Faculty Bibliography

To our knowledge, the importance of airway disease in HIV-positive patients has been infrequently noted. This deficit likely reflects a combination of factors including lack of familiarity with recent changes in clinical and epidemiologic patterns of pulmonary manifestations of HIV infection and documented limitations of chest radiography for identifying and differentiating airway disease from other causes of pulmonary disease in HIV-positive patients. Familiarity with the imaging findings for these various entities should facilitate prompt diagnosis and treatment. The accuracy of CT in detecting airway disease [55-59] is well established and should be of value in excluding more common diseases that may be initially confused with airway abnormalities [60, 61]. Small airways disease, in particular, which may be occult or mimic an interstitial infiltrate on chest radiography, can be recognized with CT as likely representing infectious bronchitis or bronchiolitis. Patients with findings suggesting bacterial infections may benefit from empiric antibiotic therapy. CT also may be valuable for differentiating between various noninfectious pulmonary diseases, allowing a presumptive diagnosis of parenchymal Kaposi's sarcoma in the appropriate clinical context. In distinction, by detecting localized endobronchial or parenchymal abnormalities in patients with mycobacterial or fungal infections or lymphoma, CT may be valuable for deciding between various invasive methods of obtaining either histologic or bacteriologic diagnoses

Mycobacterium tuberculosis and its components have been shown to stimulate mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and would have a concomitant alveolitis. We performed BAL on 26 patients with active TB and on six normal volunteers. BAL fluid from radiographically involved and uninvolved sites was evaluated separately for cell types and the spontaneous release of cytokines. The alveolar inflammation in involved sites was characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB patients that was 5- to 20-fold greater than uninvolved sites, normal controls, or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta, TNF-alpha, and IL-6 from the involved sites from two patients with TB compared with two negative controls. We conclude that BAL cells, especially alveolar macrophages, are activated in the alveolar inflammation of active TB and spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and that these cytokines are likely to be involved in directing granuloma formation and control of M. tuberculosis infection

High-resolution computed tomography (HRCT) scans have been advocated as providing greater sensitivity in detecting parenchymal opacities in asbestos-exposed individuals, especially in the presence of pleural fibrosis, and having excellent inter- and intraobserver reader interpretation. We compared the 1980 International Labor Organization (ILO) International Classification of the Radiographs of the Pneumoconioses for asbestosis with the high-resolution CT scan using a grid scoring system to better differentiate normal versus abnormal in the ILO boundary 0/1 to 1/0 chest roentgenograph. We studied 37 asbestos-exposed individuals using the ILO classification, HRCT grid scores, respiratory symptom questionnaires, pulmonary function tests, and bronchoalveolar lavage. We used Pearson correlation coefficients to evaluate the linear relationship between outcome variables and each roentgenographic method. The normal HRCT scan proved to be an excellent predictor of 'normality,' with pulmonary function values close to 100% for forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO) and no increase in BAL inflammatory cells. Concordant HRCT/ILO abnormalities were associated with reduced FEV1/FVC ratio, reduced diffusing capacity, and alveolitis consistent with a definition of asbestosis. In our study, the ILO classification and HRCT grid scores were both excellent modalities for the assessment of asbestosis and its association with impaired physiology and alveolitis, with their combined use providing statistical associations with alveolitis and reduced diffusing capacity

Asbestosis is a fibrotic and inflammatory interstitial lung disease occurring after chronic occupational exposure to asbestos. An alveolitis has been described with activated alveolar macrophages and increased neutrophils as sampled by bronchoalveolar lavage (BAL). Animal models and in vitro studies demonstrate that asbestos can stimulate alveolar macrophages to release neutrophil chemotactic factor. We performed BAL on 18 nonsmoking individuals with asbestos exposure and observed a twofold increase in percent neutrophils recovered. Alveolar macrophages cultured in vitro from the asbestos-exposed individuals spontaneously released significant amounts of the neutrophil chemotaxin, interleukin-8 (IL-8). In addition, the alveolar macrophages expressed a 2.7-fold increase in steady state mRNA levels compared to unexposed normal controls utilizing the reverse transcriptase/polymerase chain reaction. In vitro experiments confirmed that crocidolite or chrysotile asbestos could stimulate the release of IL-8 from mononuclear phagocytes in a dose-dependent fashion. We conclude that asbestos exposure causes a mild neutrophilic alveolitis, and that IL-8 is one potential mediator capable of contributing to this inflammation in the lower respiratory tract

Basaloid-squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma with biphasic basaloid and squamous features. Recognition of BSCC is important because this lesion can be confused with less aggressive lesions, such as adenoid cystic carcinoma. BSCC is typically detected at an advanced stage in smokers, alcoholics, and older individuals; adenoid cystic carcinoma is not associated with smoking or alcohol, and it typically occurs in younger individuals. Approximately 88 cases of BSCC in the upper aerodigestive tract have been recorded since its first description in 1986. We report one case of endobronchial BSCC. Cytologically, both squamous and basaloid features were identified, including elongated, irregular, globular, extracellular, hyaline material. Immunohistochemical studies showed two distinct populations of cells: the squamous component, positive for cytokeratin (AE1 + AE3) and negative for smooth-muscle actin, epithelial membrane antigen, S100 protein, and type IV collagen; and the basaloid component, positive for all of the above markers, with minimal staining for cytokeratin (AE1 + AE3). The electron microscopy demonstrated desmosomes in the squamous component and replication of the basal lamina in the basaloid component. We conclude that BSCC of the bronchus is similar to BSCC in the upper aerodigestive tract and should be regarded as a distinct entity

Despite the importance of tuberculosis as the leading cause of death due to infectious disease in the world, it has only been recently that an understanding of the human host response in this infection has begun to emerge. The key components of this response are cytokines and components of cellular immunity, predominantly T-lymphocytes and macrophages. Though the relationships among the components of the immune response are complex, it seems likely that in response to mycobacterial infection associated with active disease, cytokines such as TNF-alpha and IL-1 beta are produced; these cytokines serve to recruit more lymphocytes, generally of the T(H) (T helper) phenotype, which then produces substances such as the macrophage activating factor interferon-gamma. Macrophages activated by IFN-gamma ar thus stimulating to enhance intracellular killing of mycobacteria. The role of other cytokines, such as IL-6 and IL-8, both of which are induced by M. tuberculosis or its cell was components, is less clear. Further elucidation of the human host response to tuberculosis should help in the development of new vaccines and treatment strategies