexate, dapsone, and monoacetyldapsone, and pharmacokinetic parameters were determined. The mean parameters obtained for the early, mid-, and late collection periods were the following: trimetrexate: t1/2 = 8.29, 9.15, 10.00 hr; AUC = 16.85, 22.38, 24.49 mg.hr/l; CI = 5.58, 4.14, 3.96 l/hr, respectively. DDS: t1/2 = 14.99, 16.59, 15.13 hr; AUC = 30.60, 35.29, 36.08 mg.hr/l; CI = 3.82, 3.49, 3.01 l/hr, respectively. Monoacetyldapsone: t1/2 = 20.25, 18.66, 16.32 hr; AUC = 24.05, 24.06, 23.86 mg.hr/l, respectively. No statistically significant changes in pharmacokinetics for trimetrexate or dapsone were observed over the 21 +/- 3 day course of treatment. The results suggest that there are no major interactions between trimetrexate and dapsone when administered together in acutely ill patients.

High-resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings.

OBJECTIVE: We prospectively studied AIDS patients with a high clinical pretest probability of Pneumocystis carinii pneumonia (PCP) in whom chest radiographic findings were normal, equivocal, or nonspecific with high-resolution CT (HRCT) to determine the incidence of PCP in these patients, to assess the diagnostic accuracy of HRCT for the presence or absence of PCP, to evaluate the role of HRCT in patient management, and to determine the clinical outcome of all patients 1 month after evaluation. SUBJECTS AND METHODS: All patients were referred to the Division of Pulmonary and Critical Care Medicine for diagnosis of clinically suspected PCP. Thirty-three patients were prospectively evaluated with HRCT within 24 hr of diagnostic bronchoalveolar lavage; 18 other patients who underwent HRCT were managed according to the HRCT interpretation and followed up clinically. All HRCT scans were independently reviewed by three chest radiologists; patchy or nodular ground-glass attenuation was considered to indicate "possible PCP." RESULTS: The incidence of PCP was 12% (6/51). The sensitivity of HRCT was 100%; specificity, 89%; and accuracy, 90% (p < .005). We had five false-positive and no false-negative interpretations. Some form of "airways disease" (n = 23) was the single most common HRCT interpretation. CONCLUSION: HRCT may allow exclusion of PCP in patients with findings that are normal, equivocal, or nonspecific on chest radiographs. Empiric therapy or immediate bronchoscopy can be avoided in many patients on the basis of the HRCT findings.

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

AIDS and the lung.

Respiratory symptoms are common in HIV-infected persons. The challenge facing clinicians is to determine whether these respiratory symptoms are due to an opportunistic infection or to a chronic process, such as asthma, chronic bronchitis, bronchiectasis, or emphysema. This article reviewed the clinical presentation, diagnosis, and treatment of two important opportunistic infections, PCP and bacterial pneumonia. It also reviewed the current data on obstructive lung diseases as they relate to HIV.

Presentation of AIDS-related pulmonary Kaposi's sarcoma diagnosed by bronchoscopy.

Kaposi's sarcoma (KS) is the most common neoplasm in persons infected with the human immunodeficiency virus (HIV). However, information about the presenting features of pulmonary KS is limited. To describe the clinical, laboratory, and radiographic features of pulmonary KS, medical records and chest radiographs of 168 patients with pulmonary KS diagnosed by bronchoscopy during a 7-yr period were reviewed. All of the patients were HIV-seropositive males, of whom 95% identified homosexual or bisexual sex as a risk factor for HIV infection. The median CD4 lymphocyte count was 19 cells/microliter. The most common symptoms were cough, dyspnea, and fever. Patients with a concurrent opportunistic pneumonia had a higher median serum lactate dehydrogenase (LDH) concentration than did those with pulmonary KS alone (p<0.001). The most common chest radiograph findings were bronchial-wall thickening, nodules, Kerley B lines, and pleural effusions. The presence of granular opacities or cystic spaces usually indicated concomitant Pneumocystitis carinii pneumonia (p < 0.001). Twenty-six patients (15.5%, 95% CI = 10.2% to 20.8%) had pulmonary KS in the absence of mucocutaneous involvement. The presentation of pulmonary KS is characterized by symptoms that cannot be distinguished from those of a superimposed infection. An elevated serum LDH concentration or a chest radiograph with granular opacities or cystic spaces should raise the suspicion of concurrent opportunistic pneumonia. The diagnosis of pulmonary KS should be considered in an HIV-infected homosexual or bisexual male with respiratory symptoms even in the absence of mucocutaneous lesions.

Suspected Pneumocystis carinii pneumonia with a negative induced sputum examination. Is early bronchoscopy useful?

In U.S. patients with the acquired immunodeficiency syndrome (AIDS), Pneumocystis carinii pneumonia is the most frequent AIDS-defining opportunistic infection. Sputum induction and bronchoscopy are effective techniques for obtaining specimens used to identify P. carinii although debate continues over their optimal use, specifically whether to perform bronchoscopy after a negative induced sputum examination for P. carinii. To evaluate the usefulness of bronchoscopy in this situation, we reviewed all cases of suspected P. carinii pneumonia in which sputum induction for P. carinii was performed at San Francisco General Hospital during a 4-yr period. Bronchoscopy, performed after a negative induced sputum examination, yielded a diagnosis in 50.5% of evaluations. The most frequent diagnoses were P. carinii pneumonia (192), tracheobronchial Kaposi's sarcoma (93), tuberculosis (28), and Cryptococcus neoformans pneumonia (9). Bronchoscopy provided either the only or an earlier diagnosis in 64.3% of tuberculosis cases. Bronchoscopy with BAL was free of complications, and, importantly, a negative BAL examination for P. carinii allowed physicians to discontinue empiric P. carinii pneumonia treatment in 95%. In patients with suspected P. carinii pneumonia with a negative induced sputum examination for P. carinii, early bronchoscopy with BAL should be performed.

Routine analysis of induced sputum is not an effective strategy for screening persons infected with human immunodeficiency virus for Mycobacterium tuberculosis or Pneumocystis carinii. Pulmonary Complications of HIV Infection Study Group.

A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

Pulmonary fungal infections in HIV-infected persons.

Fungal infections account for a large number of AIDS-index diagnoses and complicate the course of most patients with HIV disease. Infection with Cryptococcus neoformans is the most commonly encountered deep-seated fungal infection in AIDS and represents a major threat to HIV-infected people worldwide. Although most patients with cryptococcosis present with meningitis, pulmonary disease may occasionally dominate the clinical picture. Treatment of symptomatic pulmonary cryptococcosis remains amphotericin-B with or without 5-flucytosine. The toxicity and difficulty of administration of amphotericin-B has engendered interest in treatment alternatives with the new triazoles. As HIV infection has become more common in the American heartland, it has overlapped areas endemic for Histoplasma capsulatum, Coccidioides immitis, and Blastomycosis dermatitidis. Disease from these deep-seated fungal pathogens, whether from de novo exposure or reactivation, has protean manifestations. Common to all is a protracted, febrile, wasting illness, with or without respiratory symptoms. Treatment of choice for all these infections remains amphotericin-B, followed by lifelong-maintenance therapy with a triazole. In this article I review the microbiology, epidemiology, presentation, diagnosis, and treatment of AIDS-associated deep-seated fungal infections.

Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus.

Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.

Fungal disease in HIV-infected persons: cryptococcosis, histoplasmosis, and coccidioidomycosis.

The AIDS epidemic has profoundly influenced the expression of deep-seated fungal disease in this country over the past 10 years. Previously an uncommon etiology of life threatening disease, deep-seated fungal infections with Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis accounted for nearly 3000 AIDS index diagnoses in 1990. As the epidemic matures, symptomatic HIV infection can be expected to rise in areas of endemic fungal infection resulting in further recognition of systemic fungal disease. Although amphotericin B and 5-flucytosine remain the initial treatments of choice for AIDS-associated deep fungal infection, clinical trials evaluating the new triazoles offer hope for more effective prophylaxis and treatment in the future.