Faculty Bibliography

OBJECTIVE AND METHODS: While pulmonary aspergilloma has been well described in immunocompetent hosts, to date and to our knowledge, there has not been a description of pulmonary aspergilloma in the HIV-infected individual. A retrospective review of cases seen by the Bellevue Hospital Chest Service from January 1992 through June 1995 identified 25 patients with aspergilloma. To investigate the impact of HIV status on pulmonary aspergilloma, we compared clinical presentation, progression of disease, treatment, and outcome in the HIV-infected patient vs the HIV-negative patient with aspergilloma. RESULTS: Of the 25 patients identified, 10 were HIV-infected and 15 were HIV-negative. Predisposing diseases included tuberculosis (18/25, 72%), sarcoidosis (4/25, 16%), and Pneumocystis carinii pneumonia (3/25, 12%). All 25 patients had evidence of aspergilloma on chest CT. In addition, 17 of 25 patients had evidence of Aspergillus species in fungal culture, pathologic specimens, or immunoprecipitins. Hemoptysis was present in 15 of 25 (60%) (11/15 [73%] of the HIV-negative group vs 4/10 [40%] of the HIV-infected group). Severe hemoptysis (> 150 mL/d) occurred in 5 of 15 (33%) of the HIV-negative group vs 1 of 10 (10%) of the HIV-infected group. Disease progression occurred more frequently among the HIV-infected group (4/8, 50% vs 1/13, 8% in HIV-negative individuals). All patients with disease progression had lymphocyte subset CD4+ < 100 cells per microliter. Four of eight (50%) of the HIV-infected group vs 1 of 13 (8%) of the HIV-negative group died. SUMMARY AND CONCLUSIONS: We conclude the following: (1) although tuberculosis and sarcoidosis are the most prevalent predisposing diseases, P carinii pneumonia in the HIV-infected individual is a risk factor for pulmonary aspergilloma; (2) HIV-infected individuals with CD4+ < 100 cells per microliter are more likely to have disease progression despite treatment; and (3) HIV-negative patients are more likely to have hemoptysis requiring intervention

We investigated the in vivo effect of coinfection of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) replication using bronchoalveolar lavage (BAL) of 11 HIV-1-infected patients with pulmonary tuberculosis and 10 patients with no lung disease. Lung segments involved with pulmonary tuberculosis had significantly elevated HIV-1 branched DNA (bDNA) levels and p24 in BAL compared with lung segments uninvolved with tuberculosis or with BAL from patients with no lung disease. The BAL viral burden was higher than plasma HIV-1 in tuberculosis patients, indicating local production of virus. BAL HIV-1 bDNA declined over the course of treatment for tuberculosis in three patients who underwent serial bronchoscopies. Tumor necrosis factor-alpha (TNF-alpha) and HIV-1 bDNA particles were strongly correlated (r2 = 0.9, p < 0.01) in lung segments involved with tuberculosis. The deduced amino acid sequence of HIV-1 gp120 V3 region from involved segments of three patients with pulmonary tuberculosis showed basic substitutions associated with altered viral phenotype. Phylogenetic analysis of V3 sequences demonstrated that BAL HIV-1 RNA had diverged from plasma. These data support the conclusion that pulmonary tuberculosis enhances local HIV-1 replication in vivo

The case history is described of a patient who presented with small rounded punctate metallic opacities widely dispersed on the chest radiograph with accumulation of metallic particles in the right ventricle. Energy dispersive x ray spectroscopy of alveolar macrophages identified a major predominant peak as bismuth. The patient had been injected with a health tonic in Honduras two years earlier

New York State (NYS) is home to 7.2% of the population and producer of 8.4% of the gross domestic product of the United States. The history and the current status of occupational and environmental medicine (OEM) research, educational resources, clinical practice patterns, and regulatory framework in NYS are reviewed. Changes anticipated or already taking place in health care financing, clinical practice patterns, occupational safety and health regulations and enforcement, and funding for research and medical education at the national level, are already having an impact in OEM activities in NYS

Asbestosis is characterized by increased collagen deposition along the walls of terminal respiratory bronchioles that extends into the alveolar ducts and septae. Alveolar macrophages are activated and release growth factors that stimulate mesenchymal cell proliferation and enhanced formation of extracellular matrix. Both insulin-like growth factor-I (IGF-I), and transforming growth factor beta (TGF-beta) regulate cellular growth and promote matrix accumulation and are hypothesized to play important roles in asbestosis. We performed immunohistochemistry using polyclonal antibodies to specific synthetic peptides of the three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) and to IGF-I on lungs of sheep treated intratracheally with chrysotile asbestos. All three TGF-beta isoforms were found in bronchial and bronchiolar epithelium, macrophages, and bronchial and vascular smooth muscle in control lungs. The distribution of TGF-beta was increased in these lung constituents as fibrotic lesions developed. Fibrotic lesions additionally demonstrated intense immunostaining of all three TGF-beta isoforms that localized to the extracellular matrix zones with little staining of interstitial cells. In the control sheep lungs, IGF-I staining was detected in bronchial and bronchiolar epithelium, bronchial glands, bronchial and vascular smooth muscle, endothelium, and macrophages. IGF-I immunostaining was detected in macrophages in peribronchial fibrosis and in fibroblasts along the periphery of and within lesions, but not in the extracellular matrix. Metaplastic proliferating epithelium and macrophages were strongly immunoreactive for IGF-I in advanced lesions. Our data demonstrate different immunostaining patterns for IGF-I and TGF-beta in asbestosis, with IGF-I in the cellular periphery and TGF-beta in the extracellular matrix consistent with a complementary role in stimulating interstitial fibroblast proliferation and new collagen deposition in areas of active fibrosis

Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous environmental microorganism whose pathogenicity ranges from innocuous colonization to disease, in immunocompetent as well as immunocompromised individuals. We sought to determine the clinical significance of MAC in sputum cultures of patients with pulmonary tuberculosis (TB). A retrospective analysis between January 1994 and March 1995 at Bellevue Hospital Center revealed both Mycobacterium tuberculosis and MAC in 35 patients (11% of all patients with TB). Of 27 patients reviewed, 52% were HIV-1 infected (median CD4 + 25 cells per microliter). Radiographic manifestations in patients with TB and MAC were similar to those seen in patients with TB alone. Both mycobacteria were cultured primarily from respiratory sources. M tuberculosis was usually cultured first or concurrent with MAC, and in nearly all cases, both species were recovered within 2 months of each other. Most patients improved clinically, bacteriologically, and radiographically with standard antituberculous therapy, except those with advanced AIDS, multidrug-resistant TB (MDR-TB), or disseminated MAC. We conclude that recovery of MAC in sputum is common in patients with pulmonary TB, regardless of HIV-1 infection, MDR-TB, or other clinical, bacteriologic, or radiographic attributes. MAC cultivation in most of these patients likely represents transient colonization, and in most cases is not clinically significant

INTRODUCTION: The lung concentration of angular and fibrous particles has been measured when cases are stratified into their job categories; 21 miners (metallic mines such as gold, zinc and copper), 18 iron foundrymen, 22 non-iron foundrymen, four welders, three sand-blast workers, four construction workers, three technicians and professionals, seven workers in other trades excluding welding. Twelve asbestos miners representing a positive exposure to asbestos and 20 people representing a background population were added to the previous groups. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: (1) The highest concentrations of quartz were found in mines (metallic mines), iron foundrymen and sand-blast workers. Notable amounts quartz were found in welders and professionals. (2) The highest concentrations of short fibres were found in non-iron foundrymen, asbestos miners and construction workers. (3) The highest concentrations of long fibres were found in non-iron foundry men and asbestos miners. (4) The highest concentrations of ferruginous bodies were found in non-iron foundrymen and asbestos miners. (5) The non-iron foundrymen were exposed to ceramic fibres and asbestos fibres. CONCLUSION: The results of the study may not be representative of the broad spectrum of workers in the industrial activities in which they have been involved. However, the detailed composition of the retained particles of our workers is explained both qualitatively and quantitatively by their work histories. Finally, the broad range of particle types identified in the lungs of these workers illustrate the complexity or trying to determine disease origins in these occupational settings

IL-6 has been characterized as a pleiotropic cytokine with multiple biologic activities, but its induction and role in asbestos diseases have not been studied. Asbestos fibers were found to stimulate IL-6 expression and secretion in pulmonary type II-like epithelial A549 cells as well as in normal human bronchial epithelial cells. IL-6 induction was dependent on the intracellular redox-oxidative state, since intracellular hydroxyl scavengers and N-acetylcysteine, a precursor of glutathione, abrogated IL-6 secretion by asbestos or H2O2. IL-6 induction paralleled increased DNA binding activity to the nuclear factor-kappa B (NF-kappa B)- and NF-IL-6-recognized sites in the IL-6 promoter. The NF-kappa B and NF-IL-6 DNA binding proteins were immunochemically characterized as a heterodimer p65/p50 and a homodimer C/EBP beta, respectively. Stimulation of DNA binding activity to the NF-kappa B and NF-IL-6 binding sites of the IL-6 promoter by asbestos or H2O2 were inhibited by tetramethylthiourea, a hydroxyl radical scavenger. The role of local IL-6 production in the pathophysiologic processes of fiber-induced lung disorders was examined. Although less active than fibroblast growth factor, human rIL-6 also stimulated lung fibroblast growth, as evidenced by increased [3H]thymidine incorporation. Furthermore, elevated IL-6 levels were found in bronchoalveolar lavage fluids from patients diagnosed with lung fibrosis and work-related histories of long term asbestos exposure. Taken together, the results suggest that asbestos-induced oxidative stress is involved in the activation of NF-kappa B and NF-IL-6 transcription factors, which recognize the IL-6 promoter. The resulting increase in IL-6 expression may be involved in both inflammatory and fibrotic processes in the lung

The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.